Case study: a young male with auditory hallucinations in paranoid schizophrenia.

PubMed

Kotowski, Abigail

2012-02-01

The purpose of this case study is to demonstrate use of the nursing process and the standardized nursing languages of NANDA International (NANDA-I), the Nursing Outcomes Classification (NOC), and the Nursing Interventions Classification (NIC) to assist a young male with paranoid schizophrenia to deal with auditory hallucinations. Data were obtained from the experience and expertise of the author and published literature. This case study demonstrates nurses' clinical decision making in providing care for an adolescent with mental illness. This case study provides the pertinent nursing diagnosis, patient outcomes, and nursing interventions for a young male with auditory hallucinations in paranoid schizophrenia. The use of NANDA-I, NOC, and NIC can provide the necessary framework for enhancing and improving the management of care with patients who experience auditory hallucinations in paranoid schizophrenia. © 2011, The Authors. International Journal of Nursing Terminologies and Classifications © 2011, NANDA International.

Pineal gland volume in schizophrenia and mood disorders.

PubMed

Fındıklı, Ebru; Inci, Mehmet Fatih; Gökçe, Mustafa; Fındıklı, Hüseyin Avni; Altun, Hatice; Karaaslan, Mehmet Fatih

2015-06-01

The majority of patients with schizophrenia and mood disorders have disruptions in sleep and circadian rhythm. Melatonin, which is secreted by the human pineal gland, plays an important role in sleep and circadian rhythm. The aim of the present study was to evaluate and compare pineal gland volumes in patients with schizophrenia and mood disorders. We retrospectively evaluated the pineal gland volumes of 80 cases, including 16 cases of unipolar depression, 17 cases of bipolar disorder, 17 cases of schizophrenia, and 30 controls. The total pineal gland volume of all cases was measured via magnetic resonance images, and the total mean pineal volume of each group was compared. The mean pineal volumes of patients with schizophrenia, bipolar disorder, unipolar depression, and the controls were 83.55±10.11 mm(3), 93.62±11.00 mm(3), 95.19±11.61 mm(3) and 99.73±12.03 mm(3), respectively. The mean pineal gland volume of the patients with schizophrenia was significantly smaller than those of the other groups. Our data show that patients with schizophrenia have smaller pineal gland volumes, and this deviation in pineal gland morphology is not seen in those with mood disorders. We hypothesize that volumetric changes in the pineal gland of patients with schizophrenia may be involved in the pathophysiology of this illness.

Schizophrenia and Deliberate Self-Harm: A Systematic Review of Risk Factors

ERIC Educational Resources Information Center

Haw, Camilla; Hawton, Keith; Sutton, Lesley; Sinclair, Julia; Deeks, Jonathan

2005-01-01

Deliberate self-harm (DSH) is a strong predictor of suicide in schizophrenia. The aim of this review was to identify risk factors for DSH in schizophrenia. This systematic review of the international literature examined cohort and case-control studies of patients with schizophrenia or related diagnoses that reported DSH as an outcome. Studies were…

Genome-Wide Association Study Reveals Greater Polygenic Loading for Schizophrenia in Cases With a Family History of Illness

PubMed Central

Bigdeli, Tim B.; Ripke, Stephan; Bacanu, Silviu-Alin; Lee, Sang Hong; Wray, Naomi R.; Gejman, Pablo V.; Rietschel, Marcella; Cichon, Sven; St Clair, David; Corvin, Aiden; Kirov, George; McQuillin, Andrew; Gurling, Hugh; Rujescu, Dan; Andreassen, Ole A.; Werge, Thomas; Blackwood, Douglas H.R.; Pato, Carlos N.; Pato, Michele T.; Malhotra, Anil K.; O’Donovan, Michael C.; Kendler, Kenneth S.; Fanous, Ayman H.

2018-01-01

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N = 978), cases reporting no such family history (N = 4,503), and unscreened controls (N = 8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke’s R2 = 0.0021; P = 0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P = 0.031).We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by previous epidemiological studies. PMID:26663532

Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.

PubMed

Rai, Vandana; Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil K; Gupta, Sanjay

2017-04-01

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.

Diagnostic profile and suicide risk in schizophrenia spectrum disorder.

PubMed

Reutfors, Johan; Bahmanyar, Shahram; Jönsson, Erik G; Ekbom, Anders; Nordström, Peter; Brandt, Lena; Ösby, Urban

2010-11-01

Earlier studies of patients with schizophrenia have investigated suicide risk in relation to specific psychiatric symptoms, but it remains to be better understood how suicide risk relates to the diagnostic profile in these patients. We identified all patients with a first clinical ICD-diagnosis of schizophrenia, schizophreniform or schizoaffective disorder in Stockholm County between 1984 and 2000. Patients who died by suicide within five years from diagnosis were defined as cases (n=84) and were individually matched with a similar number of living controls from the same population. Sociodemographic and clinical variables were retrieved from hospital records through a blind process. DSM-IV lifetime diagnoses for cases and controls were derived using the OPCRIT algorithm. A schizophrenia spectrum diagnosis (i.e. schizophrenia, schizophreniform or schizoaffective disorder) was assigned by OPCRIT to 50% of the suicide cases and 62% of the controls. Criteria for schizophrenia were met by 41% of the cases and 51% of the controls; for schizoaffective disorder by 8% of the cases and 10% of the controls; for other psychosis by 23% of the cases and 25% of the controls; and for mood disorder by 26% of the cases and 12% of the controls. Using the schizophrenia diagnosis as a reference, suicide risk was significantly higher in patients meeting criteria for a mood disorder diagnosis with an adjusted odds ratio of 3.3 (95% CI 1.2-9.0). In patients with a clinical schizophrenia spectrum diagnosis, a DSM-IV mood disorder diagnosis increases the suicide risk more than three-fold. Copyright © 2010 Elsevier B.V. All rights reserved.

Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain

PubMed Central

Purves-Tyson, T D; Owens, S J; Rothmond, D A; Halliday, G M; Double, K L; Stevens, J; McCrossin, T; Shannon Weickert, C

2017-01-01

The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per 27 controls) using immunoblotting. TH and aromatic acid decarboxylase (AADC) mRNA and TH protein were unchanged in the midbrain in schizophrenia compared with controls. Dopamine receptor D2 short, vesicular monoamine transporter (VMAT2) and DAT mRNAs were significantly decreased in schizophrenia, with no change in DRD3 mRNA, DRD3nf mRNA and DAT protein between diagnostic groups. However, DAT protein was significantly increased in putatively treatment-resistant cases of schizophrenia compared to putatively treatment-responsive cases. Midbrain monoamine oxidase A (MAOA) mRNA was increased, whereas MAOB and catechol-O-methyl transferase mRNAs were unchanged in schizophrenia. We conclude that, whereas some mRNA changes are consistent with increased dopamine action (decreased DAT mRNA), others suggest reduced dopamine action (increased MAOA mRNA) in the midbrain in schizophrenia. Here, we identify a molecular signature of dopamine dysregulation in the midbrain in schizophrenia that mainly includes gene expression changes of molecules involved in dopamine synthesis and in regulating the time course of dopamine action. PMID:28094812

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

PubMed

Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L; Kähler, Anna K; Akterin, Susanne; Bergen, Sarah E; Collins, Ann L; Crowley, James J; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K E; Sanchez, Nick; Stahl, Eli A; Williams, Stephanie; Wray, Naomi R; Xia, Kai; Bettella, Francesco; Borglum, Anders D; Bulik-Sullivan, Brendan K; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L; Holmans, Peter; Hougaard, David M; Kendler, Kenneth S; Lin, Kuang; Morris, Derek W; Mors, Ole; Mortensen, Preben B; Neale, Benjamin M; O'Neill, Francis A; Owen, Michael J; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L; Riley, Brien P; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T; Levinson, Douglas F; Gejman, Pablo V; Kendler, Kenneth S; Laurent, Claudine; Mowry, Bryan J; O'Donovan, Michael C; Owen, Michael J; Pulver, Ann E; Riley, Brien P; Schwab, Sibylle G; Wildenauer, Dieter B; Dudbridge, Frank; Holmans, Peter; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A; Nestadt, Gerald; Norton, Nadine; O'Neill, Francis A; Papadimitriou, George N; Ribble, Robert; Sanders, Alan R; Silverman, Jeremy M; Walsh, Dermot; Williams, Nigel M; Wormley, Brandon; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M; Lin, Kuang; Linszen, Don H; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M; Ophoff, Roel A; Powell, John; Rujescu, Dan; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden P; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Spencer, Chris C A; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T; Liddle, Jennifer; Potter, Simon C; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G; Blackwell, Jenefer M; Brown, Matthew A; Corvin, Aiden P; McCarthy, Mark I; Spencer, Chris C A; Bramon, Elvira; Corvin, Aiden P; O'Donovan, Michael C; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A; Sklar, Pamela; Hultman, Christina M; Sullivan, Patrick F

2013-10-01

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

A review of schizophrenia research in malaysia.

PubMed

Chee, K Y; Salina, A A

2014-08-01

Research in schizophrenia has advanced tremendously. One hundred and seventy five articles related to Schizophrenia were found from a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. This project aims to examine published research articles, in local and international journals in order to provide a glimpse of the research interest in Malaysia with regards to schizophrenia. Single case study, case series report, reviews and registry reports were not included in this review. Medication trial, unless it concerned a wider scope of psychopharmacology was also excluded from this review. A total of 105 articles were included in this review. Despite numerous genetics studies conducted and published, a definitive conclusion on the aetiology or mechanism underlying schizophrenia remains elusive. The National Mental Health - Schizophrenia Registry (NMHR) proved to be an important platform for many studies and publications. Studies stemmed from NMHR have provided significant insight into the baseline characteristic of patients with schizophrenia, pathway to care, and outcomes of the illness. International and regional collaborations have also encouraged important work involving stigma and discrimination in schizophrenia. Ministry of Health's hospitals (MOH) are the main research sites in the country with regards to schizophrenia research. Numbers of schizophrenia research are still low in relation to the number of universities and hospitals in the country. Some of the weaknesses include duplication of studies, over-emphasising clinical trials and ignoring basic clinical research, and the lack of publications in international and regional journals.

Telomere length and early trauma in schizophrenia.

PubMed

Riley, Gabriella; Perrin, Mary; Vaez-Azizi, Leila M; Ruby, Eugene; Goetz, Raymond R; Dracxler, Roberta; Walsh-Messinger, Julie; Keefe, David L; Buckley, Peter F; Szeszko, Philip R; Malaspina, Dolores

2018-04-02

Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex effects. The early trauma inventory (ETI) was administered to 48 adults with DSM-5 schizophrenia and 18 comparison participants. LTL was measured using qPCR. Cases had significantly more global trauma (F=4.10, p<0.01) and traumatic events (F=11.23, p<0.001), but case and control groups had similar LTL (1.91±0.74 and 1.83±0.62: p=0.68). The association of early trauma and LTL differed by sex in cases and controls (Fisher's R: Z<0.05). Significant negative associations were shown in male cases and, conversely, in female controls. For example, physical punishment was associated LTL shortening in males' cases (r=-0.429, p<01). Only female controls showed significant telomere shortening in association with early trauma. This data confirms the substantial excess of early trauma among schizophrenia cases. There were significant sex-differences in the relationship of the trauma to LTL, with only male cases showing the expected shortening. There were converse sex effects in the control group. Mean LTL was notably similar in cases and controls, despite the trauma-related shortening in male cases, cigarette smoking, older age and chronic illness of the cases. Factors may lengthen LTL in some schizophrenia cases. The converse sex differences in the cases are consistent with findings defective sexual differentiation in schizophrenia, consistent with other findings in the field. Copyright © 2018 Elsevier B.V. All rights reserved.

Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring?

PubMed Central

Khandaker, G M; Dibben, C R M; Jones, P B

2012-01-01

Summary Maternal obesity in pregnancy has been linked with several adverse outcomes in offspring including schizophrenia. The rising prevalence of obesity may contribute to an increase in the number of schizophrenia cases in the near future; therefore, it warrants further exploration. We reviewed current evidence regarding maternal body mass index (BMI) in pregnancy and risk of schizophrenia in adult offspring. We searched PubMed and Embase databases and included studies that were based on large and representative population-based datasets. A qualitative review was undertaken due to heterogeneity between studies. Four studies with 305 cases of schizophrenia and 24,442 controls were included. Maternal obesity (pre-pregnant BMI over 29 or 30 compared with mothers with low or average BMI) was associated with two- to threefold increased risk of schizophrenia in the adult offspring in two birth cohorts. High maternal BMI at both early and late pregnancy also increased risk of schizophrenia in the offspring. Discrepant findings from one study could be attributable to sample characteristics and other factors. The area needs more research. Future studies should take into account obstetric complications, diabetes, maternal infections and immune responses that might potentially mediate this association. PMID:22188548

Does varenicline worsen psychiatric symptoms in patients with schizophrenia or schizoaffective disorder? A review of published studies.

PubMed

Cerimele, Joseph M; Durango, Alejandra

2012-08-01

To review published cases and prospective studies describing the use of varenicline in patients with schizophrenia and schizoaffective disorder. PubMed, PsychINFO, and the Cochrane Database were searched in July 2011 using the key words schizophrenia, schizoaffective disorder, psychosis, positive symptoms, negative symptoms, aggression, hostility, suicidal ideation AND varenicline to identify reports published between January 2006 and July 2011 in English. Five case reports, 1 case series, 1 retrospective study, 10 prospective studies (17 publications), and 1 meeting abstract describing the use of varenicline in patients with schizophrenia or schizoaffective disorder were identified. Review articles and articles describing findings other than the use of varenicline in patients with schizophrenia or schizoaffective disorder were excluded. Thirteen reports were included in the final analysis. Information on each study's patient population, age, diagnosis, medication treatment, tobacco use history, adverse effects, and outcome was collected from the published reports. Of the 260 patients with schizophrenia or schizoaffective disorder who received varenicline in these published reports, 13 patients (5%) experienced the onset or worsening of any psychiatric symptom, although 3 of the 13 patients experienced a very brief negative effect after 1 dose. No patients experienced suicidal ideation or suicidal behaviors. Published reports suggest that, in most stable, closely monitored patients with schizophrenia or schizoaffective disorder, varenicline treatment is not associated with worsening of psychiatric symptoms. Current, prospective studies are assessing effectiveness and further assessing safety in this population. © Copyright 2012 Physicians Postgraduate Press, Inc.

Association of the 5′-upstream regulatory region of the α7 nicotinic acetylcholine receptor subunit gene (CHRNA7) with schizophrenia

PubMed Central

Stephens, Sarah H.; Logel, Judith; Barton, Amanda; Franks, Alexis; Schultz, Jessica; Short, Margaret; Dickenson, Jane; James, Benjamin; Fingerlin, Tasha E.; Wagner, Brandie; Hodgkinson, Colin; Graw, Sharon; Ross, Randal G.; Freedman, Robert; Leonard, Sherry

2009-01-01

Background The α7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) is localized in a chromosomal region (15q14) linked to schizophrenia in multiple independent studies. CHRNA7 was selected as the best candidate gene in the region for a well-documented endophenotype of schizophrenia, the P50 sensory processing deficit, by genetic linkage and biochemical studies. Methods Subjects included Caucasian-Non Hispanic and African-American case-control subjects collected in Denver, and schizophrenic subjects from families in the NIMH Genetics Initiative on Schizophrenia. Thirty-five single nucleotide polymorphisms (SNPs) in the 5′-upstream regulatory region of CHRNA7 were genotyped for association with schizophrenia, and for smoking in schizophrenia. Results The rs3087454 SNP, located at position −1831 bp in the upstream regulatory region of CHRNA7, was significantly associated with schizophrenia in the case-control samples after multiple-testing correction (P = 0.0009, African American; P = 0.013, Caucasian-Non Hispanic); the association was supported in family members. There was nominal association of this SNP with smoking in schizophrenia. Conclusions The data support association of regulatory region polymorphisms in the CHRNA7 gene with schizophrenia. PMID:19181484

Maintenance ECT in schizophrenia: A systematic review.

PubMed

Ward, Heather Burrell; Szabo, Steven T; Rakesh, Gopalkumar

2018-03-20

Relapse after discontinuation of ECT is significant in patients with schizophrenia. The purpose of this systematic review was to examine use of M-ECT in schizophrenia to guide clinical decision making for relapse prevention in schizophrenia. We reviewed studies examining the role of continuation (C-ECT) and maintenance electroconvulsive therapy (M-ECT) in schizophrenia. Following PRISMA guidelines, we included randomized controlled trials, open label trials, retrospective chart reviews, case reports, and case series in this review. We evaluated adjunctive pharmacological regimens; ECT treatment parameters, including frequency, duration of continued treatment, electrode placement; clinical outcomes including cognitive side effects and relapse rates from included studies. Our findings suggest M-ECT could provide an effective form of relapse prevention in these patients and persistent cognitive side effects are minimal. Copyright © 2018 Elsevier B.V. All rights reserved.

The genetic validation of heterogeneity in schizophrenia.

PubMed

Tsutsumi, Atsushi; Glatt, Stephen J; Kanazawa, Tetsufumi; Kawashige, Seiya; Uenishi, Hiroyuki; Hokyo, Akira; Kaneko, Takao; Moritani, Makiko; Kikuyama, Hiroki; Koh, Jun; Matsumura, Hitoshi; Yoneda, Hiroshi

2011-10-07

Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors. No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39). The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

Association study of NDST3 gene for schizophrenia, bipolar disorder, major depressive disorder in the Han Chinese population.

PubMed

Wang, Lin; Chen, Jianhua; Li, Zhiqiang; Sun, Weiming; Chen, Boyu; Li, Sining; Li, Weidong; Lu, Dajiang; Wang, Yonggang; Shi, Yongyong

2018-01-01

The NDST3 gene at 4q26 was a functional candidate gene for mental disorders. Recently, a novel genome-wide significant risk locus at chromosome 4q26 was identified and the top single nucleotide polymorphism rs11098403 in the vicinity of NDST3 gene was reported to confer risk of schizophrenia in Caucasian. Nevertheless, association between NDST3 gene polymorphisms and schizophrenia, bipolar disorder, or major depressive disorders has not been well studied in the Han Chinese population. To further investigate whether NDST3 is a risk gene for these mental disorders, we genotyped and analyzed eight tag SNPs (rs11098403, rs10857057, rs2389521, rs4833564, rs6837896, rs7689157, rs3817274, rs609512) covering NDST3 gene in 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls of Chinese origin. However, there was no significant difference in allelic or genotypic frequency observed between each case group and healthy controls. Accordingly, our study does not support that the NDST3 gene plays a major role in schizophrenia, bipolar disorder, and major depressive disorder in the Han Chinese population. © 2017 Wiley Periodicals, Inc.

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort

PubMed Central

Gyllenberg, David; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; McKeague, Ian W.; Brown, Alan S.

2015-01-01

Background Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early to mid-gestation is associated with offspring schizophrenia. Methods The investigation is based on the Finnish Prenatal Study of Schizophrenia (FiPS-S), a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (total N over 1 million). We identified all offspring in the cohort diagnosed with schizophrenia based on the national inpatient and outpatient register and matched them to comparison subjects (1:1) from the cohort on sex, date of birth, and residence in Finland at time of onset of the case. Maternal sera on 1010 case-control pairs were assessed for free thyroxine (fT4) and 948 for thyroid stimulating hormone (TSH). Results Maternal hypothyroxinemia (fT4≤10th percentile, normal TSH) was associated with an increased odds of schizophrenia (OR=1.75, 95% CI=1.22 – 2.50; p=0.002). When adjusted for maternal psychiatric history, province of birth and maternal smoking during pregnancy, the association remained significant (OR=1.70, 95%CI 1.13 – 2.55; p=0.010). Conclusions In a large, national birth cohort, prospectively documented early to mid-gestational hypothyroxinemia was associated with increased odds of schizophrenia in offspring. This can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia. PMID:26194598

Methylenetetrahydrofolate reductase A1298C genetic variant & risk of schizophrenia: A meta-analysis

PubMed Central

Rai, Vandana; Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil K.; Gupta, Sanjay

2017-01-01

Background & objectives: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. Methods: PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. Results: The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). Interpretation & conclusions: MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia. PMID:28862175

The struggle for schizophrenia treatment: A case study.

PubMed

Kozlowski-Gibson, Maria

Individual of legal age with schizophrenia presenting anosognosia was abandoned, as a result of a court decision. Close family members were not allowed to provide medical follow-up, treatment, protection regarding his vulnerability, and preserve the dignity of their loved one. The issue was the court's prioritization of the autonomy of the individual over his mental health status. The purpose of this case study was to identify the pitfalls of a court case seeking medical follow-up and treatment for a family member with schizophrenia and anosognosia. The method was qualitative and the design was descriptive and instrumental, linking the law to the life experience resulting from the procedures for its implementation. This study examined the difference between clinical and medical-legal evaluation of the examinee. The application of the Therapeutic Jurisprudence principles to the high number of schizophrenia cases with anosognosia, the abandonment of the mentally ill, and family crisis call healthcare providers and the Judiciary for an improvement action of the process of guardianship. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is MYO9B the missing link between schizophrenia and celiac disease?

PubMed

Jungerius, Bart J; Bakker, Steven C; Monsuur, Alienke J; Sinke, Richard J; Kahn, Rene S; Wijmenga, Cisca

2008-04-05

There has long been discussion on the correlation between schizophrenia and autoimmune diseases (especially celiac disease), which makes the recently discovered celiac disease risk factor, MYO9B, an attractive functional and positional candidate gene for schizophrenia. To test this hypothesis we compared allele frequencies of three MYO9B tag SNPs in 315 schizophrenia cases and 1,624 healthy controls in a genetic association study. Highly significant differences in allele frequencies between schizophrenia cases and healthy controls were observed for SNP rs2305767 in intron 14 of MYO9B (P = 1.16 x 10(-4); OR 1.41, 95% CI 1.18-1.67). We demonstrate significant association of allelic variants in MYO9B with schizophrenia. To our knowledge, this is the first molecular genetic evidence for a correlation between autoimmune diseases and the risk of developing schizophrenia. Copyright 2007 Wiley-Liss, Inc.

Toxoplasmosis gondii and schizophrenia: a case control study in a low Toxoplasma gondii seroprevalence Mexican population

USDA-ARS?s Scientific Manuscript database

There are conflicting reports concerning the association of T. gondii infection and schizophrenia. Therefore, we determined such association in a Mexican population of Mestizo ethnicity. Through a case-control study design, 50 schizophrenic patients and 150 control subjects matched by gender, age, r...

Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia.

PubMed

Benros, Michael E; Trabjerg, Betina B; Meier, Sandra; Mattheisen, Manuel; Mortensen, Preben B; Mors, Ole; Børglum, Anders D; Hougaard, David M; Nørgaard-Pedersen, Bent; Nordentoft, Merete; Agerbo, Esben

2016-10-15

Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability toward infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRSs) for schizophrenia on the association between infections and the risk of schizophrenia. We conducted a nested case-control study on a Danish population-based sample born after 1981 comprising of 1692 cases diagnosed with schizophrenia between 1994 and 2008 and 1724 matched controls. All individuals were linked utilizing nationwide population-based registers with virtually complete registration of all hospital contacts for infections. PRSs were calculated using discovery effect size estimates weights from an independent meta-analysis (34,600 cases and 45,968 control individuals). A prior hospital contact with infection had occurred in 41% of the individuals with schizophrenia and increased the incidence rate ratio (IRR) of schizophrenia by 1.43 (95% confidence interval [CI] = 1.22-1.67). Adding PRS, which was robustly associated with schizophrenia (by an IRR of 1.46 [95% CI = 1.34-1.60] per standard deviation of the score), did not alter the association with infections and the increased risk of schizophrenia remained (IRR = 1.41; 95% CI = 1.20-1.66). Furthermore, there were no interactions between PRS and infections on the risk of developing schizophrenia (p = .554). Neither did PRS affect the risk of acquiring infections among patients with schizophrenia (odds ratio = 1.00; 95% CI = 0.89-1.12) nor among controls (odds ratio = 1.09; 95% CI: 0.96-1.24). PRS and a history of infections have independent effects on the risk for schizophrenia, and the common genetic risk measured by PRS did not account for the association with infection in this sample. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Common variants on chromosome 6p22.1 are associated with schizophrenia

PubMed Central

Shi, Jianxin; Levinson, Douglas F.; Duan, Jubao; Sanders, Alan R.; Zheng, Yonglan; Pe'er, Itsik; Dudbridge, Frank; Holmans, Peter A.; Whittemore, Alice S.; Mowry, Bryan J.; Olincy, Ann; Amin, Farooq; Cloninger, C. Robert; Silverman, Jeremy M.; Buccola, Nancy G.; Byerley, William F.; Black, Donald W.; Crowe, Raymond R.; Oksenberg, Jorge R.; Mirel, Daniel B.; Kendler, Kenneth S.; Freedman, Robert; Gejman, Pablo V.

2009-01-01

Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission.1 Recent studies implicate rare, large, high-penetrance copy number variants (CNVs) in some cases2, but it is not known what genes or biological mechanisms underlie susceptibility. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended Major Histocompatibility Complex (MHC) region on chromosome 6. We carried out a genome-wide association study (GWAS) of common SNPs in the Molecular Genetics of Schizophrenia (MGS) case-control sample, and then a meta-analysis of data from the MGS, International Schizophrenia Consortium (ISC) and SGENE datasets. No MGS finding achieved genome-wide statistical significance. In the meta-analysis of European-ancestry subjects (8,008 cases, 19,077 controls), significant association with schizophrenia was observed in a region of linkage disequilibrium on chromosome 6p22.1 (P = 9.54 × 10−9). This region includes a histone gene cluster and several immunity-related genes, possibly implicating etiologic mechanisms involving chromatin modification, transcriptional regulation, auto-immunity and/or infection. These results demonstrate that common schizophrenia susceptibility alleles can be detected. The characterization of these signals will suggest important directions for research on susceptibility mechanisms. PMID:19571809

Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort.

PubMed

Canetta, Sarah; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; Leiviskä, Jaana; Kellendonk, Christoph; McKeague, Ian W; Brown, Alan S

2014-09-01

The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank. A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens. Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

Elevated Maternal C-Reactive Protein is Associated with Increased Risk of Schizophrenia in a National Birth Cohort

PubMed Central

Canetta, Sarah; Sourander, Andre; Surcel, Helja-Marja; Hinkka-Yli-Salomäki, Susanna; Leiviskä, Jaana; Kellendonk, Christoph; McKeague, Ian W.; Brown, Alan S.

2014-01-01

Objective The goal of the present study was to investigate an association between early gestational C-reactive protein (CRP), an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large national birth cohort with an extensive serum biobank. Methods This study utilized a nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort. 777 schizophrenia cases (630 with schizophrenia, 147 with schizoaffective disorder) that had maternal sera available for CRP testing were identified and matched to 777 controls in the analysis. Maternal CRP levels were assessed using a latex immunoassay from archived maternal serum specimens. Results Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio (OR)=1.31, 95% confidence interval (CI)=1.10-1.56, p=0.003). This finding remained significant after adjusting for potential confounders including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. Conclusion This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders. PMID:24969261

Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.

PubMed

Yu, H; Yan, H; Li, J; Li, Z; Zhang, X; Ma, Y; Mei, L; Liu, C; Cai, L; Wang, Q; Zhang, F; Iwata, N; Ikeda, M; Wang, L; Lu, T; Li, M; Xu, H; Wu, X; Liu, B; Yang, J; Li, K; Lv, L; Ma, X; Wang, C; Li, L; Yang, F; Jiang, T; Shi, Y; Li, T; Zhang, D; Yue, W

2017-07-01

Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10 -12 , odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10 -10 , OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10 -10 , OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10 -9 , OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2 : 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

Genetic liability for schizophrenia predicts risk of immune disorders.

PubMed

Stringer, Sven; Kahn, René S; de Witte, Lot D; Ophoff, Roel A; Derks, Eske M

2014-11-01

Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between schizophrenia and three immune disorders and to compare with the overlap between schizophrenia and two disorders not primarily characterized by immune dysregulation: bipolar disorder and type 2 diabetes. We performed a polygenic risk score analysis using results from the schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528 controls) and five Wellcome Trust Case Control Consortium (WTCCC) case samples as target cases: bipolar disorder (n=1998), type 1 diabetes (n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National Blood Service samples (n=3004) were used as target controls. Additionally, we tested whether schizophrenia polygenic risk scores significantly differed between patients with immune disorder, bipolar disorder, and type 2 diabetes respectively. Polygenic risk scores for schizophrenia significantly predicted disease status in all three immune disorder samples (Nagelkerke-R(2) 1.1%-1.3%; p<0.05). The polygenic risk of schizophrenia in patients with immune disorders was significantly lower than in patients with bipolar disorder (Nagelkerke-R(2) 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R(2) 0.5%; p<0.05). Our results suggest that genetic factors are shared between schizophrenia and immune disorders. This contributes to an accumulating body of evidence that immune processes may play a role in the etiology of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Autism Spectrum Disorders and Childhood-Onset Schizophrenia: Clinical and Biological Contributions to a Relation Revisited

ERIC Educational Resources Information Center

Rapopart, Judith; Chavez, Alex; Greenstein, Deanna; Addington, Anjene; Gogtay, Nitin

2009-01-01

Clinical, demographic, and brain development data on childhood-onset schizophrenia (COS) and family, imaging and genetic data from studies of autism were reviewed. It is found that COS is preceded by and comorbid with autism/pervasive developmental disorder and schizophrenia in 30 to 50 percent of cases based on two large studies.

Association of Toxoplasma gondii infection with schizophrenia and its relationship with suicide attempts in these patients.

PubMed

Ansari-Lari, Maryam; Farashbandi, Hassan; Mohammadi, Fahimeh

2017-10-01

To investigate the association between schizophrenia and Toxoplasma gondii, and to assess the association of infection with suicide attempts and age of onset of schizophrenia in these patients. Case-control study Fars Province, southern Iran. Cases were individuals with psychiatric diagnosis of schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Controls were healthy blood donors, frequency-matched with patients according to age and sex. For the detection of IgG antibodies, enzyme-linked immunosorbent assay (ELISA) was used. Data about demographic information in all subjects and duration of illness and history of suicide attempts in patients with schizophrenia were collected using a brief questionnaire and hospital records. Chi-square test and multivariable logistic regression were used for statistical analyses. Among 99 cases, 42 individuals (42%) were positive for T. gondii antibody, vs. 41 (27%) among 152 controls (OR = 2, 95% CI: 1.2-3.4, P = 0.012). We compared the suicide attempts in patients with schizophrenia based on their T. gondii serologic status. There was a lower rate of suicide attempts in seropositive male patients than seronegative ones (OR = 0.3, 95% CI: 0.1-0.97, P = 0.04). Age of onset of schizophrenia did not differ between T. gondii-infected and non-infected patients. These findings may have implications for schizophrenia and suicide prevention programmes. However, clearly further studies are required to confirm them. © 2017 John Wiley & Sons Ltd.

Results from a hypothesis generating case-control study: herpes family viruses and schizophrenia among military personnel.

PubMed

Niebuhr, David W; Millikan, Amy M; Yolken, Robert; Li, Yuanzhang; Weber, Natalya S

2008-11-01

Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research. Most existing studies of herpes viruses have used small populations and postdiagnosis specimens. As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the US military with schizophrenia and pre- and postdiagnosis sera. Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia. Controls, 3:1 matched on several factors, were members not discharged. The military routinely collects and stores members' serum specimens. We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens. Conditional logistic regression was used, and the measure of association was the hazard ratio (HR). Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32). Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1. Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6-12 months before diagnosis. Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies.

Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel

PubMed Central

Niebuhr, David W.; Millikan, Amy M.; Yolken, Robert; Li, Yuanzhang; Weber, Natalya S.

2008-01-01

Background: Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research. Most existing studies of herpes viruses have used small populations and postdiagnosis specimens. As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the US military with schizophrenia and pre- and postdiagnosis sera. Methods: Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia. Controls, 3:1 matched on several factors, were members not discharged. The military routinely collects and stores members' serum specimens. We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens. Conditional logistic regression was used, and the measure of association was the hazard ratio (HR). Results: Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32). Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1. Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6–12 months before diagnosis. Discussion: Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies. PMID:18156638

Lack of association between sigma receptor gene variants and schizophrenia.

PubMed

Satoh, Fumiaki; Miyatake, Ryosuke; Furukawa, Aizo; Suwaki, Hiroshi

2004-08-01

Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia.

Chronic catatonic schizophrenia treated successfully with right unilateral ultrabrief pulse electroconvulsive therapy: case report.

PubMed

Cupina, Denise; Patil, Sachin; Loo, Colleen

2013-06-01

Catatonia is a syndrome with prominent motor and behavioral symptoms commonly seen in acutely ill psychiatric patients. Catatonic symptoms have been considered as positive predictors of response to electroconvulsive therapy (ECT); however, few studies so far have addressed the role of ECT treatment technique in schizophrenia. We present the case of a 41-year-old woman with chronic catatonic schizophrenia who was treated successfully with a course of ultrabrief right unilateral ECT.

Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population.

PubMed

Zhang, Yanxia; Fan, Mei; Wang, Qingzhong; He, Guang; Fu, Yingmei; Li, Huafang; Yu, Shunying

2015-08-10

Disturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate-type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs in hsa-pri-miR-219/132/107 and 6 SNPs in 3'UTRs of GRIN2A/2B/3A and CAMK2G were selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study, GRIN2B rs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.

Long-Term Effect of Prefrontal Lobotomy on Verbal Fluency in Patients with Schizophrenia

ERIC Educational Resources Information Center

Stip, Emmanuel; Bigras, Marie-Josee.; Mancini-Marie, Adham; Cosset, Marie-Eve.; Black, Deborah; Lecours, Andre-Roch

2004-01-01

Objective: This study investigated the long-term effects of bilateral prefrontal leukotomy on lexical abilities in schizophrenia subjects. Method: We compared performances of leukotomized (LSP), non-leukotomized schizophrenia patients (NLSP) and normal controls, using a test of verbal fluency. Multiple case and triple comparison design were…

Schizophrenia: illness impact on family members in a traditional society--rural Ethiopia.

PubMed

Shibre, T; Kebede, D; Alem, A; Negash, A; Deyassa, N; Fekadu, A; Fekadu, D; Jacobsson, L; Kullgren, G

2003-01-01

Studies have consistently shown that both the subjective and objective dimensions of burden among family members of schizophrenia patients and other psychiatric disorders are prevalent. However, as most of these reports were from western societies, we lack information on the subject in developing countries. The study was conducted within the framework of the ongoing epidemiological study of course and outcome of schizophrenia and bipolar disorders in a rural population of 15-49 years of age. Three hundred and one cases of schizophrenia and their close relatives participated in the study. Family burden is a common problem of relatives of cases with schizophrenia. Financial difficulty is the most frequently endorsed problem among the family burden domains (74.4 %). Relatives of female cases suffered significantly higher social burden (Z = 2.103; p = 0.036). Work (Z = 2.180; p = 0.029) and financial (Z = 2.088; p = 0.037) burdens affected female relatives more often than males. Disorganised symptoms were the most important factors affecting the family members in all family burden domains. Prayer was found to be the most frequently used coping strategy in work burden (adj. OR = 1.99; 95 % CI = 1.08-3.67; p = 0.026). Negative impact of schizophrenia on family members is substantial even in traditional societies such as those in Ethiopia where family network is strong and important. The scarce existing services in the developing countries should include family interventions and support at least in the form of educating the family members about the nature of schizophrenia illness and dealing with its stigma and family burden.

Association between ErbB4 single nucleotide polymorphisms and susceptibility to schizophrenia: A meta-analysis of case-control studies.

PubMed

Feng, Yanguo; Cheng, Dejun; Zhang, Chaofeng; Li, Yuchun; Zhang, Zhiying; Wang, Juan; Feng, Xiao

2017-02-01

Accumulating studies have reported inconsistent association between ErbB4 single nucleotide polymorphisms (SNPs) and predisposition to schizophrenia. To better interpret this issue, here we conducted a meta-analysis using published case-control studies. We conducted a systematic search of MEDLINE (Pubmed), Embase (Ovid), Web of Science (Thomson-Reuters) to identify relevant references. The association between ErbB4 SNPs and schizophrenia was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was evaluated by I squared (I) statistics and Cochran's Q test. To appraise the stability of results, we employed sensitivity analysis by omitting 1 single study each time. To assess the potential publication bias, we conducted trim and fill analysis. Seven studies published in English comprising 3162 cases and 4264 controls were included in this meta-analysis. Meta-analyses showed that rs707284 is statistically significantly associated with schizophrenia susceptibility among Asian and Caucasian populations under the allelic model (OR = 0.91, 95% CI: 0.83-0.99, P = 0.035). Additionally, a marginal association (P < 0.1) was observed between rs707284 and schizophrenia risk among Asian and Caucasian populations under the recessive (OR = 0.85, 95% CI: 0.72-1.01, P = 0.065) and homozygous (OR = 0.84, 95% CI: 0.68-1.03, P = 0.094) models. In the Asian subgroup, rs707284 was also noted to be marginally associated with schizophrenia under the recessive model (OR = 0.84, 95% CI: 0.70-1.00, P = 0.053). However, no statistically significant association was found between rs839523, rs7598440, rs3748962, and rs2371276 and schizophrenia risk. This meta-analysis suggested that rs707284 may be a potential ErbB4 SNP associated with susceptibility to schizophrenia. Nevertheless, due to the limited sample size in this meta-analysis, more large-scale association studies are still needed to confirm the results.

Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study.

PubMed

Paul-Samojedny, Monika; Kowalczyk, Malgorzata; Suchanek, Renata; Owczarek, Aleksander; Fila-Danilow, Anna; Szczygiel, Aleksandra; Kowalski, Jan

2010-09-01

Schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population.

Hypothesis: Grandiosity and Guilt Cause Paranoia; Paranoid Schizophrenia is a Psychotic Mood Disorder; a Review

PubMed Central

Lake, Charles Raymond

2008-01-01

Delusional paranoia has been associated with severe mental illness for over a century. Kraepelin introduced a disorder called “paranoid depression,” but “paranoid” became linked to schizophrenia, not to mood disorders. Paranoid remains the most common subtype of schizophrenia, but some of these cases, as Kraepelin initially implied, may be unrecognized psychotic mood disorders, so the relationship of paranoid schizophrenia to psychotic bipolar disorder warrants reevaluation. To address whether paranoia associates more with schizophrenia or mood disorders, a selected literature is reviewed and 11 cases are summarized. Comparative clinical and recent molecular genetic data find phenotypic and genotypic commonalities between patients diagnosed with schizophrenia and psychotic bipolar disorder lending support to the idea that paranoid schizophrenia could be the same disorder as psychotic bipolar disorder. A selected clinical literature finds no symptom, course, or characteristic traditionally considered diagnostic of schizophrenia that cannot be accounted for by psychotic bipolar disorder patients. For example, it is hypothesized here that 2 common mood-based symptoms, grandiosity and guilt, may underlie functional paranoia. Mania explains paranoia when there are grandiose delusions that one's possessions are so valuable that others will kill for them. Similarly, depression explains paranoia when delusional guilt convinces patients that they deserve punishment. In both cases, fear becomes the overwhelming emotion but patient and physician focus on the paranoia rather than on underlying mood symptoms can cause misdiagnoses. This study uses a clinical, case-based, hypothesis generation approach that warrants follow-up with a larger representative sample of psychotic patients followed prospectively to determine the degree to which the clinical course observed herein is typical of all such patients. Differential diagnoses, nomenclature, and treatment implications are discussed because bipolar patients misdiagnosed with schizophrenia are severely misserved. PMID:18056109

Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a psychotic mood disorder; a review.

PubMed

Lake, Charles Raymond

2008-11-01

Delusional paranoia has been associated with severe mental illness for over a century. Kraepelin introduced a disorder called "paranoid depression," but "paranoid" became linked to schizophrenia, not to mood disorders. Paranoid remains the most common subtype of schizophrenia, but some of these cases, as Kraepelin initially implied, may be unrecognized psychotic mood disorders, so the relationship of paranoid schizophrenia to psychotic bipolar disorder warrants reevaluation. To address whether paranoia associates more with schizophrenia or mood disorders, a selected literature is reviewed and 11 cases are summarized. Comparative clinical and recent molecular genetic data find phenotypic and genotypic commonalities between patients diagnosed with schizophrenia and psychotic bipolar disorder lending support to the idea that paranoid schizophrenia could be the same disorder as psychotic bipolar disorder. A selected clinical literature finds no symptom, course, or characteristic traditionally considered diagnostic of schizophrenia that cannot be accounted for by psychotic bipolar disorder patients. For example, it is hypothesized here that 2 common mood-based symptoms, grandiosity and guilt, may underlie functional paranoia. Mania explains paranoia when there are grandiose delusions that one's possessions are so valuable that others will kill for them. Similarly, depression explains paranoia when delusional guilt convinces patients that they deserve punishment. In both cases, fear becomes the overwhelming emotion but patient and physician focus on the paranoia rather than on underlying mood symptoms can cause misdiagnoses. This study uses a clinical, case-based, hypothesis generation approach that warrants follow-up with a larger representative sample of psychotic patients followed prospectively to determine the degree to which the clinical course observed herein is typical of all such patients. Differential diagnoses, nomenclature, and treatment implications are discussed because bipolar patients misdiagnosed with schizophrenia are severely misserved.

Olfactory impairment in first-episode schizophrenia: a case-control study, and sex dimorphism in the relationship between olfactory impairment and psychotic symptoms.

PubMed

Chen, Xiacan; Xu, Jiajun; Li, Bin; Guo, Wanjun; Zhang, Jun; Hu, Junmei

2018-06-18

A body of studies has focused on the olfactory impairment among people with schizophrenia. The effect of sex on this relationship has attracted the attention of researchers. These issues have not been studied much in Chinese schizophrenia patients. We conducted a case-control study of 110 first-episode antipsychotic medicine naïve schizophrenia patients aged 18-35 years and 110 controls, matched by age and sex. Odour threshold, discrimination and identification were assessed by the "Sniffin' Sticks" test. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). The odour threshold, discrimination and identification scores of patients with schizophrenia were significantly lower than those of the healthy control group. The difference in identification score had statistical significance between male and female patients with schizophrenia (t = - 2.45, P < 0.05). Controlling for confounding factor, in male schizophrenia participants, the negative subscale score was significantly and inversely correlated with the discrimination (γ = - 0.37, p < 0.008), identification (γ = - 0.45, p < 0.008) and TDI (γ = - 0.50, p < 0.008) scores; the general psychopathology subscale score was inversely and significantly correlated with the identification (γ = - 0.47, p < 0.008) and TDI (γ = - 0.41, p < 0.008) scores. For female schizophrenia patients, positive and general psychopathology subscale scores had a significant inverse correlation with the identification score (positive: γ = - 0.47, p < 0.008; general psychopathology: γ = - 0.42, p < 0.008). Controlling for confounder, negative symptoms were related to impaired odour discrimination and identification in male schizophrenia patients, while positive symptoms were correlated with impaired odour identification in female schizophrenia patients. This sex dimorphism could provide useful information for future studies aiming to finding biomarkers of schizophrenia.

[Influence of paternal age in schizophrenia].

PubMed

Hubert, A; Szöke, A; Leboyer, M; Schürhoff, F

2011-06-01

Schizophrenia is an aetiologically heterogeneous syndrome, with a strong genetic component. Despite a reduced fertility in this disorder, its prevalence is maintained and could be explained by de novo genetic mutations. Advanced paternal age (APA) is a major source of new mutations in human beings and could thus be associated with an increased risk of developing schizophrenia in offspring. New mutations related to APA have been implicated as a cause of sporadic cases in several autosomal dominant diseases and also in neurodevelopmental diseases, autism, intellectual disabilities, and social functioning. The aim of the present study was to summarize the results of studies investigating the role of APA, and to discuss some interpretations. All relevant studies were identified through the National Library of Medicine (PubMed(®) database). Keywords used for research were "age" and "schizophrenia" linked to "paternal or father". We have identified and analysed eight cohort studies, five case-control studies, two meta-analyses, and one review concerning different father's mutations potentially transmitted, two studies comparing paternal age at conception between sporadic versus familial cases of schizophrenia. All studies selected have been published between 2000 and 2009. After controlling for several confounding factors including maternal age, the relative risk of schizophrenia increased from 1.84 to 4.62 in offspring of fathers with an older age of fatherhood. Mother's age showed no significant effects after adjusting for paternal age. There was a significant association between paternal age and risk of developing schizophrenia, there was a weaker association with psychosis. The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years. Two main hypotheses could explain these results. The first one is based on the presence of new mutations in the spermatogonia, possibly because of accumulating replication errors in spermatogonial cell lines. This hypothesis is confirmed by Malaspina et al. (2002) [19], who found that patients without a family history of schizophrenia had significantly older fathers than probands with a positive family history of schizophrenia. However, this result has not been confirmed by other studies, and paternal age effect could be also explained by a mechanism called imprinting, which is a form of gene regulation. The second hypothesis is based on the fact that fathers with schizophrenia spectrum personality disorder, known to be genetically related to schizophrenia, could have an advanced age at conception. However, regarding this hypothesis, advanced maternal age at conception should be a risk factor for schizophrenia, and this is not the case. Thus, the first hypothesis seems more plausible than the second. APA has been identified as a risk factor for other psychiatric disorders such as autism, bipolar disorder, obsessive-compulsive disorder, and phobia, and thus seems to be a non-specific risk factor. Furthermore, its association with impaired neurocognitive outcomes during infancy and childhood in normal populations raises the question of the phenotype linked to APA. APA at conception appears to be a risk factor for schizophrenia. This risk factor probably interacts with genetic factors in a gene-environment interaction. To date, there is no validated cut-off at which the risk is significantly increased in offspring. In the future, studies could benefit from analyzing the phenotype related to APA. Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

[Schizophrenia and toxoplasmosis].

PubMed

Dion, Sarah; Barbe, Pierre Guillaume; Leman, Samuel; Camus, Vincent; Dimier-Poisson, Isabelle

2009-01-01

Schizophrenia is one of the most severe and disabling psychiatric disease that affects about 1 % of the adult worldwide population. Aetiology of schizophrenia is still unknown but genetic and environmental factors are suspected to play a major role in its onset. Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In particular, several epidemiological, behavioural and neurochemical studies suggested the existence of an association between schizophrenia and past history of primo-infection by the Toxoplasma gondii. However, they are some limitations for this hypothesis among which the lack of correlation between the geographic distribution of both diseases and of direct evidence for the presence of the parasite in schizophrenic patients. Nevertheless the identification of physiopathological mechanisms related to the parasite could provide a better comprehension to the outcome of schizophrenia. Studies on the link between toxoplasmosis and schizophrenia may provide interesting data for the diagnosis and the development of new treatments for this disorder.

Suicide risk in schizophrenia: an analysis of 17 consecutive suicides.

PubMed

Saarinen, P I; Lehtonen, J; Lönnqvist, J

1999-01-01

The aim of this study was to investigate interactional factors related to the recognition of suicide risk in patients with schizophrenia. The study focused on 17 schizophrenia patients who had committed suicide during the National Suicide Prevention Project in Finland between April 1, 1987, and March 31, 1988, in the province of Kuopio. Consensus case reports were assembled by using the psychological autopsy method. Study methods included structured and in-depth interviews of next of kin and interviews of health care or social services workers who had treated the suicide victims. Male and female patients with schizophrenia committed suicide in equal proportions. Most had suffered from schizophrenia for more than 15 years; all but one had been receiving psychiatric treatment at the time of suicide. Retrospective assessment indicated that 59 percent of the patients were clinically depressed at the time of suicide. In 76 percent of the cases, the mental health professionals involved in treatment had not believed that there was a risk of suicide during their last contact with the patient. In 29 percent of the cases, the patient's paranoid ideas concerning treatment personnel had increased. Patients' withdrawal from human relationships because of depression was related to loss of the treatment professionals' concern for the patients. The findings in this descriptive study suggest that withdrawal by a patient with schizophrenia and an increase in the patient's paranoid behavior should be regarded as signals of risk of suicide.

Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia.

PubMed

Hartz, Sarah M; Horton, Amy C; Oehlert, Mary; Carey, Caitlin E; Agrawal, Arpana; Bogdan, Ryan; Chen, Li-Shiun; Hancock, Dana B; Johnson, Eric O; Pato, Carlos N; Pato, Michele T; Rice, John P; Bierut, Laura J

2017-11-15

There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity. We tested the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: the Collaborative Genetic Study of Nicotine Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317 control subjects). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to the 1000 Genomes reference panel. In each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo-R 2 range 0.8-3.7%; minimum p = 4 × 10 -23 ). These results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Pathological Imitative Behavior and Response Preparation in Schizophrenia.

PubMed

Dankinas, Denisas; Melynyte, Sigita; Siurkute, Aldona; Dapsys, Kastytis

2017-08-01

Pathological imitative behavior (ehopraxia) is occasionally observed in schizophrenia patients. However, only a severe form of echopraxia can be detected with the help of a direct observation. Therefore, our goal was to study a latent form of pathological imitative behavior in this disorder, which is indicated by an increase of imitative tendencies. In our study, 14 schizophrenia patients and 15 healthy subjects were employed in two tasks: (a) in an imitative task they had to copy a hand action seen on a screen; (b) in a counter-imitative task they had to make a different movement (which involves an inhibition of prepotent imitative tendency that is impaired in case of pathological imitative behavior). Imitative tendencies were assessed by an interference score - a difference between counter-imitative and imitative response parameters. We also studied a response preparation in both groups by employing precueing probabilistic information. Our results revealed that schizophrenia patients were able to employ probabilistic information to prepare properly not only the imitative, but also the counter-imitative responses, the same as the healthy subjects did. Nevertheless, we detected increased prepotent imitative tendencies in schizophrenia patients, what indicates the latent pathological imitative behavior in case of this disorder. The obtained results suggest that in the case of schizophrenia problems with pathological imitative behavior more likely occurred in executive rather than in the preparatory stage of response. Our findings can help to detect a latent echopraxia in schizophrenia patients that cannot be revealed by direct observation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population.

PubMed

Wen, Zujia; Chen, Jianhua; Khan, Raja Amjad Waheed; Song, Zhijian; Wang, Meng; Li, Zhiqiang; Shen, Jiawei; Li, Wenjin; Shi, Yongyong

2016-04-01

Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye  = 0.015) and rs4512342 (Pallele  = 0.03, Pgenotye  = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye  = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population. © 2016 Wiley Periodicals, Inc.

Simple Schizophrenia Remains a Complicated Diagnosis: Case Report and Literature Review.

PubMed

Agarwal, Vishesh; Maheshwari, Subani; Agarwal, Vivek; Kalra, Inder Darshan

2016-01-01

The diagnosis of simple schizophrenia has been challenged and criticized since it was first described by Otto Diem in 1903. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), released by the American Psychiatric Association in May 2013, classified it as a condition for further study with the name "attenuated psychosis syndrome." This clinical condition has undergone several revisions with each edition of the DSM. It is characterized by oddities in conduct, inability to meet the demands of society, and decline in total performance in the absence of obvious psychotic symptoms. We discuss the case of a 35-year-old man who presented with symptoms fitting the criteria for simple schizophrenia and review the various definitions and case reports published over the years that defend the diagnosis of simple schizophrenia.

Genome-wide association study of clinical dimensions of schizophrenia: polygenic effect on disorganized symptoms.

PubMed

Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H; Bergen, Sarah E; Amdur, Richard L; Duan, Jubao; Sanders, Alan R; Shi, Jianxin; Mowry, Bryan J; Olincy, Ann; Amin, Farooq; Cloninger, C Robert; Silverman, Jeremy M; Buccola, Nancy G; Byerley, William F; Black, Donald W; Freedman, Robert; Dudbridge, Frank; Holmans, Peter A; Ripke, Stephan; Gejman, Pablo V; Kendler, Kenneth S; Levinson, Douglas F

2012-12-01

Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia. Based on the Lifetime Dimensions of Psychosis Scale ratings of 2,454 case subjects of European ancestry from the Molecular Genetics of Schizophrenia (MGS) sample, three symptom factors (positive, negative/disorganized, and mood) were identified with exploratory factor analysis. Quantitative scores for each factor from a confirmatory factor analysis were analyzed for association with 696,491 single-nucleotide polymorphisms (SNPs) using linear regression, with correction for age, sex, clinical site, and ancestry. Polygenic score analysis was carried out to determine whether case and comparison subjects in 16 Psychiatric GWAS Consortium (PGC) schizophrenia samples (excluding MGS samples) differed in scores computed by weighting their genotypes by MGS association test results for each symptom factor. No genome-wide significant associations were observed between SNPs and factor scores. Most of the SNPs producing the strongest evidence for association were in or near genes involved in neurodevelopment, neuroprotection, or neurotransmission, including genes playing a role in Mendelian CNS diseases, but no statistically significant effect was observed for any defined gene pathway. Finally, polygenic scores based on MGS GWAS results for the negative/disorganized factor were significantly different between case and comparison subjects in the PGC data set; for MGS subjects, negative/disorganized factor scores were correlated with polygenic scores generated using case-control GWAS results from the other PGC samples. The polygenic signal that has been observed in cross-sample analyses of schizophrenia GWAS data sets could be in part related to genetic effects on negative and disorganized symptoms (i.e., core features of chronic schizophrenia).

No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes.

PubMed

Johnson, Emma C; Border, Richard; Melroy-Greif, Whitney E; de Leeuw, Christiaan A; Ehringer, Marissa A; Keller, Matthew C

2017-11-15

A recent analysis of 25 historical candidate gene polymorphisms for schizophrenia in the largest genome-wide association study conducted to date suggested that these commonly studied variants were no more associated with the disorder than would be expected by chance. However, the same study identified other variants within those candidate genes that demonstrated genome-wide significant associations with schizophrenia. As such, it is possible that variants within historic schizophrenia candidate genes are associated with schizophrenia at levels above those expected by chance, even if the most-studied specific polymorphisms are not. The present study used association statistics from the largest schizophrenia genome-wide association study conducted to date as input to a gene set analysis to investigate whether variants within schizophrenia candidate genes are enriched for association with schizophrenia. As a group, variants in the most-studied candidate genes were no more associated with schizophrenia than were variants in control sets of noncandidate genes. While a small subset of candidate genes did appear to be significantly associated with schizophrenia, these genes were not particularly noteworthy given the large number of more strongly associated noncandidate genes. The history of schizophrenia research should serve as a cautionary tale to candidate gene investigators examining other phenotypes: our findings indicate that the most investigated candidate gene hypotheses of schizophrenia are not well supported by genome-wide association studies, and it is likely that this will be the case for other complex traits as well. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies.

PubMed

Arnedo, Javier; Svrakic, Dragan M; Del Val, Coral; Romero-Zaliz, Rocío; Hernández-Cuervo, Helena; Fanous, Ayman H; Pato, Michele T; Pato, Carlos N; de Erausquin, Gabriel A; Cloninger, C Robert; Zwir, Igor

2015-02-01

The authors sought to demonstrate that schizophrenia is a heterogeneous group of heritable disorders caused by different genotypic networks that cause distinct clinical syndromes. In a large genome-wide association study of cases with schizophrenia and controls, the authors first identified sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (SNP sets) regardless of clinical status. Second, they examined the risk of schizophrenia for each SNP set and tested replicability in two independent samples. Third, they identified genotypic networks composed of SNP sets sharing SNPs or subjects. Fourth, they identified sets of distinct clinical features that cluster in particular cases (phenotypic sets or clinical syndromes) without regard for their genetic background. Fifth, they tested whether SNP sets were associated with distinct phenotypic sets in a replicable manner across the three studies. The authors identified 42 SNP sets associated with a 70% or greater risk of schizophrenia, and confirmed 34 (81%) or more with similar high risk of schizophrenia in two independent samples. Seventeen networks of SNP sets did not share any SNP or subject. These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%). Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.

Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.

PubMed

Balan, Shabeesh; Yamada, Kazuo; Iwayama, Yoshimi; Hashimoto, Takanori; Toyota, Tomoko; Shimamoto, Chie; Maekawa, Motoko; Takagai, Shu; Wakuda, Tomoyasu; Kameno, Yosuke; Kurita, Daisuke; Yamada, Kohei; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Yoshikawa, Takeo

2017-07-01

Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABA A receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABA A receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (P allele =0.002; uncorrected) and rs1157122 (P allele =0.006; uncorrected) showed top hits, followed by rs723432 (P allele =0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

PubMed

Liu, Bing; Zhang, Xiaolong; Cui, Yue; Qin, Wen; Tao, Yan; Li, Jin; Yu, Chunshui; Jiang, Tianzi

2017-05-01

Schizophrenia is highly heritable, whereas the effect of each genetic variant is very weak. Since clinical heterogeneity and complexity of schizophrenia is high, considerable effort has been made to relate genetic variants to underlying neurobiological aspects of schizophrenia (endophenotypes). Given the polygenic nature of schizophrenia, our goal was to form a measure of additive genetic risk and explore its relationship to cortical morphology. Utilizing the data from a recent genome-wide association study that included nearly 37 000 cases of schizophrenia, we computed a polygenic risk score (PGRS) for each subject in 2 independent and healthy general populations. We then investigated the effect of polygenic risk for schizophrenia on cortical gyrification calculated from 3.0T structural imaging data in the discovery dataset (N = 315) and replication dataset (N = 357). We found a consistent effect of the polygenic risk for schizophrenia on cortical gyrification in the inferior parietal lobules in 2 independent general-population samples. A higher PGRS was significantly associated with a lower local gyrification index in the bilateral inferior parietal lobles, where case-control differences have been reported in previous studies on schizophrenia. Our findings strongly support the effectiveness of both PGRSs and endophenotypes in establishing the genetic architecture of psychiatry. Our findings may provide some implications regarding individual differences in the genetic risk for schizophrenia to cortical morphology and brain development. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Association between bovine casein antibody and new onset schizophrenia among US military personnel.

PubMed

Niebuhr, David W; Li, Yuanzhang; Cowan, David N; Weber, Natalya S; Fisher, Jared A; Ford, Glen M; Yolken, Robert

2011-05-01

Schizophrenia is a pervasive neuropsychiatric disorder of uncertain etiology. Multiple studies have documented immune activation in individuals with schizophrenia. One antigen capable of inducing a prolonged immune response is bovine casein derived from ingested milk products. Increased levels of casein antibodies have been found in individuals with schizophrenia after diagnosis. This study was directed at determining the potential association between schizophrenia and pre-illness onset levels of immunoglobulin G (IgG) antibodies to bovine casein. Parallel analyses for casein antibody levels with bipolar disorder were included as comparison. Cases were service members who received medical discharges from the military with a schizophrenia diagnosis from 1992 to 2005. Serum specimens were selected for 855 cases and 1165 matched healthy controls. IgG antibodies to bovine whole-casein were measured by solid phase enzyme-linked immunosorbent assays (ELISAs). Hazard ratios (HR) were calculated to examine the associations of casein IgG level with risk of schizophrenia by time to diagnosis and by subjects' initial level. Increasing casein IgG antibody levels among those with a high initial level, drawn before diagnosis, was associated with an 18% increase in the hazard risk of schizophrenia per unit increase (value of low-positive standard) in IgG antibody levels (HR=1.18; 95% CI 1.04, 1.34). This is the first report to identify an association between the risk of schizophrenia and elevated antibodies to bovine casein prior to disease onset. Additional research is required to elucidate the complex genetic environmental interactions involved in the pathogenesis of schizophrenia and to identify potentially modifiable risk factors. Published by Elsevier B.V.

Assessment of documentation of DSM-IV-TR Criteria A for diagnosis of schizophrenia in psychiatric unit, tertiary hospital, Malaysia.

PubMed

Maung, K; Ohnmar, H; Than, W; Ramli, M; Najwa Hanim, M R; Ali Sabri, R; Ahmad Zafri, A B

The purposes of this study were to investigate the documentation of the DSM-IV-TR- Criteria A in diagnoses of schizophrenia and to identify the symptoms associated with over diagnosis of schizophrenia. This study involved a retrospective review and analysis of data from case notes. Data of 107 newly diagnosed patients with schizophrenia were keyed in and analyzed using SPSS v 19. The cases were then evaluated for the use of the DSM-IV-TR- Criteria A. Over diagnosis was noted in 37.39% of the patients. Disorganised behaviour (12.5%), affective flattening (12.5%), hallucination (16%) and non-bizarre delusion (18.3%) significantly contributed to the over-diagnosis of schizophrenia. Symptoms such as non-bizarre delusion and hallucination were the most commonly used in over-diagnosing schizophrenia and were statistically significant with p ≤0.05. There was a significant lack of DSM-IV-TR Criteria A among the data documented to diagnose schizophrenia and non-bizarre delusion and hallucination were the most commonly used in over-diagnosing schizophrenia. This key problem needs to be addressed. The reliability of a diagnosis is indispensable and achievable with the proper clinical application of DSM-IV-TR Criteria A. The DSM-IV-TR Criteria have been perceived to be useful and reliable and is most widely used throughout the world.

Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following Substance-Induced Psychosis.

PubMed

Starzer, Marie Stefanie Kejser; Nordentoft, Merete; Hjorthøj, Carsten

2018-04-01

The authors investigated the rates of conversion to schizophrenia and bipolar disorder after a substance-induced psychosis, as well as risk factors for conversion. All patient information was extracted from the Danish Civil Registration System and the Psychiatric Central Research Register. The study population included all persons who received a diagnosis of substance-induced psychosis between 1994 and 2014 (N=6,788); patients were followed until first occurrence of schizophrenia or bipolar disorder or until death, emigration, or August 2014. The Kaplan-Meier method was used to obtain cumulative probabilities for the conversion from a substance-induced psychosis to schizophrenia or bipolar disorder. Cox proportional hazards regression models were used to calculate hazard ratios for all covariates. Overall, 32.2% (95% CI=29.7-34.9) of patients with a substance-induced psychosis converted to either bipolar or schizophrenia-spectrum disorders. The highest conversion rate was found for cannabis-induced psychosis, with 47.4% (95% CI=42.7-52.3) converting to either schizophrenia or bipolar disorder. Young age was associated with a higher risk of converting to schizophrenia. Self-harm after a substance-induced psychosis was significantly linked to a higher risk of converting to both schizophrenia and bipolar disorder. Half the cases of conversion to schizophrenia occurred within 3.1 years after a substance-induced psychosis, and half the cases of conversion to bipolar disorder occurred within 4.4 years. Substance-induced psychosis is strongly associated with the development of severe mental illness, and a long follow-up period is needed to identify the majority of cases.

Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study.

PubMed

McGrath, John J; Eyles, Darryl W; Pedersen, Carsten B; Anderson, Cameron; Ko, Pauline; Burne, Thomas H; Norgaard-Pedersen, Bent; Hougaard, David M; Mortensen, Preben B

2010-09-01

Clues from the epidemiology of schizophrenia suggest that low levels of developmental vitamin D may be associated with increased risk of schizophrenia. To directly examine the association between neonatal vitamin D status and risk of schizophrenia. Individually matched case-control study drawn from a population-based cohort. Danish national health registers and neonatal biobank. A total of 424 individuals with schizophrenia and 424 controls matched for sex and date of birth. The concentration of 25 hydroxyvitamin D(3) (25[OH]D3) was assessed from neonatal dried blood samples using a highly sensitive liquid chromatography tandem mass spectroscopy method. Relative risks were calculated for the matched pairs when examined for quintiles of 25(OH)D3. Compared with neonates in the fourth quintile (with 25[OH]D3 concentrations between 40.5 and 50.9 nmol/L), those in each of the lower 3 quintiles had a significantly increased risk of schizophrenia (2-fold elevated risk). Unexpectedly, those in the highest quintile also had a significantly increased risk of schizophrenia. Based on this analysis, the population-attributable fraction associated with neonatal vitamin D status was 44%. The relationship was not explained by a wide range of potential confounding or interacting variables. Both low and high concentrations of neonatal vitamin D are associated with increased risk of schizophrenia, and it is feasible that this exposure could contribute to a sizeable proportion of cases in Denmark. In light of the substantial public health implications of this finding, there is an urgent need to further explore the effect of vitamin D status on brain development and later mental health.

Muscarinic agonists for the treatment of cognition in schizophrenia.

PubMed

Sellin, Angela K; Shad, Mujeeb; Tamminga, Carol

2008-11-01

It is widely accepted that cholinergic activity at muscarinic receptors is required to maintain cognitive functions, including learning and memory. Memory domains are especially impaired in schizophrenia, which may explain difficulties in psychosocial rehabilitation of individuals with this illness. However, little is known about the mechanism of this impairment. To understand our current knowledge, we reviewed the literature since 1990 via a PubMed search for the terms "muscarinic", "schizophrenia", "cognition", "memory", "learning", and "agonist" in combination. We found 89 basic science/laboratory studies, case reports/series, case-control studies, cross-sectional studies, standardized controlled animal trials, standardized controlled human trials, and reviews. Although further research is required to fully understand the neuropharmacology of the cholinergic system in cognitive function in schizophrenia, we have examined the data currently available. In general, these data suggest that agonist activity at acetylcholine muscarinic type 1 (M1) receptors would enhance memory and learning in schizophrenia. We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1 muscarinic agonists.

[In defence of the diagnosis of simple schizophrenia: reflections on a case presentation].

PubMed

Martínez Serrano, José; Medina Garrido, María L; Consuegra Sánchez, Rosario; Del Cerro Oñate, Matias; López-Mesa, José L; González Matás, Juana

2012-01-01

Since the first case descriptions of dementia praecox (Diem, 1903), the diagnosis of simple schizophrenia has continued to be controversial. The questioning of its descriptive validity and its reliability, as well as its infrequent use, has led to it being eliminated as a sub-type of schizophrenia in the DSM-III. Criteria for the diagnosis of «simple deteriorative disorder» are currently included in the DSM-IV-TR as a disorder requiring more studies for its possible inclusion. An attempt is made, using a clinical case, to perform a historical review of the concept of simple schizophrenia, and at the same what has led to the reflection on the possible reasons for the controversy, and a potential route to resolve it. Using a controversial clinical case, which meets ICD-10 clinical criteria for simple schizophrenia (and those of the DSM-IV-TR for the simple deteriorative disorder), we reflect on the symptoms and diagnostic difficulties. A literature review and update on the subjects was also performed. Our patient highlights, by the absence in the clinical picture of the most obvious positive psychotic symptoms, the tendency by psychiatrists to identify the diagnosis of schizophrenia with the presence of the same, at least at some time during its evolution. The use of neuroimaging tests was useful to assess the level of deterioration and prognosis of the patient. Considering simple schizophrenia in the differential diagnosis of other chronic deteriorative disorders could increase its recognition in the initial phases. The use of neuropsychological function tests, and looking for typical deteriorative patterns of the schizophrenia spectrum, could help to increase the reliability of the diagnosis. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

A Genetic Association Study of Chromosome 11q22-24 in Two Different Samples Implicates the FXYD6 Gene, Encoding Phosphohippolin, in Susceptibility to Schizophrenia

PubMed Central

Choudhury, Khalid; McQuillin, Andrew; Puri, Vinay; Pimm, Jonathan; Datta, Susmita; Thirumalai, Srinivasa; Krasucki, Robert; Lawrence, Jacob; Bass, Nicholas J.; Quested, Digby; Crombie, Caroline; Fraser, Gillian; Walker, Nicholas; Nadeem, Haitham; Johnson, Sophie; Curtis, David; St. Clair, David; Gurling, Hugh M. D.

2007-01-01

Previous linkage analyses of families with multiple cases of schizophrenia by us and others have confirmed the involvement of the chromosome 11q22-24 region in the etiology of schizophrenia, with LOD scores of 3.4 and 3.1. We now report fine mapping of a susceptibility gene in the 11q22-24 region, determined on the basis of a University College London (UCL) sample of 496 cases and 488 supernormal controls. Confirmation was then performed by the study of an Aberdeen sample consisting of 858 cases and 591 controls (for a total of 2,433 individuals: 1,354 with schizophrenia and 1,079 controls). Seven microsatellite or single-nucleotide polymorphism (SNP) markers localized within or near the FXYD6 gene showed empirically significant allelic associations with schizophrenia in the UCL sample (for D11S1998, P=.021; for rs3168238, P=.009; for TTTC20.2, P=.048; for rs1815774, P=.049; for rs4938445, P=.010; for rs4938446, P=.025; for rs497768, P=.023). Several haplotypes were also found to be associated with schizophrenia; for example, haplotype Hap-F21 comprising markers rs10790212-rs4938445-rs497768 was found to be associated with schizophrenia, by a global permutation test (P=.002). Positive markers in the UCL sample were then genotyped in the Aberdeen sample. Two of these SNPs were found to be associated with schizophrenia in the Scottish sample (for rs4938445, P=.044; for rs497768, P=.037). The Hap-F21 haplotype also showed significant association with schizophrenia in the Aberdeen sample, with the same alleles being associated (P=.013). The FXYD6 gene encodes a protein called “phosphohippolin” that is highly expressed in regions of the brain thought to be involved in schizophrenia. The protein functions by modulating the kinetic properties of Na,K-ATPase to the specific physiological requirements of the tissue. Etiological base-pair changes in FXYD6 or in associated promoter/control regions are likely to cause abnormal function or expression of phosphohippolin and to increase genetic susceptibility to schizophrenia. PMID:17357072

Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study.

PubMed

Schneider, Carolina; Papachristou, Efstathios; Wimberley, Theresa; Gasse, Christiane; Dima, Danai; MacCabe, James H; Mortensen, Preben Bo; Frangou, Sophia

2015-06-01

Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Schizophrenia Patient or Spiritually Advanced Personality? A Qualitative Case Analysis.

PubMed

Bhargav, Hemant; Jagannathan, Aarti; Raghuram, Nagarathna; Srinivasan, T M; Gangadhar, Bangalore N

2015-10-01

Many aspects of spiritual experience are similar in form and content to symptoms of psychosis. Both spiritually advanced people and patients suffering from psychopathology experience alterations in their sense of 'self.' Psychotic experiences originate from derangement of the personality, whereas spiritual experiences involve systematic thinning out of the selfish ego, allowing individual consciousness to merge into universal consciousness. Documented instances and case studies suggest possible confusion between the spiritually advanced and schizophrenia patients. Clinical practice contains no clear guidelines on how to distinguish them. Here we use a case presentation to help tabulate clinically useful points distinguishing spiritually advanced persons from schizophrenia patients. A 34-year-old unmarried male reported to our clinic with four main complaints: lack of sense of self since childhood; repeated thoughts questioning whether he existed or not; social withdrawal; and inability to continue in any occupation. Qualitative case analysis and discussions using descriptions from ancient texts and modern psychology led to the diagnosis of schizophrenia rather than spiritual advancement.

Diabetes and Cognitive Deficits in Chronic Schizophrenia: A Case-Control Study

PubMed Central

Han, Mei; Huang, Xu-Feng; Chen, Da Chun; Xiu, Meihong; Kosten, Thomas R.; Zhang, Xiang Yang

2013-01-01

Cognitive impairment occurs in both schizophrenia and diabetes. There is currently limited understanding whether schizophrenia with diabetes has more serious cognitive deficits than schizophrenia without diabetes or diabetes only. This study assessed cognitive performance in 190 healthy controls, 106 diabetes only, 127 schizophrenia without diabetes and 55 schizophrenia with diabetes. This study was conducted from January 2008 to December 2010. Compared to healthy controls, all patient groups had significantly decreased total and five index RBANS scores (all p<0.01–p<0.001), except for the visuospatial/constructional index. Schizophrenia with diabetes performed worse than schizophrenia without diabetes in immediate memory (p<0.01) and total RBANS scores (<0.05), and showed a trend for decreased attention (p = 0.052) and visuospatial/constructional capacity (p = 0.063). Schizophrenia with diabetes performed worse than diabetes only in immediate memory (p<0.001) and attention (p<0.05), and showed a trend for decreased total RBANS scores (p = 0.069). Regression analysis showed that the RBANS had modest correlations with schizophrenia’ PANSS scores, their duration of current antipsychotic treatment, and diagnosis of diabetes. Schizophrenia with co-morbid diabetes showed more cognitive impairment than schizophrenia without diabetes and diabetes only, especially in immediate memory and attention. PMID:23840437

Schizophrenia, Obsessive Covert Mental Rituals and Social Anxiety: Case Report

ERIC Educational Resources Information Center

Tully, Phillip J.; Edwards, Christopher J.

2009-01-01

This case study reports the outcomes of cognitive therapy for social anxiety in a 45-year-old man with a 27-year history of paranoid schizophrenia. The intervention targeted the overlapping and interrelated symptoms of social anxiety and delusional beliefs. After 11 sessions of treatment, the patient showed no improvement in social anxiety,…

Assessment of DNA damage and repair efficiency in drug naïve schizophrenia using comet assay.

PubMed

Muraleedharan, Aparna; Menon, Vikas; Rajkumar, Ravi Philip; Chand, Parkash

2015-09-01

The etiology of schizophrenia continues to be confounding and elusive. Some knowledge gaps exist in the neurodegenerative theory of schizophrenia. Oxidative DNA damage and repair deficits are relevant to the mechanisms of neurodegeneration but have not been studied in drug naïve schizophrenia. The present study used the comet assay technique to study the extent of DNA damage in circulating peripheral lymphocytes of patients with drug naïve schizophrenia (n = 40) along with an age and gender matched control group (n = 40). We also assessed the DNA repair efficiency in cases following incubation in a nutrient medium. All the assayed comet parameters demonstrated significantly greater baseline DNA damage in cases in comparison to the controls except for head diameter (p < 0.001 for all significant results, p = 0.32 for head diameter). Gender, age and duration of illness (p = 0.21, 0.69 and 0.12 respectively for tail length) did not influence any of the parameters significantly. Significant decrease was noted in the comet tail length and percentage of DNA in comet tail (p < 0.001 for both) in cases following incubation suggesting that the DNA repair machinery was preserved. No difference in DNA repair efficiency was noted between the genders (p = 0.23 for tail length). Our findings confirm the presence of significant baseline DNA damage in schizophrenia even prior to the initiation of anti-psychotic treatment. Additionally, intact genomic repair efficiency was noted in this group as a whole. These results provide some evidence for oxidative DNA damage as molecular link underpinning neurodegeneration in drug naïve schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera.

PubMed

McGrath, John; Eyles, Darryl; Mowry, Bryan; Yolken, Robert; Buka, Stephen

2003-09-01

Evidence from epidemiology suggests that low maternal vitamin D may be a risk factor for schizophrenia. Based on sera taken during the third trimester, we compared the level of 25 hydroxyvitamin D3 in mothers of individuals with schizophrenia or schizoaffective disorders versus mothers of unaffected controls. For each case, we selected two controls matched on race, gender and date of birth of the offspring. There was no significant difference in third trimester maternal vitamin D in the entire sample (cases = 26, controls = 51). Within the subgroup of black individuals (n = 21), there was a trend level difference in the predicted direction. Maternal vitamin D does not operate as a continuous graded risk factor for schizophrenia, however, the results in the black subgroup raise the possibility that below a certain critical threshold, low levels of maternal vitamin D may be associated with an increased risk of schizophrenia.

Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese population.

PubMed

Aoyama, N; Takahashi, N; Saito, S; Maeno, N; Ishihara, R; Ji, X; Miura, H; Ikeda, M; Suzuki, T; Kitajima, T; Yamanouchi, Y; Kinoshita, Y; Yoshida, K; Iwata, N; Inada, T; Ozaki, N

2006-06-01

Several lines of evidence suggest that metabolic changes in the kynurenic acid (KYNA) pathway are related to the etiology of schizophrenia. The inhibitor of kynurenine 3-monooxygenase (KMO) is known to increase KYNA levels, and the KMO gene is located in the chromosome region associated with schizophrenia, 1q42-q44. Single-marker and haplotype analyses for 6-tag single nucleotide polymorphisms (SNPs) of KMO were performed (cases = 465, controls = 440). Significant association of rs2275163 with schizophrenia was observed by single-marker comparisons (P = 0.032) and haplotype analysis including this SNP (P = 0.0049). Significant association of rs2275163 and haplotype was not replicated using a second, independent set of samples (cases = 480, controls = 448) (P = 0.706 and P = 0.689, respectively). These results suggest that the KMO is unlikely to be related to the development of schizophrenia in Japanese.

Association study of interleukin-4 polymorphisms with paranoid schizophrenia in the Polish population: a critical approach.

PubMed

Fila-Danilow, Anna; Kucia, Krzysztof; Kowalczyk, Malgorzata; Owczarek, Aleksander; Paul-Samojedny, Monika; Borkowska, Paulina; Suchanek, Renata; Kowalski, Jan

2012-08-01

Changes in immunological system are one of dysfunctions reported in schizophrenia. Some changes based on an imbalance between Th1 and Th2 cytokines results from cytokine gene polymorphisms. Interleukin-4 gene (IL4) is considered as a potential candidate gene in schizophrenia association studies. The aim of the current case-control study was to examine whether the -590C/T (rs2243250) and -33C/T (rs2070874) IL4 gene polymorphisms are implicated in paranoid schizophrenia development in the Polish population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. The genotypes and alleles distribution of both SNPs were analysed in patients (n = 182) and healthy individuals constituted the control group (n = 215). The connection between some clinical variables and studied polymorphisms has been examined as well. We did not revealed any association between the -590C/T and -33C/T polymorphisms and paranoid schizophrenia. In case of both SNPs the homozygous TT genotype was extremely rare. Both polymorphic sites of the IL4 gene were found to be in a very strong linkage disequilibrium. However we did not identify a haplotype predispose to paranoid schizophrenia. No associations were also observed between the clinical course and psychopathology of the disease and the genotypes of both analysed polymorphisms. Our results suggest that the polymorphisms -590C/T in IL4 gene promoter region and -33C/T in the 5'-UTR are not involved in the pathophysiology of paranoid schizophrenia in Polish residents.

The role of Pannexin gene variants in schizophrenia: systematic analysis of phenotypes.

PubMed

Gawlik, Micha; Wagner, Martin; Pfuhlmann, Bruno; Stöber, Gerald

2016-08-01

Pannexins are a group of brain-expressed channel proteins thought to be regulators of schizophrenia-linked pathways including glutamate release, synaptic plasticity and neural stem proliferation. We got evidence for linkage of a catatonic phenotype to the PANX2 locus in a family study. Aim of our study was to evaluate the role of Pannexins in schizophrenia and clinical phenotypes, particularly with regard to periodic catatonia. We genotyped six single-nucleotide polymorphisms at PANX1, five at PANX2 and three at PANX3 in 1173 German cases with schizophrenia according to DSM-5 and 480 controls. Our sample included 338 cases with periodic catatonia corresponding to Leonhard's classification. Association with schizophrenia according to DSM-5 was limited to genotype rs4838858-TT [p = 0.02, odds ratio (OR) 3.1] and haplotype rs4838858T-rs5771206G (p = 0.02, OR 2.7) at PANX2. We found no significant association with clinical phenotypes. Our limited findings do not support a major contribution of PANX1-3 to disease risk of schizophrenia according to DSM-5. We cannot confirm an association of the PANX2 loci at chromosome 22q13 with periodic catatonia.

Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia

PubMed Central

Talbot, Konrad; Eidem, Wess L.; Tinsley, Caroline L.; Benson, Matthew A.; Thompson, Edward W.; Smith, Rachel J.; Hahn, Chang-Gyu; Siegel, Steven J.; Trojanowski, John Q.; Gur, Raquel E.; Blake, Derek J.; Arnold, Steven E.

2004-01-01

Eleven studies now report significant associations between schizophrenia and certain haplotypes of single-nucleotide polymorphisms in the gene encoding dysbindin-1 at 6p22.3. Dysbindin-1 is best known as dystrobrevin-binding protein 1 (DTNBP1) and may thus be associated with the dystrophin glycoprotein complex found at certain postsynaptic sites in the brain. Contrary to expectations, however, we found that when compared to matched, nonpsychiatric controls, 73–93% of cases in two schizophrenia populations displayed presynaptic dysbindin-1 reductions averaging 18–42% (P = 0.027–0.0001) at hippocampal formation sites lacking neuronal dystrobrevin (i.e., β-dystrobrevin). The reductions, which were not observed in the anterior cingulate of the same schizophrenia cases, occurred specifically in terminal fields of intrinsic, glutamatergic afferents of the subiculum, the hippocampus proper, and especially the inner molecular layer of the dentate gyrus (DGiml). An inversely correlated increase in vesicular glutamate transporter-1 (VGluT-1) occurred in DGiml of the same schizophrenia cases. Those changes occurred without evidence of axon terminal loss or neuroleptic effects on dysbindin-1 or VGluT-1. Our findings indicate that presynaptic dysbindin-1 reductions independent of the dystrophin glycoprotein complex are frequent in schizophrenia and are related to glutamatergic alterations in intrinsic hippocampal formation connections. Such changes may contribute to the cognitive deficits common in schizophrenia. PMID:15124027

Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia.

PubMed

Talbot, Konrad; Eidem, Wess L; Tinsley, Caroline L; Benson, Matthew A; Thompson, Edward W; Smith, Rachel J; Hahn, Chang-Gyu; Siegel, Steven J; Trojanowski, John Q; Gur, Raquel E; Blake, Derek J; Arnold, Steven E

2004-05-01

Eleven studies now report significant associations between schizophrenia and certain haplotypes of single-nucleotide polymorphisms in the gene encoding dysbindin-1 at 6p22.3. Dysbindin-1 is best known as dystrobrevin-binding protein 1 (DTNBP1) and may thus be associated with the dystrophin glycoprotein complex found at certain postsynaptic sites in the brain. Contrary to expectations, however, we found that when compared to matched, nonpsychiatric controls, 73-93% of cases in two schizophrenia populations displayed presynaptic dysbindin-1 reductions averaging 18-42% (P = 0.027-0.0001) at hippocampal formation sites lacking neuronal dystrobrevin (i.e., beta-dystrobrevin). The reductions, which were not observed in the anterior cingulate of the same schizophrenia cases, occurred specifically in terminal fields of intrinsic, glutamatergic afferents of the subiculum, the hippocampus proper, and especially the inner molecular layer of the dentate gyrus (DGiml). An inversely correlated increase in vesicular glutamate transporter-1 (VGluT-1) occurred in DGiml of the same schizophrenia cases. Those changes occurred without evidence of axon terminal loss or neuroleptic effects on dysbindin-1 or VGluT-1. Our findings indicate that presynaptic dysbindin-1 reductions independent of the dystrophin glycoprotein complex are frequent in schizophrenia and are related to glutamatergic alterations in intrinsic hippocampal formation connections. Such changes may contribute to the cognitive deficits common in schizophrenia.

Changes in verbal learning and memory in schizophrenia and non-psychotic controls in midlife: A nine-year follow-up in the Northern Finland Birth Cohort study 1966.

PubMed

Rannikko, Irina; Haapea, Marianne; Miettunen, Jouko; Veijola, Juha; Murray, Graham K; Barnett, Jennifer H; Husa, Anja P; Jones, Peter B; Isohanni, Matti; Jääskeläinen, Erika

2015-08-30

Findings on longitudinal change of cognitive performance in schizophrenia are extremely variable in the case of verbal learning and memory, and it is still unclear which dimensions of verbal learning and memory exhibit possible deterioration over the long-term. Our aim was to compare the change in verbal learning and memory in individuals with schizophrenia 10-20 years after the illness onset and healthy controls during a nine-year follow-up in a general population sample. Our sample included 41 schizophrenia spectrum subjects and 73 controls from the Northern Finland Birth Cohort study 1966. The California Verbal Learning Test (CVLT) was used to estimate the degree of change in verbal learning and memory during a nine-year follow-up from age 34-years to 43- years. Both cases and controls deteriorated. There was statistically significant decline in two out of 20 CVLT items among cases and in 13 out of 20 CVLT items among controls. With the exception of two variables, the decline in verbal learning and memory over nine years was not significantly larger in cases. We conclude that during midlife verbal learning and memory in schizophrenia mostly declines in a normative fashion with aging at the same rate as the general population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genome-Wide Supported Risk Variants in MIR137, CACNA1C, CSMD1, DRD2, and GRM3 Contribute to Schizophrenia Susceptibility in Pakistani Population.

PubMed

Fatima, Ambrin; Farooq, Muhammad; Abdullah, Uzma; Tariq, Muhammad; Mustafa, Tanveer; Iqbal, Muhammad; Tommerup, Niels; Mahmood Baig, Shahid

2017-09-01

Schizophrenia is a chronic neuropsychiatric disease afflicting around 1.1% of the population worldwide. Recently, MIR137 , CACNA1C , CSMD1 , DRD2 , and GRM3 have been reported as the most robustly emerging candidates involved in the etiology of schizophrenia. In this case control study, we performed an association analysis of rs1625579 ( MIR137 ), rs1006737, rs4765905 ( CACNA1C ), rs10503253 ( CSMD1 ), rs1076560 ( DRD2 ), rs12704290, rs6465084, and rs148754219 ( GRM3 ) in Pakistani population. Schizophrenia was diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV). Detailed clinical information, family history of all patients and healthy controls were collected. RFLP based case control association study was performed in a Pakistani cohort of 508 schizophrenia patients and 300 healthy control subjects. Alleles and genotype frequencies were calculated using SPSS. A significant difference in the genotype and allele frequencies for rs4765905, rs1076560 and rs6465084 were found between the patients and controls (p=0.000). This study provides substantial evidence supporting the role of CACNA1C , GRM3 and DRD2 as schizophrenia susceptibility genes in Pakistani population.

Designing and validation of a yoga-based intervention for schizophrenia.

PubMed

Govindaraj, Ramajayam; Varambally, Shivarama; Sharma, Manjunath; Gangadhar, Bangalore Nanjundaiah

2016-06-01

Schizophrenia is a chronic mental illness which causes significant distress and dysfunction. Yoga has been found to be effective as an add-on therapy in schizophrenia. Modules of yoga used in previous studies were based on individual researcher's experience. This study aimed to develop and validate a specific generic yoga-based intervention module for patients with schizophrenia. The study was conducted at NIMHANS Integrated Centre for Yoga (NICY). A yoga module was designed based on traditional and contemporary yoga literature as well as published studies. The yoga module along with three case vignettes of adult patients with schizophrenia was sent to 10 yoga experts for their validation. Experts (n = 10) gave their opinion on the usefulness of a yoga module for patients with schizophrenia with some modifications. In total, 87% (13 of 15 items) of the items in the initial module were retained, with modification in the remainder as suggested by the experts. A specific yoga-based module for schizophrenia was designed and validated by experts. Further studies are needed to confirm efficacy and clinical utility of the module. Additional clinical validation is suggested.

Family history, place and season of birth as risk factors for schizophrenia in Denmark: a replication and reanalysis.

PubMed

Pedersen, C B; Mortensen, P B

2001-07-01

Although a family history of schizophrenia is the strongest individual risk factor for schizophrenia, environmental factors related to urbanicity may contribute to a substantial proportion of the population occurrence of the disease. This study replicates previous findings in four mutually exclusive Danish study populations, including out-patient information, ICD-10 diagnoses of schizophrenia, and a broader adjustment for mental illness in family members. We established a population-based cohort of 2.66 million Danish people using data from the Civil Registration System linked with the Psychiatric Case Register. Overall, 10 264 persons developed schizophrenia during the 50.7 million person-years of follow-up. The risk of schizophrenia was increased by urbanicity of place of birth and by family history of schizophrenia or other mental disorders. Urban-rural differences of schizophrenia risk were replicated and could not be associated with the potential sources of bias we assessed. Environmental factors underlying the effect of place of birth are major determinants of schizophrenia occurrence at the population level, although the effect of family history is the strongest at the individual level.

A Cytogenetic Abnormality and Rare Coding Variants Identify ABCA13 as a Candidate Gene in Schizophrenia, Bipolar Disorder, and Depression

PubMed Central

Knight, Helen M.; Pickard, Benjamin S.; Maclean, Alan; Malloy, Mary P.; Soares, Dinesh C.; McRae, Allan F.; Condie, Alison; White, Angela; Hawkins, William; McGhee, Kevin; van Beck, Margaret; MacIntyre, Donald J.; Starr, John M.; Deary, Ian J.; Visscher, Peter M.; Porteous, David J.; Cannon, Ronald E.; St Clair, David; Muir, Walter J.; Blackwood, Douglas H.R.

2009-01-01

Schizophrenia and bipolar disorder are leading causes of morbidity across all populations, with heritability estimates of ∼80% indicating a substantial genetic component. Population genetics and genome-wide association studies suggest an overlap of genetic risk factors between these illnesses but it is unclear how this genetic component is divided between common gene polymorphisms, rare genomic copy number variants, and rare gene sequence mutations. We report evidence that the lipid transporter gene ABCA13 is a susceptibility factor for both schizophrenia and bipolar disorder. After the initial discovery of its disruption by a chromosome abnormality in a person with schizophrenia, we resequenced ABCA13 exons in 100 cases with schizophrenia and 100 controls. Multiple rare coding variants were identified including one nonsense and nine missense mutations and compound heterozygosity/homozygosity in six cases. Variants were genotyped in additional schizophrenia, bipolar, depression (n > 1600), and control (n > 950) cohorts and the frequency of all rare variants combined was greater than controls in schizophrenia (OR = 1.93, p = 0.0057) and bipolar disorder (OR = 2.71, p = 0.00007). The population attributable risk of these mutations was 2.2% for schizophrenia and 4.0% for bipolar disorder. In a study of 21 families of mutation carriers, we genotyped affected and unaffected relatives and found significant linkage (LOD = 4.3) of rare variants with a phenotype including schizophrenia, bipolar disorder, and major depression. These data identify a candidate gene, highlight the genetic overlap between schizophrenia, bipolar disorder, and depression, and suggest that rare coding variants may contribute significantly to risk of these disorders. PMID:19944402

Schizophrenia and induced abortions: A national register-based follow-up study among Finnish women born between 1965-1980 with schizophrenia or schizoaffective disorder.

PubMed

Simoila, Laura; Isometsä, Erkki; Gissler, Mika; Suvisaari, Jaana; Sailas, Eila; Halmesmäki, Erja; Lindberg, Nina

2018-02-01

The objectives of this study were to investigate, in women with schizophrenia or schizoaffective disorder, the number and incidence of induced abortions (= pregnancy terminations performed by a physician), their demographic characteristics, use of contraceptives, plus indications of and complications related to pregnancy termination. Using the Care Register for Health Care, we identified Finnish women born between the years 1965-1980 who were diagnosed with either schizophrenia or schizoaffective disorder during the follow-up period ending 31.12.2013. For each case, five age- and place-of-birth- matched controls were obtained from the Population Register of Finland. Information about births and induced abortions were obtained from the Medical Birth Register and the Induced Abortion Register. The number and incidence of induced abortions per 1000 follow-up years did not differ between cases and their controls. However, due to fewer pregnancies, cases exhibited an over 2-fold increased risk of pregnancy termination (RR 2.28; 95% CI 2.20-2.36). Cases were younger, were more often without a partner at the time of induced abortion, and their pregnancies resulted more often from a lack of contraception. Among cases, the indication for pregnancy termination was more often mother-to-be's medical condition. Induced abortions after 12weeks gestation were more common among cases. However, cases had no more complications related to termination. The incidence of induced abortions among Finnish women with schizophrenia or schizoaffective disorder is similar to the general population, but their risk per pregnancy over two-fold. They need effective, affordable family planning services and long-term premeditated contraception. Copyright © 2017 Elsevier B.V. All rights reserved.

Low seroprevalence of Toxocara infection in schizophrenic inpatients in durango, Mexico: a case control study.

PubMed

Alvarado-Esquivel, Cosme; Hernández-Tinoco, Jesús; Sánchez-Anguiano, Luis Francisco; Cisneros-Martínez, Jorge Arturo

2014-12-01

Psychiatric patients have a higher seroprevalence of toxocariasis than general population. However, there is poor knowledge about any specific psychiatric diagnosis associated with toxocariasis. The aim of the study was to determine whether seropositivity to Toxocara was associated with schizophrenia. Through an age and gender-matched case-control seroprevalence study in Durango City, Mexico, 50 schizophrenic inpatients in a public psychiatric hospital and 100 control subjects of the general population were compared for the presence of anti-Toxocara IgG antibodies. One of the 50 (2%) schizophrenic inpatients, and 3 (3%) of the 100 controls were positive for anti-Toxocara IgG antibodies. No statistically significant difference in Toxocara seroprevalence among cases and controls was found (P=0.59). The Toxocara positive schizophrenic patient suffered from paranoid schizophrenia (F20.0) and had a number of putative risk factors for Toxocara exposure including contact with cats, dogs and other animals, worked in agriculture, and consumed undercooked meat, unwashed fruits and vegetables, and untreated water. Results suggest that seroprevalence of Toxocara infection was low and not associated with schizophrenia in psychiatric inpatients in Durango, Mexico. However, further studies to elucidate the association of toxocariasis with schizophrenia are needed.

Low Seroprevalence of Toxocara Infection in Schizophrenic Inpatients in Durango, Mexico: A Case Control Study

PubMed Central

Alvarado-Esquivel, Cosme; Hernández-Tinoco, Jesús; Sánchez-Anguiano, Luis Francisco; Cisneros-Martínez, Jorge Arturo

2014-01-01

Psychiatric patients have a higher seroprevalence of toxocariasis than general population. However, there is poor knowledge about any specific psychiatric diagnosis associated with toxocariasis. The aim of the study was to determine whether seropositivity to Toxocara was associated with schizophrenia. Through an age and gender-matched case-control seroprevalence study in Durango City, Mexico, 50 schizophrenic inpatients in a public psychiatric hospital and 100 control subjects of the general population were compared for the presence of anti-Toxocara IgG antibodies. One of the 50 (2%) schizophrenic inpatients, and 3 (3%) of the 100 controls were positive for anti-Toxocara IgG antibodies. No statistically significant difference in Toxocara seroprevalence among cases and controls was found (P=0.59). The Toxocara positive schizophrenic patient suffered from paranoid schizophrenia (F20.0) and had a number of putative risk factors for Toxocara exposure including contact with cats, dogs and other animals, worked in agriculture, and consumed undercooked meat, unwashed fruits and vegetables, and untreated water. Results suggest that seroprevalence of Toxocara infection was low and not associated with schizophrenia in psychiatric inpatients in Durango, Mexico. However, further studies to elucidate the association of toxocariasis with schizophrenia are needed. PMID:25598759

Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population.

PubMed

Cai, Lei; Chen, Tianlu; Yang, Jinglei; Zhou, Kejun; Yan, Xiaomei; Chen, Wenzhong; Sun, Liya; Li, Linlin; Qin, Shengying; Wang, Peng; Yang, Ping; Cui, Donghong; Burmeister, Margit; He, Lin; Jia, Wei; Wan, Chunling

2015-10-12

Little is known about the trace element profile differences between Schizophrenia patients and healthy controls; previous studies about the association of certain elements with Schizophrenia have obtained conflicting results. To identify these differences in the Han Chinese population, inductively coupled plasma-mass spectrometry was used to quantify the levels of 35 elements in the sera of 111 Schizophrenia patients and 110 healthy participants, which consisted of a training (61/61 for cases/controls included) and a test group including remaining participants. An orthogonal projection to latent structures model was constructed from the training group (R(2)Y = 0.465, Q(2)cum = 0.343) had a sensitivity of 76.0% and a specificity of 71.4% in the test group. Single element analysis indicated that the concentrations of cesium, zinc, and selenium were significantly reduced in patients with Schizophrenia in both the training and test groups. The meta-analysis including 522 cases and 360 controls supported that Zinc was significantly associated with Schizophrenia (standardized mean difference [SMD], -0.81; 95% confidence intervals [CI], -1.46 to -0.16, P = 0.01) in the random-effect model. Information theory analysis indicated that Zinc could play roles independently in Schizophrenia. These results suggest clear element profile differences between patients with Schizophrenia and healthy controls, and reduced Zn level is confirmed in the Schizophrenia patients.

Catatonic schizophrenia: a cohort prospective study.

PubMed

Kleinhaus, Karine; Harlap, Susan; Perrin, Mary C; Manor, Orly; Weiser, Mark; Harkavy-Friedman, Jill M; Lichtenberg, Pesach; Malaspina, Dolores

2012-03-01

In the 20th century, catatonia was usually deemed a subtype of schizophrenia. Recently, the nature and classification of catatonia are being reconsidered. This study is the first to describe catatonia using prospectively collected data and to examine how catatonic schizophrenia differs from, or resembles, other types of schizophrenia. Data were analyzed in a cohort of 90,079 offspring followed from birth till ages 29-41 years. Proportional hazards models were used, calculating time to first psychiatric hospital admission, to compare risk factors for catatonic schizophrenia vs "other schizophrenia." Of 568 cases of schizophrenia, 43 (7.6%) had catatonic schizophrenia. The sexes were equally at risk for catatonic schizophrenia in contrast to other schizophrenia, for which the incidence was higher in males (1.70, 1.42-2.03, P < .0001). Advancing paternal age had no influence on the risk of catatonic schizophrenia in contrast to other schizophrenia, in which the risk to offspring of fathers age 35+ was 1.27 (1.03-1.57, P = .03) compared with those of younger fathers. Those with catatonic schizophrenia were somewhat more likely to have older mothers (aged 35+) (relative risk = 2.14, 0.85-5.54) while maternal age was not related to other schizophrenia. Both were equally affected by parental history of schizophrenia. Patients with catatonia were significantly more likely to attempt suicide (P = .006). Patients with catatonic schizophrenia show a somewhat different profile of risk factors from those with other types of schizophrenia in this cohort and are more likely to attempt suicide. This lends some support to the hypothesis that catatonic schizophrenia may have a distinct etiology.

Systematic review and meta-analysis of homicide recidivism and Schizophrenia

PubMed Central

2014-01-01

Background The aim of this study was to estimate the proportion of homicide recidivists among population studies of homicide offenders with schizophrenia. Methods Systematic review and meta-analysis of published studies of homicide associated with schizophrenia conducted in defined populations and indexed in Medline, PsychINFO, or Embase between January 1960 and November 2013. Published data was supplemented with unpublished data about recidivism obtained by personal communication from the authors of published studies of homicide and schizophrenia. Random effects meta-analysis was used to calculate a pooled estimate of the proportion of homicide recidivists. Results Three studies reported that 4.3%, 4.5%, and 10.7% of homicide offenders with schizophrenia had committed an earlier homicide. Unpublished data were obtained from the authors of 11 studies of homicide in schizophrenia published in English between 1980 and 2013. The authors of 2 studies reported a single case of homicide recidivism and the authors of 9 studies reported no cases. The rates of homicide recidivism between studies were highly heterogeneous (I-square = 79). The pooled estimate of the proportion of homicide offenders with schizophrenia who had committed an earlier homicide was 2.3% (95% CI (Confidence Interval) 0.07% to 7.2%), a figure that was not reported in any individual study. The pooled proportion of homicide recidivists from published reports was more than ten times greater (8.6%, 95% CI 5.7%-12.9%) than the pooled proportion of homicide recidivists estimated from data provided by personal communication (0.06%, 95% CI 0.02% to 1.8%). Conclusions In most jurisdictions, homicide recidivism by people with schizophrenia is less common than published reports have suggested. The reasons for the variation in the rates of homicide recidivism between studies are unclear, although in most jurisdictions long-term secure treatment and supervision after release appears to be effective in preventing homicide recidivism. A prospective study conducted in a large population or in multiple jurisdictions over a long period of time might result in a more accurate estimate the risk of a second homicide by a person with schizophrenia. PMID:24548381

Systematic review and meta-analysis of homicide recidivism and schizophrenia.

PubMed

Golenkov, Andrei; Nielssen, Olav; Large, Matthew

2014-02-18

The aim of this study was to estimate the proportion of homicide recidivists among population studies of homicide offenders with schizophrenia. Systematic review and meta-analysis of published studies of homicide associated with schizophrenia conducted in defined populations and indexed in Medline, PsychINFO, or Embase between January 1960 and November 2013. Published data was supplemented with unpublished data about recidivism obtained by personal communication from the authors of published studies of homicide and schizophrenia. Random effects meta-analysis was used to calculate a pooled estimate of the proportion of homicide recidivists. Three studies reported that 4.3%, 4.5%, and 10.7% of homicide offenders with schizophrenia had committed an earlier homicide. Unpublished data were obtained from the authors of 11 studies of homicide in schizophrenia published in English between 1980 and 2013. The authors of 2 studies reported a single case of homicide recidivism and the authors of 9 studies reported no cases. The rates of homicide recidivism between studies were highly heterogeneous (I-square = 79). The pooled estimate of the proportion of homicide offenders with schizophrenia who had committed an earlier homicide was 2.3% (95% CI (Confidence Interval) 0.07% to 7.2%), a figure that was not reported in any individual study. The pooled proportion of homicide recidivists from published reports was more than ten times greater (8.6%, 95% CI 5.7%-12.9%) than the pooled proportion of homicide recidivists estimated from data provided by personal communication (0.06%, 95% CI 0.02% to 1.8%). In most jurisdictions, homicide recidivism by people with schizophrenia is less common than published reports have suggested. The reasons for the variation in the rates of homicide recidivism between studies are unclear, although in most jurisdictions long-term secure treatment and supervision after release appears to be effective in preventing homicide recidivism. A prospective study conducted in a large population or in multiple jurisdictions over a long period of time might result in a more accurate estimate the risk of a second homicide by a person with schizophrenia.

Common variants in the TPH2 promoter confer susceptibility to paranoid schizophrenia.

PubMed

Yi, Zhenghui; Zhang, Chen; Lu, Weihong; Song, Lisheng; Liu, Dentang; Xu, Yifeng; Fang, Yiru

2012-07-01

Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. Our previous study suggested that promoter region of tryptophan hydroxylase 2 gene (TPH2) may confer the susceptibility to paranoid schizophrenia. In this study, we investigated whether common variants within TPH2 promoter may predispose to paranoid schizophrenia in Han Chinese. A total of 509 patients who met DSM-IV criteria for paranoid schizophrenia and 510 matched healthy controls were recruited for this study. Five polymorphisms within TPH2 promoter region were tested. No statistically significant differences were found in allele or genotype frequencies between schizophrenic patients and healthy controls. The frequency of the rs4448731T-rs6582071A-rs7963803A-rs4570625T-rs11178997A haplotype was significantly higher in cases compared to the controls (P = 0.003; OR = 1.49; 95% CI, 1.15-1.95). Our results suggest that the common variants within TPH2 promoter are associated with paranoid schizophrenia in Han Chinese. Further studies in larger samples are warranted to elucidate the role of TPH2 in the etiology of paranoid schizophrenia.

PRENATAL INFECTION AND EXECUTIVE DYSFUNCTION IN ADULT SCHIZOPHRENIA

PubMed Central

Brown, Alan S.; Vinogradov, Sophia; Kremen, William S.; Poole, John H.; Deicken, Raymond F.; Penner, Justin D.; McKeague, Ian W.; Kochetkova, Anna; Kern, David; Schaefer, Catherine A.

2010-01-01

Objective Executive dysfunction is one of the most prominent and functionally important cognitive deficits in schizophrenia. Although strong associations have been identified between executive impairments and structural and functional prefrontal cortical deficits, the etiological factors that contribute to disruption of this important cognitive domain remain unclear. Increasing evidence suggests that schizophrenia has a neurodevelopmental etiology, and several prenatal infections have been associated with risk of this disorder. To date, however, no previous study has examined whether in utero infection is associated with executive dysfunction in patients with schizophrenia. Method In the present study, we assessed the relationship between serologically documented prenatal exposure to influenza and toxoplasmosis and performance on the Wisconsin Card Sorting Test (WCST) and the Trail Making Test, part B (Trails B), as well as other measures of executive function, in 26 patients with schizophrenia from a large and well-characterized birth cohort. Results Cases who were exposed in utero to infection committed significantly more total errors on the WCST and took significantly more time to complete the Trails B than unexposed cases. Exposed cases also exhibited deficits on figural fluency, letter-number sequencing, and backward digit span. Conclusion Prenatal infections previously associated with schizophrenia are related to impaired performance on the WCST and Trails B. The pattern of results suggests that cognitive set-shifting ability may be particularly vulnerable to this gestational exposure. Further work is necessary to elucidate the specificity of prenatal infection to these executive function measures and examine correlates with neuroanatomic and neurophysiologic anomalies. PMID:19369317

Use of the word schizophrenia in Portuguese newspapers.

PubMed

Rodrigues-Silva, Nuno; Falcão de Almeida, Telma; Araújo, Filipa; Molodynski, Andrew; Venâncio, Ângela; Bouça, Jorge

2017-10-01

Stigmatizing references to schizophrenia have a negative impact on self-esteem, deter treatment seeking and diminish the effectiveness of treatment. To analyze the reporting of schizophrenia in Portuguese newspapers. We analyzed five high circulation Portuguese newspapers between 2007 and 2013. We selected all news containing the word "esquizofrenia" (schizophrenia). Several variables were collected. About 1058 news items contained the word schizophrenia. Schizophrenia was mentioned metaphorically in 40% of the cases and in the context of Crime in 22%. When used in a Criminal context, schizophrenia was mostly attributed to people who were the perpetrators of the crime (93%). When used metaphorically, schizophrenia had a negative connotation in 90% of cases. We found an increasing reporting of schizophrenia in the criminal news and serious crimes. Our results suggest the media has an active role promoting stigma, as well as passively broadcasting and thus passing on prejudices.

Is there any role of latent toxoplasmosis in schizophrenia disease?

PubMed

Karabulut, Nuran; Bilgiç, Serkan; Gürok, Mehmet Gürkan; Karaboğa, Fatih

2015-09-01

A large number of studies have hypothesized that Toxoplasma gondii is a potentially relevant etiological factor in some cases of schizophrenia. By contrast, some studies have disproved this association. The aim of this study was to investigate whether latent toxoplasmosis has any role in schizophrenia disease. Additionally, the association between T. gondii and subtypes of schizophrenia, and the impacts of toxoplasmosis on psychopathology were examined in the study. A total of 85 patients with schizophrenia and 60 healthy volunteers were included in this prospective study. Immunoglobulin G (IgG) antibody to T. gondii was examined by enzyme-linked immune-sorbent assay method. Seropositivity rates were 43.5% for the patients with schizophrenia and 43.3% for the healthy controls (odds ratio: 1.008, 95% confidence interval: 0.517-1.964, p = 0.981).There was no significant difference in T. gondii IgG positivity between the schizophrenia and control groups with respect to sex and age. The difference in seroprevalence of T. gondii IgG antibodies among the schizophrenia subtypes was not statistically significant (p = 0.934). No significant difference was found in Positive and Negative Syndrome Subscales between Toxoplasma-infected and Toxoplasma-free patients. In the study area with a high prevalence of T. gondii, no association between toxoplasmosis and schizophrenia was detected. These findings showed that toxoplasmosis has no role in the risk of schizophrenia disease. Copyright © 2015. Published by Elsevier Taiwan.

Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis.

PubMed

Agerbo, Esben; Sullivan, Patrick F; Vilhjálmsson, Bjarni J; Pedersen, Carsten B; Mors, Ole; Børglum, Anders D; Hougaard, David M; Hollegaard, Mads V; Meier, Sandra; Mattheisen, Manuel; Ripke, Stephan; Wray, Naomi R; Mortensen, Preben B

2015-07-01

Schizophrenia has a complex etiology influenced both by genetic and nongenetic factors but disentangling these factors is difficult. To estimate (1) how strongly the risk for schizophrenia relates to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of psychiatric disorders; (2) the fraction of cases that could be prevented if no one was exposed to these factors; (3) whether family background interacts with an individual's genetic liability so that specific subgroups are particularly risk prone; and (4) to what extent a proband's genetic makeup mediates the risk associated with familial background. We conducted a nested case-control study based on Danish population-based registers. The study consisted of 866 patients diagnosed as having schizophrenia between January 1, 1994, and December 31, 2006, and 871 matched control individuals. Genome-wide data and family psychiatric and socioeconomic background information were obtained from neonatal biobanks and national registers. Results from a separate meta-analysis (34,600 cases and 45,968 control individuals) were applied to calculate polygenic risk scores. Polygenic risk scores, parental socioeconomic status, and family psychiatric history. Odds ratios (ORs), attributable risks, liability R2 values, and proportions mediated. Schizophrenia was associated with the polygenic risk score (OR, 8.01; 95% CI, 4.53-14.16 for highest vs lowest decile), socioeconomic status (OR, 8.10; 95% CI, 3.24-20.3 for 6 vs no exposures), and a history of schizophrenia/psychoses (OR, 4.18; 95% CI, 2.57-6.79). The R2 values were 3.4% (95% CI, 2.1-4.6) for the polygenic risk score, 3.1% (95% CI, 1.9-4.3) for parental socioeconomic status, and 3.4% (95% CI, 2.1-4.6) for family history. Socioeconomic status and psychiatric history accounted for 45.8% (95% CI, 36.1-55.5) and 25.8% (95% CI, 21.2-30.5) of cases, respectively. There was an interaction between the polygenic risk score and family history (P = .03). A total of 17.4% (95% CI, 9.1-26.6) of the effect associated with family history of schizophrenia/psychoses was mediated through the polygenic risk score. Schizophrenia was associated with the polygenic risk score, family psychiatric history, and socioeconomic status. Our study demonstrated that family history of schizophrenia/psychoses is partly mediated through the individual's genetic liability.

Association of rs1344706 in the ZNF804A gene with schizophrenia in a case/control sample from Indonesia.

PubMed

Schwab, Sibylle G; Kusumawardhani, Agung A A A; Dai, Nan; Qin, WenWen; Wildenauer, Mutiara D B; Agiananda, Feranindhya; Amir, Nurmiati; Antoni, Ronald; Arsianti, Tiana; Asmarahadi, Asmarahadi; Diatri, Hervita; Djatmiko, Prianto; Irmansyah, Irmansyah; Khalimah, Siti; Kusumadewi, Irmia; Kusumaningrum, Profitasari; Lukman, Petrin R; Mustar, Lukman; Nasrun, Martina W; Naswati, Safyuni; Prasetiyawan, Prasetiyawan; Semen, Gerald M; Siste, Kristiana; Tobing, Heriani; Widiasih, Natalia; Wiguna, Tjhin; Wulandari, Widayanti Dewi; Benyamin, Beben; Wildenauer, Dieter B

2013-06-01

Association of rs1344706 in the ZNF804A gene (2q32.1) with schizophrenia was first reported in a genome wide scan conducted in a sample of 479 cases and replicated in 6666 cases. Subsequently, evidence by replication was obtained in several samples with European- and Asian ancestral background. We report ascertainment, clinical characterization, quality control, and determination of ancestral background of a case control sample from Indonesia, comprising 1067 cases and 1111 ancestry matched controls. Genotyping was performed using a fluorescence-based allelic discrimination assay (TaqMan SNP genotyping assay) and a newly designed PCR-RFLP assay for confirmation of rs1344706 genotypes. We confirmed association of the T-allele of rs1344706 with schizophrenia in a newly ascertained sample from Indonesia with Southeast Asian ancestral background (P=0.019, OR=1.155, 95%, CI 1.025-1.301). In addition, we studied several SNPs in the vicinity of rs1344706, for which nominally significant results had been reported. None of the association P values of the additional SNPs exceeded that of rs1344706. We provide additional evidence for association of the ZNF804A gene with schizophrenia. We conclude that rs1344706 or a yet unknown polymorphism in linkage disequilibrium is also involved in conferring susceptibility to schizophrenia in samples with different (Asian) ancestral backgrounds. Copyright © 2013 Elsevier B.V. All rights reserved.

HLA DRB1*03 as a possible common etiology of schizophrenia, Graves' disease, and type 2 diabetes.

PubMed

Sayeh, Aicha; Ben Cheikh, Cheker; Mardessi, Ali; Mrad, Meriem; Nsiri, Brahim; Oumaya, Abdelaziz; Fekih-Mrissa, Najiba

2017-01-01

Autoimmune diseases and schizophrenia share many common features. Association studies confirm a shared genetic association in the human leukocyte antigen (HLA) region between schizophrenia and most autoimmune diseases. To our knowledge, the simultaneous syndromes of Graves' disease (GD) and type 2 diabetes (T2D) in schizophrenia are rare in Tunisia. We report a case of a 42-year-old woman admitted to the department of psychiatry for an acute relapse of chronic schizophrenia. Her medical history revealed that she was followed for Graves' disease and for a type 2 diabetes mellitus. A low-resolution HLA typing was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) techniques according to determine the patient's haplotype. Our study suggests that the HLA DRB1*03 allele may explain a common etiology underlying the co-morbidity of Graves' disease, type 2 diabetes, and schizophrenia in our patient.

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

PubMed

Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne Yw; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

2016-03-01

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

Catatonic Schizophrenia: A Cohort Prospective Study

PubMed Central

Kleinhaus, Karine; Harlap, Susan; Perrin, Mary C.; Manor, Orly; Weiser, Mark; Harkavy-Friedman, Jill M.; Lichtenberg, Pesach; Malaspina, Dolores

2012-01-01

Background: In the 20th century, catatonia was usually deemed a subtype of schizophrenia. Recently, the nature and classification of catatonia are being reconsidered. This study is the first to describe catatonia using prospectively collected data and to examine how catatonic schizophrenia differs from, or resembles, other types of schizophrenia. Methods: Data were analyzed in a cohort of 90 079 offspring followed from birth till ages 29–41 years. Proportional hazards models were used, calculating time to first psychiatric hospital admission, to compare risk factors for catatonic schizophrenia vs “other schizophrenia.” Results: Of 568 cases of schizophrenia, 43 (7.6%) had catatonic schizophrenia. The sexes were equally at risk for catatonic schizophrenia in contrast to other schizophrenia, for which the incidence was higher in males (1.70, 1.42–2.03, P < .0001). Advancing paternal age had no influence on the risk of catatonic schizophrenia in contrast to other schizophrenia, in which the risk to offspring of fathers age 35+ was 1.27 (1.03–1.57, P = .03) compared with those of younger fathers. Those with catatonic schizophrenia were somewhat more likely to have older mothers (aged 35+) (relative risk = 2.14, 0.85–5.54) while maternal age was not related to other schizophrenia. Both were equally affected by parental history of schizophrenia. Patients with catatonia were significantly more likely to attempt suicide (P = .006). Conclusion: Patients with catatonic schizophrenia show a somewhat different profile of risk factors from those with other types of schizophrenia in this cohort and are more likely to attempt suicide. This lends some support to the hypothesis that catatonic schizophrenia may have a distinct etiology. PMID:20693343

Common variant at 16p11.2 conferring risk of psychosis.

PubMed

Steinberg, S; de Jong, S; Mattheisen, M; Costas, J; Demontis, D; Jamain, S; Pietiläinen, O P H; Lin, K; Papiol, S; Huttenlocher, J; Sigurdsson, E; Vassos, E; Giegling, I; Breuer, R; Fraser, G; Walker, N; Melle, I; Djurovic, S; Agartz, I; Tuulio-Henriksson, A; Suvisaari, J; Lönnqvist, J; Paunio, T; Olsen, L; Hansen, T; Ingason, A; Pirinen, M; Strengman, E; Hougaard, D M; Orntoft, T; Didriksen, M; Hollegaard, M V; Nordentoft, M; Abramova, L; Kaleda, V; Arrojo, M; Sanjuán, J; Arango, C; Etain, B; Bellivier, F; Méary, A; Schürhoff, F; Szoke, A; Ribolsi, M; Magni, V; Siracusano, A; Sperling, S; Rossner, M; Christiansen, C; Kiemeney, L A; Franke, B; van den Berg, L H; Veldink, J; Curran, S; Bolton, P; Poot, M; Staal, W; Rehnstrom, K; Kilpinen, H; Freitag, C M; Meyer, J; Magnusson, P; Saemundsen, E; Martsenkovsky, I; Bikshaieva, I; Martsenkovska, I; Vashchenko, O; Raleva, M; Paketchieva, K; Stefanovski, B; Durmishi, N; Pejovic Milovancevic, M; Lecic Tosevski, D; Silagadze, T; Naneishvili, N; Mikeladze, N; Surguladze, S; Vincent, J B; Farmer, A; Mitchell, P B; Wright, A; Schofield, P R; Fullerton, J M; Montgomery, G W; Martin, N G; Rubino, I A; van Winkel, R; Kenis, G; De Hert, M; Réthelyi, J M; Bitter, I; Terenius, L; Jönsson, E G; Bakker, S; van Os, J; Jablensky, A; Leboyer, M; Bramon, E; Powell, J; Murray, R; Corvin, A; Gill, M; Morris, D; O'Neill, F A; Kendler, K; Riley, B; Craddock, N; Owen, M J; O'Donovan, M C; Thorsteinsdottir, U; Kong, A; Ehrenreich, H; Carracedo, A; Golimbet, V; Andreassen, O A; Børglum, A D; Mors, O; Mortensen, P B; Werge, T; Ophoff, R A; Nöthen, M M; Rietschel, M; Cichon, S; Ruggeri, M; Tosato, S; Palotie, A; St Clair, D; Rujescu, D; Collier, D A; Stefansson, H; Stefansson, K

2014-01-01

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Working with art in a case of schizophrenia.

PubMed

Noronha, Konrad J

2013-01-01

Schizophrenia often requires a lifetime of treatment. This study used art as a therapeutic tool in therapy with a client diagnosed with schizophrenia, along with medical management. The purpose of using art was to enable the non-communicative client to communicate. The clients' drawings were used as a process medium. Progress was seen in changes in social behaviours and communication evidenced by him speaking more, expressing feelings and gaining better insight.

Serological and molecular diagnosis of Toxoplasma gondii in patients with schizophrenia.

PubMed

Ebrahimzadeh, Adel; Shahraki, Mehdi Khoshsima; Mohammadi, Azad

2018-06-01

Schizophrenia is a persistent neuropsychiatric syndrome of uncertain source. Toxoplasmosis is the most prevalent parasitic protozoan infecting one-third of the worldwide human population. Infectious agents such as toxoplasma are the probable cause of schizophrenia. This study was aimed to evaluate the association between schizophrenia and toxoplasmosis using SAG1 and B1 Target gene. During February to December 2016, 92 patients with schizophrenia are imported in our study. All cases were assessed by serological (IgG and IgM antibodies) and molecular examinations. ELISA was performed by Commercial kits according to manufactures procedure. DNA was extracted and nested PCR was done using two pairs of primers. From 92 patients, 59 (64.13%) cases were positive for toxoplasmosis by serological examinations (14 samples positive for IgM and IgG, 40 samples positive for only IgG and 5 samples Positive for only IgM) and 58 (63.04%) were positive by Nested PCR technique. Based on the nested PCR method, 68.47 and 47.82% of samples were positive by B1 and SAG1 genes, respectively. Our results showed the importance of use both serological and molecular diagnostic methods for accurate recognition of T . gondii in patients with schizophrenia. Moreover our results indicated that B1 gene is more sensitive than SAG1 gene.

GABAergic system impairment in the hippocampus and superior temporal gyrus of patients with paranoid schizophrenia: A post-mortem study.

PubMed

Steiner, Johann; Brisch, Ralf; Schiltz, Kolja; Dobrowolny, Henrik; Mawrin, Christian; Krzyżanowska, Marta; Bernstein, Hans-Gert; Jankowski, Zbigniew; Braun, Katharina; Schmitt, Andrea; Bogerts, Bernhard; Gos, Tomasz

2016-11-01

Glutamic acid decarboxylase (GAD) is a key enzyme in GABA synthesis and alterations in GABAergic neurotransmission related to glial abnormalities are thought to play a crucial role in the pathophysiology of schizophrenia. This study aimed to identify potential differences regarding the neuropil expression of GAD between paranoid and residual schizophrenia. GAD65/67 immunostained histological sections were evaluated by quantitative densitometric analysis of GAD-immunoreactive (ir) neuropil. Regions of interest were the hippocampal formation (CA1 field and dentate gyrus [DG]), superior temporal gyrus (STG), and laterodorsal thalamic nucleus (LD). Data from 16 post-mortem schizophrenia patient samples (10 paranoid and 6 residual schizophrenia cases) were compared with those from 16 matched controls. Overall, schizophrenia patients showed a lower GAD-ir neuropil density (P=0.014), particularly in the right CA1 (P=0.033). However, the diagnostic subgroups differed significantly (P<0.001), mainly because of lower right CA1 GAD-ir neuropil density in paranoid versus residual patients (P=0.036) and controls (P<0.003). Significant GAD-ir neuropil reduction was also detected in the right STG layer V of paranoid versus residual schizophrenia cases (P=0.042). GAD-ir neuropil density correlated positively with antipsychotic dosage, particularly in CA1 (right: r=0.850, P=0.004; left: r=0.800, P=0.010). Our finding of decreased relative density of GAD-ir neuropil suggests hypofunction of the GABAergic system, particularly in hippocampal CA1 field and STG layer V of patients with paranoid schizophrenia. The finding that antipsychotic medication seems to counterbalance GABAergic hypofunction in schizophrenia patients suggests the possibility of exploring new treatment avenues which target this system. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment of Visual Hallucinations in Schizophrenia by Acetylcholinesterase Inhibitors: a case report

PubMed Central

Abad, Nazir Hashemi; Doulatabad, Najafi Shala; Mohammadi, Ali

2011-01-01

Schizophrenia and various neurological disorders have some signs and symptoms. Visual hallucinations are one of such disorders. The related studies in some diseases for example Parkinson Disease and Lewy Body Dementia indicate that Acetylcholine (Ach) plays a significant role in neuropsychiatric manifestation and its association with visual hallucination; therefore, visual hallucinations occur due to the depletion of Ach. Drug therapies such as Cholinesterase inhibitors (ChEIs) for increasing Ach level may be beneficial in treating visual hallucination. AchEI's have been used in the treatment of visual hallucinations in Dementia and Parkinson's Disease. We thought that a similar Ach depletion may cause visual hallucinations in patients with schizophrenia and may provide a target for drug treatment. We had a patient with schizophrenia whose psychotic symptoms responded to the treatment plan, but her visual hallucination did not. However, the patient's visual hallucination successfully responded to Rivastigmine (AchEI). This case illustrates the use of an AchEI in the treatment of refractory visual hallucinations in a patient with schizophrenia. PMID:22952543

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder.

PubMed

Allardyce, Judith; Leonenko, Ganna; Hamshere, Marian; Pardiñas, Antonio F; Forty, Liz; Knott, Sarah; Gordon-Smith, Katherine; Porteous, David J; Haywood, Caroline; Di Florio, Arianna; Jones, Lisa; McIntosh, Andrew M; Owen, Michael J; Holmans, Peter; Walters, James T R; Craddock, Nicholas; Jones, Ian; O'Donovan, Michael C; Escott-Price, Valentina

2018-01-01

Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms. To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD. This case-control study in the United Kingdom used multinomial logistic regression to estimate differential PRS associations across categories of cases and controls. Participants included in the final analyses were 4436 cases of BD from the Bipolar Disorder Research Network. These cases were compared with the genotypic data for 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. Data were collected between January 1, 2000, and December 31, 2013. Data analysis was conducted from March 1, 2016, to February 28, 2017. Standardized PRSs, calculated using alleles with an association threshold of P < .05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, were adjusted for the first 10 population principal components and genotyping platforms. Multinomial logit models estimated PRS associations with BD stratified by Research Diagnostic Criteria subtypes of BD, by lifetime occurrence of psychosis, and by lifetime mood-incongruent psychotic features. Ordinal logistic regression examined PRS associations across levels of mood incongruence. Ratings were derived from the Schedules for Clinical Assessment in Neuropsychiatry interview and the Bipolar Affective Disorder Dimension Scale. Of the 4436 cases of BD, 2966 (67%) were female patients, and the mean (SD) age at interview was 46 [12] years. Across clinical phenotypes, there was an exposure-response gradient, with the strongest PRS association for schizophrenia (risk ratio [RR] = 1.94; 95% CI, 1.86-2.01), followed by schizoaffective BD (RR = 1.37; 95% CI, 1.22-1.54), bipolar I disorder subtype (RR = 1.30; 95% CI, 1.24-1.36), and bipolar II disorder subtype (RR = 1.04; 95% CI, 0.97-1.11). Within BD cases, there was an effect gradient, indexed by the nature of psychosis. Prominent mood-incongruent psychotic features had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and BD with no history of psychosis (RR = 1.09; 95% CI, 1.04-1.15). For the first time to date, a study shows a polygenic-risk gradient across schizophrenia and BD, indexed by the occurrence and level of mood-incongruent psychotic symptoms.

Looking for Childhood Schizophrenia: Case Series of False Positives.

ERIC Educational Resources Information Center

Stayer, Catherine; Sporn, Alexandra; Gogtay, Nitin; Tossell, Julia; Lenane, Marge; Gochman, Peter; Rapoport, Judith L.

2004-01-01

Extensive experience with the diagnosis of childhood-onset schizophrenia indicates a high rate of false positives. Most mislabeled patients have chronic disabling, affective, or behavioral disorders. The authors report the cases of three children who passed stringent initial childhood-onset schizophrenia "screens" but had no chronic psychotic…

The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia.

PubMed

Miller, Brian J; Buckley, Peter F

2016-06-01

This article presents the case in favor of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia. Evidence for prenatal and premorbid immune risk factors for the development of schizophrenia in the offspring is highlighted. Then key evidence for immune dysfunction in patients with schizophrenia is considered. Next, previous trials of adjunctive anti-inflammatory or other immunotherapy in schizophrenia are discussed. Then evidence for psychosis as a side effect of immunotherapy for other disorders is discussed. Also presented is preliminary evidence for adjunctive monoclonal antibody immunotherapy in psychiatric disorders. Finally, important considerations in the design and implementation of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Low maternal retinol as a risk factor for schizophrenia in adult offspring

PubMed Central

Bao, YuanYuan; Ibram, Ghionul; Blaner, William S.; Quesenberry, Charles P.; Shen, Ling; McKeague, Ian W.; Schaefer, Catherine A.; Susser, Ezra S.; Brown, Alan S.

2012-01-01

Background Prenatal micronutrient deficiency has been linked to later development of schizophrenia among offspring; however, no study has specifically investigated the association between vitamin A and this disorder. Vitamin A is an essential nutrient which is required by the early embryo and fetus for gene expression and regulation, cell differentiation, proliferation and migration. Previous work suggests that vitamin A deficiency in the second trimester may be particularly relevant to the etiopathogenesis of neurobehavioral phenotypes some of which are observed in schizophrenia. Methods We examined whether low maternal vitamin A levels in the second trimester are associated with the risk of schizophrenia and other schizophrenia spectrum disorders (SSD) in the Prenatal Determinants of Schizophrenia study; third trimester vitamin A levels were also examined in relation to SSD. The cases were derived from a population-based birth cohort; all cohort members belonged to a prepaid health plan. Archived maternal serum samples were assayed for vitamin A in cases (N=55) and up to 2 controls per case (N=106) matched on length of membership in the health plan, date of birth (±28 days), sex, and gestational timing and availability of archived maternal sera. Results For the second trimester, low maternal vitamin A, defined as values in the lowest tertile of the distribution among controls, was associated with a greater than threefold increased risk of SSD, adjusting for maternal education and age (OR=3.04, 95% CI=1.06, 8.79, p=.039). No association between third trimester maternal vitamin A and SSD was observed. Conclusions Although further investigations are warranted, this is the first birth cohort study to our knowledge to report an association between low maternal vitamin A levels and SSD among offspring. PMID:22381190

Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis.

PubMed

MacCabe, J H; Sariaslan, A; Almqvist, C; Lichtenstein, P; Larsson, H; Kyaga, S

2018-06-01

Many studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.AimsTo test for an association between studying a creative subject at high school or university and later mental disorder. In a case-control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365). Compared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders. Students of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.Declaration of interestNone.

Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: a case-control study in a Tunisian population.

PubMed

Raffa, Monia; Lakhdar, Ramzi; Ghachem, Meriem; Barhoumi, Sana; Safar, Mohamed Taher; Bel Hadj Jrad, Besma; Haj Khelil, Amel; Kerkeni, Abdelhamid; Mechri, Anwar

2013-01-10

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification. Thus, in this study we investigated the association of glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) gene deletion polymorphisms and schizophrenia in a Tunisian population. A case-control study including 138 schizophrenic patients and 123 healthy controls was enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). No association was found between the GSTM1 genotype and schizophrenia, whereas the prevalence of the GSTT1 active genotype was significantly higher in the schizophrenic patients (57.2%) than in the controls (45.5%) with (OR=0.6, IC 0.37-0.99, p=0.039). Thus, we noted a significant association between schizophrenia and GSTT1 active genotype. Furthermore, the combination of the GSTM1 and GSTT1 null genotypes showed a non-significant trend to an increased risk of schizophrenia. The present finding indicated that GSTT1 seems to be a candidate gene for susceptibility to schizophrenia in at least Tunisian population. Copyright © 2012 Elsevier B.V. All rights reserved.

Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine.

PubMed

Nakazawa, Takanobu; Kikuchi, Masataka; Ishikawa, Mitsuru; Yamamori, Hidenaga; Nagayasu, Kazuki; Matsumoto, Takuya; Fujimoto, Michiko; Yasuda, Yuka; Fujiwara, Mikiya; Okada, Shota; Matsumura, Kensuke; Kasai, Atsushi; Hayata-Takano, Atsuko; Shintani, Norihito; Numata, Shusuke; Takuma, Kazuhiro; Akamatsu, Wado; Okano, Hideyuki; Nakaya, Akihiro; Hashimoto, Hitoshi; Hashimoto, Ryota

2017-03-01

Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Trimethoprim as Adjuvant Treatment in Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

PubMed Central

Shibre, Teshome; Alem, Atalay; Abdulahi, Abdulreshid; Araya, Mesfin; Beyero, Teferra; Medhin, Girmay; Deyassa, Negusse; Negash, Alemayehu; Nigatu, Alemayehu; Kebede, Derege

2010-01-01

Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable. PMID:19193743

Exome sequencing supports a de novo mutational paradigm for schizophrenia

PubMed Central

Xu, Bin; Roos, J. Louw; Dexheimer, Phillip; Boone, Braden; Plummer, Brooks; Levy, Shawn; Gogos, Joseph A.; Karayiorgou, Maria

2011-01-01

Despite high heritability, a large fraction of cases with schizophrenia do not have a family history of the disease (sporadic cases). Here, we examine the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exome of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 patients affecting 40 genes including a potentially disruptive mutation in DGCR2, a gene removed by the recurrent schizophrenia-predisposing 22q11.2 microdeletion. Comparison to rare inherited variants revealed that the identified de novo mutations show a large excess of nonsynonymous changes in cases, as well as a greater potential to affect protein structure and function. Our analysis reveals a major role of de novo mutations in schizophrenia and also a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease. PMID:21822266

Hippocampus age-related microstructural changes in schizophrenia: a case-control mean diffusivity study.

PubMed

Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

2014-08-01

Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window. Copyright © 2014 Elsevier B.V. All rights reserved.

[Schizophrenia and Liver Transplantation: Case Report].

PubMed

Diana, Restrepo B; Marle, Duque G; Carlos, Cardeño C

2012-09-01

Liver transplantation is a treatment available for many patients with liver cirrhosis who find in this treatment a way to improve life expectancy and quality of life. Paranoid schizophrenia affects 1% of the general population, produces psychotic symptoms, and runs a chronic course in some cases with significant deterioration in all areas of life. To discuss the case of a patient with liver cirrhosis diagnosed with paranoid schizophrenia during the evaluation protocol for liver transplantation. Case report. We report the case of a 47-year-old woman with liver cirrhosis whose only alternative to improve life expectancy and quality of life was access to liver transplantation. During routine evaluations the liaison psychiatrist observed first-order psychotic symptoms and documented a life story that confirmed the presence of paranoid schizophrenia. Paranoid schizophrenia is a psychiatric disorder common in the general population that can be a part of the medical comorbidities of patients requiring liver transplantation and is not an absolute contraindication to its completion. We are unaware of similar cases of liver transplantation in patients with schizophrenia in our country. We believe this is a big step on the road to overcome the stigma that mental illness imposes on patients. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Genetic variants in long non-coding RNA MIAT contribute to risk of paranoid schizophrenia in a Chinese Han population.

PubMed

Rao, Shu-Quan; Hu, Hui-Ling; Ye, Ning; Shen, Yan; Xu, Qi

2015-08-01

The heritability of schizophrenia has been reported to be as high as ~80%, but the contribution of genetic variants identified to this heritability remains to be estimated. Long non-coding RNAs (LncRNAs) are involved in multiple processes critical to normal cellular function and dysfunction of lncRNA MIAT may contribute to the pathophysiology of schizophrenia. However, the genetic evidence of lncRNAs involved in schizophrenia has not been documented. Here, we conducted a two-stage association analysis on 8 tag SNPs that cover the whole MIAT locus in two independent Han Chinese schizophrenia case-control cohorts (discovery sample from Shanxi Province: 1093 patients with paranoid schizophrenia and 1180 control subjects; replication cohort from Jilin Province: 1255 cases and 1209 healthy controls). In discovery stage, significant genetic association with paranoid schizophrenia was observed for rs1894720 (χ(2)=74.20, P=7.1E-18), of which minor allele (T) had an OR of 1.70 (95% CI=1.50-1.91). This association was confirmed in the replication cohort (χ(2)=22.66, P=1.9E-06, OR=1.32, 95%CI 1.18-1.49). Besides, a weak genotypic association was detected for rs4274 (χ(2)=4.96, df=2, P=0.03); the AA carriers showed increased disease risk (OR=1.30, 95%CI=1.03-1.64). No significant association was found between any haplotype and paranoid schizophrenia. The present studies showed that lncRNA MIAT was a novel susceptibility gene for paranoid schizophrenia in the Chinese Han population. Considering that most lncRNAs locate in non-coding regions, our result may explain why most susceptibility loci for schizophrenia identified by genome wide association studies were out of coding regions. Copyright © 2015 Elsevier B.V. All rights reserved.

Treating Obsessive-Compulsive Disorder and Schizophrenia: The Case of Sam

ERIC Educational Resources Information Center

Peasley-Miklus, Catherine; Massie, Elise; Baslett, Gaston; Carmin, Cheryl

2005-01-01

This article describes the case of Sam, a 22-year-old male with obsessive-compulsive disorder (OCD) and schizophrenia. The patient's background, the development and characteristics of his OCD and schizophrenia, and the history of what became a rather complicated treatment are described. In addition, four problem areas of therapy are identified.

Assessing dietary and lifestyle risk factors and their associations with disease comorbidities among patients with schizophrenia: A case-control study from Bahrain.

PubMed

Jahrami, Haitham Ali; Faris, Mo'ez Al-Islam Ezzat; Saif, Zahraa Qassim; Hammad, Laila Habib

2017-08-01

Acquired dietary habits and lifestyle behaviors of patients with schizophrenia may affect their life expectancy, disease complications and prognosis. The objectives of the current study were to assess the dietary habits and other lifestyle behaviors for Bahraini patients with schizophrenia, and to determine their associations with different medical comorbidities. A case-control study was conducted during the period of March to December 2016. A sample of 120 cases were recruited from the Psychiatric Hospital, Bahrain and age-sex-matched with 120 controls. Controls were recruited from primary health centres, and were free from serious mental illness. Dietary habits and lifestyle behaviors including smoking, alcohol intake and physical activity were assessed using a questionnaire. All medical records were reviewed retrospectively. Logistic regression analysis was used to identify dietary and lifestyle risk factors that are associated with one or more disease comorbidities. Cases had higher prevalence of smoking and alcohol intake, excessive dietary intake, and decreased physical activity (all P<0.05) compared with controls. Cases appeared to be at higher risk for developing chronic medical conditions such as obesity, type 2 diabetes, hypertension, cardiovascular disease, and musculoskeletal disorders. Cases were three times more likely to have up to three or more medical comorbidities compared with controls. Excessive dietary intake and decreased physical activity were identified as the main risk factors. Excessive caloric intake and decreased physical activity represent the main dietary and lifestyle risk factors associated with comorbidities among patients with schizophrenia in Bahrain. Copyright © 2017 Elsevier B.V. All rights reserved.

Abnormal parietal encephalomalacia associated with schizophrenia: A case report.

PubMed

Pan, Fen; Wang, Jun-Yuan; Xu, Yi; Huang, Man-Li

2017-03-01

It is widely believed that structural abnormalities of the brain contribute to the pathophysiology of schizophrenia. The parietal lobe is a central hub of multisensory integration, and abnormities in this region might account for the clinical features of schizophrenia. However, few cases of parietal encephalomalacia associated with schizophrenia have been described. In this paper, we present a case of a 25-year-old schizophrenia patient with abnormal parietal encephalomalacia. The patient had poor nutrition and frequently had upper respiratory infections during childhood and adolescence. She showed severe schizophrenic symptoms such as visual hallucinations for 2 years. After examining all her possible medical conditions, we found that the patient had a lesion consistent with the diagnosis of encephalomalacia in her right parietal lobe and slight brain atrophy. The patient was prescribed olanzapine (10 mg per day). Her symptoms significantly improved after antipsychotic treatment and were still well controlled 1 year later. This case suggested that parietal encephalomalacia, which might be caused by inflammatory and infectious conditions in early life and be aggravated by undernutrition, might be implicated in the etiology of schizophrenia.

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: an introduction to this Special Issue of Schizophrenia Research.

PubMed

Swerdlow, Neal R; Gur, Raquel E; Braff, David L

2015-04-01

The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Since 2003, COGS has completed studies using a family-based ascertainment strategy (COGS-1), and a case-control ascertainment strategy (COGS-2) (cumulative "n">4000). COGS-1 family study confirmed robust deficits in, and heritability of, these endophenotypes in schizophrenia, and provided evidence for a coherent genetic architecture underlying the risk for neurocognitive and neurophysiological deficits in this disorder. COGS-2 case-control findings, many reported herein, establish a foundation for fine genomic mapping and other analyses of these endophenotypes and risk genes for SZ. Several reports in this Special Issue compare findings of endophenotype deficits generated by fundamentally different COGS-1 vs. COGS-2 ascertainment strategies. Despite the expectation that family-based and case-control designs would establish demographically and potentially biologically distinct patient cohorts, findings generally revealed comparable patterns of endophenotype deficits across studies. The COGS-2 case-control design facilitated the accrual of a larger "n", permitting detailed analyses of factors moderating endophenotype performance. Some COGS-2 endophenotypes not assessed in COGS-1 are also reported, as is a new factor analytic strategy for identifying shared vs. unique factors among the COGS endophenotypes which can be used to develop composite variables with distinct genetic signatures. The path to date of COGS-1 endophenotype and genetic findings, followed by replication and extension in COGS-2, establishes benchmarks for endophenotype deficits in SZ and their moderation by specific factors, and clear expectations for informative findings from upcoming COGS-2 genetic analyses. Published by Elsevier B.V.

If cannabis caused schizophrenia--how many cannabis users may need to be prevented in order to prevent one case of schizophrenia? England and Wales calculations.

PubMed

Hickman, Matt; Vickerman, Peter; Macleod, John; Lewis, Glyn; Zammit, Stan; Kirkbride, James; Jones, Peter

2009-11-01

We consider how many cannabis users may need to be prevented in order to prevent one case of schizophrenia or psychosis [defined as number needed to prevent (NNP)]. Calculation for England and Wales using best available estimates of: incidence of schizophrenia; rates of heavy and light cannabis use; and risk that cannabis causes schizophrenia. In men the annual mean NNP for heavy cannabis and schizophrenia ranged from 2800 [90% confidence interval (CI) 2018-4530] in those aged 20-24 years to 4700 (90% CI 3114-8416) in those aged 35-39. In women, mean NNP for heavy cannabis use and schizophrenia ranged from 5470 (90% CI 3640-9839) in those aged 25-29 to 10 870 (90% CI 6786-22 732) in 35-39-year-olds. Equivalent mean NNP for heavy cannabis use and psychosis were lower, from 1360 (90% CI 1007-2124) in men aged 20-24 and 2480 (90% CI 1408-3518) in women aged 16-19. The mean and median number of light cannabis users that would need to be prevented in order to prevent one case of schizophrenia or psychosis per year are four to five times greater than among heavy users. The number of young people who need to be exposed to an intervention to generate NNP and prevent one case of schizophrenia will be even larger. The public health importance of preventing cannabis to reduce schizophrenia or psychosis remains uncertain. More attention should be given to testing the hypothesis that cannabis is related causally to psychotic outcomes, and to considering what strategies will be the most effective in reducing heavy cannabis use among young people.

A case control study of association between cognition and functional capacity in schizophrenia.

PubMed

Narayanan, Sreelatha S; Bhatia, Triptish; Velligan, Dawn I; Nimgaonkar, Vishwajit L; Deshpande, Smita N

2015-12-01

Cognitive functions are important prognostic factors for schizophrenia (SZ), while ability to perform activities of daily living are important measures of functional capacity. The relationship between cognition and functional capacity has not been tested extensively in India. To compare persons with SZ with controls on measures of cognition and functional capacity, and evaluate correlations between cognitive performance and functional capacity. Schizophrenia outpatients and controls without psychiatric illness (DSM IV) who completed the MATRICS Consensus Cognitive Battery and Functional Assessment Battery comprised of two tests from University of California San Diego (UCSD) Performance Based Skill Assessment (UPSA), one Test of Adaptive Behavior in Schizophrenia (TABS) and one test from University of California San Diego Performance Based Skill Assessment Brief edition (UPSA-B). Cognitive and functional domains were examined using regression analyses, with relevant covariates. Cases (N=51) though younger, were more educated than controls (N=41). Adjusting for education, controls performed better than cases in 3/7 cognitive and 4/5 domains of functional capacity but similarly in 'household management'. Among both cases and controls, cognitive measures of verbal learning and speed of processing overlapped with functional capacity (3 domains). Working memory was associated with one functional domain. Consistent with other studies, Indian patients with schizophrenia performed worse than controls on several domains of cognition and functional capacity; these domains were correlated. Speed of processing and verbal learning are most frequently associated with functional capacity indices and should be targeted to improve skills of daily living among persons with SZ. Copyright © 2015. Published by Elsevier B.V.

[Are risk factors in prenatal and perinatal period important for develompent of schizophrenia?

PubMed

Ambroz, P; Janoutová, J; Machaczka, O; Kovaľová, M; Pohlídalová, A; Vařechová, K; Košta, O; Tomášková, H; Šerý, O; Hosák, L; Janout, V

Schizophrenia is an important psychical disease of multifactorial origin and not yet clear etiology. In prenatal and perinatal period some potential risk factors for schizophrenia are taken into consideration. Case-control study of 815 subjects, 407 cases and 408 controls was performed in 2013 to 2015. In this study environmental and genetic risk factors were evaluated including potential risk factors of prenatal and perinatal period. Statistically important difference was found in child-birth done by cesarean section (p = 0.009) and in patients with schizophrenia were 15.7% complications in the course of childbirth (p < 0.001). Hypoxia, passed umbilical cord were the most frequent complications. In prenatal period premature childbirth, injury and psychical complications were the most frequent. On the other hand difference in weight and length of newborns, breast feeding and infection during pregnancy were found not statistically important. In this study statistically important diference were found in way of carrying childbirth and in some complications during pregnancy and delivery. Influence of infection during pregnancy and influence of weight and length of newborn were not demonstrated.

A family affair: brain abnormalities in siblings of patients with schizophrenia.

PubMed

Moran, Marcel E; Hulshoff Pol, Hilleke; Gogtay, Nitin

2013-11-01

Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development.

A family affair: brain abnormalities in siblings of patients with schizophrenia

PubMed Central

Hulshoff Pol, Hilleke; Gogtay, Nitin

2013-01-01

Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development. PMID:23698280

COMT Val158Met and MTHFR C677T moderate risk of schizophrenia in response to childhood adversity.

PubMed

Debost, J-C; Debost, M; Grove, J; Mors, O; Hougaard, D M; Børglum, A D; Mortensen, P B; Petersen, L

2017-07-01

Mesolimbic dopamine sensitization has been hypothesized to be a mediating factor of childhood adversity (CA) on schizophrenia risk. Activity of catechol-O-methyltransferase (COMT) Val158Met increases mesolimbic dopamine signaling and may be further regulated by methylenetetrahydrofolate reductase (MTHFR) C677T. This study investigates the three-way interaction between CA, COMT, and MTHFR. We conducted a nested case-control study on individuals born after 1981, linking population-based registers to study the three-way interaction. We included 1699 schizophrenia cases and 1681 controls, and used conditional logistic regression to report incidence rate ratios (IRRs). Childhood adversity was robustly associated with schizophrenia. No main genetic effects were observed. MTHFR C677T increased schizophrenia risk in a dose-dependent manner per MTHFR T allele (P = 0.005) consequent upon CA exposure. After inclusion of the significant (P = 0.03) COMT × MTHFR × CA interaction, the risk was further increased per high-activity COMT Val allele. Hence, exposed COMT Val/Val and MTHFR T/T carriers had an IRR of 2.76 (95% CI, 1.66-4.61). Additional adjustments for ancestry and parental history of mental illness attenuated the results with the interaction being only marginally significant. MTHFR C677T and COMT Val158Met interact with CA to increase risk of schizophrenia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Paranoid personality disorder and the schizophrenia spectrum-Where to draw the line?

PubMed

Birkeland, Søren Fryd

2013-08-01

By means of a case vignette, this study explores the clinical intersection between paranoid personality disorder and other schizophrenia-spectrum illness. Even though the patient described had paramount signs of a paranoid personality disorder and was diagnosed as such, psychopathological symptoms extended considerably beyond the common concept and diagnostic criteria of the disorder. Management strategies included psychopharmacological and non-pharmacological interventions, yet psychosocial functioning permanently appeared defective. While there is a persistent need for an opportunity to distinguish the characteristic syndromal pattern of paranoid personality attributes, the case exemplifies the challenges associated with classifying some largely suspicious and distrustful eccentrics within the schizophrenia spectrum. Copyright © 2013 John Wiley & Sons, Ltd.

A polydiagnostic approach to self-perceived cognitive disorders in schizophrenia.

PubMed

Peralta, V; Cuesta, M J

1992-01-01

The relationship between the self-perceived cognitive disorders (SPCD) assessed using the Frankfurt Complaint Questionnaire (FCQ) and 21 definitions of schizophrenia was studied in a sample of 118 consecutively admitted patients. The FCQ total score was significantly associated (p < 0.05) with the presence of Schneider's, Yusin's and Present State Examination criteria of schizophrenia. A significant association, in this case negative, was also found between the FCQ total score and the presence of the DSM-III-R criteria of schizophrenia. The results suggest that the SPCDs are more associated with Schneider-related criteria than with chronic or deficit models of schizophrenia. It was also found that the female sex as well as the presence of insight were significantly associated with a greater number of SPCDs.

Lack of association of IL-6 (-174 G>C) and TNF-α (-238 G>A) variants with paranoid schizophrenia in Indian Bengalee population.

PubMed

Debnath, Monojit; Mitra, Bikash; Bera, Nirmal Kumar; Chaudhuri, Tapas Kumar; Zhang, Ya-ping

2013-02-01

Schizophrenia is a chronic debilitating neuropsychiatric disorder with complex etiopathology. Growing evidence suggests a significant role of chronic low grade inflammation in the pathophysiology of schizophrenia. Multiple immunological, genetic polymorphism and gene expression studies have established crucial roles of certain pro-inflammatory cytokines in the immune-mediated risk of schizophrenia. Although genetic studies suggest some variants within the pro-inflammatory IL-1β, IL-6, and TNF-α genes conferring risk to schizophrenia, the results however have been contradictory in various populations. In the present investigation, promoter SNPs of IL-6 (-174 G>C) and TNF-α (-238 G>A) genes have been studied to evaluate whether these variants contribute to schizophrenia susceptibility in Indian Bengalee population. Genotyping of the above SNPs was done in 100 well characterized and confirmed cases of paranoid schizophrenia and equal number of healthy donors belonging to the same ethnic group by using ABI 3730 Genetic Analyzer. No significant differences in genotype as well as allele frequencies were observed for IL-6 and TNF-α variants between the patient and control groups. Copyright © 2012 Elsevier Ltd. All rights reserved.

Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism

PubMed Central

Brown, Alan S.

2012-01-01

In this review, we provide a synopsis of work on the epidemiologic evidence for prenatal infection in the etiology of schizophrenia and autism. In birth cohort studies conducted by our group and others, in utero exposure to infectious agents, prospectively obtained following biomarker assays of archived maternal sera and by obstetric records was related to an elevated risk of schizophrenia. Thus far, it has been demonstrated that prenatal exposure to influenza, elevated toxoplasma antibody, genital/reproductive infections, rubella, and other pathogens are associated with schizophrenia. Anomalies of the immune system, including enhanced maternal cytokine levels are also related to schizophrenia. Some evidence also suggests that maternal infection and immune dysfunction may be associated with autism. Although replication is required, these findings suggest that public health interventions targeting infectious exposures have the potential for preventing cases of schizophrenia and autism. Moreover, this work has stimulated translational research on the neurobiological and genetic determinants of these conditions. PMID:22488761

Salivary Alpha-Amylase Activity Levels in Catatonic Schizophrenia Decrease after Electroconvulsive Therapy.

PubMed

Kanayama, Misako; Miyaoka, Tsuyoshi; Araki, Tomoko; Hayashida, Maiko; Hashioka, Sadayuki; Horiguchi, Jun

2018-01-01

Dysfunction of the autonomic nervous system (ANS) in schizophrenia has been detected by electrophysiological methods, but the underlying mechanisms remain unknown. Several studies have suggested that measuring salivary alpha-amylase activity levels is useful for evaluating the ANS activity and that sAA levels increase in schizophrenia and correlate with Brief Psychiatric Rating Scale (BPRS) scores. However, no study has examined the relationship between sAA activity levels and symptoms of schizophrenia with catatonic state. We present the case of a 59-year-old female with persistent catatonic schizophrenia treated by electroconvulsive therapy. We evaluated the ANS activity by measuring sAA activity levels before and after ECT, and we evaluated her symptoms using the BPRS and Bush-Francis Catatonia Rating Scale (BFCRS). ECT was highly effective and BPRS and BFCRS scores substantially decreased. sAA activity levels decreased from 125 kU/l to 33 kU/l. sAA activity levels could be a potential biomarker of schizophrenia with catatonic state.

No association between FOXP2 rs10447760 and schizophrenia in a replication study of the Chinese Han population.

PubMed

Yin, Jiajun; Jia, Ningren; Liu, Yansong; Jin, Chunhui; Zhang, Fuquan; Yu, Shui; Wang, Jun; Yuan, Jianmin

2018-04-01

Schizophrenia (SCZ) is a severe and heritable psychiatric disorder, and previous studies have shown that regulation of the forkhead-box P2 gene (FOXP2) may play a role in schizophrenia. Moreover, just a few studies have identified a single nucleotide polymorphism (SNP) rs10447760 within the gene that was a risk variant for SCZ in the Chinese Han population. To examine whether the variant in the FOXP2 gene contributes toward SCZ susceptibility, we carried out an association analysis of the SNP rs10447760 of the FOXP2 gene in a case-control study (1405 cases, 1137 controls) from China. We identified no association of rs10447760 in the FOXP2 gene with SCZ (all P>0.05). In addition, a meta-analysis indicated that the SNP rs10447760 was not associated with susceptibility to SCZ in Han Chinese populations (pooled odds ratio=1.44, 95% confidence interval: 0.63-3.31, P=0.39). Thus, our results did not support the association between FOXP2 rs10447760 and schizophrenia in a Chinese Han population, and large-scale genetic replication studies with different racial and geographic origins are required in the future.

N-Methyl-D-aspartate receptor antibody could be a cause of catatonic symptoms in psychiatric patients: case reports and methods for detection.

PubMed

Tsutsui, Ko; Kanbayashi, Takashi; Takaki, Manabu; Omori, Yuki; Imai, Yumiko; Nishino, Seiji; Tanaka, Keiko; Shimizu, Tetsuo

2017-01-01

The symptoms of catatonia have been reported to be similar to the initial symptoms of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Subsequently, this autoimmune limbic encephalitis has been noticed by many psychiatrists. For a differential diagnosis of catatonic state, it is important to detect anti-NMDAR encephalitis. This encephalitis is expected to be in remission by early detection and treatment. We should be more cautious about catatonic symptoms of schizophrenia. When a patient is suspected of having encephalitis, we should screen for anti-NMDAR antibodies in cerebrospinal fluid samples using a cell-based assay. We describe the methods of NMDAR antibody detection and the etiology of this encephalitis with case reports. Two representative cases with catatonia and non-catatonia (brief psychotic disorder) were reported. Schizophrenia is a general, heterogeneous, and complicated disorder, and its pathophysiology is unknown. There is an established evidence of NMDAR hypofunction, which is the functional disconnection of the central component; this is one of the most recognized models for schizophrenia. Furthermore, it is said that autoimmune mechanisms have been involved, at least in subgroups of schizophrenia patients. Further study of anti-NMDAR antibody and its related encephalitis would give essential clues for the research of schizophrenia, catatonia, and atypical psychosis.

Improving quality and diffusing best practices: the case of schizophrenia.

PubMed Central

Donohue, Julie M.; Domino, Marisa E.; Normand, Sharon-Lise T.

2009-01-01

The slow diffusion of empirically supported treatments and the rapid diffusion of treatments lacking empirical support play a significant role in the quality gap in the care of people with severe mental illnesses. Further, the rapid diffusion of treatments of low cost-effectiveness limits the system's ability to provide the full gamut of high-value treatments available to treat this vulnerable population. Using the case of schizophrenia as an illustrative case study, we review the context in which these paradoxical patterns of diffusion have occurred and propose policy solutions. PMID:19414878

Systematic meta-analysis of childhood social withdrawal in schizophrenia, and comparison with data from at-risk children aged 9-14 years.

PubMed

Matheson, Sandra L; Vijayan, Hena; Dickson, Hannah; Shepherd, Alana M; Carr, Vaughan J; Laurens, Kristin R

2013-08-01

Social withdrawal is a robust childhood risk factor for later schizophrenia. The aims of this paper were to assess the evidence for childhood social withdrawal among adults with schizophrenia and, comparatively, in children aged 9-14 years who are putatively at-risk of developing schizophrenia. We conducted a meta-analysis, including cohort and case-control studies reporting social withdrawal measured by the Child Behavior Checklist (CBCL) in adults with schizophrenia vs. controls. Further, an experimental study compared CBCL withdrawal scores from typically-developing children with scores from two groups of putatively at-risk children: (i) children displaying a triad of replicated antecedents for schizophrenia, and (ii) children with at least one first- or second-degree relative with schizophrenia or schizoaffective disorder. Six studies met inclusion criteria for the meta-analysis (N = 3828), which demonstrated a large effect of increased childhood social withdrawal in adults with schizophrenia (standardized mean difference [SMD] score = 1.035, 95% CI = 0.304-1.766, p = 0.006), with no indication of publication bias, but considerable heterogeneity (I(2) = 91%). Results from the experimental study also indicated a large effect of increased social withdrawal in children displaying the antecedent triad (SMD = 0.743, p = 0.001), and a weaker effect in children with a family history of schizophrenia (SMD = 0.442, p = 0.051). Childhood social withdrawal may constitute a vulnerability marker for schizophrenia in the presence of other antecedents and/or genetic risk factors for schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Guidelines for the Pharmacotherapy of Schizophrenia in Adults.

PubMed

Remington, Gary; Addington, Donald; Honer, William; Ismail, Zahinoor; Raedler, Thomas; Teehan, Michael

2017-09-01

The present guidelines address the pharmacotherapy of schizophrenia in adults across different stages, phases, and symptom domains. Guidelines were developed using the ADAPTE process, which takes advantage of existing guidelines. Six guidelines were identified for adaptation, with recommendations extracted from each. For those specific to the pharmacotherapy of schizophrenia in adults, a working group selected between guidelines and recommendations to create an adapted guideline. Recommendations can be categorized into 6 areas that include 1) first-episode schizophrenia, 2) acute exacerbation, 3) relapse prevention and maintenance treatment, 4) treatment-resistant schizophrenia, 5) clozapine-resistant schizophrenia, and 6) specific symptom domains. For each category, recommendations are made based on the available evidence, which is discussed and linked to other established guidelines. In most cases, evidence-based recommendations are made that can be used to guide current clinical treatment and decision making. Notably, however, there is a paucity of established evidence to guide treatment decision making in the case of clozapine-resistant schizophrenia, a subsample that represents a sizable proportion of those with schizophrenia.

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

PubMed Central

Ruderfer, Douglas M; Charney, Alexander W; Readhead, Ben; Kidd, Brian A; Kähler, Anna K; Kenny, Paul J; Keiser, Michael J; Moran, Jennifer L; Hultman, Christina M; Scott, Stuart A; Sullivan, Patrick F; Purcell, Shaun M; Dudley, Joel T; Sklar, Pamela

2016-01-01

Summary Background Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia. Methods We defined schizophrenia risk loci as genomic regions reaching genome-wide significance in the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study (GWAS) of 36 989 cases and 113 075 controls and loss of function variants observed only once among 5079 individuals in an exome-sequencing study of 2536 schizophrenia cases and 2543 controls (Swedish Schizophrenia Study). Using two large and orthogonally created databases, we collated drug targets into 167 gene sets targeted by pharmacologically similar drugs and examined enrichment of schizophrenia risk loci in these sets. We further linked the exome-sequenced data with a national drug registry (the Swedish Prescribed Drug Register) to assess the contribution of rare variants to treatment response, using clozapine prescription as a proxy for treatment resistance. Findings We combined results from testing rare and common variation and, after correction for multiple testing, two gene sets were associated with schizophrenia risk: agents against amoebiasis and other protozoal diseases (106 genes, p=0·00046, pcorrected =0·024) and antipsychotics (347 genes, p=0·00078, pcorrected=0·046). Further analysis pointed to antipsychotics as having independent enrichment after removing genes that overlapped these two target sets. We noted significant enrichment both in known targets of antipsychotics (70 genes, p=0·0078) and novel predicted targets (277 genes, p=0·019). Patients with treatment-resistant schizophrenia had an excess of rare disruptive variants in gene targets of antipsychotics (347 genes, p=0·0067) and in genes with evidence for a role in antipsychotic efficacy (91 genes, p=0·0029). Interpretation Our results support genetic overlap between schizophrenia pathogenesis and antipsychotic mechanism of action. This finding is consistent with treatment efficacy being polygenic and suggests that single-target therapeutics might be insufficient. We provide evidence of a role for rare functional variants in antipsychotic treatment response, pointing to a subset of patients where their genetic information could inform treatment. Finally, we present a novel framework for identifying treatments from genetic data and improving our understanding of therapeutic mechanism. PMID:26915512

Analyzing the presentation and the stigma of schizophrenia in French newspapers.

PubMed

Lampropoulos, Dimitrios; Wolman, Angelika; Apostolidis, Thémis

2017-12-01

It has been suggested that the stigmatizing presentation of people with schizophrenia by newspapers is an example of structural stigma. In this study, we explore how French newspapers contribute to the stigma of people with schizophrenia. All the articles of eight major newspapers (four national and four regional) that include the term schizophr* and that were published in 2015 were therefore analyzed using a coding scheme that we developed inductively. This analysis showed that among the identified themes, 40.4% of the articles used the term schizophrenia metaphorically and 28.3% referred to dangerousness. The first concerned mostly national newspapers, while the second were mostly published by regional newspapers. A more selective analysis was also carried out on these major themes in order to investigate how the "us" against "them" distinction is created and how negative stereotypes are associated with this distinction. In the case of the metaphorical use of the term, schizophrenia was presented as a "split personality" disorder and the label used in order to devalue the political opposition. Schizophrenia was presented either as a deterministic cause of dangerousness or as a potential cause of crime. In either case, the question of control was clearly present in these articles. These results are discussed in terms of the "us" against "them" distinction as a double process of stigmatization of people with schizophrenia and of reinforcement of one's own identity and security.

Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study.

PubMed

Wu, Chi-Shin; Chang, Chia-Ming; Tsai, Yu-Ting; Huang, Ya-Wen; Tsai, Hui-Ju

2015-09-01

To investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. Among patients with schizophrenia (ICD-9-CM code 295), 605 cases with hip fracture and 2,828 matched controls were identified from 2002 to 2011 using the National Health Insurance Research Database in Taiwan. The authors conducted a nested case-control study to investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. The modifiable effects of age and gender were evaluated by stratified analysis. In addition, the effects of antipsychotic use, antipsychotic classes, and receptor-binding profiles of antipsychotics, individually, on hip fracture were estimated, and potential confounding factors were adjusted in subsequent analysis. Conditional logistic regressions were applied to determine the effect of antipsychotic treatment on hip fracture. Current antipsychotic use was associated with an increased risk for hip fracture (adjusted odds ratio [AOR] = 1.61; 95% CI, 1.24-2.10). Among current users, new users had a higher risk of hip fracture (AOR = 4.28; 95% CI, 1.76-10.36) than past users (AOR = 1.11; 95% CI, 0.79-1.56). In addition, a significant increased risk of hip fracture was noted in schizophrenia subjects with first-generation antipsychotic use (AOR = 1.59; 95%CI, 1.15-2.20) but not in those with second-generation antipsychotic use (AOR = 1.16; 95% CI, 0.91-1.48). These results extend previous findings and demonstrate an increased risk of hip fracture associated with antipsychotic use in schizophrenia subjects. Further investigation is needed to dissect the underlying mechanisms related to the effect of antipsychotic use on hip fracture in subjects at risk. © Copyright 2015 Physicians Postgraduate Press, Inc.

Using short-range and long-range functional connectivity to identify schizophrenia with a family-based case-control design.

PubMed

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Li, Lehua; Zhang, Zhikun; Chen, Huafu; Zhao, Jingping

2017-06-30

Abnormal short-range and long-range functional connectivities (FCs) have been implicated in the neurophysiology of schizophrenia. This study was conducted to examine the potential of short-range and long-range FCs for differentiating the patients from the controls with a family-based case-control design. Twenty-eight first-episode, drug-naive patients with schizophrenia, 28 unaffected siblings of the patients (family-based controls, FBCs), and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. The data were analyzed by short-range and long-range FC analyses, receiver operating characteristic curve (ROC) and support vector machine (SVM). Compared with the FBCs/HCs, the patients exhibit increased short-range positive FC strength (spFCS) and/or long-range positive FC strength (lpFCS) in the default-mode network (DMN) and decreased spFCS and lpFCS in the sensorimotor circuits. Furthermore, a combination of the spFCS values in the right superior parietal lobule and the lpFCS values in the left fusiform gyrus/cerebellum VI can differentiate the patients from the FBCs with high sensitivity and specificity. The findings highlight the importance of the DMN and sensorimotor circuits in the pathogenesis of schizophrenia. Combining with family-based case-control design may be a viable option to limit the confounding effects of environmental risk factors in neuroimaging studies of schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Endophenotypes, Epigenetics, Polygenicity and More: Irv Gottesman’s Dynamic Legacy

PubMed Central

Braff, David L.; Tamminga, Carol A.

2017-01-01

First, we describe the hallmark contributions of Irv Gottesman’s pioneering scholarship for schizophrenia research including concepts of polygenicity, gene × environment interactions, epigenetics and the endophenotype concept. Gottesman and colleagues’ twin studies showed that genes, not social factors, mediate schizophrenia risk. He then showed that schizophrenia is highly polygenic. Next, he introduced the concept of epigenetics into schizophrenia research. Gottesman then introduced the quantitative endophenotype concept. Endophenotypes are laboratory-based measures that show deficits in schizophrenia patients and lesser deficits in their first degree “unaffected” relatives and are viewed as being more proximal to genes and having a simpler genetic architecture than are “fuzzy” qualitative diagnostic disorders. Endophenotypes offer an exciting path to gene discovery, neural circuits, genetic architecture and new treatment pathways of schizophrenia and related psychotic disorders. Second, we were asked to discuss 2 of many endophenotype Consortia and related studies, in order to illustrate the impact of Gottesman’s work. We describe the Consortium on the Genetics of Schizophrenia (COGS) exploring neurocognitive and neurophysiological endophenotypes in family and case-control studies. Association, linkage, sequencing and epigenetic studies are described. The Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) uses an array of endophenotypes including brain imaging in studies across the psychosis dimension, allowing for dimensional analyses. BSNIP results have led to the concept of biotypes, advancing the field. Irv Gottesman was imaginatively prescient in generating novel insights and predicting many major issues which challenge schizophrenia researchers who still use his concepts to guide current research approaches. PMID:27872267

Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

PubMed

Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

2011-03-01

Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

PubMed

St Pourcain, B; Robinson, E B; Anttila, V; Sullivan, B B; Maller, J; Golding, J; Skuse, D; Ring, S; Evans, D M; Zammit, S; Fisher, S E; Neale, B M; Anney, R J L; Ripke, S; Hollegaard, M V; Werge, T; Ronald, A; Grove, J; Hougaard, D M; Børglum, A D; Mortensen, P B; Daly, M J; Davey Smith, G

2018-02-01

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

Case history and genome-wide scans for copy number variants in a family with patient having 15q11.1-q11.2 duplication and 22q11.2 deletion, and schizophrenia.

PubMed

Takahashi, Sakae; Suzuki, Takahiro; Nakamura-Tomizuka, Sakura; Osaki, Koichi; Sotome, Yuta; Sagawa, Tomoaki; Uchiyama, Makoto

2015-06-01

Many studies have indicated that chromosomes 15q11 and 22q11 may be associated with the genetic etiologies of schizophrenia. We have followed an adult schizophrenia case with 15q11.1-q11.2 duplication and 22q11.2 deletion. Here we report his clinical history, and copy number variants (CNVs) identified by microarray and real-time PCR in the patient and his parents. This is the first report describing a detailed phenotype of an adult schizophrenic case with both 15q11 and 22q11 CNVs as revealed by novel and trustworthy technologies. Subjects were a 33-year-old male patient with 15q11 and 22q11 CNVs, and his normal parents. He fulfilled the DSM-IV criteria for schizophrenia at age 18 years. He was also diagnosed with 22q11.2 deletion syndrome by fluorescence in situ hybridization (FISH) at age 18 years. To search for CNVs in more detail, whole-genome array-CGH analyses including ∼ 420,000 probes were carried out in the patient and his parents. For validations of the CNVs detected by array-CGH, real-time PCR analyses of these CNVs were performed. The patient had two disease-specific CNVs, 15q11.1-q11.2 duplication (∼ 2.7 Mb) and 22q11.21 deletion (∼ 2.9 Mb). These two regions are important for the development of schizophrenia, and this patient had shown symptoms of schizophrenia. Thus, the two areas may contain causal genes for schizophrenia. © 2015 Wiley Periodicals, Inc.

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

PubMed Central

Weickert, Cynthia Shannon; Sheedy, Donna; Rothmond, Debora A.; Dedova, Irina; Fung, Samantha; Garrick, Therese; Wong, Jenny; Harding, Antony J.; Sivagnanansundaram, Sinthuja; Hunt, Clare; Duncan, Carlotta; Sundqvist, Nina; Tsai, Shan-Yuan; Anand, Jasna; Draganic, Daren; Harper, Clive

2010-01-01

Objective To conduct postmortem human brain research into the neuropathological basis of schizophrenia, it is critical to establish cohorts that are well-characterised and well-matched. Our objective was to determine if specimen characteristics, including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs. Methods We selected a matched cohort of 74 cases (37 schizophrenia / schizoaffective disorder cases and 37 controls cases). Middle frontal gyrus tissue was pulverised, tissue pH was measured, RNA isolated for cDNA from each case, and RNA integrity number (RIN) measurements were assessed. Using RT-PCR, we measured nine housekeeper genes and calculated a geomean in each diagnostic group. Results We found that the RINs were very good (mean 7.3) and all nine housekeeper control genes were significantly correlated with RIN. Seven of nine housekeeper genes were also correlated with pH, and two clinical variables, agonal state and duration of illness did have an effect on some control mRNAs. No major impact of PMI or freezer time on housekeeper mRNAs was detected. Our results show that people with schizophrenia had significantly less PPIA, and SDHA and tended to have less GUSB and B2M mRNA suggesting that these control genes may not be good candidates for normalisation. Conclusions In our cohort, less than 10% variability in RIN values was detected and the diagnostic groups were well matched overall. Our cohort was adequately powered (0.80–0.90) to detect mRNA differences (25%) due to disease. Our study suggests that multiple factors should be considered in mRNA expression studies of human brain tissues. When schizophrenia cases are adequately matched to control cases subtle differences in gene expression can be reliably detected. PMID:20073568

Seroprevalence of anti-Toxoplasma gondii and anti-Borrelia species antibodies in patients with schizophrenia: a case-control study from western Turkey.

PubMed

Cevizci, Sibel; Celik, Merve; Akcali, Alper; Oyekcin, Demet Gulec; Sahin, Ozlem Oztürk; Bakar, Coskun

2015-06-01

We examined IgG antibody seroprevalence and risk factors for anti-Toxoplasma gondii and anti-Borrelia sp. in schizophrenic patients. This case-control study included 30 schizophrenic patients and 60 healthy individuals. Serological analyses were identified by using ELISA technique. In the case group the Toxoplasma seropositivity was 33.3% and Borrelia seropositivity was 13.3%, while in the control group the Toxoplasma positivity was 21.7% and Borrelia seropositivity was 15.0%. There was no significant difference with regard to seroprevalence between the groups (P = 0.232; P = 0.832, respectively). There was statistically significant difference between case and control groups related to hand and kitchen utensil hygiene after dealing with raw meat (P = 0.001). Our data showed the rate of Toxoplasma antibodies was higher in the case group, while the rate of Borrelia antibodies was higher in the control group. In both groups the high rates of seropositivity for Toxoplasma gondii and Borrelia sp. is thought to be due to neglect of personal hygiene. The present study also is the first to examine the association between Borrelia sp. and schizophrenia. Further studies are needed to determine whether there is an association between Borrelia sp. and schizophrenia or not.

TREATMENT OF OBSESSIVE COMPULSIVE SYMPTOMS IN SCHIZOPHRENIA WITH FLUOXETINE

PubMed Central

Agarwal, Vivek; Agarwal, K.M.

2000-01-01

Obsessive compulsive symptoms have been reported to occur in high proportion in schizophrenia. Presence of obsessive compulsive symptoms in schizophrenia has poor prognostic significance. Because of the antiobsessional effect of the fluoxetine, present study was undertaken as preliminary investigation in cases of schizophrenia with obsessive compulsive symptoms. We conducted an open trial of 12 weeks duration in which fluoxetine was added up to 80 mg to the maintenance neuroleptic medication of outpatients of schizophrenia with obsessive compulsive symptoms diagnosed by DSM-IV criteria. Five patients showed a significant reduction in scores of Positive and Negative Syndrome Scale, Yale Brown Obsessive Compulsive Scale and Clinical Global Impression Scale. Two patients did not show any response. Fluoxetine was well tolerated by all the patients. The positive findings of this preliminary investigation supports the further investigations of fluoxetine as potential treatment in the obsessive compulsive symptoms in schizophrenia. PMID:21407959

Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders.

PubMed

Canellas, Francesca; Lin, Ling; Julià, Maria Rosa; Clemente, Antonio; Vives-Bauza, Cristofol; Ollila, Hanna M; Hong, Seung Chul; Arboleya, Susana M; Einen, Mali A; Faraco, Juliette; Fernandez-Vina, Marcelo; Mignot, Emmanuel

2014-09-15

Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. © 2014 American Academy of Sleep Medicine.

Famotidine adjunctive pharmacotherapy of schizophrenia: a case report.

PubMed

Rosse, R B; Kendrick, K; Tsui, L C; Fay-McCarthy, M; Collins, J P; Rosenberg, P; Wyatt, R J; Deutsch, S I

1995-08-01

Recent reports suggest some utility for famotidine, a histamine type 2 (H2) antagonist, in the treatment of schizophrenia. The current report describes a treatment-resistant patient with chronic undifferentiated schizophrenia whose most dramatic symptomatic improvements were temporarily related to the open-label addition of famotidine (40-100 mg/day) to conventional neuroleptic treatment (molindone 150-200 mg/day) over the course of approximately 10 months. During one 2-week interval, his symptoms were controlled with famotidine (40 mg/day) alone. The case suggests that some adjuvant efficacy exists for famotidine in at least some patients with schizophrenia. Placebo-controlled trials are needed to more fully evaluate the utility of famotidine in the treatment of schizophrenia.

Reawakening reflective capacity in the psychotherapy of schizophrenia: a case study.

PubMed

Bargenquast, Rebecca; Schweitzer, Robert D; Drake, Suzanne

2015-02-01

Disturbed sense of self has long been identified as a common experience among people suffering with schizophrenia. More recently, metacognitive deficits have been found to be a stable and independent feature of schizophrenia that contributes to disturbed self-experience and impedes recovery. Individual psychotherapy designed to target poor metacognition has been shown to promote a more coherent sense of self and enhanced recovery in people with schizophrenia. We provide a report of a 2-year individual psychotherapy with a patient suffering with chronic schizophrenia. Progress was assessed over the course of treatment using the Metacognition Assessment Scale and the Brief Psychiatric Rating Scale. The patient experienced improved metacognitive capacity and reduced symptom severity over the course of therapy. Implications for clinical practice are discussed. © 2015 Wiley Periodicals, Inc.

Segment-Wise Genome-Wide Association Analysis Identifies a Candidate Region Associated with Schizophrenia in Three Independent Samples

PubMed Central

Rietschel, Marcella; Mattheisen, Manuel; Breuer, René; Schulze, Thomas G.; Nöthen, Markus M.; Levinson, Douglas; Shi, Jianxin; Gejman, Pablo V.; Cichon, Sven; Ophoff, Roel A.

2012-01-01

Recent studies suggest that variation in complex disorders (e.g., schizophrenia) is explained by a large number of genetic variants with small effect size (Odds Ratio∼1.05–1.1). The statistical power to detect these genetic variants in Genome Wide Association (GWA) studies with large numbers of cases and controls (∼15,000) is still low. As it will be difficult to further increase sample size, we decided to explore an alternative method for analyzing GWA data in a study of schizophrenia, dramatically reducing the number of statistical tests. The underlying hypothesis was that at least some of the genetic variants related to a common outcome are collocated in segments of chromosomes at a wider scale than single genes. Our approach was therefore to study the association between relatively large segments of DNA and disease status. An association test was performed for each SNP and the number of nominally significant tests in a segment was counted. We then performed a permutation-based binomial test to determine whether this region contained significantly more nominally significant SNPs than expected under the null hypothesis of no association, taking linkage into account. Genome Wide Association data of three independent schizophrenia case/control cohorts with European ancestry (Dutch, German, and US) using segments of DNA with variable length (2 to 32 Mbp) was analyzed. Using this approach we identified a region at chromosome 5q23.3-q31.3 (128–160 Mbp) that was significantly enriched with nominally associated SNPs in three independent case-control samples. We conclude that considering relatively wide segments of chromosomes may reveal reliable relationships between the genome and schizophrenia, suggesting novel methodological possibilities as well as raising theoretical questions. PMID:22723893

Emotional face processing deficit in schizophrenia: A replication study in a South African Xhosa population.

PubMed

Leppänen, J M; Niehaus, D J H; Koen, L; Du Toit, E; Schoeman, R; Emsley, R

2006-06-01

Schizophrenia is associated with a deficit in the recognition of negative emotions from facial expressions. The present study examined the universality of this finding by studying facial expression recognition in African Xhosa population. Forty-four Xhosa patients with schizophrenia and forty healthy controls were tested with a computerized task requiring rapid perceptual discrimination of matched positive (i.e. happy), negative (i.e. angry), and neutral faces. Patients were equally accurate as controls in recognizing happy faces but showed a marked impairment in recognition of angry faces. The impairment was particularly pronounced for high-intensity (open-mouth) angry faces. Patients also exhibited more false happy and angry responses to neutral faces than controls. No correlation between level of education or illness duration and emotion recognition was found but the deficit in the recognition of negative emotions was more pronounced in familial compared to non-familial cases of schizophrenia. These findings suggest that the deficit in the recognition of negative facial expressions may constitute a universal neurocognitive marker of schizophrenia.

Investigating causality in the association between 25(OH)D and schizophrenia.

PubMed

Taylor, Amy E; Burgess, Stephen; Ware, Jennifer J; Gage, Suzanne H; Richards, J Brent; Davey Smith, George; Munafò, Marcus R

2016-05-24

Vitamin D deficiency is associated with increased risk of schizophrenia. However, it is not known whether this association is causal or what the direction of causality is. We performed two sample bidirectional Mendelian randomization analysis using single nucleotide polymorphisms (SNPs) robustly associated with serum 25(OH)D to investigate the causal effect of 25(OH)D on risk of schizophrenia, and SNPs robustly associated with schizophrenia to investigate the causal effect of schizophrenia on 25(OH)D. We used summary data from genome-wide association studies and meta-analyses of schizophrenia and 25(OH)D to obtain betas and standard errors for the SNP-exposure and SNP-outcome associations. These were combined using inverse variance weighted fixed effects meta-analyses. In 34,241 schizophrenia cases and 45,604 controls, there was no clear evidence for a causal effect of 25(OH)D on schizophrenia risk. The odds ratio for schizophrenia per 10% increase in 25(OH)D conferred by the four 25(OH)D increasing SNPs was 0.992 (95% CI: 0.969 to 1.015). In up to 16,125 individuals with measured serum 25(OH)D, there was no clear evidence that genetic risk for schizophrenia causally lowers serum 25(OH)D. These findings suggest that associations between schizophrenia and serum 25(OH)D may not be causal. Therefore, vitamin D supplementation may not prevent schizophrenia.

Association study of schizophrenia and IL-2 receptor {beta} chain gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nimgaonkar, V.L.; Yang, Z.W.; Zhang, X.R.

1995-10-09

A case-control association study was conducted in Caucasian patients with schizophrenia (DSM-III-R, n = 42) and unaffected controls (n = 47) matched for ethnicity and area of residence. Serum interleukin-2 receptor (IL-2R) concentrations, as well as a dinucleotide repeat polymorphism in the IL-2RP chain gene, were examined in both groups. No significant differences in IL-2R concentrations or in the distribution of the polymorphism were noted. This study does not support an association between schizophrenia and the IL-2RP gene locus, contrary to the suggestive evidence from linkage analysis in multicase families. 17 refs., 2 tabs.

Culturally Based Intervention Development: The Case of Latino Families Dealing with Schizophrenia

ERIC Educational Resources Information Center

Barrio, Concepcion; Yamada, Ann-Marie

2010-01-01

Objectives: This article describes the process of developing a culturally based family intervention for Spanish-speaking Latino families with a relative diagnosed with schizophrenia. Method: Our iterative intervention development process was guided by a cultural exchange framework and based on findings from an ethnographic study. We piloted this…

Low vitamin D levels predict clinical features of schizophrenia.

PubMed

Cieslak, Kristina; Feingold, Jordyn; Antonius, Daniel; Walsh-Messinger, Julie; Dracxler, Roberta; Rosedale, Mary; Aujero, Nicole; Keefe, David; Goetz, Deborah; Goetz, Raymond; Malaspina, Dolores

2014-11-01

Vitamin D plays crucial roles in neuroprotection and neurodevelopment, and low levels are commonly associated with schizophrenia. We considered if the association was spurious or causal by examining the association of Vitamin D with Leukocyte Telomere Length (LTL), a marker of cellular aging. Vitamin D levels in 22 well-characterized schizophrenia cases were examined with respect to symptoms, cognition, and functioning. LTL was assessed using quantitative polymerase chain reaction (qPCR). The results showed that 91% (20) had deficient or insufficient Vitamin D levels, which were associated with excitement and grandiosity, social anhedonia, and poverty of speech. Sex-specific analyses showed strong associations of hypovitamintosis D to negative symptoms and decreased premorbid adjustment in males, and to lesser hallucinations and emotional withdrawal, but increased anti-social aggression in females. In females LTL was furthermore associated with Vitamin D levels. This study demonstrates a relationship of low vitamin D levels with increased cellular aging in females. It is also the first study to demonstrate potential sex-specific profiles among schizophrenia cases with hypovitaminosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Fewer but heavier caffeine consumers in schizophrenia: a case-control study.

PubMed

Gurpegui, Manuel; Aguilar, M Carmen; Martínez-Ortega, José M; Jurado, Dolores; Diaz, Francisco J; Quintana, Hernando M; de Leon, Jose

2006-09-01

According to the literature, there is an association between schizophrenia and caffeine consumption, but it is not clear whether schizophrenia is associated with either higher prevalence of daily caffeine intake or the amount consumed. In this study we compared our previously published schizophrenia patients (n=250) with a control sample (n=290) after controlling for demographic variables and tobacco and alcohol consumption. Current caffeine intake was less frequent in schizophrenia patients (59%, 147/250) than in controls (70%, 204/290). In the multivariate analyses, caffeine intake was less frequent at an older age and in schizophrenia patients, and more frequent in smokers and alcohol users. Among caffeine consumers, heavy caffeine intake (> or =200 mg/day) was significantly associated with schizophrenia (64%, 94/147 in schizophrenia versus 36%, 73/204 in controls), as well as older age and smoking. Daily amount of caffeine intake and smoked cigarettes correlated significantly in the schizophrenia group but not in the control group; the correlation of caffeine intake with nicotine dependence was low and non-significant in both groups. The association between current smoking and heavy caffeine intake may be partly explained by a pharmacokinetic effect: tobacco smoke compounds induce caffeine metabolism by the cytochrome P450 1A2. Although schizophrenia by itself may be associated with heavy caffeine intake in caffeine users, part of this association was explained by the association between schizophrenia and smoking. The relationship between caffeine and alcohol intake appeared to be more complex; alcohol and caffeine use were significantly associated, but within caffeine users alcohol was associated with less frequent heavy caffeine consumption among smokers. In future studies, the measurement of plasma caffeine levels will help both to better define heavy caffeine intake and to control for smoking pharmacokinetic effects.

[Ultrastructural pathology of oligodendrocytes in the white matter in continuous paranoid schizophrenia: a role for microglia].

PubMed

Uranova, N A; Vikhreva, O V; Rakhmanova, V I; Orlovskaya, D D

Previously the authors have reported the ultrastructural pathology and deficit of oligodendrocytes in gray and white matter of the prefrontal cortex in schizophrenia. The aim of the study was to determine of the effects of microglia on the ultrastructure of oligodendrocytes in the white matter underlying the prefrontal cortex in continuous schizophrenia. Postmortem morphometric electron microscopic study of oligodendrocytes in close apposition to microglia was performed in white matter underlying the prefrontal cortex (BA10). Eleven cases of chronic continuous schizophrenia and 11 normal controls were studied. Areas of oligodendrocytes, of their nuclei and cytoplasm, volume density (Vv) and the number of mitochondria, vacuoles of endoplasmic reticulum and lipofuscin granules were estimated. Group comparison was performed using ANCOVA. The schizophrenia group differed from the control group by paucity of ribosomes in the cytoplasm of oligodendrocytes, a significant decrease in Vv and the number of mitochondria and increase in the number of lipofuscin granules. Significant correlations between the parameters of lipofuscin granules, mitochondria and vacuoles were found only in the schizophrenia group. The number of lipofuscin granules were correlated positively with the illness duration. Dystrophic alterations of oligodendrocytes attached to microglial cells were found in the white matter of the prefrontal cortex in chronic paranoid schizophrenia as compared to controls. The data obtained suggest that microglia might contribute to abnormalities of energy, lipid and protein metabolism of oligodendrocytes in schizophrenia.

Refractive errors and schizophrenia.

PubMed

Caspi, Asaf; Vishne, Tali; Reichenberg, Abraham; Weiser, Mark; Dishon, Ayelet; Lubin, Gadi; Shmushkevitz, Motti; Mandel, Yossi; Noy, Shlomo; Davidson, Michael

2009-02-01

Refractive errors (myopia, hyperopia and amblyopia), like schizophrenia, have a strong genetic cause, and dopamine has been proposed as a potential mediator in their pathophysiology. The present study explored the association between refractive errors in adolescence and schizophrenia, and the potential familiality of this association. The Israeli Draft Board carries a mandatory standardized visual accuracy assessment. 678,674 males consecutively assessed by the Draft Board and found to be psychiatrically healthy at age 17 were followed for psychiatric hospitalization with schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Sib-ships were also identified within the cohort. There was a negative association between refractive errors and later hospitalization for schizophrenia. Future male schizophrenia patients were two times less likely to have refractive errors compared with never-hospitalized individuals, controlling for intelligence, years of education and socioeconomic status [adjusted Hazard Ratio=.55; 95% confidence interval .35-.85]. The non-schizophrenic male siblings of schizophrenia patients also had lower prevalence of refractive errors compared to never-hospitalized individuals. Presence of refractive errors in adolescence is related to lower risk for schizophrenia. The familiality of this association suggests that refractive errors may be associated with the genetic liability to schizophrenia.

Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula.

PubMed

Bernstein, Hans-Gert; Hildebrandt, Jens; Dobrowolny, Henrik; Steiner, Johann; Bogerts, Bernhard; Pahnke, Jens

2016-11-01

There is increasing evidence that microvascular abnormalities and malfunction of the blood-brain barrier (BBB) significantly contribute to schizophrenia pathophysiology. The ATP-binding cassette transporter ABCB1 is an important molecular component of the intact BBB, which has been implicated in a number of neurodegenerative and psychiatric disorders, including schizophrenia. However, the regional and cellular expression of ABCB1 in schizophrenia is yet unexplored. Therefore, we studied ABCB1 protein expression immunohistochemically in twelve human post-mortem brain regions known to play a role in schizophrenia, in 13 patients with schizophrenia and nine controls. In ten out of twelve brain regions under study, no significant differences were found with regard to the numerical density of ABCB1-expressing capillaries between all patients with schizophrenia and control cases. The left and right habenular complex, however, showed significantly reduced capillary densities in schizophrenia patients. In addition, we found a significantly reduced density of ABCB1-expressing neurons in the left habenula. Reduced ABCB1 expression in habenular capillaries might contribute to increased brain levels of proinflammatory cytokines in patients with schizophrenia, while decreased expression of this protein in a subpopulation of medial habenular neurons (which are probably purinergic) might be related to abnormalities of purines and their receptors found in this disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia.

PubMed

Torrell, Helena; Salas, Antonio; Abasolo, Nerea; Morén, Constanza; Garrabou, Glòria; Valero, Joaquín; Alonso, Yolanda; Vilella, Elisabet; Costas, Javier; Martorell, Lourdes

2014-10-01

It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia. © 2014 Wiley Periodicals, Inc.

Association study of dopamine D3 receptor gene and schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kennedy, J.L.; Billett, E.A.; Macciardi, F.M.

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex,more » and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. 32 refs., 2 tabs.« less

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

PubMed

Leonenko, Ganna; Richards, Alexander L; Walters, James T; Pocklington, Andrew; Chambert, Kimberly; Al Eissa, Mariam M; Sharp, Sally I; O'Brien, Niamh L; Curtis, David; Bass, Nicholas J; McQuillin, Andrew; Hultman, Christina; Moran, Jennifer L; McCarroll, Steven A; Sklar, Pamela; Neale, Benjamin M; Holmans, Peter A; Owen, Michael J; Sullivan, Patrick F; O'Donovan, Michael C

2017-10-01

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] < 0.001) in genes intolerant of loss-of-function (LoF) variation and in genes whose messenger RNAs bind to fragile X mental retardation protein (FMRP). We further delineate the genetic architecture of schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. © 2017 Wiley Periodicals, Inc.

Is cerebrovascular disease a silent condition in patients with chronic schizophrenia-related disorders?

PubMed

Berrocal-Izquierdo, Nuria; Bioque, Miquel; Bernardo, Miguel

2017-03-01

Patients with chronic schizophrenia-related disorders are at a heightened risk of developing cardiovascular disease. The presence and interpretation of cerebral vascular lesions in neuroimaging tests in these patients represents a common clinical challenge. Nevertheless, the literature on cerebrovascular disease in this population is scarce and contradictory. The aim of this study was to analyse the relationship between schizophrenia-related disorders and cerebrovascular morbidity. A case-control study compared cerebrovascular morbidity in a group of patients with schizophrenia-related disorder versus a group of patients with another severe mental illness. The risk of presenting cerebrovascular morbidity was four times higher and statistically significant in patients with schizophrenia-related disorders compared with controls, paired by age and sex. However, both groups were homogeneous in terms of cardiovascular risk factors. There were significant differences between the two groups only in the time using first-generation antipsychotic drugs and taking two or more antipsychotic medications simultaneously. The relationship between chronic schizophrenia-related disorders and cerebrovascular disease may be beyond the classic cardiovascular risk factors and related to certain medications. This is one of the first studies to focus on the relation among cerebrovascular morbidity, antipsychotic drugs and disorders related to schizophrenia in middle-aged and elderly adults.

Association of Folate Level in Blood with the Risk of Schizophrenia.

PubMed

Ding, Yujie; Ju, Mingliang; He, Lin; Chen, Wenzhong

2017-01-01

The aim of this study was to evaluate the association between folate level and the risk of schizophrenia and to identify possible biomarker for schizophrenia. Data about folate were extracted from 16 high quality studies. The association of folate level in blood and schizophrenia was evaluated using standardized mean difference (SMD) and 95% confidence interval (CI). Totally 1183 (52.1%) cases and 1089 (47.9%) controls were included in the current metaanalysis. Folate level in schizophrenia patients was significantly lower than that in healthy controls (SMD= -0.65; 95% CI: [-0.86, -0.45]; P <0.00001). Subgroup analysis demonstrated that the decreased folate level was found in both Asian and European patients (SMD=-0.86, P<0.00001; SMD=-0.44, P<0.00001, respectively), while there were no significant differences in patients from other areas (P>0.05). Sensitivity analysis confirmed that these results were stable and reliable, no publication bias existed in our meta-analysis based on Egger's and Begg's tests (P=0.48 and 0.30, respectively). These results suggest that decreased folate may be a risk factor for schizophrenia. More epidemiological and biochemistry studies are required to describe how folate or folate supplementation play roles in the progress of schizophrenia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Guidelines for the Pharmacotherapy of Schizophrenia in Adults

PubMed Central

Addington, Donald; Honer, William; Ismail, Zahinoor; Raedler, Thomas; Teehan, Michael

2017-01-01

Objective: The present guidelines address the pharmacotherapy of schizophrenia in adults across different stages, phases, and symptom domains. Method: Guidelines were developed using the ADAPTE process, which takes advantage of existing guidelines. Six guidelines were identified for adaptation, with recommendations extracted from each. For those specific to the pharmacotherapy of schizophrenia in adults, a working group selected between guidelines and recommendations to create an adapted guideline. Results: Recommendations can be categorized into 6 areas that include 1) first-episode schizophrenia, 2) acute exacerbation, 3) relapse prevention and maintenance treatment, 4) treatment-resistant schizophrenia, 5) clozapine-resistant schizophrenia, and 6) specific symptom domains. For each category, recommendations are made based on the available evidence, which is discussed and linked to other established guidelines. Conclusions: In most cases, evidence-based recommendations are made that can be used to guide current clinical treatment and decision making. Notably, however, there is a paucity of established evidence to guide treatment decision making in the case of clozapine-resistant schizophrenia, a subsample that represents a sizable proportion of those with schizophrenia. PMID:28703015

Topiramate-induced weight loss in schizophrenia: a retrospective case series study.

PubMed

Lévy, Emmanuel; Agbokou, Catherine; Ferreri, Florian; Chouinard, Guy; Margolese, Howard C

2007-01-01

Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain. A 2-year retrospective case analysis was performed in all 300 patients of the outpatient Special Follow-up Clinic for chronic schizophrenia and related psychoses at the Allan Memorial Institute, McGill University Health Centre (Montreal, Canada), a tertiary care University teaching hospital. 10 patients met study inclusion criteria. Mean daily topiramate dose was 197.5 mg (A+/-77) (range, 125-400 mg). Topiramate produced continued weight loss throughout the study duration without tolerance. Patients treated for 6 months and more had significantly higher Body Mass Index (BMI) differences than those treated for shorter durations (BMI-d6 months=-4.7A+/-2.4; BMI-d2 months=-3.2A+/-2.3; P=0.015). BMI changes were similar across genders. This study supports topiramate use to target weight loss in stable overweight schizophrenic patients as a potential therapy that requires further investigation.

The Hyperactivity of Efferent Auditory System in Patients with Schizophrenia: A Transient Evoked Otoacoustic Emissions Study

PubMed Central

Wahab, Suzaily; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Zakaria, Mohd. Normani

2016-01-01

Objective Electrophysiological studies, which are mostly focused on afferent pathway, have proven that auditory processing deficits exist in patients with schizophrenia. Nevertheless, reports on the suppressive effect of efferent auditory pathway on cochlear outer hair cells among schizophrenia patients are limited. The present, case-control, study examined the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) in patients with schizophrenia. Methods Participants were twenty-three healthy controls and sixteen schizophrenia patients with normal hearing, middle ear and cochlear outer hair cells function. Absolute non-linear and linear TEOAEs were measured in both ears by delivering clicks stimuli at 80 dB SPL and 60 dB SPL respectively. Subsequently, contralateral suppression was determined by subtracting the absolute TEOAEs response obtained at 60 dBpe SPL during the absence and presence of contralateral white noise delivered at 65 dB HL. No attention tasks were conducted during measurements. Results We found no significant difference in absolute TEOAEs responses at 80 dB SPL, in either diagnosis or ear groups (p>0.05). However, the overall contralateral suppression was significantly larger in schizophrenia patients (p<0.05). Specifically, patients with schizophrenia demonstrated significantly increased right ear contralateral suppression compared to healthy control (p<0.05). Conclusion The present findings suggest increased inhibitory effect of efferent auditory pathway especially on the right cochlear outer hair cells. Further studies to investigate increased suppressive effects are crucial to expand the current understanding of auditory hallucination mechanisms in schizophrenia patients. PMID:26766950

Co-occurrence of Marfan syndrome and bipolar disorder: A fifteen year follow up.

PubMed

Jha, Vijendra Nath; Kumar, Manoj; Tarwani, Jatin

2016-12-01

Marfan syndrome, a chromosomal disorder, has been commonly associated with schizophrenia but no association with Bipolar affective disorder has been reported in the scientific literature. This case depicts the occurrence of Bipolar affective disorder in a previously undiagnosed case of Marfan syndrome. In this case patient had all manic episodes without any depressive or schizophrenia-like episodes, suggesting a diagnostic stability over a long period of over fifteen years. Studies and research are needed in this regard to look for any possible potential association between the two illnesses. Copyright © 2016 Elsevier B.V. All rights reserved.

Case study of first episode schizophrenia in pregnancy and postpartum.

PubMed

Kast, Kristopher A; Agarkar, Smita

2017-08-01

Patients with first-episode psychosis of peripartum onset commonly prove to have a mood-disorder diathesis; however, a proportion of cases represent first-episode schizophrenia. We present such a case and discuss the clinical relevance of recognizing this small but important population of new mothers. These patients are at considerable risk of misdiagnosis, resulting in ineffective maintenance therapy, poorer recovery of function, and development of treatment resistance. Accurate diagnosis in the peripartum period will impact treatment decisions and long-term therapy. Clinicians need to be vigilant, especially during maintenance therapy, to identify these patients and ensure appropriate antipsychotic therapy is provided.

Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis

PubMed Central

Kim, Su Kang; Kang, Sang Wook; Chung, Joo-Ho; Park, Hae Jeong; Cho, Kyu Bong; Park, Min-Su

2015-01-01

The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025–1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. PMID:26295386

Population-Specific Haplotype Association of the Postsynaptic Density Gene DLG4 with Schizophrenia, in Family-Based Association Studies

PubMed Central

Balan, Shabeesh; Yamada, Kazuo; Hattori, Eiji; Iwayama, Yoshimi; Toyota, Tomoko; Ohnishi, Tetsuo; Maekawa, Motoko; Toyoshima, Manabu; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Yoshikawa, Takeo

2013-01-01

The post-synaptic density (PSD) of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects). Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02), although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects) or in a Japanese case-control sample (n = 4182 subjects). The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009) and Chinese (p = 0.0007) schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes. PMID:23936182

Physical Health, Medication, and Healthcare Utilization among 70-Year-Old People with Schizophrenia: A Nationwide Danish Register Study.

PubMed

Brink, Maria; Green, Anders; Bojesen, Anders Bo; Lamberti, J Steven; Conwell, Yeates; Andersen, Kjeld

2017-05-01

In light of the excess early mortality in schizophrenia, mainly due to physical illnesses, we investigated medical comorbidity, use of medication, and healthcare utilization among individuals with schizophrenia who survived into older ages to uncover potential factors contributing to their longevity. A nationwide register-based case-control study comparing 70-year-olds with and without schizophrenia. Cases were drawn from the Danish Psychiatric Central Register. Age- and sex-matched controls were drawn from the general population via the Civil Registration System. All Danish inhabitants who were diagnosed and registered with early onset schizophrenia in 1970-1979 and still alive at age 70 years. Controls alive at age 70 years. Chronic medical comorbidity, medications, and inpatient and outpatient healthcare utilization extracted from Danish healthcare registers. Older adults with schizophrenia did not differ from controls with regard to registered chronic medical illnesses, but were significantly less likely to receive medication for cardiovascular diseases (OR: 0.65; 99.29% CI: 0.50, 0.83) and more likely to be treated with analgesics (OR: 1.46; 99.29% CI: 1.04, 2.05). Overall, hospital admissions and number of days hospitalized were equal to controls, but with significantly fewer general medical outpatient contacts (RR: 0.37; 98.75% CI: 0.24, 0.55). Because the literature suggests that excess mortality continues into old age, it is possible that medical diseases were under-registered and/or under-treated. Focus on adequate medical treatment, in particular for cardiovascular disease, is needed. Future integration of psychiatric and general medical healthcare, especially outpatient care, might further optimize health outcomes for older adults with schizophrenia. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

PubMed Central

Bjelland, Douglas W.; Howrigan, Daniel P.; Abdellaoui, Abdel; Breen, Gerome; Borglum, Anders; Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Genovese, Giulio; Heilmann-Heimbach, Stefanie; Hoffman, Per; Maier, Wolfgang; Mattheisen, Manuel; Morris, Derek; Mowry, Bryan; Müller-Mhysok, Betram; Neale, Benjamin; Nenadic, Igor; Nöthen, Markus M.; O’Dushlaine, Colm; Rietschel, Marcella; Ruderfer, Douglas M.; Rujescu, Dan; Schulze, Thomas G.; Simonson, Matthew A.; Stahl, Eli; Strohmaier, Jana; Sullivan, Patrick F.; Keller, Matthew C.

2016-01-01

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest. PMID:27792727

Inflammatory Biomarkers and Risk of Schizophrenia: A 2-Sample Mendelian Randomization Study.

PubMed

Hartwig, Fernando Pires; Borges, Maria Carolina; Horta, Bernardo Lessa; Bowden, Jack; Davey Smith, George

2017-12-01

Positive associations between inflammatory biomarkers and risk of psychiatric disorders, including schizophrenia, have been reported in observational studies. However, conventional observational studies are prone to bias, such as reverse causation and residual confounding, thus limiting our understanding of the effect (if any) of inflammatory biomarkers on schizophrenia risk. To evaluate whether inflammatory biomarkers have an effect on the risk of developing schizophrenia. Two-sample mendelian randomization study using genetic variants associated with inflammatory biomarkers as instrumental variables to improve inference. Summary association results from large consortia of candidate gene or genome-wide association studies, including several epidemiologic studies with different designs, were used. Gene-inflammatory biomarker associations were estimated in pooled samples ranging from 1645 to more than 80 000 individuals, while gene-schizophrenia associations were estimated in more than 30 000 cases and more than 45 000 ancestry-matched controls. In most studies included in the consortia, participants were of European ancestry, and the prevalence of men was approximately 50%. All studies were conducted in adults, with a wide age range (18 to 80 years). Genetically elevated circulating levels of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), and soluble interleukin-6 receptor (sIL-6R). Risk of developing schizophrenia. Individuals with schizophrenia or schizoaffective disorders were included as cases. Given that many studies contributed to the analyses, different diagnostic procedures were used. The pooled odds ratio estimate using 18 CRP genetic instruments was 0.90 (random effects 95% CI, 0.84-0.97; P = .005) per 2-fold increment in CRP levels; consistent results were obtained using different mendelian randomization methods and a more conservative set of instruments. The odds ratio for sIL-6R was 1.06 (95% CI, 1.01-1.12; P = .02) per 2-fold increment. Estimates for IL-1Ra were inconsistent among instruments, and pooled estimates were imprecise and centered on the null. Under mendelian randomization assumptions, our findings suggest a protective effect of CRP and a risk-increasing effect of sIL-6R (potentially mediated at least in part by CRP) on schizophrenia risk. It is possible that such effects are a result of increased susceptibility to early life infection.

Childhood-onset schizophrenia case with 2.2 Mb deletion at chromosome 3p12.2-p12.1 and two large chromosomal abnormalities at 16q22.3-q24.3 and Xq23-q28.

PubMed

Rudd, Danielle; Axelsen, Michael; Epping, Eric A; Andreasen, Nancy; Wassink, Thomas

2015-04-01

Childhood-onset schizophrenia is rare, comprising 1% of known schizophrenia cases. Here, we report a patient with childhood-onset schizophrenia who has three large chromosomal abnormalities: an inherited 2.2 Mb deletion of chromosome 3p12.2-p12.1, a de novo 16.7 Mb duplication of 16q22.3-24.3, and a de novo 43 Mb deletion of Xq23-q28.

Neural circuit of verbal humor comprehension in schizophrenia - an fMRI study.

PubMed

Adamczyk, Przemysław; Wyczesany, Miroslaw; Domagalik, Aleksandra; Daren, Artur; Cepuch, Kamil; Błądziński, Piotr; Cechnicki, Andrzej; Marek, Tadeusz

2017-01-01

Individuals with schizophrenia exhibit problems with understanding the figurative meaning of language. This study evaluates neural correlates of diminished humor comprehension observed in schizophrenia. The study included chronic schizophrenia (SCH) outpatients (n = 20), and sex, age and education level matched healthy controls (n = 20). The fMRI punchline based humor comprehension task consisted of 60 stories of which 20 had funny, 20 nonsensical and 20 neutral (not funny) punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible and how funny it was. Three contrasts were analyzed in both groups reflecting stages of humor processing: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution and elaboration; and funny vs neutral - complete humor processing. Additionally, parametric modulation analysis was performed using both subjective ratings separately. Between-group comparisons revealed that the SCH subjects had attenuated activation in the right posterior superior temporal gyrus (BA 41) in case of irresolvable incongruity processing of nonsensical puns; in the left dorsomedial middle and superior frontal gyri (BA 8/9) in case of incongruity resolution and elaboration processing of funny puns; and in the interhemispheric dorsal anterior cingulate cortex (BA 24) in case of complete processing of funny puns. Additionally, during comprehensibility ratings the SCH group showed a suppressed activity in the left dorsomedial middle and superior frontal gyri (BA 8/9) and revealed weaker activation during funniness ratings in the left dorsal anterior cingulate cortex (BA 24). Interestingly, these differences in the SCH group were accompanied behaviorally by a protraction of time in both types of rating responses and by indicating funny punchlines less comprehensible. Summarizing, our results indicate neural substrates of humor comprehension processing impairments in schizophrenia, which is accompanied by fronto-temporal hypoactivation.

Cognitive behavioral therapy for schizophrenia: an empirical review.

PubMed

Rector, Neil A; Beck, Aaron T

2012-10-01

Early case studies and noncontrolled trial studies focusing on the treatment of delusions and hallucinations have laid the foundation for more recent developments in comprehensive cognitive behavioral therapy (CBT) interventions for schizophrenia. Seven randomized, controlled trial studies testing the efficacy of CBT for schizophrenia were identified by electronic search (MEDLINE and PsychInfo) and by personal correspondence. After a review of these studies, effect size (ES) estimates were computed to determine the statistical magnitude of clinical change in CBT and control treatment conditions. CBT has been shown to produce large clinical effects on measures of positive and negative symptoms of schizophrenia. Patients receiving routine care and adjunctive CBT have experienced additional benefits above and beyond the gains achieved with routine care and adjunctive supportive therapy. These results reveal promise for the role of CBT in the treatment of schizophrenia although additional research is required to test its efficacy, long-term durability, and impact on relapse rates and quality of life. Clinical refinements are needed also to help those who show only minimal benefit with the intervention.

[The Role of Neurotrophins and Neurexins Genes in the Risk of Paranoid Schizophrenia in Russians and Tatars].

PubMed

Gareeva, A E; Traks, T; Koks, S; Khusnutdinova, E K

2015-07-01

Schizophrenia affects about 1% of the population. Its etiology is not fully understood. Environmental conditions certainly contribute to the development of schizophrenia, but the determining factor is genetic predisposition: the coefficient of heritability of schizophrenia is about 80%, which is typical for the most highly heritable multifactorial diseases. Polymorphic loci of genes of enzymes and receptors involved in the processes of neuroprotection and neurotrophia play significant role in the development of this disease. In this paper we investigated 48 polymorphic variants of genes of the neurotrophins and neurexins family (BDNF, NTRK2, NTRK3, NGF, NXPH1, and NRXN1) in Russian and Tatar cases and in a control group living in the Republic of Bashkortostan. The results of this study confirm the important role of neurotrophin and neurexin genes in paranoid schizophrenia development.

Assessing clinicians' management of first episode schizophrenia using clinical case vignettes.

PubMed

Huffman, Jeff C; Freudenreich, Oliver; Romeo, Sarah; Baer, Lee; Sutton-Skinner, Kelly; Petersen, Tim; Fromson, John A; Birnbaum, Robert J

2010-02-01

Patients with first episode schizophrenia may present in a variety of clinical settings to providers who have a range of knowledge and skills. A thoughtful workup of patients with new-onset psychosis is critical, and the treatment of first episode schizophrenia differs from that of chronic psychotic disorders. Clinical case vignettes with free-form responses can be used to carefully assess whether front line practitioners provide guideline-adherent management of first episode psychosis. A clinical case vignette, presenting a patient with first episode schizophrenia, was created and administered to the attendees of a continuing medical education programme. Free-form responses to questions regarding differential diagnosis, workup, treatment and treatment duration were scored based on published practice guidelines. Response frequencies were tabulated and performance was compared among professional disciplines. Sixty-two attendees completed the vignette. Though the attendees typically considered a broad differential diagnosis and appropriately initiated treatment with antipsychotics, the respondents' proposed medical workup was limited, and they prescribed antipsychotics at higher doses and for a shorter duration than recommended in the literature. The prescribers outperformed the non-prescribers on treatment questions (P = 0.006), but the two groups' performance did not significantly differ on the assessment questions (P = 0.08). The front line clinicians who encounter patients with first episode schizophrenia may have significant practice gaps in the initial and follow-up care of these patients. Given the preliminary nature of this study and the debate about the optimal care for first episode psychosis, further study is needed. If such gaps are confirmed, additional educational interventions are required to align clinical management with published practice guidelines.

Relapse and hospitalization in patients with schizophrenia and bipolar disorder at the St Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia: a comparative quantitative cross-sectional study.

PubMed

Ayano, Getnet; Duko, Bereket

2017-01-01

Relapse and hospital admission are common among, and carry a heavy burden in, patients with schizophrenia and bipolar disorder. The aim of this study was to assess the risk of relapse and hospitalizations in patients with schizophrenia and bipolar disorder at the St Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. A hospital-based comparative cross-sectional study was conducted in June 2016. Systematic random sampling technique was used to recruit 521 (260 schizophrenia cases and 261 bipolar disorder cases) study participants. Face-to-face interviews were conducted by trained psychiatry professionals. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and Structured Clinical Interview of DSM-IV (SCID) were used. The risk of relapse and hospitalizations was slightly higher in patients with bipolar disorder than in patients with schizophrenia. A majority of schizophrenic (213 [81.92%]) and bipolar (215 [82.37%]) patients had a history of hospital admission, and 228 (87.69%) schizophrenic and 230 (88.12%) bipolar patients had a history of relapse. Patients who had a history of hospitalizations also had co-occurring substance use disorders compared to those who had no history of hospitalizations for schizophrenia (81.5% vs 37.9%) and bipolar disorder (82.56% vs 38.2%), respectively. Similarly, those patients who had a history of relapse had high comorbid substance use disorders than those who had no history of relapse for both schizophrenia (87.88% vs 47.37%) and bipolar disorder (88.37% vs 47.19%), respectively. It is vital that, in the local context, mental health professionals strengthen their therapeutic relationships with patients and their caregivers. This might enable patients and their caregivers to express their needs and concerns to them, as well as help to plan proper interventions for patients. Attention needs to be given to screening for comorbid substance use disorders in patients with schizophrenia and bipolar disorder, especially in those who have had a history of relapse and hospitalizations.

Comparison of catatonia presentation in patients with schizophrenia and mood disorders in lagos, Nigeria.

PubMed

Usman, Dada Mobolaji; Olubunmi, Okewole Adeniran; Taiwo, Oduguwa; Taiwo, Afe; Rahman, Lawal; Oladipo, Adepoju

2011-01-01

To compare the clinical profile and pattern of catatonic symptoms of patients with schizophrenia and mood disorder. Records of 13,968 patients seen between 1983-1985 and 2003-2005 were reviewed for symptoms of catatonia by resident doctors in psychiatry. Cases in which the diagnosis were schizophrenia or mood disorder were then noted. Socio-demographic and clinical features were described for each diagnosis. There were a total of 98 cases with catatonia out of the 13,968 case notes reviewed. Schizophrenia accounted for 82.5% and 53.4% in the two periods, while the proportion associated with mood disorders increased from 10% to 20.7%. Male to female ratio was 1.2:1 in schizophrenia and 1:3 in mood disorder. Those with schizophrenia were younger and with an earlier age of onset of symptoms than those with mood disorders. Catatonia associated with mood disorder was found to be increasing over the years when compared with schizophrenia. Differences were observed in socio-demographic characteristics and number of predominant catatonic symptoms. Having a separate category for catatonia due to the mood disorders in the current diagnostic guidelines (10(th) edition of the International Classification of Diseases and the 4(th) edition of the Diagnostic and Statistical Manual) will help in better diagnosis of catatonia.

Dilemma of treating schizophrenia during pregnancy: a Case series and a review of literature.

PubMed

Teodorescu, Andreea; Ifteni, Petru; Moga, Marius Alexandru; Burtea, Victoria; Bigiu, Nicusor

2017-08-29

The choice of antipsychotic treatment during pregnancy remains controversial, mainly due to a lack of exposure and outcome data. Randomized clinical trials are practically impossible due to ethical reasons. Our reports describe three cases of closely monitored female patients with schizophrenia who were treated with olanzapine during pregnancy. The novelty of reports is that all patients were previously treated with olanzapine long acting injectable (LAI) for an average period of 3.8 years. During the LAI treatment period they were in remission and then refused to continue with LAI mainly due to treatment modality (injectable administration). The patients were relatively young, diagnosed with schizophrenia and were previously successfully treated with long acting injectable. The women were pregnant for the first time. In two cases, the patients had become pregnant during remission and they continued treatment with oral olanzapine. In the third case, olanzapine treatment was initiated during admission for a relapse. There are no controlled studies for the use of olanzapine therapy in pregnant women. More studies are needed to determine the effects of antipsychotics, including olanzapine, on pregnant women and the developing fetus. Schizophrenia relapse during pregnancy may expose the mother and the fetus to high risk if olanzapine is stopped. It is important to assess the risks and benefits of treating pregnant or breastfeeding women with antipsychotics, and weigh these against possible risks of anomalies and developmental problems to the fetus or child.

The role of complex emotions in inconsistent diagnoses of schizophrenia.

PubMed

Gara, Michael A; Vega, William A; Lesser, Ira; Escamilla, Michael; Lawson, William B; Wilson, Daniel R; Fleck, David E; Strakowski, Stephen M

2010-09-01

In the case of large-scale epidemiological studies, there is evidence of substantial disagreement when lay diagnoses of schizophrenia based on structured interviews are compared with expert diagnoses of the same patients. Reasons for this level of disagreement are investigated in the current study, which made use of advances in text-mining techniques and associated structural representations of language expressions. Specifically, the current study examined whether content analyses of transcribed diagnostic interviews obtained from 150 persons with serious psychiatric disorders yielded any discernable patterns that correlated with diagnostic inconsistencies of schizophrenia. In summary, it was found that the patterning or structure of spontaneous self-reports of emotion states in the diagnostic interview was associated with diagnostic inconsistencies of schizophrenia, irrespective of confounders; i.e., age of patient, gender, or ethnicity. In particular, complex emotion patterns were associated with greater disagreement between experts and trained lay interviewers than were simpler patterns.

Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia.

PubMed

Ingason, A; Giegling, I; Hartmann, A M; Genius, J; Konte, B; Friedl, M; Ripke, S; Sullivan, P F; St Clair, D; Collier, D A; O'Donovan, M C; Mirnics, K; Rujescu, D

2015-10-13

Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.

Biological Insights From 108 Schizophrenia-Associated Genetic Loci

PubMed Central

Ripke, Stephan; Neale, Benjamin M; Corvin, Aiden; Walters, James TR; Farh, Kai-How; Holmans, Peter A; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A; Huang, Hailiang; Pers, Tune H; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A; Begemann, Martin; Belliveau, Richard A; Bene, Judit; Bergen, Sarah E; Bevilacqua, Elizabeth; Bigdeli, Tim B; Black, Donald W; Bruggeman, Richard; Buccola, Nancy G; Buckner, Randy L; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M; Carr, Vaughan J; Carrera, Noa; Catts, Stanley V; Chambert, Kimberley D; Chan, Raymond CK; Chan, Ronald YL; Chen, Eric YH; Cheng, Wei; Cheung, Eric FC; Chong, Siow Ann; Cloninger, C Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J; Curtis, David; Davidson, Michael; Davis, Kenneth L; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H; Farrell, Martilias S; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B; Friedl, Marion; Friedman, Joseph I; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M; Henskens, Frans A; Herms, Stefan; Hirschhorn, Joel N; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V; Hougaard, David M; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C; Kennedy, James L; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K; Laurent, Claudine; Lee, Jimmy; Lee, S Hong; Legge, Sophie E; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik KE; Maher, Brion S; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W; McDonald, Colm; McIntosh, Andrew M; Meier, Sandra; Meijer, Carin J; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I; Metspalu, Andres; Michie, Patricia T; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W; Mors, Ole; Murphy, Kieran C; Murray, Robin M; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A; Nestadt, Gerald; Nicodemus, Kristin K; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J; Powell, John; Price, Alkes; Pulver, Ann E; Purcell, Shaun M; Quested, Digby; Rasmussen, Henrik B; Reichenberg, Abraham; Reimers, Mark A; Richards, Alexander L; Roffman, Joshua L; Roussos, Panos; Ruderfer, Douglas M; Salomaa, Veikko; Sanders, Alan R; Schall, Ulrich; Schubert, Christian R; Schulze, Thomas G; Schwab, Sibylle G; Scolnick, Edward M; Scott, Rodney J; Seidman, Larry J; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M; Sim, Kang; Slominsky, Petr; Smoller, Jordan W; So, Hon-Cheong; Spencer, Chris C A; Stahl, Eli A; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E; Strengman, Eric; Strohmaier, Jana; Stroup, T Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M; Szatkiewicz, Jin P; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T; Weiser, Mark; Wildenauer, Dieter B; Williams, Nigel M; Williams, Stephanie; Witt, Stephanie H; Wolen, Aaron R; Wong, Emily HM; Wormley, Brandon K; Xi, Hualin Simon; Zai, Clement C; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R; Stefansson, Kari; Visscher, Peter M; Adolfsson, Rolf; Andreassen, Ole A; Blackwood, Douglas HR; Bramon, Elvira; Buxbaum, Joseph D; Børglum, Anders D; Cichon, Sven; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V; Gill, Michael; Gurling, Hugh; Hultman, Christina M; Iwata, Nakao; Jablensky, Assen V; Jönsson, Erik G; Kendler, Kenneth S; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F; Li, Qingqin S; Liu, Jianjun; Malhotra, Anil K; McCarroll, Steven A; McQuillin, Andrew; Moran, Jennifer L; Mortensen, Preben B; Mowry, Bryan J; Nöthen, Markus M; Ophoff, Roel A; Owen, Michael J; Palotie, Aarno; Pato, Carlos N; Petryshen, Tracey L; Posthuma, Danielle; Rietschel, Marcella; Riley, Brien P; Rujescu, Dan; Sham, Pak C; Sklar, Pamela; St Clair, David; Weinberger, Daniel R; Wendland, Jens R; Werge, Thomas; Daly, Mark J; Sullivan, Patrick F; O’Donovan, Michael C

2014-01-01

Summary Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia. PMID:25056061

May selective serotonin reuptake inhibitors (SSRIs) provide some benefit for the treatment of schizophrenia?

PubMed

Buoli, Massimiliano; Serati, Marta; Ciappolino, Valentina; Altamura, A Carlo

2016-07-01

The treatment of some psychopathological dimensions of schizophrenia (e.g. negative and depressive symptoms) is still challenging for the modest efficacy of atypical antipsychotics. Among pharmacological alternatives, augmentative Selective Serotonin Reuptake Inhibitors (SSRIs) to antipsychotics are frequently prescribed in clinical practice to improve negative/depressive symptoms of schizophrenia patients; however, the data about the efficacy of these molecules on negative, depressive and obsessive-compulsive symptoms of schizophrenia are contrasting. Research using the main database sources has been conducted to obtain an overview of the use and efficacy of SSRIs in schizophrenia. Data are too scanty to draw definitive recommendations. In a preliminary way, it can be said that available data do not show effectiveness of SSRIs on depressive symptoms of schizophrenia. Regarding negative symptoms, studies are contrasting, but paroxetine appears to be the most effective compound among SSRIs. Despite limited data, SSRIs appear to be useful for the treatment of obsessive-compulsive symptoms of schizophrenia, particularly fluvoxamine. Close clinical and pharmacological monitoring is needed in case of concomitant administration of antipsychotics and antidepressants for potential serious side effects and influence on plasma drug dosages.

Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition.

PubMed

Gonzalez-Liencres, Cristina; Tas, Cumhur; Brown, Elliot C; Erdin, Soner; Onur, Ece; Cubukcoglu, Zeynep; Aydemir, Omer; Esen-Danaci, Aysen; Brüne, Martin

2014-09-24

Schizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia. We assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty-one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group. We found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress. We propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

Schizophrenia and anorexia nervosa - reciprocal relationships. A literature review.

PubMed

Morylowska-Topolska, Justyna; Ziemiński, Rafał; Molas, Agnieszka; Gajewski, Jacek; Flis, Marta; Stelmach, Ewa; Karakuła-Juchnowicz, Hanna

2017-04-30

Although schizophrenia and anorexia nervosa are seemingly very distinct psychiatric disorders, their symptoms are connected by various types of relationships. The present article reviews the literature and recapitulates the views of various authors on the links between these two disorders. Symptoms of anorexia may 1) precede the onset of psychosis; 2) evolve in its active phase or more rarely manifest in remission; and, conversely, 3) psychotic symptoms may occur transiently in the course of anorexia nervosa. When anorexia precedes the manifestation of psychosis, symptoms of anorexia can be treated as a component of the prodromal phase of schizophrenia. Another possibility of co-existence of a psychosis (e.g., schizophrenia) with anorexia is when the eating disorder syndrome manifests at the same time as the full-blown psychotic syndrome. In such cases, when the symptoms of the two disorders occur simultaneously, it is often difficult to say whether the patient is suffering from schizophrenia, in the course of which anorexia has arisen secondary to psychotic symptoms or whether he/she is suffering from anorexia during which he/she has developed psychotic symptoms, usually thematically associated with eating. Studies published so far, mainly case reports, point to the complex nature of the interrelationships between schizophrenia and anorexia nervosa. Further research is needed to conclusively explain the relationships between psychotic disorders and anorexia nervosa, which would allow physicians to use more effective methods of treatment in this group of patients.

[Spontaneous speech prosody and discourse analysis in schizophrenia and Fronto Temporal Dementia (FTD) patients].

PubMed

Martínez, Angela; Felizzola Donado, Carlos Alberto; Matallana Eslava, Diana Lucía

2015-01-01

Patients with schizophrenia and Frontotemporal Dementia (FTD) in their linguistic variants share some language characteristics such as the lexical access difficulties, disordered speech with disruptions, many pauses, interruptions and reformulations. For the schizophrenia patients it reflects a difficulty of affect expression, while for the FTD patients it reflects a linguistic issue. This study, through an analysis of a series of cases assessed Clinic both in memory and on the Mental Health Unit of HUSI-PUJ (Hospital Universitario San Ignacio), with additional language assessment (analysis speech and acoustic analysis), present distinctive features of the DFT in its linguistic variants and schizophrenia that will guide the specialist in finding early markers of a differential diagnosis. In patients with FTD language variants, in 100% of cases there is a difficulty understanding linguistic structure of complex type; and important speech fluency problems. In patients with schizophrenia, there are significant alterations in the expression of the suprasegmental elements of speech, as well as disruptions in discourse. We present how depth language assessment allows to reassess some of the rules for the speech and prosody analysis of patients with dementia and schizophrenia; we suggest how elements of speech are useful in guiding the diagnosis and correlate functional compromise in everyday psychiatrist's practice. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study.

PubMed

Tzeng, Nian-Sheng; Hsu, Yung-Ho; Ho, Shinn-Ying; Kuo, Yu-Ching; Lee, Hua-Chin; Yin, Yun-Ju; Chen, Hong-An; Chen, Wen-Liang; Chu, William Cheng-Chung; Huang, Hui-Ling

2015-01-27

The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. A nationwide matched cohort study. Taiwan's National Health Insurance Research Database. A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Identification of Candidate Single-Nucleotide Polymorphisms in NRXN1 Related to Antipsychotic Treatment Response in Patients with Schizophrenia

PubMed Central

Jenkins, Aaron; Apud, José A; Zhang, Fengyu; Decot, Heather; Weinberger, Daniel R; Law, Amanda J

2014-01-01

Neurexins are presynaptic neuronal adhesion molecules that interact with postsynaptic neuroligins to form an inter-synaptic complex required for synaptic specification and efficient neurotransmission. Deletions and point mutations in the neurexin 1 (NRXN1) gene are associated with a broad spectrum of neuropsychiatric and neurodevelopmental disorders, including autism, intellectual disability, epilepsy, developmental delay, and schizophrenia. Recently, small nucleotide polymorphisms in NRXN1 have been associated with antipsychotic drug response in patients with schizophrenia. Based on previous suggestive evidence of an impact on clozapine response in patients with schizophrenia, we conducted an association study of NRXN1 polymorphisms (rs12467557 and rs10490162) with antipsychotic treatment response in 54 patients with schizophrenia in a double blind, placebo-controlled NIMH inpatient crossover trial and examined for association with risk for schizophrenia in independent case-control and family-based clinical cohorts. Pharmacogenetic analysis in the placebo controlled trial revealed significant association of rs12467557and rs10490162 with drug response, whereby individuals homozygous for the A allele, at either SNP, showed significant improvement in positive symptoms, general psychopathology, thought disturbance, and negative symptoms, whereas patients carrying the G allele showed no overall response. Although we did not find evidence of the same NRXN1 SNPs being associated with results of the NIMH sponsored CATIE trial, other SNPs showed weakly positive signals. The family and case-control analyses for schizophrenia risk were negative. Our results provide confirmatory evidence of genetically determined differences in drug response in patients with schizophrenia related to NRXN1 variation. Furthermore, these findings potentially implicate NRXN1 in the therapeutic actions of antipsychotic drugs. PMID:24633560

Clinical symptoms and cognitive impairment associated with male schizophrenia relate to plasma manganese superoxide dismutase activity: a case-control study.

PubMed

Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Tan, Yun Long; Yang, Fu De; Zhang, Laurence Y; Zhang, Laura Y; Haile, Colin N; Kosten, Thomas R

2013-08-01

Several lines of evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie cognitive impairment in psychiatric disorders. A growing body of evidence show that oxidative damage may relate to the range of cognitive deficits associated with schizophrenia. In this study we examine one of the primary antioxidant defense enzymes manganese superoxide dismutase (MnSOD), and whether it relates to cognitive deficits in schizophrenia. We recruited 185 chronic male schizophrenia patients and 132 male controls and compared results from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and plasma MnSOD activity between groups. Symptom severity in patients with schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Our results showed that MnSOD activities were significantly lower in patients than controls (p<0.05). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.001) except for the Visuospatial/Constructional index were significantly lower in schizophrenia patients than normal controls. MnSOD was negatively correlated with the general psychopathology subscale of PANSS, PANSS total score, positive symptoms and RBANS total score in patients with schizophrenia. Our findings add to growing evidence that oxidative stress may be involved in the psychopathology of male schizophrenia, and its associated cognitive impairment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

PubMed

Tomescu, Miralena I; Rihs, Tonia A; Becker, Robert; Britz, Juliane; Custo, Anna; Grouiller, Frédéric; Schneider, Maude; Debbané, Martin; Eliez, Stephan; Michel, Christoph M

2014-08-01

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates. If this is the case, temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high-density (204 channel) EEG to explore between-group microstate differences in 30 adolescents with 22q11DS and 28 age-matched controls. We found an increased presence of one microstate class (class C) in the 22q11DS adolescents with respect to controls that was associated with positive prodromal symptoms (hallucinations). A previous across-age study showed that the class C microstate was more present during adolescence and a combined EEG-fMRI study associated the class C microstate with the salience resting state network, a network known to be dysfunctional in schizophrenia. Therefore, the increased class C microstates could be indexing the increased risk of 22q11DS individuals to develop schizophrenia if confirmed by our ongoing longitudinal study comparing both the adult 22q11DS individuals with and without schizophrenia, as well as schizophrenic individuals with and without 22q11DS. Copyright © 2014 Elsevier B.V. All rights reserved.

Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study.

PubMed

Martin, Joanna; Tilling, Kate; Hubbard, Leon; Stergiakouli, Evie; Thapar, Anita; Davey Smith, George; O'Donovan, Michael C; Zammit, Stanley

2016-06-15

Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Brief Report: Cases for an Association between Tourette Syndrome, Autistic Disorder, and Schizophrenia-Like Disorder.

ERIC Educational Resources Information Center

Sverd, Jeffrey; And Others

1993-01-01

This paper reports on two children diagnosed as having co-occurring autistic disorder, schizophrenia-like psychosis, and Tourette syndrome, and two autistic adults who had tics and episodes of schizophrenia-like psychosis. (JDD)

A population-specific uncommon variant in GRIN3A associated with schizophrenia.

PubMed

Takata, Atsushi; Iwayama, Yoshimi; Fukuo, Yasuhisa; Ikeda, Masashi; Okochi, Tomo; Maekawa, Motoko; Toyota, Tomoko; Yamada, Kazuo; Hattori, Eiji; Ohnishi, Tetsuo; Toyoshima, Manabu; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Nanko, Shinichiro; Nakamura, Kazuhiko; Mori, Norio; Kanba, Shigenobu; Iwata, Nakao; Kato, Tadafumi; Yoshikawa, Takeo

2013-03-15

Genome-wide association studies have successfully identified several common variants showing robust association with schizophrenia. However, individually, these variants only produce a weak effect. To identify genetic variants with larger effect sizes, increasing attention is now being paid to uncommon and rare variants. From the 1000 Genomes Project data, we selected 47 candidate single nucleotide variants (SNVs), which were: 1) uncommon (minor allele frequency < 5%); 2) Asian-specific; 3) missense, nonsense, or splice site variants predicted to be damaging; and 4) located in candidate genes for schizophrenia and bipolar disorder. We examined their association with schizophrenia, using a Japanese case-control cohort (2012 cases and 2781 control subjects). Additional meta-analysis was performed using genotyping data from independent Han-Chinese case-control (333 cases and 369 control subjects) and family samples (9 trios and 284 quads). We identified disease association of a missense variant in GRIN3A (p.R480G, rs149729514, p = .00042, odds ratio [OR] = 1.58), encoding a subunit of the N-methyl-D-aspartate type glutamate receptor, with study-wide significance (threshold p = .0012). This association was supported by meta-analysis (combined p = 3.3 × 10(-5), OR = 1.61). Nominally significant association was observed in missense variants from FAAH, DNMT1, MYO18B, and CFB, with ORs of risk alleles ranging from 1.41 to 2.35. The identified SNVs, particularly the GRIN3A R480G variant, are good candidates for further replication studies and functional evaluation. The results of this study indicate that association analyses focusing on uncommon and rare SNVs are a promising way to discover risk variants with larger effects. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Childhood-onset schizophrenia case with 2.2 Mb deletion at chromosome 3p12.2–p12.1 and two large chromosomal abnormalities at 16q22.3–q24.3 and Xq23–q28

PubMed Central

Rudd, Danielle; Axelsen, Michael; Epping, Eric A; Andreasen, Nancy; Wassink, Thomas

2015-01-01

Key Clinical Message Childhood-onset schizophrenia is rare, comprising 1% of known schizophrenia cases. Here, we report a patient with childhood-onset schizophrenia who has three large chromosomal abnormalities: an inherited 2.2 Mb deletion of chromosome 3p12.2–p12.1, a de novo 16.7 Mb duplication of 16q22.3–24.3, and a de novo 43 Mb deletion of Xq23–q28. PMID:25914809

Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing.

PubMed

Veras, Andre B; Getz, Mara; Froemke, Robert C; Nardi, Antonio Egidio; Alves, Gilberto Sousa; Walsh-Messinger, Julie; Chao, Moses V; Kranz, Thorsten M; Malaspina, Dolores

2018-02-01

Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific clinical features could aid in evaluating any role of oxytocin in the pathogenesis of schizophrenia. Schizophrenia cases with rare missense coding OXTR single nucleotide variants (SNVs) were identified from a well-characterized sample of cases and controls who were assessed for symptoms, cognition and early life trauma. Five of 48 cases showed rare OXTR variants. Compared to the other cases they had less severe negative symptoms (deficits in emotional expression and motivation) and less severe general psychopathology scores (depression and anxiety). They demonstrated lower nonverbal (performance) than verbal intelligence due to deficient perceptual organization and slow processing speed. They also reported greater early trauma exposure (physical and sexual abuse and emotional trauma). Cases carrying rare OXTR SNVs had less negative and affective symptoms than other cases, but similar psychotic symptoms, along with specific cognitive deficits. The clinical characterization of these cases occurred in association with environmental exposure to early trauma, especially sexual abuse, which may have influenced the expression of schizophrenia in subjects harboring specific SNVs in the OXTR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between forkhead-box P2 gene polymorphism and clinical symptoms in chronic schizophrenia in a Chinese population.

PubMed

Rao, Wenwang; Du, Xiangdong; Zhang, Yingyang; Yu, Qiong; Hui, Li; Yu, Yaqin; Kou, Changgui; Yin, Guangzhong; Zhu, Xiaomin; Man, Lijuan; Soares, Jair C; Zhang, Xiang Yang

2017-07-01

The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in the susceptibility to schizophrenia; however, few studies have investigated the association between FOXP2 gene polymorphism and clinical symptoms in schizophrenia. This study investigated whether the FOXP2 gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped in 1069 schizophrenia inpatients and 410 healthy controls using a case-control design. The patients' psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). We found no significant differences in the genotype and allele distributions between the patient and control groups. Interestingly, we found significant differences in PANSS total, positive symptom, and general psychopathology scores between genotypic subgroups in patients, with the higher score in patients with CC genotype than those with CT genotype (all p < 0.05). After adjusting demographic and clinical variables, the difference still remained significant for the PANSS positive symptom score and general psychopathology (both p < 0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may not contribute to the development of schizophrenia, but may contribute to the clinical symptoms of schizophrenia among Han Chinese.

Altered brain arginine metabolism in schizophrenia.

PubMed

Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-08-16

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

Auditory P300 event related potentials in acute and transient psychosis-Comparison with schizophrenia.

PubMed

Sahoo, Swapnajeet; Malhotra, Savita; Basu, Debasish; Modi, Manish

2016-10-01

Limited biological research data are available on acute and transient psychotic disorder (ATPD) vis-à-vis schizophrenia. P300 event related potentials (ERP) have been extensively studied as an important neurophysiological parameter in schizophrenia. However, no P300 ERP studies comparing the two disorders are available. We compared auditory P300 ERP in patients remitted from ATPD with schizophrenia in remission and biologically unrelated healthy controls. In this case-control study design, 25 subjects remitted from ATPD were age-/gender-matched with healthy controls and patients with schizophrenia in remission. Clinical assessment and auditory P300 ERP (amplitude and latencies at central and parietal sites, reaction time) were recorded. The ERP parameters were compared across the three groups. All three groups showed significant differences in P300 amplitudes and latencies at central and parietal sites. Schizophrenia group differed significantly (p<0.001) from the ATPD group in all the P300 parameters. The ATPD group was found to have lower Pz latency (p<0.05) and lower mean reaction time (p<0.001) as compared to healthy controls. The results suggest that P300 could easily distinguish between ATPD and schizophrenia in remission, thus neurophysiologically differentiating the two disorders. Lower P300 latency and reaction time, which indicate hyper-arousability, distinguished ATPD from normal controls, with implications for a better understanding of ATPD. Copyright © 2016 Elsevier B.V. All rights reserved.

Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls: A Danish Case-Control Study.

PubMed

Bertelsen, Birgitte; Oranje, Bob; Melchior, Linea; Fagerlund, Birgitte; Werge, Thomas M; Mikkelsen, Jens D; Tümer, Zeynep; Glenthøj, Birte Y

2015-12-01

Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (α7nAChR), is suggested as a susceptibility factor for schizophrenia. CHRNA7 has also been genetically linked to the P50 auditory evoked potential deficit, a candidate endophenotype of schizophrenia, but not to prepulse inhibition of the startle reflex (PPI). In this study, 95 antipsychotic-naïve schizophrenic patients and 450 unaffected controls were screened for CHRNA7 promoter variants to investigate the association with schizophrenia, P50 suppression and PPI. We found that the promoter variant -194C (rs28531779) was significantly associated with schizophrenia, but did not find any association of this variant with P50 suppression or PPI. In addition, individuals with CHRNA7 promoter variants had elevated startle magnitude in pulse-alone trials compared to individuals without a variant. The present findings provide further support for a role of the α7nAChR in schizophrenia and show a genetic link between CHRNA7 and startle magnitude, indicating that cholinergic neurotransmission involving the α7nAChR could be involved in sensory registration processes.

Selected infectious agents and risk of schizophrenia among U.S. military personnel.

PubMed

Niebuhr, David W; Millikan, Amy M; Cowan, David N; Yolken, Robert; Li, Yuanzhang; Weber, Natalya S

2008-01-01

A number of studies have reported associations between Toxoplasma gondii (T. gondii) infection and the risk of schizophrenia. Most existing studies have used small populations and postdiagnosis specimens. As part of a larger research program, the authors conducted a hypothesis-generating case control study of T. gondii antibodies among individuals discharged from the U.S. military with a diagnosis of schizophrenia and serum specimens available from both before and after diagnosis. The patients (N=180) were military members who had been hospitalized and discharged from military service with a diagnosis of schizophrenia. Healthy comparison subjects (3:1 matched on several factors) were members of the military who were not discharged. The U.S. military routinely collects and stores serum specimens of military service members. The authors used microplate-enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to T. gondii, six herpes viruses, and influenza A and B viruses and immunoglobulin M (IgM) antibody levels to T. gondii in pre- and postdiagnosis serum specimens. A significant positive association between the T. gondii IgG antibody and schizophrenia was found; the overall hazard ratio was 1.24. The association between IgG and schizophrenia varied by the time between the serum specimen collection and onset of illness. The authors found significant associations between increased levels of scaled T. gondii IgG antibodies and schizophrenia for antibodies measured both prior to and after diagnosis.

Health care use, drug treatment and comorbidity in patients with schizophrenia or non-affective psychosis in Sweden: a cross-sectional study.

PubMed

Brostedt, Erica M; Msghina, Mussie; Persson, Marie; Wettermark, Björn

2017-12-29

This study investigated the prevalence of schizophrenia (ICD-10 F 20) and of other non-affective psychosis (NAP, ICD-10 F 21 - F 29) in Sweden. It further assessed health care use, comorbidity and medication for these patient groups. Most studies either have a study population of patients with strictly defined schizophrenia or a psychosis population of which strict schizophrenia cases form a smaller set. The present study permits comparison of the two mutually exclusive patient groups using data at the individual level in the diagnosis of non-affective psychosis, use of health care, medical treatment and comorbidity by diagnosis or medical treatment. In 2012, data were extracted from a regional registry containing patient-level data on consultations, hospitalisations, diagnoses and dispensed drugs for the total population in the region of Stockholm (2.1 million inhabitants). The size of the total psychosis population was 18,769, of which 7284 had a diagnosis of schizophrenia. Crude prevalence rates and risk rates with 95% confidence intervals were calculated. In 2012, the prevalence of schizophrenia and NAP was 3.5/1000 and 5.5/1000, respectively. Schizophrenia was most common among patients aged 50-59 years and NAP most common among patients aged 40-49 years. Schizophrenia patients used psychiatric health care more often than the NAP patients but less overall inpatient care (78.6 vs. 60.0%). The most prevalent comorbidities were substance abuse/dependence (7.9% in the schizophrenia group vs. 11.7% in the NAP group), hypertension (7.9 vs. 9.7%) and diabetes (6.9 vs. 4.8%). The parenteral form of long-acting injectable antipsychotics was more often dispensed to patients with schizophrenia (10 vs. 2%). This study, analysing all diagnoses recorded in a large health region, confirmed prevalence rates found in previous studies. Schizophrenia patients use more psychiatric and less overall inpatient health care than NAP patients. Differences between the two patient groups in comorbidity and drug treatment were found. The registered rates of a substance abuse/dependence diagnosis were the most common comorbidity observed among the patients investigated. The observed differences between the schizophrenia and the NAP patients in health care consumption, comorbidity and drug treatment are relevant and warrant further studies.

Improving Social Cognition in People with Schizophrenia with RC2S: Two Single-Case Studies.

PubMed

Peyroux, Elodie; Franck, Nicolas

2016-01-01

Difficulties in social interactions are a central characteristic of people with schizophrenia, and can be partly explained by impairments of social cognitive processes. New strategies of cognitive remediation have been recently developed to target these deficits. The RC2S therapy is an individualized and partly computerized program through which patients practice social interactions and develop social cognitive abilities with simulation techniques in a realistic environment. Here, we present the results of two case-studies involving two patients with schizophrenia presenting with specific profiles of impaired social cognition. Each patient completed three baseline sessions, 14 treatment sessions, and 3 follow-up sessions at the end of the therapy - and for 1 patient, another 3 sessions 9 months later. We used a multiple baseline design to assess specific components of social cognition according to the patients' profiles. Functioning and symptomatology were also assessed at the end of the treatment and 6 months later. Results highlight significant improvements in the targeted social cognitive processes and positive changes in functioning in the long term. The RC2S program seems, thus, to be a new useful program for social cognitive remediation in schizophrenia.

Improving Social Cognition in People with Schizophrenia with RC2S: Two Single-Case Studies

PubMed Central

Peyroux, Elodie; Franck, Nicolas

2016-01-01

Difficulties in social interactions are a central characteristic of people with schizophrenia, and can be partly explained by impairments of social cognitive processes. New strategies of cognitive remediation have been recently developed to target these deficits. The RC2S therapy is an individualized and partly computerized program through which patients practice social interactions and develop social cognitive abilities with simulation techniques in a realistic environment. Here, we present the results of two case-studies involving two patients with schizophrenia presenting with specific profiles of impaired social cognition. Each patient completed three baseline sessions, 14 treatment sessions, and 3 follow-up sessions at the end of the therapy – and for 1 patient, another 3 sessions 9 months later. We used a multiple baseline design to assess specific components of social cognition according to the patients’ profiles. Functioning and symptomatology were also assessed at the end of the treatment and 6 months later. Results highlight significant improvements in the targeted social cognitive processes and positive changes in functioning in the long term. The RC2S program seems, thus, to be a new useful program for social cognitive remediation in schizophrenia. PMID:27199776

Summer birth and deficit schizophrenia: Cantabria, Spain.

PubMed

Kirkpatrick, Brian; Herrera Castanedo, Sara; Vazquez-Barquero, Jose L

2002-08-01

An association between deficit schizophrenia and summer birth has previously been reported. The authors attempted to replicate this association in a population-based study of incident cases of psychosis in the autonomous region of Cantabria, in northern Spain. Schizophrenia patients were categorized into deficit (N = 22) and nondeficit (N = 55) groups, and the pattern in the two groups was compared. After accounting for the variance due to disorganization, hallucinations and delusions, and demographic variables, deficit schizophrenia had a significant association with summer birth; this association did not depend on a single definition of summer. For instance, among the deficit patients, 59% were born from May to August, in contrast to 18% of nondeficit patients and 34% of the general population. These results confirm the association between summer birth in the Northern Hemisphere and deficit as opposed to nondeficit schizophrenia. The existence of a different risk factor for the two groups suggests a difference in etiology and pathophysiology.

CASE REPORT : GRAVE'S DISEASE PRESENTING AS PARANOID SCHIZOPHRENIA

PubMed Central

Singh, S.K.; Hatwal, A.; Agarwal, J.K.; Bajpai, H.S.; Sharma, I.

1989-01-01

SUMMARY The case of a 37 year old male is described who initially presented as paranoid schizophrenia unresponsive to anti-psychotic drug treatment and subsequently developed features of Grave's disease. Treatment with carbimazole alone improved his psychiatric symptoms. PMID:21927380

Switching to aripiprazole for the treatment of residual mutism resulted in distinct clinical courses in two catatonic schizophrenia cases.

PubMed

Muneoka, Katsumasa; Kanahara, Nobuhisa; Kimura, Shou

2017-01-01

The efficacy of a partial agonist for the dopamine D 2 receptor, aripiprazole, for catatonia in schizophrenia has been reported. We report distinct clinical courses in challenging aripiprazole to treat residual mutism after severe catatonic symptoms improved. In the first case, mutism was successfully treated when the patient was switched from olanzapine to aripiprazole. In contract, switching to aripiprazole from risperidone aggravated auditory hallucinations in the second case. We will discuss the benefits and risks of using aripiprazole for the treatment of catatonic schizophrenia and the possibility of dopamine supersensitivity psychosis.

Cultural considerations in the diagnosis and treatment of schizophrenia: A case example from India.

PubMed

Dhanasekaran, Saranya; Loganathan, Santosh; Dahale, Ajit; Varghese, Mathew

2017-06-01

Culture plays an important role in the presentation, help seeking, treatment and outcomes of psychiatric illnesses like schizophrenia. We report a case of paranoid schizophrenia in a 35-year-old lady, from South India, whose clinical presentation was influenced by various sociocultural factors. These cultural constructs were taken into consideration to formulate an acceptable and effective management plan. A detailed case description using a cultural formulation to highlight the etic and emic perspectives and challenges in treatment and management are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of Catatonia Presentation in Patients with Schizophrenia and Mood Disorders in Lagos, Nigeria

PubMed Central

Olubunmi, Okewole Adeniran; Taiwo, Oduguwa; Taiwo, Afe; Rahman, Lawal; Oladipo, Adepoju

2011-01-01

Objective To compare the clinical profile and pattern of catatonic symptoms of patients with schizophrenia and mood disorder. Method Records of 13,968 patients seen between 1983–1985 and 2003–2005 were reviewed for symptoms of catatonia by resident doctors in psychiatry. Cases in which the diagnosis were schizophrenia or mood disorder were then noted. Socio-demographic and clinical features were described for each diagnosis. Results There were a total of 98 cases with catatonia out of the 13,968 case notes reviewed. Schizophrenia accounted for 82.5% and 53.4% in the two periods, while the proportion associated with mood disorders increased from 10% to 20.7%. Male to female ratio was 1.2:1 in schizophrenia and 1:3 in mood disorder. Those with schizophrenia were younger and with an earlier age of onset of symptoms than those with mood disorders. Conclusion Catatonia associated with mood disorder was found to be increasing over the years when compared with schizophrenia. Differences were observed in socio-demographic characteristics and number of predominant catatonic symptoms. Having a separate category for catatonia due to the mood disorders in the current diagnostic guidelines (10th edition of the International Classification of Diseases and the 4th edition of the Diagnostic and Statistical Manual) will help in better diagnosis of catatonia. PMID:22952514

Top-Down Computerized Cognitive Remediation in Schizophrenia: A Case Study of an Individual with Impairment in Verbal Fluency

PubMed Central

Masson, Marjolaine; Wykes, Til; Maziade, Michel; Reeder, Clare; Gariépy, Marie-Anne; Roy, Marc-André; Ivers, Hans; Cellard, Caroline

2015-01-01

The objective of this case study was to assess the specific effect of cognitive remediation for schizophrenia on the pattern of cognitive impairments. Case A is a 33-year-old man with a schizophrenia diagnosis and impairments in visual memory, inhibition, problem solving, and verbal fluency. He was provided with a therapist delivered cognitive remediation program involving practice and strategy which was designed to train attention, memory, executive functioning, visual-perceptual processing, and metacognitive skills. Neuropsychological and clinical assessments were administered at baseline and after three months of treatment. At posttest assessment, Case A had improved significantly on targeted (visual memory and problem solving) and nontargeted (verbal fluency) cognitive processes. The results of the current case study suggest that (1) it is possible to improve specific cognitive processes with targeted exercises, as seen by the improvement in visual memory due to training exercises targeting this cognitive domain; (2) cognitive remediation can produce improvements in cognitive processes not targeted during remediation since verbal fluency was improved while there was no training exercise on this specific cognitive process; and (3) including learning strategies in cognitive remediation increases the value of the approach and enhances participant improvement, possibly because strategies using verbalization can lead to improvement in verbal fluency even if it was not practiced. PMID:25949840

Relationship between toxoplasmosis and schizophrenia: A review.

PubMed

Fuglewicz, Aleksander J; Piotrowski, Patryk; Stodolak, Anna

2017-09-01

A growing body of evidence suggests a correlation between schizophrenia and exposure to infectious agents. The majority of studied cases concerns the infection caused by T. gondii, an obligatory intracellular parasite that infects about 1/3 of the entire human population, according to the available data. The acute stage of the disease, predominantly short-lived and transient, transforms into the latent and chronic phase in which the parasite localizes within tissue cysts, mainly in the central nervous system. The chronic toxoplasmosis, primarily regarded as benign and asymptomatic, might be responsible, in light of current scientific evidence, for a vast array of neuropsychiatric symptoms. Numerous epidemiological case-control studies show a higher prevalence of T. gondii infestation in individuals with various psychiatric and behavior disorders, including schizophrenia. This paper tends to review the relevant studies that demonstrate links between schizophrenia and T. gondii infestation, of which the latter may be acquired in different developmental phases. Apart from epidemiological correlation studies, some papers on other associations were also presented, describing putative patophysiological mechanisms that might be at least partly responsible for chronic infection-induced neuromediator disturbances, together with morphological and functional alterations, e.g., low-grade neuroinflammation, which are likely to induce psychopathological symptoms. Toxoplasmosis is only one of the putative infectious agents that derange correct brain growth and differentiation, alongside genetic and environmental factors. All of them may lead eventually to schizophrenia. A better knowledge of infection mechanisms and its influence on neurobiochemical and neuropathological pathways may enable more efficient therapy and the prevention of this devastating disease.

Dopamine D3 receptor gene locus: Association with schizophrenia, as well age of onset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nimgsonkar, V.L.; Zhang, X.R.; Brar, J.S.

Genetic factors are clearly involved in the etiology of schizophrenia, but their specific nature is unknown. If the genetic etiology is multifactorial or polygenic, the role of specific genes as susceptibility factors can be directly evaluated by examining allelic variation at these loci among cases in comparison with controls. Two studies have independently demonstrated an association of schizophrenia with homozygosity at the dopamine D3 receptor gene (D3RG) locus, using a biallelic polymorphism in the first exon of D3RG. These results are important because D3RG is a favored candidate gene. Three other studies have identified associations among sub-groups of patients, butmore » the majority were negative. The present study involved patients with schizophrenia (DSM-III-R criteria) of Caucasian or African-American ethnicity (n=130). Two groups of controls, matched for ethnicity, were used: adults screened for schizophrenia (n=128) and unselected neonates (n=160). Multivariate analysis revealed an association between allele no. 1 homozygosity and schizophrenia in comparison with adult, but not neonatal controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.7, C.I. 1.8, 104.3). An association of the D3RG locus with age of onset (AOO) was also noted. The discrepancies in earlier studies may due to variations in control groups, differencies in mean AOO among different cohorts, or ethnic variations in susceptibility attributable to D3RG.« less

Disturbance of Intentionality: A Phenomenological Study of Body-Affecting First-Rank Symptoms in Schizophrenia

PubMed Central

Thomann, Philipp Arthur; Fuchs, Thomas

2013-01-01

Objectives In 1950, Kurt Schneider proposed that a considerable number of schizophrenia patients develop first-rank symptoms (FRS). In such cases, patients report made experiences, replaced control of will, thought insertion, broadcast or withdrawal and delusional perception, respectively. Although a number of recent studies tend to explain FRS in terms of neurobiological and neuropsychological processes, the origin of these symptoms still remains unknown. In this paper, we explore the subjective experience of patients with the following two FRS: (1) "made" impulses and (2) “made" volitional acts. Method The method applied for the study of two FRS consists first in the overview of psychiatric and philosophical literature and second in the further investigation of subjective experience in patients with FRS. Psychopathological and phenomenological aspects of FRS are discussed by means of patient cases. Results We discovered a profound transformation of intentionality and agency in schizophrenia patients with body-affecting FRS. This concept offers an insight into the interrelatedness between particular FRS. Conclusion We propose that the subjective experience of schizophrenia patients with body-affecting FRS is rooted in the disturbance of intentionality and diminished sense of agency. This theoretical account of body-affecting FRS will open up new directions in both phenomenological and neurobiological psychiatric research. PMID:24019932

Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats.

PubMed

Demeter, Kornél; Török, Bibiána; Fodor, Anna; Varga, János; Ferenczi, Szilamér; Kovács, Krisztina J; Eszik, Ildikó; Szegedi, Viktor; Zelena, Dóra

2016-03-01

Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases. Copyright © 2015 Elsevier B.V. All rights reserved.

A two fold risk of metabolic syndrome in a sample of patients with schizophrenia: do consanguinity and family history increase risk?

PubMed

Bener, Abdulbari; Al-Hamaq, Abdulla O A A; Dafeeah, Elnour E

2014-01-01

Patients with schizophrenia are at greater risk for metabolic syndrome (MetS) and other cardiovascular risk factors. The objective of the study was to examine the prevalence of metabolic syndrome (MetS) and its criteria among patients with schizophrenia (Sz) according to the revised criteria of NCEP ATP III and assess which component contributed to the increased risk of the MetS in schizophrenia patients. This was a matched case-control study. Outpatient clinics of the Psychiatry department and Primary Health Care (PHC) Centers of the Supreme Council of Health, State of Qatar. The study was carried out among patients with schizophrenia (SZ) and healthy subjects above 20 years old. The study based on matched by age and gender of 233 cases and 466 controls. The survey was conducted from June 2010 to May 2011. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program - Third Adult Treatment Panel (ATP III). The prevalence of metabolic syndrome among schizophrenic patients (36.5%) were significantly higher than healthy subjects (18.7%) (p<0.001). The prevalence of MetS in schizophrenic subjects was reported to be two times higher than in the general population. The MetS components were higher among schizophrenic patients than healthy subjects. Among the components of MetS, central obesity (63.9%) was the most common criteria among patients compared to healthy subjects (45.7%) (p<0.001). Schizophrenic patients (27%) were significantly obese than the healthy subjects (13.1%). Female schizophrenia patients were more likely to have three or more metabolic abnormalities compared to men. The study indicated that metabolic syndrome was highly prevalent in patients with schizophrenia. The female gender was significantly associated with a higher prevalence of metabolic syndrome. The identification and clinical management of this high risk group is of great importance. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Intersubjectivity in schizophrenia: life story analysis of three cases

PubMed Central

Irarrázaval, Leonor; Sharim, Dariela

2014-01-01

The processes involved in schizophrenia are approached from a viewpoint of understanding, revealing those social elements susceptible to integration for psychotherapeutic purposes, as a complement to the predominant medical-psychiatric focus. Firstly, the paper describes the patients’ disturbances of self-experience and body alienations manifested in acute phases of schizophrenia. Secondly, the paper examines the patients’ personal biographical milestones and consequently the acute episode is contextualized within the intersubjective scenario in which it manifested itself in each case. Thirdly, the patients’ life stories are analyzed from a clinical psychological perspective, meaningfully connecting symptoms and life-world. Finally, it will be argued that the intersubjective dimension of the patients’ life stories shed light not only on the interpersonal processes involved in schizophrenia but also upon the psychotherapeutic treatment best suited to each individual case. PMID:24575073

Gene Expression Elucidates Functional Impact of Polygenic Risk for Schizophrenia

PubMed Central

Fromer, Menachem; Roussos, Panos; Sieberts, Solveig K; Johnson, Jessica S; Kavanagh, David H; Perumal, Thanneer M; Ruderfer, Douglas M; Oh, Edwin C; Topol, Aaron; Shah, Hardik R; Klei, Lambertus L; Kramer, Robin; Pinto, Dalila; Gümüş, Zeynep H; Cicek, A. Ercument; Dang, Kristen K; Browne, Andrew; Lu, Cong; Xie, Lu; Readhead, Ben; Stahl, Eli A; Parvizi, Mahsa; Hamamsy, Tymor; Fullard, John F; Wang, Ying-Chih; Mahajan, Milind C; Derry, Jonathan M J; Dudley, Joel; Hemby, Scott E; Logsdon, Benjamin A; Talbot, Konrad; Raj, Towfique; Bennett, David A; De Jager, Philip L; Zhu, Jun; Zhang, Bin; Sullivan, Patrick F; Chess, Andrew; Purcell, Shaun M; Shinobu, Leslie A; Mangravite, Lara M; Toyoshiba, Hiroyoshi; Gur, Raquel E; Hahn, Chang-Gyu; Lewis, David A; Haroutunian, Vahram; Peters, Mette A; Lipska, Barbara K; Buxbaum, Joseph D; Schadt, Eric E; Hirai, Keisuke; Roeder, Kathryn; Brennand, Kristen J; Katsanis, Nicholas; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela

2016-01-01

Over 100 genetic loci harbor schizophrenia associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of schizophrenia cases (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ~20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3, or SNAP91. Altering expression of FURIN, TSNARE1, or CNTN4 changes neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yields abnormal migration. Of 693 genes showing significant case/control differential expression, their fold changes are ≤ 1.33, and an independent cohort yields similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases. PMID:27668389

Transcriptome-Wide Mega-Analyses Reveal Joint Dysregulation of Immunologic Genes and Transcription Regulators in Brain and Blood in Schizophrenia

PubMed Central

Hess, Jonathan L.; Tylee, Daniel S.; Barve, Rahul; de Jong, Simone; Ophoff, Roel A.; Kumarasinghe, Nishantha; Tooney, Paul; Schall, Ulrich; Gardiner, Erin; Beveridge, Natalie Jane; Scott, Rodney J.; Yasawardene, Surangi; Perera, Antionette; Mendis, Jayan; Carr, Vaughan; Kelly, Brian; Cairns, Murray; Tsuang, Ming T.; Glatt, Stephen J.

2016-01-01

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia. PMID:27450777

Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia.

PubMed

Hess, Jonathan L; Tylee, Daniel S; Barve, Rahul; de Jong, Simone; Ophoff, Roel A; Kumarasinghe, Nishantha; Tooney, Paul; Schall, Ulrich; Gardiner, Erin; Beveridge, Natalie Jane; Scott, Rodney J; Yasawardene, Surangi; Perera, Antionette; Mendis, Jayan; Carr, Vaughan; Kelly, Brian; Cairns, Murray; Tsuang, Ming T; Glatt, Stephen J

2016-10-01

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n=315) and from ex-vivo blood tissues (n=578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia. Published by Elsevier B.V.

Further evidence for the association between LRP8 and schizophrenia.

PubMed

Xiao, Xiao; Yu, Hao; Li, Jun; Wang, Lu; Li, Lingyi; Chang, Hong; Zhang, Dai; Yue, Weihua; Li, Ming

2017-05-08

Previous studies (including genome-wide association study (GWAS) and candidate gene studies) have revealed the important roles of genetic risk factors in schizophrenia, and RELN has been identified as a risk gene for this illness. We recently found that the low-density lipoprotein receptor-related protein 8 (LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly associated with schizophrenia and bipolar disorder in European populations. To further enhance our understanding of its role in the risk of psychiatric illnesses, we conducted meta-analyses of a higher density of single nucleotide polymorphisms (SNPs, N=173) in LRP8 to understand their associations with schizophrenia in much larger samples (39,400 cases and 50,357 controls) from populations of European, Chinese and African American ancestries. The significant risk SNPs then underwent further analyses to understand their correlations with bipolar disorder and anxiety disorders, as well as LRP8 expression. We observed that rs5177 in the 3' untranslated region (3'UTR) of LRP8 was associated with schizophrenia and other psychiatric disorders, and rs5177 was also associated with LRP8 mRNA expression. These data further support LRP8 as a schizophrenia susceptibility gene, and suggest that this variant is likely a risk locus in general populations. Copyright © 2017 Elsevier B.V. All rights reserved.

A meta-analysis of data associating DRD4 gene polymorphisms with schizophrenia.

PubMed

Xu, Feng-Ling; Wu, Xue; Zhang, Jing-Jing; Wang, Bao-Jie; Yao, Jun

2018-01-01

To explore the association between DRD4 polymorphisms and schizophrenia risk, a meta-analysis was carried out with 41 case-control articles. Specifically, we included 28 articles (5,735 cases and 5,278 controls) that pertained to the 48 bp variable number tandem repeat (VNTR) polymorphism, nine articles (1,517 cases and 1,746 controls) that corresponded to the 12 bp tandem repeat (TR), six articles (1,912 cases and 1,836 controls) that addressed the 120 bp TR, 10 articles (2,927 cases and 2,938 controls) that entailed the -521 C>T polymorphism, six articles (1,735 cases and 1,724 controls) that pertained to the -616 C>G polymorphism, and four articles (1,191 cases and 1,215 controls) that involved the -376 C>T polymorphism. Pooled analysis, subgroup analysis, and sensitivity analysis were performed, and the data were visualized by means of forest and funnel plots. Results of pooled analysis indicated that the -521 CC variant ( P z =0.009, odds ratio [OR] =1.218, 95% confidence interval [CI] =1.050-1.413) and genotype L/L (ie, long allele) of the 120 bp TR were risk factors of schizophrenia ( P z =0.004, OR =1.275, 95% CI =1.081-1.504). The 48 bp VNTR, the 12 bp TR, the -616 C>G polymorphism, and the -376 C>T polymorphism were not associated with schizophrenia. Additional research is warranted to explore the association between polymorphisms of DRD4 and schizophrenia risk.

Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study.

PubMed

Tregellas, Jason R; Smucny, Jason; Legget, Kristina T; Stevens, Karen E

2015-12-01

Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia. Published by Elsevier B.V.

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans.

PubMed

Xu, Bin; Woodroffe, Abigail; Rodriguez-Murillo, Laura; Roos, J Louw; van Rensburg, Elizabeth J; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2009-09-29

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease.

Association of the Met-196-Arg variation of human tumor necrosis factor receptor 2 (TNFR2) with paranoid schizophrenia.

PubMed

Thabet, Sihem; Ben Nejma, Mouna; Zaafrane, Ferid; Gaha, Lotfi; Ben Salem, Kamel; Romdhane, Abdelaziz; Nour, Mohamed; Jrad, Besma Bel Hadj

2011-03-01

Research has provided strong evidence for oligodendrocyte and myelin-related genes dysfunction in schizophrenia. Several studies have suggested abnormalities in the expression of myelin-related genes including tumor necrosis factor receptor 2 (TNFR2) involved in the neurodegeneration and remyelination. In order to further assess the role of TNFR2 in schizophrenia, we examined a functional bi-allelic polymorphism associated with an impaired NF-KB signaling and cell survival. In the present case/control study, 220 patients with schizophrenia and 176 healthy controls were genotyped by RFLP-PCR for the T/G polymorphism at the position 676 in exon 6 of the TNFR2 gene. We found a trend towards over-representation of TNFR2 676G in the patients compared to the controls (p=0.19 and 0.09 respectively). Interestingly, when we evaluated the association between this genetic polymorphism and the clinical variables of schizophrenia, our findings indicated that the frequencies of the G/G genotype and the G allele were significantly higher in paranoid (p=0.014 and p=0.012 respectively) and adult-onset paranoid (p=0.004 and p=0.004 respectively) schizophrenia patient group compared to the controls. The potential association was confirmed by a logistic regression model only for development of the paranoid form of schizophrenia (p=0.022) indicating a substantially increased risk for paranoid schizophrenia with inheritance of the TNFR2(G) allele. In conclusion, this polymorphism in TNFR2 or a gene in proximity seems to be associated specifically with paranoid schizophrenia, at least in the Tunisian population. A replication of our findings in other and larger populations could be of particular importance to establish TNFR2 as one of the susceptibility genes of paranoid schizophrenia.

Theory of mind impairments in patients with first-episode schizophrenia and their unaffected siblings.

PubMed

Ho, Karen K Y; Lui, Simon S Y; Hung, Karen S Y; Wang, Yi; Li, Zhi; Cheung, Eric F C; Chan, Raymond C K

2015-08-01

Theory of mind (ToM) impairment has been consistently demonstrated in patients with schizophrenia, but whether ToM impairments exist in unaffected siblings of patients with schizophrenia remains unclear. Few studies have examined the affective and cognitive components of ToM in schizophrenia. This study aimed to examine whether ToM impairments exist in patients with first-episode schizophrenia and their unaffected siblings, and whether there is any dissociation between the affective and cognitive components of ToM. We adopted a family-based case-control design. Participants were 41 patients with first-episode schizophrenia, 43 unaffected siblings, and 42 healthy controls. The Yoni Task which measures the participants' ability to understand first- and second-order affective versus cognitive ToM and the Faux Pas Task which taps into integration of the affective and cognitive components of ToM were administered. Multivariate and univariate ANCOVAs were used to examine the group differences in ToM, while controlling for other neurocognitive functions. Compared with controls, patients with schizophrenia and their unaffected siblings performed poorer on the Faux Pas Task (p<0.001), with siblings having intermediate performance between patients and controls. Patients with schizophrenia performed worse than controls on second-order affective condition of the Yoni Task (p=0.004), but their unaffected siblings did not (p=0.063). We did not find any significant Group-by-Condition interaction in the Yoni Task (p=0.358). Patients with first-episode schizophrenia and their unaffected siblings exhibit ToM impairments, but no dissociation between affective and cognitive component of ToM was found. Our findings support the notion that ToM deficit may be a trait marker of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Educational achievement in psychiatric patients and their siblings: a register-based study in 30 000 individuals in The Netherlands.

PubMed

Tempelaar, W M; Termorshuizen, F; MacCabe, J H; Boks, M P M; Kahn, R S

2017-03-01

Poor educational achievement is associated with a range of psychiatric disorders. Several studies suggest that this underperformance is due to cognitive deficits that commence before disease onset and reflect a genetic risk for this disorder. However, the specificity and the familial contribution of this cognitive deficit are not clear. We analysed lifetime educational achievement of psychiatric patients diagnosed with schizophrenia, bipolar or depressive disorder and their unaffected siblings. In a register-based case-control study, 1561 patients with schizophrenia, 813 patients with bipolar disorder, 8112 patients with depression, and their siblings were each matched with eight population controls. Patients, siblings and controls were compared on the highest educational stream they completed. Lower educational achievement was present in schizophrenia patients from primary school onwards [completing primary school: odds ratio (OR) 0.69; completing secondary school: OR 0.69; completing academic education: OR 0.46], compared to patients with bipolar disorder or depression. Siblings of schizophrenia, bipolar or depressed patients showed no underachievement at primary or secondary school, but siblings of schizophrenia patients as well as siblings of depressed patients were less successful in their educational achievement after secondary school (completing academic education, schizophrenia siblings: OR 0.90; depressive disorder siblings: OR 0.91). Educational underachievement from primary school onwards is specifically related to schizophrenia and not to bipolar disorder or depression. Moreover, it appears to be a harbinger of the illness, since it is not found in their siblings. These results add to evidence that early cognitive deficits are a distinct feature of the schizophrenia phenotype.

Lack of Gender Influence on Cortical and Subcortical Gray Matter Development in Childhood-Onset Schizophrenia

PubMed Central

Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sara; Miller, Rachel; Tossell, Julia W.; Vyas, Nora S.; Stidd, Reva; David, Christopher; Gogtay, Nitin

2013-01-01

Background: Progressive cortical gray matter (GM) abnormalities are an established feature of schizophrenia and are more pronounced in rare, severe, and treatment refractory childhood-onset schizophrenia (COS) cases. The effect of sex on brain development in schizophrenia is poorly understood and studies to date have produced inconsistent results. >Methods: Using the largest to date longitudinal sample of COS cases (n = 104, scans = 249, Male/Female [M/F] = 57/47), we compared COS sex differences with sex differences in a sample of matched typically developing children (n = 104, scans = 244, M/F = 57/47), to determine whether or not sex had differential effects on cortical and subcortical brain development in COS. Results: Our results showed no significant differential sex effects in COS for either GM cortical thickness or subcortical volume development (sex × diagnosis × age interaction; false discovery rate q = 0.05). Conclusion: Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children. PMID:21613381

[Epigenetic research of cognitive deficit in schizophrenia: some methodological considerations].

PubMed

Lezheiko, T V; Alfimova, M V

To highlights the problems of assessing cognitive deficits in schizophrenia, relevant to the epigenetic, as well as a wide range of other approaches to the search for biological bases of cognition. The literature on the weaknesses in the evaluation of cognitive functions in patients with schizophrenia are summarized and discussed. The analysis is illustrated by our experience in developing a cognitive battery and a sample to examine relationships between DNA methylation in blood cells and cognitive deficits in schizophrenia. It has been shown that to assess cognitive deficits in patients and to reduce the influence of confounders in epigenetic analysis it is necessary (1) to use a battery with the existing co-normative data in the target population, which allows to evaluate representativeness of control and patients included in the study sample, (2) to verify the theoretically driven battery structure using normative population and a cohort of patients, (3) to balance groups of cases and controls on the number, age and sex, for which an individual matching of cases and controls is best suited, (4) to conduct an additional statistical analysis controlling for education and smoking.

The phenotypic manifestations of rare CNVs in schizophrenia.

PubMed

Merikangas, Alison K; Segurado, Ricardo; Cormican, Paul; Heron, Elizabeth A; Anney, Richard J L; Moore, Susan; Kelleher, Eric; Hargreaves, April; Anderson-Schmidt, Heike; Gill, Michael; Gallagher, Louise; Corvin, Aiden

2014-09-01

There is compelling evidence for the role of copy number variants (CNVs) in schizophrenia susceptibility, and it has been estimated that up to 2-3% of schizophrenia cases may carry rare CNVs. Despite evidence that these events are associated with an increased risk across categorical neurodevelopmental disorders, there is limited understanding of the impact of CNVs on the core features of disorders like schizophrenia. Our objective was to evaluate associations between rare CNVs in differentially brain expressed (BE) genes and the core features and clinical correlates of schizophrenia. The sample included 386 cases of Irish ancestry with a diagnosis of schizophrenia, at least one rare CNV impacting any gene, and a core set of phenotypic measures. Statistically significant associations between deletions in differentially BE genes were found for family history of mental illness (decreased prevalence of all CNVs and deletions, unadjusted and adjusted) and for paternal age (increase in deletions only, unadjusted, among those with later ages at birth of patient). The strong effect of a lack of a family history on BE genes suggests that CNVs may comprise one pathway to schizophrenia, whereas a positive family history could index other genetic mechanisms that increase schizophrenia vulnerability. To our knowledge, this is the first investigation of the association between genome-wide CNVs and risk factors and sub-phenotypic features of schizophrenia beyond cognitive function. Copyright © 2014 Elsevier B.V. All rights reserved.

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report.

PubMed

Okazaki, Kosuke; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2017-01-01

Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases. We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine. The weight gain improved after switching the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no significant worsening of psychological symptoms or other adverse effects. Asenapine might be effective for treating patients with schizophrenia who experience olanzapine-induced weight gain.

Schizophrenia, vitamin D, and brain development.

PubMed

Mackay-Sim, Alan; Féron, François; Eyles, Darryl; Burne, Thomas; McGrath, John

2004-01-01

Schizophrenia research is invigorated at present by the recent discovery of several plausible candidate susceptibility genes identified from genetic linkage and gene expression studies of brains from persons with schizophrenia. It is a current challenge to reconcile this gathering evidence for specific candidate susceptibility genes with the "neurodevelopmental hypothesis," which posits that schizophrenia arises from gene-environment interactions that disrupt brain development. We make the case here that schizophrenia may result not from numerous genes of small effect, but a few genes of transcriptional regulation acting during brain development. In particular we propose that low vitamin D during brain development interacts with susceptibility genes to alter the trajectory of brain development, probably by epigenetic regulation that alters gene expression throughout adult life. Vitamin D is an attractive "environmental" candidate because it appears to explain several key epidemiological features of schizophrenia. Vitamin D is an attractive "genetic" candidate because its nuclear hormone receptor regulates gene expression and nervous system development. The polygenic quality of schizophrenia, with linkage to many genes of small effect, maybe brought together via this "vitamin D hypothesis." We also discuss the possibility of a broader set of environmental and genetic factors interacting via the nuclear hormone receptors to affect the development of the brain leading to schizophrenia.

Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

PubMed

Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

2018-02-01

Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Exposure to genocide and the risk of schizophrenia: a population-based study.

PubMed

Levine, S Z; Levav, I; Goldberg, Y; Pugachova, I; Becher, Y; Yoffe, R

2016-03-01

No evidence exists on the association between genocide and the incidence of schizophrenia. This study aims to identify critical periods of exposure to genocide on the risk of schizophrenia. This population-based study comprised of all subjects born in European nations where the Holocaust occurred from 1928 to 1945, who immigrated to Israel by 1965 and were indexed in the Population Register (N = 113 932). Subjects were followed for schizophrenia disorder in the National Psychiatric Case Registry from 1950 to 2014. The population was disaggregated to compare groups that immigrated before (indirect exposure: n = 8886, 7.8%) or after (direct exposure: n = 105 046, 92.2%) the Nazi or fascist era of persecutions began. The latter group was further disaggregated to examine likely initial prenatal or postnatal genocide exposures. Cox regression modelling was computed to compare the risk of schizophrenia between the groups, adjusting for confounders. The likely direct group was at a statistically (p < 0.05) greater risk of schizophrenia (hazard ratio = 1.27, 95% confidence interval 1.06-1.51) than the indirect group. Also, the likely combined in utero and postnatal, and late postnatal (over age 2 years) exposure subgroups were statistically at greater risk of schizophrenia than the indirect group (p < 0.05). The likely in utero only and early postnatal (up to age 2 years) exposure subgroups compared with the indirect exposure group did not significantly differ. These results were replicated across three sensitivity analyses. This study showed that genocide exposure elevated the risk of schizophrenia, and identified in utero and postnatal (combined) and late postnatal (age over 2 years) exposures as critical periods of risk.

A 30-year study of homicide recidivism and schizophrenia.

PubMed

Golenkov, Andrei; Large, Matthew; Nielssen, Olav

2013-12-01

A second homicide by a released mentally ill person is a potentially avoidable tragedy that can reduce the prospects of conditional release for other mentally ill offenders. The aim of this study was to compare the clinical and criminological features of single and recidivist homicide offenders with schizophrenia from the Chuvash Republic of the Russian Federation. Data were extracted from the criminal and clinical records of all people with schizophrenia who had been convicted of a homicide in the Chuvash Republic at any time between 1 January 1981 and 31 December 2010. Those convicted of a second homicide offence during the 30 years of the study were compared with those convicted of a single homicide. Sixteen (10.7%) of 149 homicide offenders with schizophrenia had committed a previous homicide. The 16 recidivists included nine offenders who were diagnosed with schizophrenia at the time of their first homicide (after January 1981), three who were diagnosed with schizophrenia only after the first homicide and four who had already been diagnosed with schizophrenia at the time of a pre-1981 homicide. Time at risk for recidivists and non-recidivists differed, but the average time back in the community for the non-recidivists just exceeded the average time to second homicide for the recidivists. All the recidivists were men. Living in a rural area and dissocial personality traits were associated with homicide recidivism. In the Chuvash republic, most of the repeat homicide offences by people with schizophrenia were committed by people residing in rural areas with less access to psychiatric services, which provides indirect evidence for the efficacy of ongoing treatment and supervision in preventing repeat homicides. This area of study is, however, limited by the small numbers of cases and the long follow-up required. International collaborative studies are indicated to provide a more accurate estimate of the rate of recidivist homicide in schizophrenia. Copyright © 2013 John Wiley & Sons, Ltd.

Obstetric and perinatal health outcomes related to schizophrenia: A national register-based follow-up study among Finnish women born between 1965 and 1980 and their offspring.

PubMed

Simoila, Laura; Isometsä, Erkki; Gissler, Mika; Suvisaari, Jaana; Halmesmäki, Erja; Lindberg, Nina

2018-05-04

This national register-based study assesses obstetric and perinatal health outcomes in women with schizophrenia and their offspring. Using the Care Register for Health Care, we identified Finnish women who were born in 1965- 1980 and diagnosed with schizophrenia. For each case, five age- and place-of-birth- matched controls were obtained from the Central Population Register of Finland. They were followed from the day when the disorder was diagnosed in specialized health-care (the index day) until 31.12.2013. Information related to births was obtained from the Medical Birth Register and the Register of Congenital Malformations. We focused on singleton pregnancies that led to a delivery after the index day. We restricted the analysis of deliveries in controls to those that occurred after the index day of the case. Maternal age, marital status, smoking status, sex of the newborn, and parity were used as covariates in adjusted models. We identified 1162 singleton births among women with schizophrenia and 4683 among controls. Schizophrenic women had a 1.4-fold increased risk of induction of labor, delivery by cesarean section, and delivery by elective cesarean section. Regarding offspring, the risk of premature birth and the risk of low Apgar score at 1 min (<7) were 1.6-fold, of resuscitation 2.5-fold, and of neonatal monitoring 2.1-fold higher. Schizophrenia associates with some specific delivery methods, but delivery complications are rare and their prevalence does not differ from that observed among community women. Maternal schizophrenia associates with some negative perinatal health outcomes of the offspring. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia

PubMed Central

Catts, Vibeke Sørensen; Derminio, Dominique Suzanne; Hahn, Chang-Gyu; Weickert, Cynthia Shannon

2015-01-01

Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. Aims: To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Methods: Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. Results: We found a 20% decrease in NR1 protein (t(66)=−2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=−2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls. Conclusions: Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient. PMID:27336043

Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia.

PubMed

Catts, Vibeke Sørensen; Derminio, Dominique Suzanne; Hahn, Chang-Gyu; Weickert, Cynthia Shannon

2015-01-01

There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. We found a 20% decrease in NR1 protein (t(66)=-2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=-2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls. Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient.

Genome-Wide Association Study Implicates HLA-C*01: 02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

PubMed Central

2012-01-01

Background We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. Methods The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. Results One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10−9 and in combined samples (rs2523722 p combined = 2.88 × 10−16) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. Conclusions This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci. PMID:22883433

Stability of personality traits over a five-year period in Swedish patients with schizophrenia spectrum disorder and non-psychotic individuals: a study using the Swedish universities scales of personality.

PubMed

Fagerberg, Tomas; Söderman, Erik; Petter Gustavsson, J; Agartz, Ingrid; Jönsson, Erik G

2018-02-27

Personality is considered as an important aspect in persons with psychotic disorders. Several studies have investigated personality in schizophrenia. However, no study has investigated stability of personality traits exceeding three years in patients with schizophrenia. This study aims to investigate the stability of personality traits over a five-year period among patients with schizophrenia and non-psychotic individuals and to evaluate case-control differences. Patients with psychotic disorders (n = 36) and non-psychotic individuals (n = 76) completed Swedish universities Scales of Personality (SSP) at two occasions five years apart. SSP scores were analysed for effect of time and case-control differences by multiple analysis of covariance (MANCOVA) and within-subjects correlation. MANCOVA within-subjects analysis did not show any effect of time. Thus, SSP mean scale scores did not significantly vary during the five-year interval. Within subject correlations (Spearman) ranged 0.30-0.68 and 0.54-0.75 for the different SSP scales in patients and controls, respectively. Patients scored higher than controls in SSP scales Somatic Trait Anxiety, Psychic Trait Anxiety, Stress Susceptibility, Lack of Assertiveness, Detachment, Embitterment, and Mistrust. The stability of the SSP personality trait was reasonably high among patients with psychotic disorder, although lower than among non-psychotic individuals, which is in accordance with previous research.

Characteristics of alleged homicide offenders with and without schizophrenia in Sichuan, China.

PubMed

Chen, Xiacan; Zhang, Xueli; Wong, Stephen C P; Yang, Min; Kong, Di; Hu, Junmei

2018-04-01

Little is known about the characteristics of people with and without schizophrenia who have been charged with homicide in China. Our research question was what differences are there between alleged homicide offenders with and without psychosis? All archival records of alleged homicide cases referred for assessment to the West China Forensic Central Medical Service during 1998-2006 were retrieved. The centre serves a large catchment area in the mainly rural province of Sichuan. A random 20% of cases with schizophrenia and all cases without psychosis were selected for comparison. Demographic, criminological and mental health data were extracted from the records, and violence was rated by using the Violence Risk Scale (Chinese version). The two groups differed significantly in age, education, occupation, marital status and relationships to victim. The estimated risk of reoffending was higher in the schizophrenia group than the non-psychotic group, even after controlling for demographic differences. Despite many individuals reporting long histories of mental illness, about 40% of those with schizophrenia had never had any psychiatric treatment and less than 4% were in treatment at the time of the alleged homicide. The tendency for homicidal people with schizophrenia to be older, less educated and more socially isolated than their non-psychotic peers is similar to experience in Western countries, but the apparently higher risk scale scores of the Chinese schizophrenia group and their greater tendency to attack strangers are different. The lack of reported previous engagement with mental health services by a clearly ill and risky group of people is a likely explanation. Similar rural problems compared with better served urban areas have been reported in the Chuvash Republic. The case for better rural mental health services seems strong. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Case Report: Successful Use of the Combination of Electroconvulsive Therapy and Clozapine in Treating Treatment-Resistant Schizophrenia and Catatonia in an Adult with Intellectual Disability.

PubMed

Desarkar, Pushpal; Blumberger, Daniel; Daskalakis, Zafiris Jeff

2018-04-25

There is paucity of empirical data regarding the use of either clozapine or electroconvulsive therapy (ECT) in the acute phase and maintenance treatment of schizophrenia in adults with intellectual disability. Herein we report the successful acute and long-term remission of psychotic symptoms and catatonia with the combination of clozapine and ECT in a 26-year-old female with moderate ID and treatment-resistant schizophrenia. To our knowledge, this is the first case example of the successful use of the combination of bilateral, standard-pulse ECT and clozapine in both acute and long-term treatment of treatment-resistant schizophrenia and catatonia in an adult with ID. Our report adds further support to the emerging evidence regarding the efficacy and safety of this combination in treatment-resistant schizophrenia.

Dynamic changes in near-infrared spectroscopy (NIRS) findings in first-episode schizophrenia: a case report.

PubMed

Hatakeyama, Tsuyoshi; Kunii, Yasuto; Miura, Itaru; Itagaki, Shuntaro; Kono, Soichi; Shiga, Tetsuya; Oshima, Sachie; Nozaki, Keiko; Suzuki, Rieko; Yabe, Hirooki

2017-04-28

The clinical course of schizophrenia is characterized by recurrence and chronicity and has a large burden on society.　Nevertheless, diagnosis of schizophrenia is based only on distinctive symptoms and the disease course.　Near-infrared spectroscopy (NIRS) is a useful method for measuring changes in the hemoglobin concentration in the cortical surface area and reflects brain function.　We measured NIRS four times during the clinical course in a patient with first-episode schizophrenia.A 17-year-old woman admitted to our hospital because of hallucinations, delusions and appetite loss. After treatment with low-dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood volume in the frontal region.　On the basis of the clinical course of this patient, we introduce a new point of view, namely, that NIRS findings may be useful as a state marker that indicates the severity of schizophrenia in some cases.

Dynamic changes in near-infrared spectroscopy (NIRS) findings in first-episode schizophrenia: a case report

PubMed Central

Hatakeyama, Tsuyoshi; Kunii, Yasuto; Miura, Itaru; Itagaki, Shuntaro; Kono, Soichi; Shiga, Tetsuya; Oshima, Sachie; Nozaki, Keiko; Suzuki, Rieko; Yabe, Hirooki

2017-01-01

Abstract The clinical course of schizophrenia is characterized by recurrence and chronicity and has a large burden on society. Nevertheless, diagnosis of schizophrenia is based only on distinctive symptoms and the disease course. Near-infrared spectroscopy (NIRS) is a useful method for measuring changes in the hemoglobin concentration in the cortical surface area and reflects brain function. We measured NIRS four times during the clinical course in a patient with first-episode schizophrenia. A 17-year-old woman admitted to our hospital because of hallucinations, delusions and appetite loss. After treatment with low-dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood volume in the frontal region. On the basis of the clinical course of this patient, we introduce a new point of view, namely, that NIRS findings may be useful as a state marker that indicates the severity of schizophrenia in some cases. PMID:28420824

Altered brain arginine metabolism in schizophrenia

PubMed Central

Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-01-01

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease. PMID:27529679

Prevalence of Vitamin D Deficiency in Adult Outpatients With Bipolar Disorder or Schizophrenia.

PubMed

Boerman, Remco; Cohen, Dan; Schulte, Peter F J; Nugter, Annet

2016-12-01

Several studies show an association between schizophrenia and low levels of vitamin D. To date, there are only few studies about the prevalence of vitamin D deficiency in patients with bipolar disorder. We hypothesized that vitamin D deficiency is less common among patients with bipolar disorder than among patients with schizophrenia or schizoaffective disorder. A second hypothesis is that vitamin D deficiency is more prevalent among patients with schizophrenia, schizoaffective disorder, or bipolar disorders than among the general Dutch population.Most studies have been conducted with hospitalized patients; in this study, we only included outpatients. All outpatients of a center for bipolar disorders and all outpatients of 3 flexible assertive community treatment teams were asked to participate in this cross-sectional study. We included 118 patients with bipolar disorder and 202 patients with schizophrenia or schizoaffective disorder. Vitamin D levels were deficient in 30.3% (95% confidence interval, 25.5-35.6) of the cases. The type of psychiatric disorder was not a predictor of vitamin D deficiency. The absolute difference in risk of deficiency between the study population and the Dutch Caucasian population was 23.8% (95% confidence interval, 18.3%-29.3%). In this study, vitamin D deficiency was 4.7 times more common among outpatients with bipolar disorder, schizophrenia, or schizoaffective disorder than among the Dutch general population.Given the high prevalence of vitamin D deficiency, we believe that outpatients with bipolar disorder, schizophrenia, or schizoaffective disorder should be considered at risk of having low levels of vitamin D. Annual measurement of vitamin D levels in psychiatric outpatients with these disorders seems to be justified to maintain bone health, muscle strength, and to prevent osteoporosis.

Evidence for rare and common genetic risk variants for schizophrenia at protein kinase C, alpha.

PubMed

Carroll, L S; Williams, N M; Moskvina, V; Russell, E; Norton, N; Williams, H J; Peirce, T; Georgieva, L; Dwyer, S; Grozeva, D; Greene, E; Farmer, A; McGuffin, P; Morris, D W; Corvin, A; Gill, M; Rujescu, D; Sham, P; Holmans, P; Jones, I; Kirov, G; Craddock, N; O'Donovan, M C; Owen, M J

2010-11-01

We earlier reported a genome-wide significant linkage to schizophrenia at chromosome 17 that was identified in a single pedigree (C702) consisting of six affected, male siblings with DSM-IV schizophrenia and prominent mood symptoms. In this study, we adopted several approaches in an attempt to map the putative disease locus. First, mapping the source of linkage to chromosome 17 in pedigree C702. We refined the linkage region in family C702 to a 21-marker segment spanning 11.7 Mb at 17q23-q24 by genotyping a total of 50 microsatellites across chromosome 17 in the pedigree. Analysis of data from 1028 single nucleotide polymorphisms (SNPs) across the refined linkage region identified a single region of homozygosity present in pedigree C702 but not in 2938 UK controls. This spanned ~432 kb of the gene encoding protein kinase C, alpha (PRKCA), the encoded protein of which has been implicated in the pathogenesis of psychiatric disorders. Analysis of pedigree C702 by oligonucleotide-array comparative genome hybridization excluded the possibility that this region of homozygosity was because of a deletion. Mutation screening of PRKCA identified a rare, four-marker haplotype (C-HAP) in the 3' untranslated region of the gene, which was present in the homozygous state in all six affected members of pedigree C702. No other homozygotes were observed in genotype data for a total of 6597 unrelated Europeans (case N=1755, control N=3580 and parents of probands N=1262). Second, association analysis of C702 alleles at PRKCA. The low-frequency haplotype (C-HAP) showed a trend for association in a study of unrelated schizophrenia cases and controls from the UK (661 cases, 2824 controls, P=0.078 and odd ratio (OR)=1.9) and significant evidence for association when the sample was expanded to include cases with bipolar (N=710) and schizoaffective disorder (N=50) (psychosis sample: 1421 cases, 2824 controls, P=0.037 and OR=1.9). Given that all the affected members of C702 are male, we also undertook sex-specific analyses. This revealed that the association was strongest in males for both schizophrenia (446 male cases, 1421 male controls, P=0.008 and OR=3.9) and in the broader psychosis group (730 male cases, 1421 male controls, P=0.008 and OR=3.6). Analysis of C-HAP in follow-up samples from Ireland and Bulgaria revealed no evidence for association in either the whole sample or in males alone, and meta-analysis of all male psychosis samples yielded no significant evidence of association (969 male cases, 1939 male controls, 311 male probands P=0.304 and OR=1.4). Third, association mapping of the pedigree C702 linkage region. Independent of pedigree C702, genotype data from the Affymetrix 500k GeneChip set were available for 476 patients with schizophrenia and 2938 controls from the United Kingdom. SNPs in PRKCA showed evidence for association with schizophrenia that achieved gene-wide significance (P=0.027). Moreover, the same SNP was the most significantly associated marker out of the 1028 SNPs genotyped across the linkage region (rs873417, allelic P=0.0004). Follow-up genotyping in samples from Ireland, Bulgaria and Germany did not show consistent replication, but meta-analysis of all samples (4116 cases and 6491 controls) remained nominally significant (meta-analysis P=0.026, OR=1.1). We conclude that, although we have obtained convergent lines of evidence implicating both rare and common schizophrenia risk variants at PRKCA, none of these is individually compelling. However, the evidence across all approaches suggests that further study of this locus is warranted.

Cotard's Syndrome in a Patient with Schizophrenia: Case Report and Review of the Literature

PubMed Central

Ledesma-Gastañadui, Mario

2016-01-01

Jules Cotard described, in 1880, the case of a patient characterized by delusions of negation, immortality, and guilt as well as melancholic anxiety among other clinical features. Later this constellation of symptoms was given the eponym Cotard's syndrome, going through a series of theoretical vicissitudes, considering itself currently as just the presence of nihilistic delusions. The presentation of the complete clinical features described by Cotard is a rare occurrence, especially in the context of schizophrenia. Here we present the case of a 50-year-old male patient with schizophrenia who developed Cotard's syndrome. The patient was treated with aripiprazole, showing improvement after two weeks of treatment. A review of the literature is performed about this case. PMID:28053798

Cotard's Syndrome in a Patient with Schizophrenia: Case Report and Review of the Literature.

PubMed

Huarcaya-Victoria, Jeff; Ledesma-Gastañadui, Mario; Huete-Cordova, Maria

2016-01-01

Jules Cotard described, in 1880, the case of a patient characterized by delusions of negation, immortality, and guilt as well as melancholic anxiety among other clinical features. Later this constellation of symptoms was given the eponym Cotard's syndrome, going through a series of theoretical vicissitudes, considering itself currently as just the presence of nihilistic delusions. The presentation of the complete clinical features described by Cotard is a rare occurrence, especially in the context of schizophrenia. Here we present the case of a 50-year-old male patient with schizophrenia who developed Cotard's syndrome. The patient was treated with aripiprazole, showing improvement after two weeks of treatment. A review of the literature is performed about this case.

Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes

PubMed Central

Wonodi, Ikwunga; Stine, O. Colin; Sathyasaikumar, Korrapati V.; Roberts, Rosalinda C.; Mitchell, Braxton D.; Hong, L. Elliot; Kajii, Yasushi; Thaker, Gunvant K.; Schwarcz, Robert

2013-01-01

Context Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway. Objectives To examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. Design Case-control postmortem and clinical study. Setting Maryland Brain Collection, outpatient clinics. Participants Postmortem specimens from schizophrenia patients (n=32) and control donors (n=32) and a clinical sample of schizophrenia patients (n=248) and healthy controls (n=228). Main Outcome Measures Comparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). Results In postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. Conclusion Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits. PMID:21727251

Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes.

PubMed

Wonodi, Ikwunga; Stine, O Colin; Sathyasaikumar, Korrapati V; Roberts, Rosalinda C; Mitchell, Braxton D; Hong, L Elliot; Kajii, Yasushi; Thaker, Gunvant K; Schwarcz, Robert

2011-07-01

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway. To examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. Case-control postmortem and clinical study. Maryland Brain Collection, outpatient clinics. Postmortem specimens from schizophrenia patients (n = 32) and control donors (n = 32) and a clinical sample of schizophrenia patients (n = 248) and healthy controls (n = 228). Comparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). In postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits.

Intensive psychotherapy of schizophrenia.

PubMed Central

Keats, C. J.; McGlashan, T. H.

1985-01-01

The literature on strategies of investigative psychotherapy of schizophrenia is selectively reviewed, and a case history is presented. The format is modelled on the authors' research technique of contrasting theory with practice. While long-term observation of single cases does not address cause and effect, descriptions of cases with a variety of known outcomes can help to build a typology of treatment processes. PMID:4049907

The Capgras syndrome in paranoid schizophrenia.

PubMed

Silva, J A; Leong, G B

1992-01-01

Capgras syndrome is characterized by a delusion of impostors who are thought to be physically similar but psychologically distinct from the misidentified person. This syndrome is generally thought to be relatively rare. Most of our knowledge about Capgras syndrome derives from single case studies and small series of cases usually from diagnostically heterogeneous groups. In this article, a series of 31 patients suffering from both paranoid schizophrenia and Capgras syndrome is described. Issues pertaining to the phenomenology of Capgras syndrome, the possible relation between Capgras syndrome and other delusional misidentification syndromes, and a neurobiological hypothesis aimed at explaining Capgras syndrome are discussed.

[Cost analyses of medical care for schizophrenia and depression in México, 2005-2013].

PubMed

Arredondo, Armando; Díaz-Castro, Lina; Cabello-Rangel, Hector; Arredondo, Pablo; Recaman, Ana Lucía

2018-02-05

The study aimed to analyze the costs of medical care for mental disorders in the Mexican health system. This was a retrospective cross-sectional evaluation study. As markers for the problem, the study selected two of the principal psychological processes in mental disorders in recent years: depression and schizophrenia. Annual accumulated incidence was identified based on epidemiological reporting by type of institution in 2005-2013. The mean annual case management cost was determined with the instrumentation and consensus technique, identifying the production functions, types of inputs, costs, and amounts of inputs ordered, concentrated in the mean case matrix. Finally, an econometric adjustment factor was applied to control the inflationary effect for each year in the study period. Mean annual case management cost was USD 2,216.00 for schizophrenia and USD 2,456.00 for depression. All the institutions in the Mexican health system showed upward and constant epidemiological and economic trends. The total cost for the two disorders in the last year of the period (2013) was USD 39,081,234.00 (USD 18,119,877.00 for schizophrenia and USD 20,961,357.00 for depression). The largest impact for the two disorders combined was in institutions serving the population without health insurance (USD 24,852,321.00) versus the population with private insurance (USD 12,891,977.00). The cost of meeting the demand for services for the two disorders differs considerably between institutions that treat the population with private health service versus the population without, and is higher in the latter. The study's epidemiological and economic indicators provide evidence for decision-making in the use and allocation of healthcare resources for these two disorders in the coming years.

Activation of kynurenine pathway in ex vivo fibroblasts from patients with bipolar disorder or schizophrenia: cytokine challenge increases production of 3-hydroxykynurenine.

PubMed

Johansson, Anne-Sofie; Owe-Larsson, Björn; Asp, Linnéa; Kocki, Tomasz; Adler, Mats; Hetta, Jerker; Gardner, Renee; Lundkvist, Gabriella B S; Urbanska, Ewa M; Karlsson, Håkan

2013-11-01

Accumulating data suggest a causative link between immune stimulation, disturbed metabolism of tryptophan, and pathogenesis of bipolar disorder and schizophrenia. The goal of this study was to examine the production of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and the expression of kynurenine pathway enzymes involved in their synthesis and metabolism in cultured skin fibroblasts obtained from patients with bipolar disorder, schizophrenia or from healthy control individuals. The assessment was performed under basal conditions or following treatment with interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, or their combinations, in cells exposed to exogenous kynurenine. In both groups of patients, the baseline production of KYNA and 3-HK was increased, as compared to control subjects. Case-treatment analyses revealed significant interactions between bipolar case status and IL-1β, IL-6, IFN-γ + TNF-α, or IFN-γ + IL-1β, as well as between schizophrenia case status and IL-1β, IFN-γ + TNF-α, or IFN-γ + IL-1β, in terms of higher 3-HK. Noteworthy, no case-treatment interactions in terms of KYNA production were found. Observed changes did not appear to correlate with the expression of genes encoding kynurenine aminotransferases (KATs), kynureninase (KYNU) or kynurenine-3-monooxygenase (KMO). The single nucleotide polymorphisms (SNPs), rs1053230 and rs2275163, in KMO influenced KYNA levels yet did not explain the case-treatment discrepancies. In conclusion, our present findings indicate the utility of skin-derived fibroblasts for kynurenines research and support the concept of kynurenine pathway alterations in bipolar disorder and schizophrenia. The increase in ratio between neurotoxic 3-HK and neuroinhibitory/neuroprotective KYNA following exposure to cytokines may account for altered neurogenesis and structural abnormalities characteristic for both diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical case management for patients with schizophrenia with high care needs.

PubMed

Mas-Expósito, Laia; Amador-Campos, Juan Antonio; Gómez-Benito, Juana; Mauri-Mas, Lluís; Lalucat-Jo, Lluís

2015-02-01

The aim of this study is to establish the effectiveness of a clinical case management (CM) programme compared to a standard treatment programme (STP) in patients with schizophrenia. Patients for the CM programme were consecutively selected among patients in the STP with schizophrenia who had poor functioning. Seventy-five patients were admitted to the CM programme and were matched to 75 patients in the STP. Patients were evaluated at baseline and at 1 year follow-up. At baseline, patients in the CM programme showed lower levels of clinical and psychosocial functioning and more care needs than patients in the STP. Both treatment programmes were effective in maintaining contact with services but the CM programme did not show advantages over the STP on outcomes. Differences between groups at baseline may be masking the effects of CM at one year follow-up. A longer follow-up may be required to evaluate the real CM practices effects.

[Assessing beliefs and attitudes of relatives of patients with schizophrenia: a study in a Tunisian sample].

PubMed

Bouhlel, S; Ben Haouala, S; Klibi, A; Ghaouar, M; Chennoufi, L; Melki, W; El-Hechmi, Z

2013-06-01

Investigating and understanding family member's causal beliefs and attitudes about schizophrenia is an important step in the management of the illness. They likely influence the family's help-seeking decisions and affect both adherence with biomedical interventions and social integration of the patients. The aim of this study was to describe Tunisian families' beliefs about the causes, the symptoms and the treatments of schizophrenia. We led a transversal study including 91 relatives of patients with schizophrenia or schizoaffective disorder (DSM-IV). We excluded patients with mental retardation or neurological diseases. For family members, we excluded participants with a history of mental disorders or cognitive impairments. We collected basic socio-demographic data for both patients and relatives. We asked relatives to respond by "yes/no/I am not certain" to a three-part questionnaire including 27 items dealing with causal explanations, symptoms and optimal cures for schizophrenia. The mean age of the relatives was 49.8 (±13.7) years; 54.9% were men; 49.4% were parents, 8.8% spouses, 39.6% brothers or sisters; 25.3% had not attended school, 24.2% had attended primary school, 37.4% junior high school or high school and 13.2% had a university degree; 63.7% lived in an urban area; 33% had low economic status and 41.8% reported having another family member with mental disorder. Only 46.2% of participants had asked psychiatrists about the diagnosis of their sick relatives and only 16.5% were able to label the term "schizophrenia". Among the cited etiologies of schizophrenia, religious causes were found in 76.9% of cases, they first cited God's will or fate and secondly God's punishment. Magical explanations such as witchcraft and possession by "djinns" were found in 47.3% of cases. The biological causes were cited by 59.3% of participants. The majority of participants (95.6%) proved the need for drugs and 81.3% the utility of psychotherapies. However, 30.8% believed in non-medical practices such as reading Holy Koran verses, charity and exorcism. Significant correlations were found between relatives' low level of education, low economic status, living in a rural area and supernatural beliefs, traditional practices, stigma and the use of the term 'madness'. Significant correlations were also found between family history of mental disorders and beliefs on family and hereditary causes. In this study, opinions and attitudes regarding schizophrenia were related to education level, economic status and geographic origin. Few persons recognized the term "schizophrenia" despite a long contact with the mental health system. This fact points out the need to improve the psychoeducation of family members of persons with schizophrenia. Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia.

PubMed

Nordentoft, Merete; Larsen, Janne Tidselbak; Pedersen, Carsten Bøcker; Sørensen, Holger Jelling; Hollegaard, Mads Villiam; Hougaard, David Michael; Mortensen, Preben Bo; Petersen, Liselotte

2015-03-01

The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia. A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case, matched on sex and exact date of birth. Both early and late blood sampling was associated with increased risk for schizophrenia. Compared to blood sampling at day 5, sampling at days 0 to 4 after birth was associated with an incidence rate ratio (IRR) of 1.46 (95% CI 1.15-1.87) for development of schizophrenia, and sampling at days 6 to 9 and at days 10 to 53 was associated with an IRR of 1.5 (95% CI 1.13-1.98) and 3.00 (95% CI 1.59-5.67), respectively. After adjusting the estimates for place of birth, both parents' psychiatric illness, maternal and paternal age, parents' country of origin, child admission, and parental education and income, the estimates were slightly different. Thus, blood collection at 0-4days was associated with an IRR of 1.27 (95% CI 0.94-1.71), 6-9days 1.31 (95% CI 0.94-1.84) and 10+days 3.52 (95% CI 1.50 to 8.24). After adjusting risk estimates for well-known risk factors, delay in sampling of blood for neonatal screening was associated with unexplained increased risk of schizophrenia. Thus, a key finding is that age at test is a proxy for unobserved risk factors for schizophrenia due to unexplained reasons for late blood sampling. Date of sampling will be included in future analyses of genetic and environmental risk factors. Copyright © 2015 Elsevier B.V. All rights reserved.

Bus hijacking by a pre-schizophrenic: from a viewpoint of criminal romance.

PubMed

Satoh, S; Obata, S; Tanaka, H; Ito, S; Ishizuka, C; Minoshita, S; Morita, N

1997-08-01

There are cases in which no clear symptoms of schizophrenia are observed in a person at the time of a crime but are diagnosed to have schizophrenia after the crime due to the appearance of typical symptoms. We present psychiatric evidence of a patient who saw a bus hijacking incident on TV during several years of isolation at home after graduation from junior high school, and was then determined to hijack a bus, and carried out the crime 6 months later. The patient exhibited clear symptoms of schizophrenia 3 days after the crime. This case of a crime committed before the appearance of clear symptoms of schizophrenia was evaluated from the viewpoint of verbrecherromantik or 'criminal romance'.

Sequencing and Analyzing the "t" (1;7) Reciprocal Translocation Breakpoints Associated with a Case of Childhood-Onset Schizophrenia/Autistic Disorder

ERIC Educational Resources Information Center

Idol, Jacquelyn R.; Addington, Anjene M.; Long, Robert T.; Rapoport, Judith L.; Green, Eric D.

2008-01-01

We characterized a "t"(1;7)(p22;q21) reciprocal translocation in a patient with childhood-onset schizophrenia (COS) and autism using genome mapping and sequencing methods. Based on genomic maps of human chromosome 7 and fluorescence in situ hybridization (FISH) studies, we delimited the region of 7q21 harboring the translocation breakpoint to a…

[Clinical features of depression in the remission phase of paranoid schizophrenia].

PubMed

Petrova, N N; Vishnevskaya, O A

2013-01-01

Phenomenological and pathogenetic features of depression developed in the remission phase of paranoid schizophrenia were studied in 75 patients (mean age 44.9±1.22 years). Depression was diagnosed in 58.7% patients. It has been shown that the psychopathological structure of depression was not homogenous and 63.6% cases were atypical. In 25% patients, depressive disorders were psychogenic. Depression concomitant with anxiety disorders was most common. Depression in the phase of remission developed most often in female patients older than 39 years and in male patients younger than 39 years. Cognitive function was not impaired in patients with depression in the remission phase of paranoid schizophrenia.

Feasibility and Clinical Utility of High-definition Transcranial Direct Current Stimulation in the Treatment of Persistent Hallucinations in Schizophrenia.

PubMed

Bose, A; Shivakumar, V; Chhabra, H; Parlikar, R; Sreeraj, V S; Dinakaran, D; Narayanaswamy, J C; Venkatasubramanian, G

2017-12-01

Persistent auditory verbal hallucination is a clinically significant problem in schizophrenia. Recent studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in treatment. An optimised version of tDCS, namely high-definition tDCS (HD-tDCS), uses smaller electrodes arranged in a 4x1 ring configuration and may offer more focal and predictable neuromodulation than conventional tDCS. This case report illustrates the feasibility and clinical utility of add-on HD-tDCS over the left temporoparietal junction in a 4x1 ring configuration to treat persistent auditory verbal hallucination in schizophrenia.

Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis.

PubMed

Torrey, E Fuller; Bartko, John J; Lun, Zhao-Rong; Yolken, Robert H

2007-05-01

Recent studies have linked infectious agents to schizophrenia. The largest number of studies has involved the analysis of Toxoplasma gondii; these studies were subjected to a meta-analysis. Published articles and abstracts were identified by searches of MEDLINE, Ovid, and Google Scholar; by a search of Chinese publications; through letters to researchers; and by visiting China. Published and unpublished controlled studies that used serological methods for measuring T. gondii antibodies to assess inpatients and/or outpatients diagnosed with schizophrenia were selected for analysis, and source documents were translated as needed. Forty-two studies carried out in 17 countries over 5 decades were identified; 23 of these (6 unpublished) met selection criteria. The combined odds ratio (OR) was 2.73 (95% confidence interval, 2.10 to 3.60; chi-square with 1 df 263; P < .000001). Seven studies that included only patients with first-episode schizophrenia (OR 2.54) did not differ significantly from 16 studies that included patients in all clinical phases (OR 2.79). The results suggest that individuals with schizophrenia have an increased prevalence of antibodies to T. gondii. This association is consistent with other epidemiological studies as well as with animal studies. Although the OR of 2.73 is modest, it exceeds that for genetic or other environmental factors identified to date and suggests that Toxoplasma is in some way associated with a large number of cases of schizophrenia. If an etiological association can be proven, it would have implications for the design of measures for the prevention and treatment of this disease.

A Review of the Pharmacotherapy of Obsessive-Compulsive Disorder and Schizophrenia: The Case of Sam

ERIC Educational Resources Information Center

Randhawa, Ramandeep S.

2005-01-01

Obsessive-compulsive symptoms are a common feature of schizophrenia, and high rates of obsessive-compulsive disorder (OCD) have been reported in schizophrenic patients. Effective pharmacotherapeutic options are available for both OCD and schizophrenia, and for some patients combining medications targeted at both conditions may be a helpful…

Awareness and Coping with Emotion in Schizophrenia: Acceptability, Feasibility and Case Illustrations

PubMed Central

Caponigro, Janelle M.; Moran, Erin K.; Kring, Ann M.; Moskowitz, Judith T.

2014-01-01

Although current treatments help to alleviate some of the symptoms of schizophrenia, people with schizophrenia often continue to experience residual symptoms. An emotion-focused treatment approach may help to improve well-being in this population by increasing positive experiences and resources. In this article, we discuss the feasibility and acceptability of a skills-based group treatment for people schizophrenia or schizoaffective disorder. As part of the Awareness and Coping with Emotion in Schizophrenia (ACES) intervention, group members learned eight empirically supported cognitive and behavioural skills covering emotional awareness and coping. Group member feedback and three case illustrations illuminate participants’ experiences with the group, as well as the potential benefits and challenges of this treatment approach. These data suggest that ACES is a feasible and acceptable group intervention. Future research is needed to examine whether ACES has a selective impact on well-being, but these initial findings point to the promise of this intervention to improve quality of life for individuals with schizophrenia and schizoaffective disorder, thus filling a void in existing treatments options. PMID:23553953

Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

PubMed

Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

2016-08-01

Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

A population-based longitudinal study of suicide risk in male schizophrenia patients: Proximity to hospital discharge and the moderating effect of premorbid IQ.

PubMed

Weiser, Mark; Kapra, Ori; Werbeloff, Nomi; Goldberg, Shira; Fenchel, Daphna; Reichenberg, Abraham; Yoffe, Rinat; Ginat, Keren; Fruchter, Eyal; Davidson, Michael

2015-12-01

Suicide is a major cause of death in schizophrenia. Identifying factors which increase the risk of suicide among schizophrenia patients might help focus prevention efforts. This study examined risk of suicide in male schizophrenia patients using population-based data, examining the timing of suicide in relation to the last hospital discharge, and the effect of premorbid IQ on risk of suicide. Data on 930,000 male adolescents from the Israeli military draft board were linked with data from the Israeli Psychiatric Hospitalization Case Registry and vital statistics from the Israeli Ministry of Health. The relationship between premorbid IQ and risk for suicide was examined among 2881 males hospitalized with schizophrenia and compared to a control group of 566,726 males from the same cohort, who were not hospitalized for a psychiatric disorder, using survival analysis methods. Over a mean follow-up period of 9.9 years (SD=5.8, range: 0-22 years), 77/3806 males with schizophrenia died by suicide (a suicide rate of 204.4 per 100,000 person-years). Approximately 48% of the suicides occurred within a year of discharge from the last hospital admission for schizophrenia. Risk of suicide was higher in male schizophrenia patients with high premorbid IQ (HR=4.45, 95% CI=1.37-14.43) compared to those with normal premorbid IQ. These data indicate that male schizophrenia patients with high premorbid IQ are at particularly high risk of suicide, and the time of peak risk is during the first year after the last hospitalization discharge. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome-wide association study with the risk of schizophrenia in a Korean population.

PubMed

Kim, Lyoung Hyo; Park, Byung Lae; Cheong, Hyun Sub; Namgoong, Suhg; Kim, Ji On; Kim, Jeong-Hyun; Shin, Joong-Gon; Park, Chul Soo; Kim, Bong-Jo; Kim, Jae Won; Choi, Ihn-Geun; Hwang, Jaeuk; Shin, Hyoung Doo; Woo, Sung-Il

2016-03-01

Schizophrenia is regarded as a multifactorial and polygenic brain disorder that is attributed to different combinations of genetic and environmental risk factors. Recently, several genome-wide association studies (GWASs) of schizophrenia have identified numerous risk factors, but the replication results remain controversial and ambiguous. To identify schizophrenia susceptibility loci in the Korean population, we performed a GWAS using the Illumina HumanOmni1-Quad V1.0 Microarray. We genotyped 1,140,419 single nucleotide polymorphisms (SNPs) in 350 Korea schizophrenia patients and 700 control subjects, and approximately 620,001 autosomal SNPs were passed our quality control. In the case-control analysis, the rs9607195 A>G on intergenic area 250 kb away from the ISX gene and the rs12738007 A>G on the intron of the MECR gene were the most strongly associated SNPs with the risk of schizophrenia (P = 6.2 × 10(-8) , OR = 0.50 and P = 3.7 × 10(-7) , OR = 2.39, respectively). In subsequent fine-mapping analysis, 6 SNPs of MECR were genotyped with 310 schizophrenia patients and 604 control subjects. The association of the MECR rs12738007, a top ranked-SNP in GWAS, was replicated (P = 1.5 × 10(-2) , OR = 1.53 in fine mapping analysis, P = 1.5 × 10(-6) , OR = 1.90 in combined analysis). The identification of putative schizophrenia susceptibility loci could provide new insights into genetic factors related with schizophrenia and clues for the development of diagnosis strategies. © 2015 Wiley Periodicals, Inc.

[Schizophrenia and pain reactivity].

PubMed

Bonnot, Olivier; Tordjman, Sylvie

2008-11-01

Medical practitioners do not for a long time pay enough attention to patient's pain. This approach is in the line of society feelings. Pain was long consider to be a contingency to withstand as showed in Christian's bible or Stoicism's principle. Changes in mentality appear in present times. It Seems obvious that for sociological and scientific reasons pain's care in medical and psychiatric disorders is now an important subject. Recent research in autistic disorders suggest that insensitivity observed in autism is not and analgesic phenomenon but a different behavioural reactivity to pain. Prevalence of schizophrenic disorder is from 0.5 to 1%. It is also a complex disorder that has defied decades of concerted efforts to uncover its origins and attenuate its symptoms. The most promising hypotheses suggest that neurodevelopmental impairment increases the risk of later schizophrenia. Most of recent researches in this topic did focus to trait or state markers. According to the vulnerability models of schizophrenia, trait marker are clinical, psychological, physiological, anatomical or cognitive impairments found in patients with schizophrenia during all the course of the illness and even before the onset. Several lines of evidence (case report, epidemiological studies, experimental studies) suggest that patients with schizophrenia shows a relative insensitivity to physical pain. We will review and critic the scientific literature in this specific topic. We will see if datas are relevant with the neurodevelopmental hypothesis and vulnerability models. An OLDMEDLINE/MEDLINE query was performed to identify 50 articles relevant to our subject. 9 were case report or case series, 21 were clinical or epidemiological studies, 15 were experimental studies and we also found 5 previous review. Clinical and experimental data strongly suggest a decrease of Behavioural Reactivity to Pain (BRP) but there is a lack of argument to prove a real analgesia. Because schizophrenia is a severe disease with impairment in communication and social skills it may be very difficult to affirm that the insensitivity to pain does really exist for patients. It seems inappropriate at this point to speak about insensitivity or analgesia. We could hypothesis that the decrease of BRP is less a consequence of analgesia than a different way to express emotion in general and pain in particular. It is well known that patients with schizophrenia show communication and thinking impairment, not adapted social skills and also a lack of body representation. However, this decrease of behavioural response seems to be frequent and may be explore by objective research protocol to understand if patients don't feel pain or probably don't express pain by adapted social skills. Furthermore, decrease of BRP may take place in a comprehensive theory of schizophrenia. in the line of stress-vulnerability model. Impairment or lack of behavioural pain reactivity could induce an increasing anxiety level for patient with vulnerability to schizophrenia and a higher risk of onset of the pathology. We may argue that pain stimuli would conduct to a nociceptive stress witch couldn't discharge by usual ways of regulation and behavioural expression of pain. Exploration and interview about pain reactivity in vulnerable to schizophrenia subjects could be interesting to increase a the amount of information in a vulnerability check-up. Further studies in this axis may be useful to test this hypothesis.

Verbal Working Memory in Schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) Study: The Moderating Role of Smoking Status and Antipsychotic Medications

PubMed Central

Lee, Junghee; Green, Michael F.; Calkins, Monica E.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Objectives Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. Methods From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the Letter-Number Span (LNS) Task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the Forward condition, participants repeated the letters and numbers in the order they were presented. In the Reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. Results Schizophrenia patients performed more poorly than controls, with a larger difference on Reorder than Forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the Reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. Conclusions Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke. PMID:25248939

Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia.

PubMed

Kort, Naomi S; Ford, Judith M; Roach, Brian J; Gunduz-Bruce, Handan; Krystal, John H; Jaeger, Judith; Reinhart, Robert M G; Mathalon, Daniel H

2017-03-15

Recent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. To test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them with the effects of schizophrenia. In two separate studies, the N1 component of the event-related potential elicited by speech sounds during vocalization (talk) and passive playback (listen) were compared to assess the degree of N1 suppression during vocalization, a putative measure of auditory predictive coding. In the crossover study, 31 healthy volunteers completed two randomly ordered test days, a saline day and a ketamine day. Event-related potentials during the talk/listen task were obtained before infusion and during infusion on both days, and N1 amplitudes were compared across days. In the case-control study, N1 amplitudes from 34 schizophrenia patients and 33 healthy control volunteers were compared. N1 suppression to self-produced vocalizations was significantly and similarly diminished by ketamine (Cohen's d = 1.14) and schizophrenia (Cohen's d = .85). Disruption of NMDARs causes dysfunction in predictive coding during vocalization in a manner similar to the dysfunction observed in schizophrenia patients, consistent with the theorized contribution of NMDAR hypofunction to predictive coding deficits in schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Transcriptome study of differential expression in schizophrenia

PubMed Central

Sanders, Alan R.; Göring, Harald H. H.; Duan, Jubao; Drigalenko, Eugene I.; Moy, Winton; Freda, Jessica; He, Deli; Shi, Jianxin; Gejman, Pablo V.

2013-01-01

Schizophrenia genome-wide association studies (GWAS) have identified common SNPs, rare copy number variants (CNVs) and a large polygenic contribution to illness risk, but biological mechanisms remain unclear. Bioinformatic analyses of significantly associated genetic variants point to a large role for regulatory variants. To identify gene expression abnormalities in schizophrenia, we generated whole-genome gene expression profiles using microarrays on lymphoblastoid cell lines (LCLs) from 413 cases and 446 controls. Regression analysis identified 95 transcripts differentially expressed by affection status at a genome-wide false discovery rate (FDR) of 0.05, while simultaneously controlling for confounding effects. These transcripts represented 89 genes with functions such as neurotransmission, gene regulation, cell cycle progression, differentiation, apoptosis, microRNA (miRNA) processing and immunity. This functional diversity is consistent with schizophrenia's likely significant pathophysiological heterogeneity. The overall enrichment of immune-related genes among those differentially expressed by affection status is consistent with hypothesized immune contributions to schizophrenia risk. The observed differential expression of extended major histocompatibility complex (xMHC) region histones (HIST1H2BD, HIST1H2BC, HIST1H2BH, HIST1H2BG and HIST1H4K) converges with the genetic evidence from GWAS, which find the xMHC to be the most significant susceptibility locus. Among the differentially expressed immune-related genes, B3GNT2 is implicated in autoimmune disorders previously tied to schizophrenia risk (rheumatoid arthritis and Graves’ disease), and DICER1 is pivotal in miRNA processing potentially linking to miRNA alterations in schizophrenia (e.g. MIR137, the second strongest GWAS finding). Our analysis provides novel candidate genes for further study to assess their potential contribution to schizophrenia. PMID:23904455

Verbal working memory in schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) study: the moderating role of smoking status and antipsychotic medications.

PubMed

Lee, Junghee; Green, Michael F; Calkins, Monica E; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2015-04-01

Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the letter-number span (LNS) task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the forward condition, participants repeated the letters and numbers in the order they were presented. In the reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. Schizophrenia patients performed more poorly than controls, with a larger difference on reorder than forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke. Copyright © 2014 Elsevier B.V. All rights reserved.

Public stigma and schizophrenia in São Paulo city.

PubMed

Peluso, Erica Toledo Piza; Blay, Sérgio Luís

2011-06-01

To assess public stigma in relation to people with schizophrenia and possible factors associated with this phenomenon. A cross-sectional study was conducted with a probabilistic sample of 500 individuals who live in the city of São Paulo, Brazil, and are aged between 18 and 65 years. A structured questionnaire was used, and it was applied in person. Questionnaire began with the presentation of a vignette describing an individual with schizophrenia (according to DSM-IV and ICD-10 criteria). This was followed by questions that assessed perceived negative reactions and discrimination, perceived dangerousness and emotional reactions in relation to the case presented in the vignette. People with schizophrenia were perceived as potentially dangerous by 74.2% of interviewees. In addition, 59.0% of the sample perceived them as capable of arousing negative reactions, and 57.2% as capable of arousing discrimination in society. However, emotional reactions reported by the interviewees themselves were mainly pro-social in nature. The most important factors associated with these responses were: attribution of "biological" causes and perceived dangerousness. This study indicated that beliefs related to public stigma towards people with schizophrenia are commonly held in São Paulo city. An important focus for future studies is to investigate the scope and impact of public stigma on the everyday experiences of people with schizophrenia in the Brazilian context.

Identifying aspects of neighbourhood deprivation associated with increased incidence of schizophrenia.

PubMed

Bhavsar, Vishal; Boydell, Jane; Murray, Robin; Power, Paddy

2014-06-01

Several studies have found an association between area deprivation and incidence of schizophrenia. However, not all studies have concurred and definitions of deprivation have varied between studies. Relative deprivation and inequality seem to be particularly important, but which aspects of deprivation or how this effect might operate is not known. The Lambeth Early Onset case register is a database of all cases of first episode psychosis aged 16 to 35years from the London Borough of Lambeth, a highly urban area. We identified 405 people with first onset schizophrenia who presented between 2000 and 2007. We calculated the overall incidence of first onset schizophrenia and tested for an association with area-level deprivation, using a multi-domain index of deprivation (IMD 2004). Specific analyses into associations with individual sub-domains of deprivation were then undertaken. Incidence rates, directly standardized for age and gender, were calculated for Lambeth at two geographical levels (small and large neighbourhood level). The Poisson regression model predicting incidence rate ratios for schizophrenia using overall deprivation score was statistically significant at both levels after adjusting for ethnicity, ethnic density, population density and population turnover. The incidence rate ratio for electoral ward deprivation was 1.03 (95% CI=1.004-1.04) and for the super output area deprivation was 1.04 (95% CI=1.02-1.06). The individual domains of crime, employment deprivation and educational deprivation were statistically significant predictors of incidence but, after adjusting for the other domains as well as age, gender, ethnicity and population density, only crime and educational deprivation, remained statistically significant. Low income, poor housing and deprived living environment did not predict incidence. In a highly urban area, an association was found between area-level deprivation and incidence of schizophrenia, after controlling for age, gender, ethnicity and population density; high crime and low levels of education accounted for this. As both of these are potentially modifiable, this suggests a possible means to reduce the incidence of schizophrenia. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case-control study.

PubMed

Cao, Bing; Wang, Dongfang; Brietzke, Elisa; McIntyre, Roger S; Pan, Zihang; Cha, Danielle; Rosenblat, Joshua D; Zuckerman, Hannah; Liu, Yaqiong; Xie, Qing; Wang, Jingyu

2018-05-23

Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty-five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography-tandem mass spectrometry (LC-MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, L-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia.

Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia.

PubMed

Takeda, Mayu; Ohnuma, Tohru; Takeuchi, Masayoshi; Katsuta, Narimasa; Maeshima, Hitoshi; Takebayashi, Yuto; Higa, Motoyuki; Nakamura, Toru; Nishimon, Shohei; Sannohe, Takahiro; Hotta, Yuri; Hanzawa, Ryo; Higashiyama, Ryoko; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-ichi; Tomino, Yasuhiko; Arai, Heii

2015-04-23

Recent cross-sectional and longitudinal studies indicate that measurements of peripheral blood carbonyl stress markers such as the advanced glycation end product (AGE) pentosidine and the reactive carbonyl-detoxifying B6 vitamin pyridoxal could be used as therapeutic biological markers in subpopulations of schizophrenia patients. Glyceraldehyde-derived AGEs (Glycer-AGE) have strong neurotoxicity, and soluble receptors for AGEs (sRAGE) may ameliorate the effects of AGEs. In the present study, we measured Glycer-AGEs and sRAGE levels to determine their potential as diagnostic, therapeutic, or clinical biological markers in patients with schizophrenia. After enrollment of 61 admitted Japanese patients with acute schizophrenia and 39 healthy volunteers, 54 patients were followed up from the acute stage to remission. Serum biomarkers were measured in blood samples taken before breakfast using competitive enzyme-linked immunosorbent assays, and Glycer-AGEs were significantly higher and sRAGE levels were significantly lower in patients with acute schizophrenia than in healthy controls. Glycer-AGEs/sRAGE ratios were also higher in schizophrenia patients and were stable during the clinical course. Furthermore, discriminant analyses confirmed that Glycer-AGEs and Glycer-AGEs/sRAGE ratios are significant diagnostic markers for schizophrenia, and distinguished between patients and healthy controls in 70.0% of cases. However, these markers of carbonyl stress were not correlated with clinical features, including disease severity, or with daily chlorpromazine doses. These data indicate the potential of Glycer-AGEs, RAGEs, and their relative ratios as diagnostic markers for patients with schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

MCP-1 gene (SCYA2) and schizophrenia: a case-control association study.

PubMed

Mundo, Emanuela; Altamura, A Carlo; Vismara, Serena; Zanardini, Roberta; Bignotti, Stefano; Randazzo, Roberto; Montresor, Claudio; Gennarelli, Massimo

2005-01-05

Dysregulation of the inflammatory response system has been linked to the pathophysiology of schizophrenia. Abnormal levels of proinflammatory cytokines and their receptors have been found in peripheral blood and cerebrospinal fluid of schizophrenic patients, suggesting the presence of immune activation. Monocyte chemoattractant protein 1 (MCP-1) influences the expression of cytokines related to T helper responses. MCP-1 also exerts several effects on monocytes, including the expression of several proinflammatory genes. The A-2518G polymorphism of the MCP-1 gene (SCYA2) appears to affect the transcriptional activity and monocyte MCP-1 production. The aim of this case-control study was to investigate the potential role of SCYA2 (A-2518G polymorphism) in conferring susceptibility to schizophrenia and to the resistance to antipsychotic treatment. The sample studied consisted of 191 DSM-IV schizophrenia or schizoaffective disorder (depressive subtype) patients and 161 matched healthy controls. No significant genotypic (chi(2) = 0.278, df = 2, P = 0.986) or allelic (chi(2) = 0.021, df = 1, P = 0.884) association was found between the A-2518G variant of the SCYA2 and the diagnosis. No differences in the age at onset of schizophrenia were found between the three genotype groups identified. Significant genotypic association was found between the A-2518G variant of the SCYA2 and the resistance to antipsychotic treatment (chi(2) = 6.26, df = 2, P = 0.04), with resistant patients more frequently carrying the G allele. The odds ratio associated to the presence of the G allele was 2.39 (95% CI = 1.14-4.98). These data suggest that the A-2518G variant of the SCYA2 has not a major role in the pathogenesis of schizophrenia, while it could be implicated in the resistance to antipsychotic treatment. Copyright 2004 Wiley-Liss, Inc.

The GSK3B gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

PubMed

Chen, Jianhua; Wang, Meng; Waheed Khan, Raja Amjad; He, Kuanjun; Wang, Qingzhong; Li, Zhiqiang; Shen, Jiawei; Song, Zhijian; Li, Wenjin; Wen, Zujia; Jiang, Yiwen; Xu, Yifeng; Shi, Yongyong; Ji, Weidong

2015-10-01

Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia. To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 tag single nucleotide polymorphisms using TaqMan® technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin. We found rs334535 (Pallele=2.79E-03, Pgenotype=5.00E-03, OR=1.429) and rs2199503 (Pallele=0.020, Pgenotype= 0.040, OR=1.157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted Pallele=1.64E-03, adjusted Pgenotype=6.00E-03, OR=0.701) and rs2199503 (adjusted Pallele=0.001, adjusted Pgenotype=0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted Pallele=1.70E-03, adjusted Pgenotype=0.006, OR=1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders. Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references. Copyright © 2015. Published by Elsevier B.V.

No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology in a Mexican population.

PubMed

Tovilla-Zárate, Carlos; Medellín, Beatriz Camarena; Fresán, Ana; López-Narváez, Lilia; Castro, Thelma Beatriz Gonzalez; Juárez Rojop, Isela; Ramírez-Bello, Julián; Genis, Alma; Nicolini, Humberto

2013-02-01

The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. We determined the relation of the COMT Val108/158Met polymorphism with schizophrenia or its symptomatology (negative, disorganized and psychotic dimension). We conducted a case-control study comprising 186 patients with schizophrenia and 247 controls. The diagnosis of schizophrenia was established using the DSM-IV criteria for this illness. The clinical symptomatology was assessed through the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. No significant differences were found in the distribution of alleles (χ2 = 0.01, df = 1, p = 0.90) or genotypes (χ2 = 1.66, df = 2, p = 0.43) between schizophrenic patients and the control group. Multivariate analysis showed that the COMT Val108/158Met polymorphism has no influence in the clinical symptomatology of schizophrenia. Our results showed no association between COMT Val108/158Met and schizophrenia or evidence for an association between COMT and the clinical symptomatology of this illness. This suggests that the COMT gene may not contribute to the risk for schizophrenia among the Mexican population.

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans

PubMed Central

Xu, Bin; Woodroffe, Abigail; Rodriguez-Murillo, Laura; Roos, J. Louw; van Rensburg, Elizabeth J.; Abecasis, Gonçalo R.; Gogos, Joseph A.; Karayiorgou, Maria

2009-01-01

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease. PMID:19805367

[Statistics for initial admission for schizophrenia in hospitals in Costa Rica].

PubMed

Handal, N; Dodds, J H

1997-06-01

The factors that influence hospital admissions for schizophrenia in Costa Rica were investigated in people of both sexes who were admitted for the first time with this diagnosis (codes 295.0 to 295.9 of the International Classification of Diseases, Ninth Revision) in the period 1979 to 1981. Annual incidence rates were calculated using the number of hospitalized cases and the total population of the country. The average annual incidence was found to be 48.2 cases per 100000 inhabitants. High frequencies of first admissions were seen among males 40 to 44 years of age and females 45 to 49. Incidence was highest among unmarried women, followed by divorced women. There was a significant inverse relationship between educational attainment and rates of admission for schizophrenia, and incidence rates were highest among unemployed women and housewives. The association between rate of hospitalization for schizophrenia and 10 characteristics of the cantons was studied by means of logistic regression. Only two variables-the distance between the canton's principal town and the hospital and the volume of coffee harvest per resident-showed a direct significant association with admission rates for schizophrenia. The cantons which had the highest number of births of children who were diagnosed as schizophrenic in adulthood were those closest to the psychiatric hospital and those that had a low level of industrial or agricultural activity, low population density, and high proportions of single or divorced persons.

A Case Report on Management of Father Daughter Incest with Schizophrenia.

PubMed

Soron, Tanjir Rashid

2016-01-01

Incest is a neglected and hidden public health problem. This case is about a patient who was victim of sexual abuse, suffered from schizophrenia and abused his biological daughter. He was physically and sexually abused by seniors and classmates, developed paranoid delusion and auditory hallucination. During the course of the illness, he was hospitalized several times as a case of schizophrenia and sexual dysfunction was his main concern. The patient's illness followed a waxing and waning course. He took medication on on-and-off basis. He abused his biological daughter sexually at the later stage of the illness. Ultimately, the patient attempted suicide after an indecent sexual act with another relative and he was admitted to the hospital. He was treated with risperidone that was titrated to 10 mg per day. After continuing the medication for 2 years he regained a functioning life and remained stable with medication. This case shows the importance of exploring the sexual behavior of the patients and sharing the experience may help in the treatment of schizophrenia patients with incest.

A Case Report on Management of Father Daughter Incest with Schizophrenia

PubMed Central

2016-01-01

Incest is a neglected and hidden public health problem. This case is about a patient who was victim of sexual abuse, suffered from schizophrenia and abused his biological daughter. He was physically and sexually abused by seniors and classmates, developed paranoid delusion and auditory hallucination. During the course of the illness, he was hospitalized several times as a case of schizophrenia and sexual dysfunction was his main concern. The patient's illness followed a waxing and waning course. He took medication on on-and-off basis. He abused his biological daughter sexually at the later stage of the illness. Ultimately, the patient attempted suicide after an indecent sexual act with another relative and he was admitted to the hospital. He was treated with risperidone that was titrated to 10 mg per day. After continuing the medication for 2 years he regained a functioning life and remained stable with medication. This case shows the importance of exploring the sexual behavior of the patients and sharing the experience may help in the treatment of schizophrenia patients with incest. PMID:28050302

Changes in values of cholesterol and tryglicerides after weight loss during treatment with aripiprazole in a patient with schizophrenia - Case report.

PubMed

Uzun, Suzana; Kozumplik, Oliver; Sedić, Biserka

2010-06-01

Metabolic syndrome can contribute to significant morbidity and premature mortality and should be accounted for in the treatment of mental disorders. Patients with schizophrenia are at risk of undetected somatic comorbidity. Patients with schizophrenia have metabolically unfavorable body composition, comprising abdominal obesity, high fat percentage and low muscle mass, leading to increased risk of metabolic and cardiovascular diseases. Smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall cardiovascular disease risk. Side effects of antipsychotics may cause diagnostic problems in deciding regarding the origin of particular symptoms (somatic illness vs. side effects) during treatment of psychotic disorders. Bearing in mind frequent comorbidity between of psychotic and somatic disorders, early recognition of such comorbidity is important, as well as the selection of antipsychotics. The aim of this article is to report a case of changes in values of cholesterol and tryglicerides after weight loss, during treatment with aripiprazole in a patient with schizophrenia. This case report emphasizes the importance of regular monitoring of values of cholesterol and tryglicerides during treatment with antipsychotics.

FoxP2 is significantly associated with schizophrenia and major depression in the Chinese Han population.

PubMed

Li, Tao; Zeng, Zhen; Zhao, Qian; Wang, Ti; Huang, Ke; Li, Junyan; Li, You; Liu, Jie; Wei, Zhiyun; Wang, Yang; Feng, Guoyin; He, Lin; Shi, Yongyong

2013-03-01

The FoxP2 gene, located on 7q31, encodes a transcription factor. It was first discovered through investigations of a large multigenerational family (the KE family) with a rare severe speech and language disorder (Fisher et al., Nat. Genet. 1998;18:168; Lai et al., Nature 2001;413:519). Subsequent studies gave powerful and convincing functional evidence to the connection between FoxP2 and language disorder ( Vernes et al. 2006 ; Groszer et al., Curr Biol 2008;18:354; Vernes et al., New Engl J Med 359(22):2337). Language disorder is commonly considered as a core symptom of schizophrenia and some other mental diseases; thus, we decided to investigate whether the FoxP2 gene played a significant role in schizophrenia, major depression or bipolar disorder in a sample set recruited from the Chinese Han population. In this study, we focused on 12 SNPs in the FoxP2 gene and carried out case-control studies in 1135 schizophrenia patients, 1135 unrelated major depression patients, 1135 unrelated bipolar disorder patients and 1135 unrelated normal controls recruited from the Chinese Han population. We found rs10447760 was significantly associated with schizophrenia (allelic P = 0.00069) and major depression (allelic P = 0.0011). Our study indicated that the rare variant rs10447760 in FoxP2 may play an important role in schizophrenia and major depression in the Chinese Han population.

Genetic vulnerability and premature death in schizophrenia spectrum disorders: a 28-year follow-up of adoptees in the Finnish Adoptive Family Study of Schizophrenia.

PubMed

Hakko, Helinä; Wahlberg, Karl-Erik; Tienari, Pekka; Räsänen, Sami

2011-09-01

Excess mortality is widely reported among schizophrenia patients, but rarely examined in adoption study settings. We investigated whether genetic background plays a role in the premature death of adoptees with schizophrenia. Mortality among 382 adoptees in the Finnish Adoptive Family Study of Schizophrenia was monitored from 1977 to 2005 through the national causes-of-death register. The sample covered 190 adoptees with a high genetic risk of schizophrenia (HR) and 192 with a low risk (LR). Overall mortality among the adoptees did not differ between the HR and LR groups, as 10% and 9% respectively had died during the follow-up, at mean ages of 45 and 46 years. Schizophrenia spectrum disorder was the most significant predictor of premature death in both groups, with dysfunction in the rearing family environment associated with mortality, unnatural deaths and suicides in the HR but not in the LR group. All the suicides involved HR cases. Mortality among the adoptees was not related to genetic factors but to environmental ones. The association of unnatural deaths and suicides with dysfunction in the rearing environment among the HR adoptees may indicate that they had a greater genetically determined vulnerability to environmental effects than their LR counterparts. The genetic and rearing environments can be disentangled in this setting because the biological parents give the offspring their genes and the adoptive parents give them their rearing environment. Our findings add to knowledge of the factors associated with the premature death of adoptees in mid-life.

Balzac's Louis Lambert : schizophrenia before Kraepelin and Bleuler.

PubMed

Dieguez, Sebastian

2013-01-01

Honoré de Balzac (1799-1850) is well known for his penetrating observations and descriptions of the burgeoning social life and emerging modernity of 19th century France. This chapter focuses on the novel Louis Lambert, first published in 1832. It is argued that its main character provides the first complete and convincing description of schizophrenia - 69 years before Kraepelin fully developed the concept of dementia praecox and 76 years before Bleuler coined the word 'schizophrenia'. We consider the history of the concept of schizophrenia and the intriguing possibility that it is a recent disease. Indeed, if schizophrenia had always existed, it would seem odd that Balzac's novel should be the very first convincing and complete literary account of the disease. This claim is examined by a thorough description of Louis Lambert's symptoms as they appear in the text, and compared to other claims of priority (namely, Shakespeare's King Lear and Gogol's Diary of a Madman). The chapter also provides some background on Balzac's relationship with mysticism, mental illness, and the world of psychiatry. We conclude with remarks regarding influences of Louis Lambert, the case for the priority of the novel as the princeps case of schizophrenia, and its relevance to the recency hypothesis of schizophrenia. Copyright © 2013 S. Karger AG, Basel.

S187. SEARCHING FOR BRAIN CO-EXPRESSION MODULES THAT CONTRIBUTE DISPROPORTIONATELY TO THE COMMON POLYGENIC RISK FOR SCHIZOPHRENIA

PubMed Central

Costas, Javier; Paramo, Mario; Arrojo, Manuel

2018-01-01

Abstract Background Genomic research has revealed that schizophrenia is a highly polygenic disease. Recent estimates indicate that at least 71% of genomic segments of 1 Mb include one or more risk loci for schizophrenia (Loh et al., Nature Genet 2015). This extremely high polygenicity represents a challenge to decipher the biological basis of schizophrenia, as it is expected that any set of SNPs with enough size will be associated with the disorder. Among the different gene sets available for study (such as those from Gene Ontology, KEGG pathway, Reactome pathways or protein protein interaction datasets), those based on brain co-expression networks represent putative functional relationships in the relevant tissue. The aim of this work was to identify brain co-expression networks that contribute disproportionately to the common polygenic risk for schizophrenia to get more insight on schizophrenia etiopathology. Methods We analyzed a case -control dataset consisting of 582 schizophrenia patients from Galicia, NW Spain, and 591 ancestrally matched controls, genotyped with the Illumina PsychArray. Using as discovery sample the summary results from the largest GWAS of schizophrenia to date (Psychiatric Genomics Consortium, SCZ2), we generated polygenic risk scores (PRS) in our sample based on SNPs located at genes belonging to brain co-expression modules determined by the CommonMind Consortium (Fromer et al., Nature Neurosci 2016). PRS were generated using the clumping procedure of PLINK, considering several different thresholds to select SNPs from the discovery sample. In order to test if any specific module increased risk to schizophrenia more than expected by their size, we generated up to 10,000 random permutations of the same number of SNPs, matched by frequency, distance to nearest gene, number of SNPs in LD and gene density, using SNPsnap. Results As expected, most modules with enough number of independent SNPs belonging to them showed a significant increase in Nagelkerke’s R2 in our case-control sample after the addition of the module-specific PRS in a logistic regression model. Our permutation strategy revealed that most modules did not show an excess of risk, measured by increase in Nagelkerke’s R2, in comparison to equal number of SNPs with similar characteristics. But one module, M2c from Fromer et al., remained highly significant after multiple tests’ correction. Reactome pathways analysis revealed an over-representation of genes involved in “Neuronal System” and “Axon guidance” among genes from this module. Using the same protocol, we detected that the 84 genes from the neuronal system pathway at this module, representing less than 6% of the genes from the module, explained a higher level of risk than expected. “Voltage-gated Potassium channels” and “Neurexins and neuroligins” are overrepresented among the Neuronal System genes from module M2c. Discussion Here, we show that, in spite of the high polygenicity of schizophrenia, it is possible to identify gene sets contributing disproportionately to total risk, as it was the case for the M2c module from Fromer et al. These authors have previously reported that the M2c module was enriched in GWAS signals, as well as CNVs and rare variants associated with schizophrenia. Therefore, this module shows a disproportionately contribution to schizophrenia risk. Study supported by Grant PI14/01020 from Instituto de Salud Carlos III, Ministry of Health, Spanish Government.

Where's the problem? Considering Laing and Esterson's account of schizophrenia, social models of disability, and extended mental disorder.

PubMed

Cooper, Rachel

2017-08-01

In this article, I compare and evaluate R. D. Laing and A. Esterson's account of schizophrenia as developed in Sanity, Madness and the Family (1964), social models of disability, and accounts of extended mental disorder. These accounts claim that some putative disorders (schizophrenia, disability, certain mental disorders) should not be thought of as reflecting biological or psychological dysfunction within the afflicted individual, but instead as external problems (to be located in the family, or in the material and social environment). In this article, I consider the grounds on which such claims might be supported. I argue that problems should not be located within an individual putative patient in cases where there is some acceptable test environment in which there is no problem. A number of cases where such an argument can show that there is no internal disorder are discussed. I argue, however, that Laing and Esterson's argument-that schizophrenia is not within diagnosed patients-does not work. The problem with their argument is that they fail to show that the diagnosed women in their study function adequately in any environment.

Metabolic syndrome in drug-naïve and drug-free patients with schizophrenia and in their siblings.

PubMed

Enez Darcin, Aslı; Yalcin Cavus, Sercin; Dilbaz, Nesrin; Kaya, Hasan; Dogan, Eylem

2015-08-01

We tested the hypothesis that metabolic disturbances in people with schizophrenia exist as a part of the schizophrenic syndrome, even when the antipsychotic drug effect is eliminated. We aimed to determine the prevalence of metabolic syndrome among patients with schizophrenia who were antipsychotic drug-naive or drug-free and their siblings for comparison with healthy controls. One-hundred-two patients with schizophrenia (drug-naïve or drug-free), 64 siblings and 70 age-matched healthy subjects were recruited for this case-control study. Metabolic syndrome was assessed based on Adult Treatment Panel (ATP) III, adapted ATP III and International Diabetes Federation criteria. Student's t-tests, chi-squared tests, Kruskal-Wallis tests and Bonferroni corrections were used as appropriate. The diagnoses of metabolic syndrome and metabolic disturbances as a subsyndromal state were found to be significantly more frequent in patients and their siblings than in the controls. Low levels of high-density lipoprotein cholesterol and disturbances in blood pressure put the patient group at risk for metabolic syndrome even before they were exposed to antipsychotic drugs. Although antipsychotic drugs have consistently been related to disturbances of glucose and lipid metabolism in patients with schizophrenia, this study showed that patients with schizophrenia and their siblings are already at a high risk for metabolic syndrome independent of any antipsychotic effects. These individuals should be monitored regularly following a diagnosis of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Medications Development for the Treatment of Nicotine Dependence in Individuals with Schizophrenia

PubMed Central

Montoya, Ivan D.; Vocci, Frank

2008-01-01

The development of medications for the treatment of nicotine dependence in patients with schizophrenia is a public health priority due to its high prevalence rates, devastating medical consequences, and difficulty to treat. It has been hypothesized that the high prevalence of nicotine dependence among patients with schizophrenia may be due to a shared neurobiological vulnerability. This shared vulnerability has been evidenced in reports showing that nicotine improves neuropsychological deficits associated with schizophrenia such as in the P50 evoked auditory potentials, spatial working memory, and attention. The common pathophysiologic pathways of smoking and schizophrenia may serve as the basis for the pharmacological evaluation of medications for the treatment of these concurrent disorders. Currently, little research of medications for the treatment of this comorbidity has been conducted. Studies have evaluated the efficacy of smoking cessation medications in patients with schizophrenia. These include the nicotine replacement therapy (patch, nasal spray) and sustained release bupropion. Others have evaluated the anti-smoking effect of medications (e.g., clozapine, haloperidol) used for the treatment of schizophrenia. In both cases, the results have not been conclusive. Newer smoking cessation approaches such as varenicline, selegiline, rimonabant, and nicotine vaccine, among others, have yet to be tested in this population. The purpose of this article is to review the results of the studies conducted to date and propose some potential pharmacotherapies based on the current knowledge of the pathophysiology of both disorders. PMID:19194522

Serious delinquency and later schizophrenia: A nationwide register-based follow-up study of Finnish pretrial 15- to 19-year-old offenders sent for a forensic psychiatric examination.

PubMed

Lindberg, N; Miettunen, J; Heiskala, A; Kaltiala-Heino, R

2017-07-01

Aggressive and disruptive behaviors often precede the onset of schizophrenia. In this register-based follow-up study with a case-control design, we wanted to investigate if serious delinquency was associated with future diagnoses of schizophrenia or schizoaffective disorder (here, broadly defined schizophrenia) among a nationwide consecutive sample of 15- to 19-year-old Finnish delinquents sent for a forensic psychiatric examination in 1989-2010. The sample comprised 313 delinquents with no past or current psychotic disorder. For each delinquent, four age-, gender- and place of birth -matched controls were randomly selected from the Central Population Register. Five controls (0.4%) had been treated for schizophrenia before their respective index-dates and were thus excluded from further analysis, leaving us with a control population of 1247 individuals. The subjects were followed till death, emigration or the end of 2015, whichever occurred first. Diagnoses were obtained from the Care Register for Health Care. Forty (12.8%) of the delinquents and 11 (0.9%) of the controls were diagnosed with schizophrenia later in life (HR 16.6, 95% CI 8.53-32.39, P<0.001). Almost half of the pretrial adolescents with later schizophrenia were diagnosed within 5years of the forensic psychiatric examination, but latency was longer among the other half of the sample, reaching up to 20.5years. The study supports the previous research indicating a potential link between serious delinquency and later schizophrenia. Accurate psychiatric assessments should be made in correctional services but also later in life so that any possible psychotic symptoms can be detected in individuals with a history of serious delinquency even if there were no signs of psychosis before or at the time of the crime. Future research should explore which factors influence the delinquent's risk of developing later schizophrenia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection

PubMed Central

Pardiñas, Antonio F.; Holmans, Peter; Pocklington, Andrew J.; Escott-Price, Valentina; Ripke, Stephan; Carrera, Noa; Legge, Sophie E.; Bishop, Sophie; Cameron, Darren; Hamshere, Marian L.; Han, Jun; Hubbard, Leon; Lynham, Amy; Mantripragada, Kiran; Rees, Elliott; MacCabe, James H.; McCarroll, Steven A.; Baune, Bernhard T.; Breen, Gerome; Byrne, Enda M.; Dannlowski, Udo; Eley, Thalia C.; Hayward, Caroline; Martin, Nicholas G.; McIntosh, Andrew M.; Plomin, Robert; Porteous, David J.; Wray, Naomi R.; Caballero, Armando; Geschwind, Daniel H.; Huckins, Laura M.; Ruderfer, Douglas M.; Santiago, Enrique; Sklar, Pamela; Stahl, Eli A.; Won, Hyejung; Agerbo, Esben; Als, Thomas D.; Andreassen, Ole A.; Bækvad-Hansen, Marie; Mortensen, Preben Bo; Pedersen, Carsten Bøcker; Børglum, Anders D.; Bybjerg-Grauholm, Jonas; Djurovic, Srdjan; Durmishi, Naser; Pedersen, Marianne Giørtz; Golimbet, Vera; Grove, Jakob; Hougaard, David M.; Mattheisen, Manuel; Molden, Espen; Mors, Ole; Nordentoft, Merete; Pejovic-Milovancevic, Milica; Sigurdsson, Engilbert; Silagadze, Teimuraz; Hansen, Christine Søholm; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Tosato, Sarah; Werge, Thomas; Collier, David A.; Rujescu, Dan; Kirov, George; Owen, Michael J.; O’Donovan, Michael C.; Walters, James T. R.

2018-01-01

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population. PMID:29483656

Elevated peripheral cytokines characterize a subgroup of people with schizophrenia displaying poor verbal fluency and reduced Broca's area volume

PubMed Central

Fillman, S G; Weickert, T W; Lenroot, R K; Catts, S V; Bruggemann, J M; Catts, V S; Weickert, C S

2016-01-01

Previous studies on schizophrenia have detected elevated cytokines in both brain and blood, suggesting neuroinflammation may contribute to the pathophysiology in some cases. We aimed to determine the extent to which elevated peripheral cytokine messenger RNA (mRNA) expression: (1) characterizes a subgroup of people with schizophrenia and (2) shows a relationship to cognition, brain volume and/or symptoms. Forty-three outpatients with schizophrenia or schizoaffective disorder and matched healthy controls were assessed for peripheral cytokine mRNAs (interleukin (IL)-1β, IL-2, IL-6, IL-8 and IL-18), intelligence quotient, memory and verbal fluency, symptom severity and cortical brain volumes integral to language (that is, Broca's and Wernicke's areas). IL-1β mRNA levels were 28% increased in schizophrenia compared with controls (t(82)=2.64, P<0.01). Using a two-step clustering procedure, we identified a subgroup of people displaying relatively elevated cytokine mRNA levels (17/43 people with schizophrenia and 9/42 controls). Individuals with schizophrenia in the elevated cytokine subgroup performed significantly worse than the low-cytokine subgroup on verbal fluency (F(1,40)=15.7, P<0.001). There was a 17% volume reduction of the left pars opercularis (POp) (Broca's area) in patients with elevated cytokines compared with patients with lower cytokines (F(1,29)=9.41, P=0.005). Negative linear relationships between IL-1β mRNA levels and both verbal fluency and left POp volume were found in schizophrenia. This study is among the first to link blood biomarkers of inflammation with both cognitive deficits and brain volume reductions in people with schizophrenia, supporting that those with elevated cytokines represent a neurobiologically meaningful subgroup. These findings raise the possibility that targeted anti-inflammatory treatments may ameliorate cognitive and brain morphological abnormalities in some people with schizophrenia. PMID:26194183

Chronic non-fatal Datura abuse in a patient of paranoid schizophrenia: a case report.

PubMed

Khanra, Sourav; Khess, C R J; Srivastava, Naveen

2015-04-01

A range of psychoactive substances used by patients suffering from schizophrenia varies and may include those which are fatal and may cause serious toxicity leading to death. We here present a case report of a patient suffering from paranoid schizophrenia, who was abusing Datura stramonium over a prolonged period. A 32 year old male presented with aggressive behaviour, irritability for 6 years and regular intake of Datura seeds for 3 years. After taking detailed history and mental status examination (MSE), diagnoses of paranoid schizophrenia and mental and behavioral disorder due to use of hallucinogen were made. He had shown improvement on standard treatment with antipsychotics. D. stramonium is recognized among emerging new psychoactive substances being used across the world. Among various theories we discuss self-medication hypothesis as a mediating factor for this case. Though D. stramonium is notorious for its life threatening sequelae, clinicians should be aware of its chronic abuse as self-medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Serum vitamin D and hippocampal gray matter volume in schizophrenia.

PubMed

Shivakumar, Venkataram; Kalmady, Sunil V; Amaresha, Anekal C; Jose, Dania; Narayanaswamy, Janardhanan C; Agarwal, Sri Mahavir; Joseph, Boban; Venkatasubramanian, Ganesan; Ravi, Vasanthapuram; Keshavan, Matcheri S; Gangadhar, Bangalore N

2015-08-30

Disparate lines of evidence including epidemiological and case-control studies have increasingly implicated vitamin D in the pathogenesis of schizophrenia. Vitamin D deficiency can lead to dysfunction of the hippocampus--a brain region hypothesized to be critically involved in schizophrenia. In this study, we examined for potential association between serum vitamin D level and hippocampal gray matter volume in antipsychotic-naïve or antipsychotic-free schizophrenia patients (n = 35). Serum vitamin D level was estimated using 25-OH vitamin D immunoassay. Optimized voxel-based morphometry was used to analyze 3-Tesla magnetic resonance imaging (MRI) (1-mm slice thickness). Ninety-seven percent of the schizophrenia patients (n = 34) had sub-optimal levels of serum vitamin D (83%, deficiency; 14%, insufficiency). A significant positive correlation was seen between vitamin D and regional gray matter volume in the right hippocampus after controlling for age, years of education and total intracranial volume (Montreal Neurological Institute (MNI) coordinates: x = 35, y = -18, z = -8; t = 4.34 pFWE(Corrected) = 0.018). These observations support a potential role of vitamin D deficiency in mediating hippocampal volume deficits, possibly through neurotrophic, neuroimmunomodulatory and glutamatergic effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An investigation of family environmental alteration affecting short-term recovery from Schizophrenia in China.

PubMed

Rong-Min Chen, R M

1995-02-01

It has been hypothesised that change in the family environment affects short-term recovery from schizophrenia. Observation and study of 210 schizophrenic patients who were influenced by family environmental alteration show that the prognosis of schizophrenia caused suddenly by family environmental alteration is better than that of schizophrenia caused by a persistently unfavourable family environment. Hence, we think sudden family environmental alterations do not cause psychorrhoea, but slow family environmental alteration may cause change in the mental state of patients. The prognosis is worse in the countryside than in the city. From the study group, we conclude that the first cure rate was 28%, and that 26% of patients were able to work. This indicates that there were no typical cases of the core pattern of schizophrenia, and that there was a certain potential for recovery. In the future, the emphasis of prevention and treatment must be placed on the countryside, and attention should be paid to the improvement of living and working conditions there, to the correct administration of patients, and to the improvement of recovery measures and therapy. We advocate that efforts should be made in the countryside to raise the national educational and cultural level.

Irony and proverb comprehension in schizophrenia: do female patients "dislike" ironic remarks?

PubMed

Rapp, Alexander M; Langohr, Karin; Mutschler, Dorothee E; Wild, Barbara

2014-01-01

Difficulties in understanding irony and sarcasm are part of the social cognition deficits in patients with schizophrenia. A number of studies have reported higher error rates during comprehension in patients with schizophrenia. However, the relationships of these impairments to schizotypal personality traits and other language deficits, such as the comprehension of proverbs, are unclear. We investigated irony and proverb comprehension in an all-female sample of 20 schizophrenia patients and 27 matched controls. Subjects indicated if a statement was intended to be ironic, literal, or meaningless and furthermore rated the meanness and funniness of the stimuli and certainty of their decision. Patients made significantly more errors than controls did. Globally, there were no overall differences in the ratings. However, patients rated the subgroup of stimuli with answers given incorrectly as having significantly less meanness and in case of an error indicated a significantly higher certainty than controls. Across all of the study participants, performances in irony (r = -0.51) and proverb (r = 0.56) comprehension were significantly correlated with schizotypal personality traits, suggesting a continuum of nonliteral language understanding. Because irony is so frequent in everyday conversations, this makes irony an especially promising candidate for social cognition training in schizophrenia.

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.

PubMed

Asherson, P; Mant, R; Williams, N; Cardno, A; Jones, L; Murphy, K; Collier, D A; Nanko, S; Craddock, N; Morris, S; Muir, W; Blackwood, B; McGuffin, P; Owen, M J

1998-07-01

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

The role of hippocampus dysfunction in deficient memory encoding and positive symptoms in schizophrenia.

PubMed

Zierhut, Kathrin; Bogerts, Bernhard; Schott, Björn; Fenker, Daniela; Walter, Martin; Albrecht, Dominik; Steiner, Johann; Schütze, Hartmut; Northoff, Georg; Düzel, Emrah; Schiltz, Kolja

2010-09-30

Declarative memory disturbances, known to substantially contribute to cognitive impairment in schizophrenia, have previously been attributed to prefrontal as well as hippocampal dysfunction. To characterize the role of prefrontal and mesolimbic/hippocampal dysfunction during memory encoding in schizophrenia. Neuronal activation in schizophrenia patients and controls was assessed using functional magnetic resonance imaging (fMRI) during encoding of words in a deep (semantic judgement) and shallow (case judgment) task. A free recall (no delay) and a recognition task (24h delay) were performed. Free recall, but not recognition performance was reduced in patients. Reduced performance was correlated with positive symptoms which in turn were related to increased left hippocampal activity during successful encoding. Furthermore, schizophrenia patients displayed a hippocampal hyperactivity during deep encoding irrespective of encoding success along with a reduced anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (DMPFC) activity in successful encoding but an intact left inferior frontal cortex (LIFC) activity. This study provides the first evidence directly linking positive symptoms and memory deficits to dysfunctional hippocampal hyperactivity. It thereby underscores the pivotal pathophysiological role of a hyperdopaminergic mesolimbic state in schizophrenia. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of Antipsychotic Drugs for 24-Month Maintenance Treatment in First-Episode Schizophrenia: Evidence From a Community-Based "Real-World" Study.

PubMed

Zhang, Chen; Chen, Mei-Juan; Wu, Guo-Jun; Wang, Zuo-Wei; Rao, Shun-Zeng; Zhang, Yi; Yi, Zheng-Hui; Yang, Wei-Min; Gao, Ke-Ming; Song, Li-Sheng

2016-11-01

Maintenance treatment of schizophrenia with antipsychotic medications has become a standard for the prevention of psychotic relapse. However, little is known about the effectiveness of antipsychotic drugs for maintenance treatment in "real-world" populations with schizophrenia. We carried out a prospective study to assess the effectiveness of the most frequently prescribed antipsychotic drugs in the maintenance treatment of schizophrenia from 2 community settings. This study was conducted from October 2011 to December 2014. All participants were diagnosed with schizophrenia according to DSM-IV, were treated with an antipsychotic monotherapy, and were registered in a case management program with monthly monitoring for 24 months. The primary outcome measure, Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales were used to evaluate symptom severity and treatment response. The Personal and Social Performance scale (PSP) was used to evaluate the patients' social functioning. The Medication Adherence Rating Scale (MARS) was used to assess medication adherence behavior. On the basis of antipsychotic used at baseline, patients were clustered into 7 groups: aripiprazole (n = 21), clozapine (n = 84), chlorpromazine (n = 61), olanzapine (n = 34), perphenazine (n = 21), quetiapine (n = 27), and risperidone (n = 99). Of the 347 patients enrolled in the study, 312 completed the 24-month follow-up. There were no significant differences among the treatment groups in the PANSS total and subscale scores or the CGI-S and CGI-I scores over 24 months (all P values > .05). There were also no significant differences in interactions between PSP scores and antipsychotic drugs (P = .17). The remission rates increased as the follow-time lapsed in all groups, but no significant difference was observed in remission rates at each time point among the 7 groups (P values > .05). At the endpoint, MARS total scores were over 6, but did not significantly differ among the studied drugs (P = .24). These findings suggest that antipsychotic drugs can achieve equivalent effectiveness in maintenance treatment of first-episode schizophrenia through a well-organized case management program and family participation. © Copyright 2016 Physicians Postgraduate Press, Inc.

Updating the mild encephalitis hypothesis of schizophrenia.

PubMed

Bechter, K

2013-04-05

Schizophrenia seems to be a heterogeneous disorder. Emerging evidence indicates that low level neuroinflammation (LLNI) may not occur infrequently. Many infectious agents with low overall pathogenicity are risk factors for psychoses including schizophrenia and for autoimmune disorders. According to the mild encephalitis (ME) hypothesis, LLNI represents the core pathogenetic mechanism in a schizophrenia subgroup that has syndromal overlap with other psychiatric disorders. ME may be triggered by infections, autoimmunity, toxicity, or trauma. A 'late hit' and gene-environment interaction are required to explain major findings about schizophrenia, and both aspects would be consistent with the ME hypothesis. Schizophrenia risk genes stay rather constant within populations despite a resulting low number of progeny; this may result from advantages associated with risk genes, e.g., an improved immune response, which may act protectively within changing environments, although they are associated with the disadvantage of increased susceptibility to psychotic disorders. Specific schizophrenic symptoms may arise with instances of LLNI when certain brain functional systems are involved, in addition to being shaped by pre-existing liability factors. Prodrome phase and the transition to a diseased status may be related to LLNI processes emerging and varying over time. The variability in the course of schizophrenia resembles the varying courses of autoimmune disorders, which result from three required factors: genes, the environment, and the immune system. Preliminary criteria for subgrouping neurodevelopmental, genetic, ME, and other types of schizophrenias are provided. A rare example of ME schizophrenia may be observed in Borna disease virus infection. Neurodevelopmental schizophrenia due to early infections has been estimated by others to explain approximately 30% of cases, but the underlying pathomechanisms of transition to disease remain in question. LLNI (e.g. from reactivation related to persistent infection) may be involved and other pathomechanisms including dysfunction of the blood-brain barrier or the blood-CSF barrier, CNS-endogenous immunity and the volume transmission mode balancing wiring transmission (the latter represented mainly by synaptic transmission, which is often described as being disturbed in schizophrenia). Volume transmission is linked to CSF signaling; and together could represent a common pathogenetic link for the distributed brain dysfunction, dysconnectivity, and brain structural abnormalities observed in schizophrenia. In addition, CSF signaling may extend into peripheral tissues via the CSF outflow pathway along brain nerves and peripheral nerves, and it may explain the peripheral topology of neuronal dysfunctions found, like in olfactory dysfunction, dysautonomia, and even in peripheral tissues, i.e., the muscle lesions that were found in 50% of cases. Modulating factors in schizophrenia, such as stress, hormones, and diet, are also modulating factors in the immune response. Considering recent investigations of CSF, the ME schizophrenia subgroup may constitute approximately 40% of cases. Copyright © 2012 Elsevier Inc. All rights reserved.

"To Give an Outsider an Idea of What It Could Be Like": A Case Study of the Creative Representation of Hearing Voices

ERIC Educational Resources Information Center

Flavin, Michael; James, Bethany

2018-01-01

This paper reports on a case study which aims to recreate the hearing voices symptom in schizophrenia. The case study was submitted for a co-curricular module at King's College London by a first-year undergraduate Music student, Bethany James, and was created using the web application, Mahara. The core of the case study consists of a soundscape of…

Basic self-disturbance predicts psychosis onset in the ultra high risk for psychosis "prodromal" population.

PubMed

Nelson, Barnaby; Thompson, Andrew; Yung, Alison R

2012-11-01

Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to a disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. In this study, we investigated the presence of basic self-disturbance in an "ultra high risk" (UHR) for psychosis sample compared with a healthy control sample and whether it predicted transition to psychotic disorder. Forty-nine UHR patients and 52 matched healthy control participants were recruited to the study. Participants were assessed for basic self-disturbance using the Examination of Anomalous Self-Experience (EASE) instrument. UHR participants were followed for a mean of 569 days. Levels of self-disturbance were significantly higher in the UHR sample compared with the healthy control sample (P < .001). Cox regression indicated that total EASE score significantly predicted time to transition (P < .05) when other significant predictors were controlled for. Exploratory analyses indicated that basic self-disturbance scores were higher in schizophrenia spectrum cases, irrespective of transition to psychosis, than nonschizophrenia spectrum cases. The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further "closing in" on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders. This may be of practical value by reducing inclusion of "false positive" cases in UHR samples and of theoretical value by shedding light on core phenotypic features of schizophrenia spectrum pathology.

No significant association between the genetic polymorphisms in the GSK-3 beta gene and schizophrenia in the Chinese population.

PubMed

Meng, Junwei; Shi, Yongyong; Zhao, Xinzhi; Zhou, Jian; Zheng, Yonglan; Tang, Ruqi; Ma, Gang; Zhu, Xuming; He, Zangdong; Wang, Zhe; Xu, Yifeng; Feng, Guoyin; He, Lin

2008-04-01

The GSK-3 beta gene encodes a protein kinase which is abundant in the brain, and its product is involved in signal transduction cascades of neuronal cell development, energy metabolism and body pattern formation. Previous studies have suggested that GSK-3 beta might act as a potential candidate locus for schizophrenia susceptibility. We genotyped six SNPs within the gene and conducted a case-control study involving 329 schizophrenic patients and 288 healthy subjects in the Chinese population. We examined allele and genotype frequencies and haplotype distributions in the subtype of paranoid schizophrenic patients as well as schizophrenic subjects in general. Our results fail to replicate the association of the GSK-3 beta gene with susceptibility to schizophrenia in the Chinese population.

The use of electroconvulsive therapy in atypical psychotic presentations: a case review.

PubMed

Montgomery, John H; Vasu, Devi

2007-10-01

Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial.CASE REPORTS HAVE SUGGESTED A ROLE FOR ECT IN TWO SPECIFIC ATYPICAL PSYCHOTIC DISORDERS: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis.

A manual-based individual therapy to improve metacognition in schizophrenia: protocol of a multi-center RCT

PubMed Central

2014-01-01

Background Metacognitive dysfunction has been widely recognized as a feature of schizophrenia. As it is linked with deficits in several aspects of daily life functioning, improvement of metacognition may lead to improvement in functioning. Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia; multiple case reports and a pilot study show promising results. The present study aims to measure the effectiveness of an individual, manual-based therapy (Metacognitive Reflection and Insight Therapy, MERIT) in improving metacognition in patients with schizophrenia. We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning, experience of symptoms, quality of life, depression, work readiness, insight and experience of stigma. Methods/Design MERIT is currently evaluated in a multicenter randomized controlled trial. Thirteen therapists in six mental health institutions in the Netherlands participate in this study. Patients are randomly assigned to either MERIT or the control condition: treatment as usual (TAU). Discussion If proven effective, MERIT can be a useful addition to the care for schizophrenia patients. The design brings along some methodological difficulties, these issues are addressed in the discussion of this paper. Trial registration Current Controlled Trials: ISRCTN16659871. PMID:24490942

Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update.

PubMed

McGrath, John J; Burne, Thomas H; Féron, François; Mackay-Sim, Allan; Eyles, Darryl W

2010-11-01

There is an urgent need to generate and test candidate risk factors that may explain gradients in the incidence of schizophrenia. Based on clues from epidemiology, we proposed that developmental vitamin D deficiency may contribute to the risk of developing schizophrenia. This hypothesis may explain diverse epidemiological findings including season of birth, the latitude gradients in incidence and prevalence, the increased risk in dark-skinned migrants to certain countries, and the urban-rural gradient. Animal experiments demonstrate that transient prenatal hypovitaminosis D is associated with persisting changes in brain structure and function, including convergent evidence of altered dopaminergic function. A recent case-control study based on neonatal blood samples identified a significant association between neonatal vitamin D status and risk of schizophrenia. This article provides a concise summary of the epidemiological and animal experimental research that has explored this hypothesis.

Exposure to herpes simplex virus type 1 and cognitive impairments in individuals with schizophrenia.

PubMed

Prasad, Konasale M; Watson, Annie M M; Dickerson, Faith B; Yolken, Robert H; Nimgaonkar, Vishwajit L

2012-11-01

Latent infection with neurotropic herpes viruses, such as herpes simplex virus, type 1 (HSV1), has been generally considered benign in most immunocompetent individuals except for rare cases of encephalitis. However, several recent studies have shown impaired cognitive functions among individuals with schizophrenia exposed to HSV1 compared with schizophrenia patients not exposed to HSV1. Such impairments are robust and are prominently observed in working memory, verbal memory, and executive functions. Brain regions that play a key role in the regulation of these domains have shown smaller volumes, along with correlation between these morphometric changes and cognitive impairments in schizophrenia. One study noted temporal decline in executive function and gray matter loss among HSV1-exposed first-episode antipsychotic-naïve schizophrenia patients. Furthermore, a proof-of-concept double-blind placebo-controlled trial indicated improvement in cognitive performance following supplemental anti-herpes-specific medication among HSV1 seropositive schizophrenia patients. Cross-sectional studies have also identified an association between HSV1 exposure and lesser degrees of cognitive impairment among healthy control individuals and patients with bipolar disorder. These studies fulfill several Bradford-Hill criteria, suggesting etiological links between HSV1 exposure and cognitive impairment. Exposure to other human herpes viruses such as cytomegalovirus and herpes simplex virus type 2 (HSV2) may also be associated with cognitive impairment, but the data are less consistent. These studies are reviewed critically and further lines of enquiry recommended. The results are important from a public health perspective, as HSV1 exposure is highly prevalent in many populations.

Exposure to Herpes Simplex Virus Type 1 and Cognitive Impairments in Individuals With Schizophrenia

PubMed Central

Prasad, Konasale M.; Watson, Annie M. M.; Dickerson, Faith B.; Yolken, Robert H.; Nimgaonkar, Vishwajit L.

2012-01-01

Latent infection with neurotropic herpes viruses, such as herpes simplex virus, type 1 (HSV1), has been generally considered benign in most immunocompetent individuals except for rare cases of encephalitis. However, several recent studies have shown impaired cognitive functions among individuals with schizophrenia exposed to HSV1 compared with schizophrenia patients not exposed to HSV1. Such impairments are robust and are prominently observed in working memory, verbal memory, and executive functions. Brain regions that play a key role in the regulation of these domains have shown smaller volumes, along with correlation between these morphometric changes and cognitive impairments in schizophrenia. One study noted temporal decline in executive function and gray matter loss among HSV1-exposed first-episode antipsychotic-naïve schizophrenia patients. Furthermore, a proof-of-concept double-blind placebo-controlled trial indicated improvement in cognitive performance following supplemental anti-herpes–specific medication among HSV1 seropositive schizophrenia patients. Cross-sectional studies have also identified an association between HSV1 exposure and lesser degrees of cognitive impairment among healthy control individuals and patients with bipolar disorder. These studies fulfill several Bradford-Hill criteria, suggesting etiological links between HSV1 exposure and cognitive impairment. Exposure to other human herpes viruses such as cytomegalovirus and herpes simplex virus type 2 (HSV2) may also be associated with cognitive impairment, but the data are less consistent. These studies are reviewed critically and further lines of enquiry recommended. The results are important from a public health perspective, as HSV1 exposure is highly prevalent in many populations. PMID:22490995

Investigating the benefits of sport participation for individuals with schizophrenia: a systematic review.

PubMed

Soundy, Andrew; Roskell, Carolyn; Stubbs, Brendon; Probst, Michel; Vancampfort, Davy

2015-03-01

The purpose of this review was to consider the impact of being introduced to a sport and sport participation on (a) weight loss and psychiatric symptoms, (b) any other health benefits in people with schizophrenia, supported by quantitative and qualitative findings. A systematic review in accordance with the PRISMA statement was conducted. Searches were undertaken in January 2014. Articles were eligible that (1) considered the effect (quantitative studies) and experience (qualitative and case studies) of either; being introduced to a 'sport' or undertaking a sport activity, (2) included >85% of patients diagnosed with schizophrenia or schizo-affective spectrum disorders according to recognised criteria. A total of 10 studies including 5 trials (2*pre-experimental, 2*controlled trials, 1*randomised control trial), 2 qualitative studies and 3 case studies were included (n=185). Two out of 3 studies that considered weight as an outcome measure reported significant reductions in weight and psychiatric symptoms following sports participation. The mean reduction in body mass index (BMI) ranged from -0.7kg.m2 (p<0.001) following 12 weeks of basketball to -1.33 kg.m2 (p<0.001) after 12-weeks of soccer. The mean reduction in the Positive and Negative Symptoms score ranged from 2.4 points (F=-19.0, p<0.001) following 12 weeks of basketball to 7.4 points (t=-5.0, p<0.001) following a 40 week programme of horse riding. A range of secondary health and wellbeing outcomes identified some significant results. Qualitative findings showed that participants had positive experiences from participating in sports. Sport participation may result in reduced BMI and psychiatric symptoms in patients with schizophrenia. Sport has the potential to improve an individual's quality of life through providing a meaningful normalizing activity that leads to achievement, success and satisfaction. Well-designed randomised controlled trials are required to fully determine the health effects of sports participation in schizophrenia.

Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

PubMed

Ruderfer, Douglas M; Fanous, Ayman H; Ripke, Stephan; McQuillin, Andrew; Amdur, Richard L; Gejman, Pablo V; O'Donovan, Michael C; Andreassen, Ole A; Djurovic, Srdjan; Hultman, Christina M; Kelsoe, John R; Jamain, Stephane; Landén, Mikael; Leboyer, Marion; Nimgaonkar, Vishwajit; Nurnberger, John; Smoller, Jordan W; Craddock, Nick; Corvin, Aiden; Sullivan, Patrick F; Holmans, Peter; Sklar, Pamela; Kendler, Kenneth S

2014-09-01

Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.

The impact of substance use on brain structure in people at high risk of developing schizophrenia.

PubMed

Welch, Killian A; McIntosh, Andrew M; Job, Dominic E; Whalley, Heather C; Moorhead, Thomas W; Hall, Jeremy; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

2011-09-01

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

Electroconvulsive therapy (ECT) for catatonia in a patient with schizophrenia and synthetic cannabinoid abuse: a case report.

PubMed

Leibu, Evan; Garakani, Amir; McGonigle, Daniel P; Liebman, Lauren S; Loh, Daniella; Bryson, Ethan O; Kellner, Charles H

2013-12-01

We present the case of a young man with a long-standing history of schizophrenia who presented with severe and life-threatening catatonia in the setting of synthetic cannabis use who was successfully treated with electroconvulsive therapy. To our knowledge, this is the first reported case of severe and persistent catatonia in the setting of synthetic cannabis use and the first documented successful treatment.

Association of BDNF gene polymorphisms with schizophrenia and clinical symptoms in a Chinese population.

PubMed

Li, Wenjun; Zhou, Na; Yu, Qiong; Li, Xiaokun; Yu, Yaqin; Sun, Shilong; Kou, Changgui; Chen, Da Chun; Xiu, Mei Hong; Kosten, Thomas R; Zhang, Xiang Yang

2013-09-01

The neurodevelopmental hypothesis is well established in schizophrenia. Accumulating evidence has shown that BDNF may be involved in the pathogenesis of schizophrenia. This study aimed to investigate the potential association of BDNF gene polymorphisms with susceptibility to schizophrenia and with the psychopathological symptoms in patients with schizophrenia in a Han Chinese population. Three polymorphisms (rs6265, rs12273539, and rs10835210) of the BDNF gene were analyzed in a case-control study of 709 Han Chinese individuals (375 patients and 334 controls). The patients' psychopathology was assessed using the positive and negative syndrome scale (PANSS). We found no significant differences in the genotype and allele distributions of all three polymorphisms between the patient and control groups; however, we found a trend toward to significant overall difference in the estimated haplotype frequencies, with more frequent haplotype ATC of rs6265-rs12273539-rs10835210 in the schizophrenic patients than in controls (P = 0.027). The quantitative trait analysis by the UNPHASED program showed significant associations between the rs6265 (A)-rs12273539 (C)-rs10835210 (A) haplotype and negative symptom scores from the PANSS (x(2)  = 5.79, P = 0.016). Our findings suggest that the BDNF gene polymorphisms may play a small effect on susceptibility to schizophrenia, but may contribute to the negative symptoms of the disease. Copyright © 2013 Wiley Periodicals, Inc.

Clinical practice variations in prescribing antipsychotics for patients with schizophrenia.

PubMed

Owen, Richard R; Fischer, Ellen P; Kirchner, JoAnn E; Thrush, Carol R; Williams, D Keith; Cuffel, Brian J; Elliott, Carl E; Booth, Brenda M

2003-01-01

Few studies have examined the variations among individual physicians in prescribing antipsychotics for schizophrenia. This study examined clinical practice variations in the route and dosage of antipsychotic medication prescribed for inpatients with schizophrenia by 11 different psychiatrists. The sample consisted of 130 patients with a DSM-III-R diagnosis of schizophrenia who had received inpatient care at a state hospital or Veterans Affairs medical center in the southeastern United States in 1992-1993. Mixed-effects regression models were developed to explore the influence of individual physicians and hospitals on route of antipsychotic administration (oral or depot) and daily antipsychotic dose, controlling for patient case-mix variables (age, race, sex, duration of illness, symptom severity, and substance-abuse diagnosis). The average daily antipsychotic dose was 1092 +/- 892 chlorpromazine mg equivalents. Almost half of the patients (48%) were prescribed doses above or below the range recommended by current practice guidelines. The proportion of patients prescribed depot antipsychotics was significantly different at the 2 hospitals, as was the antipsychotic dose prescribed at discharge. Individual physicians and patient characteristics were not significantly associated with prescribing practices. These data, which were obtained before clinical practice guidelines were widely disseminated, provide a benchmark against which to examine more current practice variations in antipsychotic prescribing. The results raise several questions about deviations from practice guidelines in the pharmacological treatment of schizophrenia. To adequately assess quality and inform and possibly further develop clinical practice guideline recommendations for schizophrenia, well-designed research studies conducted in routine clinical settings are needed.

The importance of endophenotypes in schizophrenia research.

PubMed

Braff, David L

2015-04-01

Endophenotypes provide a powerful neurobiological platform from which we can understand the genomic and neural substrates of schizophrenia and other common complex neuropsychiatric disorders. The Consortium on the Genetics of Schizophrenia (COGS) has conducted multisite studies on carefully selected key neurocognitive and neurophysiological endophenotypes in 300 families (COGS-1) and then in a follow up multisite case-control study of 2471 subjects (COGS-2). Endophenotypes are neurobiologically informed quantitative measures that show deficits in probands and their first degree relatives. They are more amenable to statistical analysis than are "fuzzy" qualitative clinical traits or confoundingly heterogeneous diagnostic categories. Endophenotypes are also viewed as uniquely informative in traditional diagnosis-based as well as emerging NIMH Research Domain (RDoC) contexts, offering a bridge between the two approaches to psychopathology classification and research. Endo- or intermediate phenotypes are heritable, and in the COGS-1 cohort their level of heritability is in the same range as is the heritability of schizophrenia itself, using the same statistical methods and subjects to assess both. Because we can demonstrate endophenotypes link to both gene networks and neural circuits on the one hand and also to real-life function, endophenotypes provide a critically important bridge for "connecting the dots" between genes, cells, circuits, information processing, neurocognition and functional impairment and personalized treatment selection in schizophrenia patients. By connecting schizophrenia risk genes with neurobiologically informed endophenotypes, and via the use of association, linkage, sequencing, stem cell and other strategies, we can provide our field with new neurobiologically informed information in our efforts to understand and treat schizophrenia. Evolving views, data and new analytic strategies about schizophrenia risk, pathology and treatment are described in this Viewpoint and in the accompanying Special Issue reports. Published by Elsevier B.V.

Association of the IFN-γ (+874A/T) Genetic Polymorphism with Paranoid Schizophrenia in Tunisian Population.

PubMed

Jemli, Achraf; Eshili, Awatef; Trifa, Fatma; Mechri, Anouar; Zaafrane, Ferid; Gaha, Lotfi; Juckel, George; Tensaout, Besma Bel Hadj Jrad

2017-02-01

Since growing evidence suggests a significant role of chronic low-grade inflammation in the physiopathology of schizophrenia, we have hypothesized that functional genetic variant of the IFN gamma (IFN-γ; +874A/T; rs2430561) gene may be involved in the predisposition to schizophrenia. This research is based on a case-control study which aims to identify whether polymorphism of the IFN-γ gene is a risk factor for the development of schizophrenia. The RFLP-PCR genotyping of the IFN-γ gene was conducted on a Tunisian population composed of 218 patients and 162 controls. The IFN-γ (+874A/T) polymorphism analysis showed higher frequencies of minor homozygous genotype (TT) and allele (T) in all patients compared with controls (11.5 vs. 4.9%; p = 0.03, OR = 2.64 and 30.7 vs. 24.1%, p = 0.04, OR = 1.4, respectively). This correlation was confirmed for male but not for female patients. Also, the T allele was significantly more common among patients with paranoid schizophrenia when compared with controls (25.8 vs. 4.9%, p = 0.0001; OR = 6.7). Using the binary regression analysis to eliminate confounding factors as age and sex, only this last association remained significant (p = 0.03; OR = 1.76, CI = 1.05-2.93). In conclusion, our results showed a significant association between +874A/T polymorphism of IFN-γ and paranoid schizophrenia, suggesting that this single nucleotide polymorphism (SNP) or another at proximity could predispose to paranoid schizophrenia. Since the minor allele of this polymorphism was correlated with an increased expression of their product, our study validates the hypothesis of excessive pro-inflammatory cytokine in the physiopathology of paranoid schizophrenia.

Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia

PubMed Central

Borgmann-Winter, Karin E.; Wang, Hoau-Yan; Ray, Rabindranath; Willis, Brooke R.; Moberg, Paul J.; Rawson, Nancy E.; Gur, Raquel E.; Turetsky, Bruce I.; Hahn, Chang-Gyu

2016-01-01

Increasing evidence suggests that olfactory dysfunction is an endophenotype of schizophrenia, and thus the olfactory system can be studied both in relation to this sensory dysfunction and also as a means of examining pathophysiologic mechanisms of schizophrenia. In this study, we examined human olfactory neuroepithelial (ON) biopsy tissues and their in vitro culture cells for ligand-induced guanine nucleotide-binding protein (G protein) activation and downstream signaling. We assessed the binding of a nonhydrolyzable GTP analogue [35S]GTPγS binding to specific G protein subtypes in response to odorants, dopamine, or serotonin in ON cell membranes from matched schizophrenia-control subjects. In response to odorant mixtures, we found decreased [35S]GTPγS binding to Gαs/olf in schizophrenia patients. These changes were not mediated by mRNA expression of key molecules of G protein coupling, including adenylate cyclase III (ACIII), protein kinase A (PKA), protein kinase Cγ (PKCγ), or Gαs or Gαolf in ON cells or ON biopsy tissues. In contrast, dopamine (DA)- and serotonin (5HT)-induced S35-GTPγS binding to Gαs/olf and Gαq/11 were significantly increased in schizophrenia cases, while these parameters were strikingly reduced by in vitro treatment with antipsychotics. Patients with schizophrenia exhibit increases in electrolfactogram (EOG) recordings, suggesting enhanced odorant-induced activation. Our results of decreased odorant-induced G protein activation may point further downstream for underlying mechanisms for increased EOG measures. Increased G protein activation in response to DA and 5HT may suggest increased postreceptor DA or 5HT signaling as an additional mechanism of dopaminergic or serotonergic dysregulation in schizophrenia. PMID:26373539

Changes in event-related potentials in patients with first-episode schizophrenia and their siblings.

PubMed

Yang, Chengqing; Zhang, Tianhong; Li, Zezhi; Heeramun-Aubeeluck, Anisha; Liu, Na; Huang, Nan; Zhang, Jie; He, Leiying; Li, Hui; Tang, Yingying; Chen, Fazhan; Wang, Jijun; Lu, Zheng

2017-01-17

This study aimed to explore the characteristics of event-related potentials induced by facial emotion recognition in patients with first-episode schizophrenia and in their siblings. In this case-control study, 30 first-episode schizophrenia patients, 26 siblings, and 30 healthy controls were enrolled. They completed facial emotion recognition tasks from the Ekman Standard Faces Database as an induction for evoked potentials. Evoked potential data were obtained using a 64-channel electroencephalography system. Average evoked potential waveforms were computed from epochs for each stimulus type. The amplitudes and latency of the event-related potentials for P100 (positive potential 100 ms after stimulus onset), N170 (negative potential 170 ms after stimulus onset), and N250 (fronto-central peak) were investigated at O1, O2, P7, and P8 electrode locations. There were significant differences between the groups for P100 amplitude (F = 11.526, P < 0.001), electrode position (F = 450.592, P < 0.001), emotion (disgust vs. happiness vs. fear) (F = 1722.467, P < 0.001), and emotion intensity (low vs. moderate vs. high) (F = 1737.169, P < 0.001). Post hoc analysis showed significantly larger amplitudes in the schizophrenia group at the O1, O2, P7, and P8 electrode positions. There were no significant differences between the siblings of schizophrenia patients and the healthy controls. Patients with schizophrenia showed abnormalities in P100 amplitude, but similar results were not observed in their siblings. These results provide evidence of dysfunctional event-related potential patterns underlying facial emotion processing in patients with schizophrenia. P100 may be a characteristic index of schizophrenia.

Relative Risk of Acute Myocardial Infarction in People with Schizophrenia and Bipolar Disorder: A Population-Based Cohort Study.

PubMed

Wu, Shu-I; Chen, Su-Chiu; Liu, Shen-Ing; Sun, Fang-Ju; Juang, Jimmy J M; Lee, Hsin-Chien; Kao, Kai-Liang; Dewey, Michael E; Prince, Martin; Stewart, Robert

2015-01-01

Despite high mortality associated with serious mental illness, risk of acute myocardial infarction (AMI) remains unclear, especially for patients with bipolar disorder. The main objective was to investigate the relative risk of AMI associated with schizophrenia and bipolar disorders in a national sample. Using nationwide administrative data, an 11-year historic cohort study was assembled, comprised of cases aged 18 and above who had received a diagnosis of schizophrenia or bipolar disorder, compared to a random sample of all other adults excluding those with diagnoses of serious mental illness. Incident AMI as a primary diagnosis was ascertained. Hazard ratios stratified by age and gender were calculated and Cox regression models were used to adjust for other covariates. A total of 70,225 people with schizophrenia or bipolar disorder and 207,592 people without serious mental illness were compared. Hazard ratios in men adjusted for age, income and urbanization were 1.15 (95% CI 1.01~1.32) for schizophrenia and 1.37 (1.08~1.73)for bipolar disorder, and in women, 1.85 (1.58~2.18) and 1.88(1.47~2.41) respectively. Further adjustment for treated hypertension, diabetes and hyperlipidaemia attenuated the hazard ratio for men with schizophrenia but not the other comparison groups. Hazard ratios were significantly stronger in women than men and were stronger in younger compared to older age groups for both disorders; however, gender modification was only significant in people with schizophrenia, and age modification only significant in people with bipolar disorder. In this large national sample, schizophrenia and bipolar disorder were associated with raised risk of AMI in women and in the younger age groups although showed differences in potential confounding and modifying factors.

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

PubMed

Smeland, Olav B; Frei, Oleksandr; Kauppi, Karolina; Hill, W David; Li, Wen; Wang, Yunpeng; Krull, Florian; Bettella, Francesco; Eriksen, Jon A; Witoelar, Aree; Davies, Gail; Fan, Chun C; Thompson, Wesley K; Lam, Max; Lencz, Todd; Chen, Chi-Hua; Ueland, Torill; Jönsson, Erik G; Djurovic, Srdjan; Deary, Ian J; Dale, Anders M; Andreassen, Ole A

2017-10-01

Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study.

PubMed

Reutfors, Johan; Clapham, Eric; Bahmanyar, Shahram; Brandt, Lena; Jönsson, Erik G; Ekbom, Anders; Bodén, Robert; Ösby, Urban

2016-07-01

This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: implications for the concept of cannabis psychosis.

PubMed

Boydell, J; Dean, K; Dutta, R; Giouroukou, E; Fearon, P; Murray, R

2007-07-01

There is considerable interest in cannabis use in psychosis. It has been suggested that the chronic psychosis associated with cannabis use, is symptomatically distinct from idiopathic schizophrenia. Several studies have reported differences in psychopathology and family history in people with schizophrenia according to whether or not they were cannabis users. We set out to test the hypotheses arising from these studies that cannabis use is associated with more bizarre behaviour, more thought disorder, fewer negative symptoms including blunted affect, more delusions of reference, more paranoid delusions and a stronger family history of schizophrenia. We used a case register that contained 757 cases of first onset schizophrenia, 182 (24%) of whom had used cannabis in the year prior to first presentation, 552 (73%) had not and 3% had missing data. We completed the OPCRIT checklist on all patients and investigated differences in the proportion of people with distractibility, bizarre behaviour, positive formal thought disorder, delusions of reference, well organised delusions, any first rank symptom, persecutory delusions, abusive/accusatory hallucinations, blunted affect, negative thought disorder, any negative symptoms (catatonia, blunted affect, negative thought disorder, or deterioration), lack of insight, suicidal ideation and a positive family history of schizophrenia, using chi square tests. Logistic regression modelling was then used to determine whether prior cannabis use affected the presence of the characteristics after controlling for age, sex and ethnicity. There was no statistically significant effect of cannabis use on the presence of any of the above. There remained however a non-significant trend towards more insight (OR 0.65 p=0.055 for "loss of insight") and a finding of fewer abusive or accusatory hallucinations (OR 0.65 p=0.049) of borderline significance amongst the cannabis users. These were in the hypothesised direction. There was no evidence of fewer negative symptoms or greater family history amongst cannabis users. We found few appreciable differences in symptomatology between schizophrenic patients who were or were not cannabis users. There were no differences in the proportion of people with a positive family history of schizophrenia between cannabis users and non-users. This argues against a distinct schizophrenia-like psychosis caused by cannabis.

Blunted vocal affect and expression is not associated with schizophrenia: A computerized acoustic analysis of speech under ambiguous conditions.

PubMed

Meaux, Lauren T; Mitchell, Kyle R; Cohen, Alex S

2018-05-01

Patients with schizophrenia are consistently rated by clinicians as having high levels of blunted vocal affect and alogia. However, objective technologies have often failed to substantiate these abnormalities. It could be the case that negative symptoms are context-dependent. The present study examined speech elicited under conditions demonstrated to exacerbate thought disorder. The Rorschach Test was administered to 36 outpatients with schizophrenia and 25 nonpatient controls. Replies to separate "perceptual" and "memory" phases were analyzed using validated acoustic analytic methods. Compared to nonpatient controls, schizophrenia patients did not display abnormal speech expression on objective measure of blunted vocal affect or alogia. Moreover, clinical ratings of negative symptoms were not significantly correlated with objective measures. These findings suggest that in patients with schizophrenia, vocal affect/alogia is generally unremarkable under ambiguous conditions. Clarifying the nature of blunted vocal affect and alogia, and how objective measures correspond to what clinicians attend to when making clinical ratings are important directions for future research. Copyright © 2018 Elsevier Inc. All rights reserved.

Education and the public's desire for social distance from people with depression and schizophrenia: the contribution of emotional reactions and causal attributions.

PubMed

von dem Knesebeck, Olaf; Angermeyer, Matthias C; Kofahl, Christopher; Makowski, Anna Christin; Mnich, Eva

2014-08-01

Association between education and desire for social distance from people with mental illness is unclear. (1) Is there an association between education and social distance from people with a depression or schizophrenia? (2) Can this association be explained by beliefs about causes of and emotional reactions to the mental disorders? (3) Are there differences between the two mental disorders? Analyses are based on a telephone survey in two large German cities (Hamburg and Munich, N = 2,014, response rate 51%). Vignettes with typical signs and symptoms suggestive of depression and schizophrenia were presented. Respondents were asked about beliefs about causes of the mental disorders, their emotional reactions and their desire for social distance. Lower education is significantly associated with a stronger tendency for social distance in the case of depression but not in case of schizophrenia, when age and gender are controlled. In case of depression, the association decreases when beliefs about possible causes are additionally controlled. In terms of schizophrenia, associations between education and social distance become stronger when emotional reactions are introduced. Our results underline that campaigns aimed at reducing stigma and social distance should consider specific emotional reactions and information needs of people with low education regarding different mental disorders. © The Author(s) 2013.

Rapid Response of Long-Standing, Treatment-Resistant Non-Catatonic Mutism in Paranoid Schizophrenia with Single ECT session.

PubMed

Dar, Mansoor Ahmad; Rather, Yasir Hassan; Shah, Majid Shafi; Wani, Rayees Ahmad; Hussain, Arshad

2014-11-01

Mutism is a common manifestation of catatonia, but mutism due to other forms of psychopathology and neurological disorders have also been described. Although not common, long-standing mutism has also been a feature of non-catatonic schizophrenia and traditionally responds less to conventional therapies. We describe a rare case of paranoid schizophrenia presenting with continuous mutism for about 4 years. This 26-year-old male had symptoms of schizophrenia without catatonia. After failed trial of adequate pharmacotherapy and psychological intervention and considering his level of dysfunction, he was started on electroconvulsive therapy (ECT). To our surprise, he improved with a single session of ECT while he was on concurrent pharmacotherapy. We also discuss the possible explanation for this rapid effect of ECT in such clinical presentation. To our knowledge, this is the first case of non-catatonic mutism of schizophrenia of this long duration responding so promptly to ECT, although there are other reports as well in literature, but multiple ECT sessions were applied in those cases. Non-catatonic mutism is perhaps presenting as a cultural variant in this part of the world and whenever encountered, ECT should be an option. Further research should be carried out to validate this idea.

Cognitive analysis of schizophrenia risk genes that function as epigenetic regulators of gene expression.

PubMed

Whitton, Laura; Cosgrove, Donna; Clarkson, Christopher; Harold, Denise; Kendall, Kimberley; Richards, Alex; Mantripragada, Kiran; Owen, Michael J; O'Donovan, Michael C; Walters, James; Hartmann, Annette; Konte, Betina; Rujescu, Dan; Gill, Michael; Corvin, Aiden; Rea, Stephen; Donohoe, Gary; Morris, Derek W

2016-12-01

Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription. Evidence now supports some shared genetic aetiology between schizophrenia and intellectual disability. GWAS have identified 108 chromosomal regions associated with schizophrenia risk that span 350 genes. This study identified genes mapping to those loci that have epigenetic functions, and tested the risk alleles defining those loci for association with cognitive deficits. We developed a list of 350 genes with epigenetic functions and cross-referenced this with the GWAS loci. This identified eight candidate genes: BCL11B, CHD7, EP300, EPC2, GATAD2A, KDM3B, RERE, SATB2. Using a dataset of Irish psychosis cases and controls (n = 1235), the schizophrenia risk SNPs at these loci were tested for effects on IQ, working memory, episodic memory, and attention. Strongest associations were for rs6984242 with both measures of IQ (P = 0.001) and episodic memory (P = 0.007). We link rs6984242 to CHD7 via a long range eQTL. These associations were not replicated in independent samples. Our study highlights that a number of genes mapping to risk loci for schizophrenia may function as epigenetic regulators of gene expression but further studies are required to establish a role for these genes in cognition. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Evidence suggesting possible SCA1 gene involvement in schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diehl, S.R.; Wange, S.; Sun, C.

Several findings suggest a possible role for the SCA1 gene on chromosome 6p in some cases of schizophrenia. First, linkage analyses in Irish pedigrees provided LOD scores up to 3.0 for one model tested using microsatellites closely linked to SCA1. Reanalysis of these data using affected sibpair methods yielded a significant result (p = 0.01) for one marker. An attempt to replicate this linkage finding was made using 44 NIMH families (206 individuals, 80 affected) and 12 Utah families (120 individuals, 49 affected). LOD scores were negative in these new families, even allowing for heterogeneity, as were results using affectedmore » sibpair methods. However, one Utah family provided a LOD score of 1.3. We also screened the SCA1 trinucleotide repeat to search for expansions characteristic of this disorder in these families and in 38 additional unrelated schizophrenics. We found 1 schizophrenic with 41 repeats, which is substantially larger than the maximum size of 36 repeats observed in previous studies of several hundred controls. We are now assessing whether the distribution of SCA1 repeats differs significantly in schizophrenia versus controls. Recent reports suggest possible anticipation in schizophrenia (also characteristic of SCA1) and a few cases of psychiatric symptoms suggesting schizophrenia have been observed in the highly related disorder DRPLA (SCA2), which is also based on trinucleotide repeat expansion. These findings suggest that further investigations of this gene and chromosome region may be a priority.« less

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia

PubMed Central

Rees, E; Kirov, G; Walters, J T; Richards, A L; Howrigan, D; Kavanagh, D H; Pocklington, A J; Fromer, M; Ruderfer, D M; Georgieva, L; Carrera, N; Gormley, P; Palta, P; Williams, H; Dwyer, S; Johnson, J S; Roussos, P; Barker, D D; Banks, E; Milanova, V; Rose, S A; Chambert, K; Mahajan, M; Scolnick, E M; Moran, J L; Tsuang, M T; Glatt, S J; Chen, W J; Hwu, H-G; Faraone, Stephen V; Roe, Cheri A; Chandler, Sharon D; Liu, Chih-Min; Liu, Chen-Chung; Yeh, Ling-Ling; Ouyang, Wen-Chen; Chan, Hung-Yu; Chen, Chun-Ying; Neale, B M; Palotie, A; Sklar, P; Purcell, S M; McCarroll, S A; Holmans, P; Owen, M J; O'Donovan, M C

2015-01-01

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband–parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P=1.5 × 10−4). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P=0.018) and de novo mutations (P=0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N=614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios. PMID:26196440

Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta.

PubMed

Shirts, Brian H; Wood, Joel; Yolken, Robert H; Nimgaonkar, Vishwajit L

2006-12-01

Genetic association studies of several candidate cytokine genes have been motivated by evidence of immune dysfunction among patients with schizophrenia. Intriguing but inconsistent associations have been reported with polymorphisms of three positional candidate genes, namely IL1beta, IL1RN, and IL10. We used comprehensive sequencing data from the Seattle SNPs database to select tag SNPs that represent all common polymorphisms in the Caucasian population at these loci. Associations with 28 tag SNPs were evaluated in 478 cases and 501 unscreened control individuals, while accounting for population sub-structure using the genomic control method. The samples were also stratified by gender, diagnostic category, and exposure to infectious agents. Significant association was not detected after correcting for multiple comparisons. However, meta-analysis of our data combined with previously published association studies of rs16944 (IL1beta -511) suggests that the C allele confers modest risk for schizophrenia among individuals reporting Caucasian ancestry, but not Asians (Caucasians, n=819 cases, 1292 controls; p=0.0013, OR=1.24, 95% CI 1.09, 1.41).

Zonisamide-induced weight loss in schizophrenia: case series.

PubMed

Yang, Jaewon; Lee, Moon-Soo; Joe, Sook-Haeng; Jung, In-Kwa; Kim, Seung-Hyun

2010-01-01

Weight gain and metabolic disturbances constitute bothersome problems in schizophrenic patients treated with atypical antipsychotics. Several medications, exercise regimens, and lifestyle changes have been used in attempts to ameliorate these problems. We describe 3 patients with schizophrenia who manifested distinct weight loss and reduction in waist circumference during medication with zonisamide. This report suggests that zonisamide might be associated with weight loss in patients with schizophrenia.

Obstructive sleep apnea and schizophrenia: A systematic review to inform clinical practice.

PubMed

Myles, Hannah; Myles, Nicholas; Antic, Nick A; Adams, Robert; Chandratilleke, Madhu; Liu, Dennis; Mercer, Jeremy; Vakulin, Andrew; Vincent, Andrew; Wittert, Gary; Galletly, Cherrie

2016-01-01

Risk factors for obstructive sleep apnea (OSA) are common in people with schizophrenia. Identification and treatment of OSA may improve physical health in this population; however there are no guidelines to inform screening and management. Systematic review to determine, in people with schizophrenia and related disorders: the prevalence of OSA; the prevalence of OSA compared to general population controls; the physical and psychiatric correlates of OSA, associations between antipsychotic medications and OSA; the impact of treatment of OSA on psychiatric and physical health; and the diagnostic validity of OSA screening tools. Medline, EMBASE, ISI Web of Science and PsycINFO electronic databases. Cohort, case-control and cross-sectional studies and RCTs reporting on prevalence of OSA in subjects with schizophrenia and related disorders were reviewed. The prevalence of OSA varied between 1.6% and 52%. The prevalence of OSA was similar between people with schizophrenia and population controls in two studies. Diagnosis of OSA was associated with larger neck circumference, BMI>25, male sex and age>50years. There were no data on physical or psychiatric outcomes following treatment of OSA. The diagnostic utility of OSA screening tools had not been investigated. OSA may be prevalent and potentially under-recognized in people with schizophrenia. Further research is required to determine utility of OSA screening tools, the relationships between antipsychotic medications and OSA and any benefits of treating OSA. We propose a strategy for the identification of OSA in people with schizophrenia and related disorders. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

[Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

PubMed

Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

2012-06-01

The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia.

PubMed

Bernstein, Hans-Gert; Jauch, Esther; Dobrowolny, Henrik; Mawrin, Christian; Steiner, Johann; Bogerts, Bernhard

2016-09-01

Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.

Genetics of schizophrenia and smoking: an approach to studying their comorbidity based on epidemiological findings

PubMed Central

de Leon, Jose; Diaz, Francisco J.

2012-01-01

The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simultaneously significant within the non-psychiatric controls, the bipolar disorder controls and the schizophrenia cases will be selected. Only those genetic variations that are simultaneously significant in the three hypothesis tests will be tested in the second stage, where the prevalence of the genes must be significantly higher in schizophrenia than in bipolar disorder, and significantly higher in bipolar disorder than in controls. The genes simultaneously significant in the second stage will be included in a third stage where the gene variations must be significantly more frequent in schizophrenia patients who did not start smoking daily until their 20s (late start) versus those who had an early start. Any genetic approach to psychiatric disorders may fail if attention is not given to comorbidity and epidemiological studies that suggest which comorbidities are likely to be explained by genetics and which are not. Our approach, which examines the results of epidemiological studies on comorbidities and then looks for genes that simultaneously satisfy epidemiologically suggested sets of hypotheses, may also apply to the study of other major illnesses. PMID:22190153

[A case of transient auditory agnosia and schizophrenia].

PubMed

Kanzaki, Jin; Harada, Tatsuhiko; Kanzaki, Sho

2011-03-01

We report a case of transient functional auditory agnosia and schizophrenia and discuss their relationship. A 30-year-old woman with schizophrenia reporting bilateral hearing loss was found in history taking to be able to hear but could neither understand speech nor discriminate among environmental sounds. Audiometry clarified normal but low speech discrimination. Otoacoustic emission and auditory brainstem response were normal. Magnetic resonance imaging (MRI) elsewhere evidenced no abnormal findings. We assumed that taking care of her grandparents who had been discharged from the hospital had unduly stressed her, and her condition improved shortly after she stopped caring for them, returned home and started taking a minor tranquilizer.

Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia.

PubMed

Lee, Tae Young; Kim, Minah; Kim, Sung Nyun; Kwon, Jun Soo

2017-01-01

The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status.

An Integrative Psychotherapy Approach to Foster Community Engagement and Rehabilitation in Schizophrenia: A Case Study Illustration.

PubMed

Kukla, Marina; Whitesel, Frankie; Lysaker, Paul H

2016-02-01

This case study illustrates the use of a long-term integrative psychotherapy approach with a middle- aged man with chronic schizophrenia and a mood disorder. The case of "Holst" describes a man with a history of insecure attachment and trauma who later went on to contract a serious chronic illness, precipitating the onset of psychotic symptoms, depression, and chronic suicidal ideation, resulting in multiple hospitalizations. Combining metacognition-oriented therapy with elements of cognitive behavioral therapy and psychiatric rehabilitation, this approach fostered significantly improved community functioning and attainment of personal goals over time. Through the journey of therapy, the patient also developed a more coherent narrative about his life, established a stable sense of self, and became an active agent in the world. This case illustration demonstrates that these three different approaches can be used in a sequential and complementary fashion to foster recovery in the midst of serious physical and mental illness. © 2015 Wiley Periodicals, Inc.

Risk factors for sudden cardiac death among patients with schizophrenia.

PubMed

Hou, Ping-Yi; Hung, Galen Chin-Lun; Jhong, Jia-Rong; Tsai, Shang-Ying; Chen, Chiao-Chicy; Kuo, Chian-Jue

2015-10-01

Patients with schizophrenia suffer from excessive premature mortality, and sudden cardiac death (SCD) is receiving growing attention as a potential cause. The present study investigated the incidence of SCD and its risk factors in a large schizophrenia cohort. We enrolled a consecutive series of 8264 patients diagnosed with schizophrenia (according to DSM-III-R and DSM-IV criteria) who were admitted to a psychiatric center in northern Taiwan from January 1, 1985 through December 31, 2008. By linking with national mortality database, 64 cases of SCD were identified. The standardized mortality ratio (SMR) for SCD was estimated. The cases were matched with controls randomly selected using risk-set sampling in a 1:2 ratio. A standardized chart review process was used to collect socio-demographic and clinical characteristics and the prescribed drugs for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of SCD at the index admission and the latest admission. The SMR for SCD was 4.5. For the clinical profiles at the index admission, physical disease (adjusted risk ratio [aRR]=2.91, P<.01) and aggressive behaviors (aRR=3.99, P<.01) were associated with the risk of SCD. Regarding the latest admission, electrocardiographic abnormalities (aRR=5.46, P<.05) and administration of first-generation antipsychotics (aRR=5.13, P<.01) elevated the risk for SCD. Consistently, aggressive behaviors (aRR=3.26, P<.05) were associated with increased risk as well. Apart from cardiovascular profiles and antipsychotics, physical aggression is a crucial risk factor that deserves ongoing work for clarifying the mechanisms mediating SCD in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Schizophrenia in Croatia: interregional differences in prevalence and a comment on constant incidence.

PubMed Central

Folnegović, Z; Folnegović-Smalc, V

1992-01-01

STUDY OBJECTIVE--The aim was to examine why differences exist in schizophrenia prevalence and risk in some areas of Croatia, when schizophrenia incidence rates do not appear to vary. DESIGN--Areas differing by schizophrenia admission rates in patients born in 1953 and admitted by the age of 31 years are compared using a number of indicators relating both to general population characteristics and to those of schizophrenic cases in these populations. SETTING--The study covers the whole of Croatia (4,601,469 inhabitants, 1981 census). SUBJECTS--By the age of 31 years, out of 80,445 individuals born in Croatia in 1953, 464 were admitted for and diagnosed as having schizophrenia. MAIN RESULTS--Admission risk rates are higher in those parts of Croatia where emigration rates are high and lower where immigration rates are high. There is also a positive correlation with schizophrenia prevalence and manic depressive psychosis rates. There is a negative correlation with age of onset of schizophrenia and with schizophrenic reproduction rates. In the study areas, hospital incidence rates are not significantly different. CONCLUSIONS--Economic migration and negative selection in the domestic population are likely to be the most significant factors leading to differences in schizophrenia prevalence. The approximately equal incidence rates in the population, with different prevalence and admission risks, are linked to differences in the disease onset among schizophrenics with a positive family history for this condition. In other words, these patients, when part of the population with a greater prevalence and a greater hereditary loading, experience the onset more often at an earlier age. Thus they have a lower reproduction rate than in a population with a lower prevalence and a lower hereditary loading. Thus incidence rates in populations with different prevalences and different hereditary loads are maintained roughly equal over generations. Images PMID:1645081

Involvement of PTPN5, the gene encoding the STriatal-Enriched protein tyrosine Phosphatase (STEP), in schizophrenia and cognition

PubMed Central

Pelov, Ilana; Teltsh, Omri; Greenbaum, Lior; Rigbi, Amihai; Kanyas-Sarner, Kyra; Lerer, Bernard; Lombroso, Paul; Kohn, Yoav

2013-01-01

Objective STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific member of the PTP family that has been implicated in learning and memory. In this study, we examined the association of the PTPN5 (protein-tyrosine-phosphatase non-receptor 5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population. Methods A 868 subjects schizophrenia (SZ) case-control study was performed (286 cases and 582 controls). Eleven STEP tagging SNPs were selected, and single markers and haplotypes association analyses were performed. A cognitive variability study included 437 healthy females who completed a computerized cognitive battery. We performed univariate associations between the SNPs and cognitive performance. The possible functional role of these variants was examined by studying their association with gene expression levels in the brain. Results In the SZ study, we found nominal association in the whole sample between rs4075664 and SZ. SZ males showed a more significant association for 3 SNPs (rs4075664, rs2278732, rs4757710). Haplotypes of the studied SNPs were associated with SZ both in the overall sample and within the male sub-sample. Expression analysis provided some support for the effects of the associated SNPs on PTPN5 expression level. The cognitive variability study showed positive associations between PTPN5 SNPs and different cognitive subtests. Principal component analysis demonstrated an “Attention Index” neurocognitive component that was associated with two SNP pairs (rs10832983*rs10766504 and rs7932938*rs4757718). Conclusion The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contributes to aspects of the neuropathology of schizophrenia. PMID:22555153

Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study

PubMed Central

Trotta, Antonella; Iyegbe, Conrad; Di Forti, Marta; Sham, Pak C.; Campbell, Desmond D.; Cherny, Stacey S.; Mondelli, Valeria; Aitchison, Katherine J.; Murray, Robin M.

2016-01-01

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis. PMID:27648571

TESTING HIGH-DIMENSIONAL COVARIANCE MATRICES, WITH APPLICATION TO DETECTING SCHIZOPHRENIA RISK GENES

PubMed Central

Zhu, Lingxue; Lei, Jing; Devlin, Bernie; Roeder, Kathryn

2017-01-01

Scientists routinely compare gene expression levels in cases versus controls in part to determine genes associated with a disease. Similarly, detecting case-control differences in co-expression among genes can be critical to understanding complex human diseases; however statistical methods have been limited by the high dimensional nature of this problem. In this paper, we construct a sparse-Leading-Eigenvalue-Driven (sLED) test for comparing two high-dimensional covariance matrices. By focusing on the spectrum of the differential matrix, sLED provides a novel perspective that accommodates what we assume to be common, namely sparse and weak signals in gene expression data, and it is closely related with Sparse Principal Component Analysis. We prove that sLED achieves full power asymptotically under mild assumptions, and simulation studies verify that it outperforms other existing procedures under many biologically plausible scenarios. Applying sLED to the largest gene-expression dataset obtained from post-mortem brain tissue from Schizophrenia patients and controls, we provide a novel list of genes implicated in Schizophrenia and reveal intriguing patterns in gene co-expression change for Schizophrenia subjects. We also illustrate that sLED can be generalized to compare other gene-gene “relationship” matrices that are of practical interest, such as the weighted adjacency matrices. PMID:29081874

TESTING HIGH-DIMENSIONAL COVARIANCE MATRICES, WITH APPLICATION TO DETECTING SCHIZOPHRENIA RISK GENES.

PubMed

Zhu, Lingxue; Lei, Jing; Devlin, Bernie; Roeder, Kathryn

2017-09-01

Scientists routinely compare gene expression levels in cases versus controls in part to determine genes associated with a disease. Similarly, detecting case-control differences in co-expression among genes can be critical to understanding complex human diseases; however statistical methods have been limited by the high dimensional nature of this problem. In this paper, we construct a sparse-Leading-Eigenvalue-Driven (sLED) test for comparing two high-dimensional covariance matrices. By focusing on the spectrum of the differential matrix, sLED provides a novel perspective that accommodates what we assume to be common, namely sparse and weak signals in gene expression data, and it is closely related with Sparse Principal Component Analysis. We prove that sLED achieves full power asymptotically under mild assumptions, and simulation studies verify that it outperforms other existing procedures under many biologically plausible scenarios. Applying sLED to the largest gene-expression dataset obtained from post-mortem brain tissue from Schizophrenia patients and controls, we provide a novel list of genes implicated in Schizophrenia and reveal intriguing patterns in gene co-expression change for Schizophrenia subjects. We also illustrate that sLED can be generalized to compare other gene-gene "relationship" matrices that are of practical interest, such as the weighted adjacency matrices.

Experiences, perspectives and priorities of people with schizophrenia spectrum disorders regarding sleep disturbance and its treatment: a qualitative study.

PubMed

Faulkner, Sophie; Bee, Penny

2017-05-02

Sleep problems are very common in people with schizophrenia spectrum disorders, and impact negatively on functioning and wellbeing. Research regarding interventions to improve sleep in this population has been lacking. Little is known regarding these patient's perspectives on sleep problems and their treatment, providing very little foundation on which to develop acceptable and patient-centred treatments. This study aims to explore perspectives and priorities of participants with schizophrenia spectrum disorders regarding sleep and sleep disturbance, and their perspectives on existing treatments. An Interpretive Phenomenological Analysis (IPA) study was conducted; data were gathered through in depth interviews with 15 people with schizophrenia spectrum disorders and varying degrees of self-reported sleep disturbance, each case was analysed individually before cross-case comparisons were made. Sleep maintenance and sleep quality were universally valued. Changes to sleep were interpreted as part of a perceived loss of normality relating to diagnosis. Participants differed in the extent of any hopes that sleep would improve. Sleep disturbances were linked to a reduced ability or opportunity to participate in valued activities, and were entangled with self-image due to a wish to be perceived as alert and in control. During difficult times, sleep could be seen as an escape. Concerns were expressed regarding the negative effects of using hypnotics or anti-psychotics to aid sleep, although typically antipsychotics were deemed more acceptable than hypnotics. Concerns regarding barriers to adherence and effectiveness of self-help approaches were common. Non-pharmacological interventions were noted to require a personalised whole-lifestyle approach. This is the first study to explore sleep perspectives in participants with established schizophrenia spectrum disorders, recruited from a population receiving usual care. Findings re-enforce the importance of considering sleep within recovery focused practice. In developing and adapting interventions routine-based approaches should be considered. Approaches should attempt to make gradual changes more easily perceptible, should support motivation for behaviour change, and should consider the impact of regular psychotropic medications.

RARE VARIANTS IN THE NEUROTROPHIN SIGNALING PATHWAY IMPLICATED IN SCHIZOPHRENIA RISK

PubMed Central

Kranz, Thorsten M.; Goetz, Ray R.; Walsh-Messinger, Julie; Goetz, Deborah; Antonius, Daniel; Dolgalev, Igor; Heguy, Adriana; Seandel, Marco; Malaspina, Dolores; Chao, Moses V.

2015-01-01

Multiple lines of evidence corroborate impaired signaling pathways as relevant to the underpinnings of schizophrenia. There has been an interest in neurotrophins, since they are crucial mediators of neurodevelopment and in synaptic connectivity in the adult brain. Neurotrophins and their receptors demonstrate aberrant expression patterns in cortical areas for schizophrenia cases in comparison to control subjects. There is little known about the contribution of neurotrophin genes in psychiatric disorders. To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis. We herein report rare missense polymorphisms and novel missense mutations in neurotrophin receptor signaling pathway genes. Furthermore, we observed that several genes have a higher propensity to harbor missense coding variants than others. Based on this initial analysis we suggest that rare variants and missense mutations in neurotrophin genes might represent genetic contributions involved across psychiatric disorders. PMID:26215504

De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia

PubMed Central

Xu, Bin; Ionita-Laza, Iuliana; Roos, J. Louw; Boone, Braden; Woodrick, Scarlet; Sun, Yan; Levy, Shawn; Gogos, Joseph A.; Karayiorgou, Maria

2013-01-01

To evaluate evidence for de novo etiologies in schizophrenia, we sequenced at high coverage the exomes of families recruited from two populations with distinct demographic structure and history. We sequenced a total of 795 exomes from 231 parent-proband trios enriched for sporadic schizophrenia cases, as well as 34 unaffected trios. We observed in cases an excess of non-synonymous single nucleotide variants as well as a higher prevalence of gene-disruptive de novo mutations. We found four genes (LAMA2, DPYD, TRRAP and VPS39) affected by recurrent de novo events within or across the two populations, a finding unlikely to have occurred by chance. We show that de novo mutations affect genes with diverse functions and developmental profiles but we also find a substantial contribution of mutations in genes with higher expression in early fetal life. Our results help define the pattern of genomic and neural architecture of schizophrenia. PMID:23042115

Sleep Disturbances and Suicide Risk in an 8-Year Longitudinal Study of Schizophrenia-Spectrum Disorders

PubMed Central

Li, Shirley Xin; Lam, Siu Ping; Zhang, Jihui; Yu, Mandy Wai Man; Chan, Joey Wing Yan; Chan, Cassandra Sheung Yan; Espie, Colin A.; Freeman, Daniel; Mason, Oliver; Wing, Yun-Kwok

2016-01-01

Study Objectives: Disrupted sleep is one of the prominent but often overlooked presenting symptoms in the clinical course of psychotic disorders. The aims of this study were to examine the prevalence of sleep disturbances, particularly insomnia and nightmares, and their prospective associations with the risk of suicide attempts in patients with schizophrenia-spectrum disorders. Methods: A naturalistic longitudinal study was conducted in outpatients diagnosed with schizophrenia-spectrum disorders recruited from the psychiatric outpatient clinic of a regional university-affiliated public hospital in Hong Kong. A detailed sleep questionnaire was completed by 388 patients at baseline in May–June 2006. Relevant clinical information was extracted from clinical case notes from June 2007–October 2014. Results: Prevalence of frequent insomnia and frequent nightmares was 19% and 9%, respectively. Baseline frequent insomnia was significantly associated with an increased incidence of suicide attempts during the follow-up period (adjusted hazard ratio = 4.63, 95% confidence interval 1.40–15.36, P < 0.05). Nightmare complaint alone did not predict the occurrence of suicide attempts, but the comorbidity of nightmares and insomnia was associated with the risk of suicide attempt over follow-up (adjusted HR = 11.10, 95% confidence interval: 1.68–73.43, P < 0.05). Conclusions: Sleep disturbances are common in patients with schizophrenia-spectrum disorders. The association between sleep disturbances and suicidal risk underscores the need for enhanced clinical attention and intervention on sleep disturbances in patients with schizophrenia. Citation: Li SX, Lam SP, Zhang J, Yu MW, Chan JW, Chan CS, Espie CA, Freeman D, Mason O, Wing YK. Sleep disturbances and suicide risk in an 8-year longitudinal study of schizophrenia-spectrum disorders. SLEEP 2016;39(6):1275–1282. PMID:27091530

Is the Acute NMDA Receptor Hypofunction a Valid Model of Schizophrenia?

PubMed Central

Adell, Albert; Jiménez-Sánchez, Laura; López-Gil, Xavier; Romón, Tamara

2012-01-01

Several genetic, neurodevelopmental, and pharmacological animal models of schizophrenia have been established. This short review examines the validity of one of the most used pharmacological model of the illness, ie, the acute administration of N-methyl-D-aspartate (NMDA) receptor antagonists in rodents. In some cases, data on chronic or prenatal NMDA receptor antagonist exposure have been introduced for comparison. The face validity of acute NMDA receptor blockade is granted inasmuch as hyperlocomotion and stereotypies induced by phencyclidine, ketamine, and MK-801 are regarded as a surrogate for the positive symptoms of schizophrenia. In addition, the loss of parvalbumin-containing cells (which is one of the most compelling finding in postmortem schizophrenia brain) following NMDA receptor blockade adds construct validity to this model. However, the lack of changes in glutamic acid decarboxylase (GAD67) is at variance with human studies. It is possible that changes in GAD67 are more reflective of the neurodevelopmental condition of schizophrenia. Finally, the model also has predictive validity, in that its behavioral and transmitter activation in rodents are responsive to antipsychotic treatment. Overall, although not devoid of drawbacks, the acute administration of NMDA receptor antagonists can be considered as a good model of schizophrenia bearing a satisfactory degree of validity. PMID:21965469

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia.

PubMed

Abdul Wahab, Noor Alaudin; Zakaria, Mohd Normani; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Wahab, Suzaily

2017-11-01

The present, case-control, study investigates binaural hearing performance in schizophrenia patients towards sentences presented in quiet and noise. Participants were twenty-one healthy controls and sixteen schizophrenia patients with normal peripheral auditory functions. The binaural hearing was examined in four listening conditions by using the Malay version of hearing in noise test. The syntactically and semantically correct sentences were presented via headphones to the randomly selected subjects. In each condition, the adaptively obtained reception thresholds for speech (RTS) were used to determine RTS noise composite and spatial release from masking. Schizophrenia patients demonstrated significantly higher mean RTS value relative to healthy controls (p=0.018). The large effect size found in three listening conditions, i.e., in quiet (d=1.07), noise right (d=0.88) and noise composite (d=0.90) indicates statistically significant difference between the groups. However, noise front and noise left conditions show medium (d=0.61) and small (d=0.50) effect size respectively. No statistical difference between groups was noted in regards to spatial release from masking on right (p=0.305) and left (p=0.970) ear. The present findings suggest an abnormal unilateral auditory processing in central auditory pathway in schizophrenia patients. Future studies to explore the role of binaural and spatial auditory processing were recommended.

Irony and Proverb Comprehension in Schizophrenia: Do Female Patients “Dislike” Ironic Remarks?

PubMed Central

Rapp, Alexander M.; Langohr, Karin; Mutschler, Dorothee E.; Wild, Barbara

2014-01-01

Difficulties in understanding irony and sarcasm are part of the social cognition deficits in patients with schizophrenia. A number of studies have reported higher error rates during comprehension in patients with schizophrenia. However, the relationships of these impairments to schizotypal personality traits and other language deficits, such as the comprehension of proverbs, are unclear. We investigated irony and proverb comprehension in an all-female sample of 20 schizophrenia patients and 27 matched controls. Subjects indicated if a statement was intended to be ironic, literal, or meaningless and furthermore rated the meanness and funniness of the stimuli and certainty of their decision. Patients made significantly more errors than controls did. Globally, there were no overall differences in the ratings. However, patients rated the subgroup of stimuli with answers given incorrectly as having significantly less meanness and in case of an error indicated a significantly higher certainty than controls. Across all of the study participants, performances in irony (r = −0.51) and proverb (r = 0.56) comprehension were significantly correlated with schizotypal personality traits, suggesting a continuum of nonliteral language understanding. Because irony is so frequent in everyday conversations, this makes irony an especially promising candidate for social cognition training in schizophrenia. PMID:24991434

Pharmacological treatment for schizoaffective disorder : A comparison with schizophrenia and bipolar disorder.

PubMed

Assion, H-J; Schweppe, A; Reinbold, H; Frommberger, U

2018-03-21

Bipolar disorder and schizophrenia are severe mental illnesses, each with a prevalence of approximately 1-2% in the general population. There is considerable controversy about differentiating schizophrenia from schizoaffective or bipolar disorder owing to many similarities in psychopathology, progression, and biological factors. The aim of this study was to identify similarities and differences in the pharmacological treatment of these disorders by comparing the prescription patterns. In this retrospective, explorative study we analyzed the prescribed medication of 300 patients with bipolar, schizophrenic, or schizoaffective disorders from data obtained from ten German adult psychiatric clinics of the LWL ("Landschaftsverband Westfalen-Lippe") psychiatric network. Only 21.8% of patients analyzed were consistently compliant in taking their medication before hospitalization. Polypharmacy was applied in 75.6% of cases, whereby 2.27 psychopharmacological agents were prescribed at discharge. Briefly, we observed greater similarity between prescription patterns associated with bipolar and schizoaffective disorders than with schizophrenia prescription patterns. Polypharmacy tends to be more the rule than the exception, especially when patients present with affective psychotic features. Bipolar and schizoaffective disorders cannot be differentiated according to their prescription patterns.

Social Stigma and Well-Being in a Sample of Schizophrenia Patients.

PubMed

Magallares, Alejandro; Perez-Garin, Daniel; Molero, Fernando

2016-01-01

The present study analyzes the existing relationship between three variables related to social rejection (perception of overt and subtle discrimination and stigma consciousness) and the psychological and subjective well-being among people with schizophrenia. Likewise, we will analyze the relationship between two possible strategies to cope with stigma (active coping and avoidant coping) and well-being. A cross-sectional study was conducted in a sample of 50 people with schizophrenia recruited from the social care network for people with mental illness in the Community of Madrid. Results show, as expected, the existence of a negative association between the variables related to social rejection and psychological and subjective well-being. It was also found that avoidant coping is negatively related to well-being, while active coping is positively related, although in the latter case relations do not reach significance. In view of the implementation of interventions to improve the well-being of people with schizophrenia, our results suggest implementing strategies to reduce the perception of discrimination (especially subtle or indirect discrimination) and encouraging the use of active strategies to cope with stigma as opposed to avoidant-coping strategies.

Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.

PubMed

Kim, Ju Young; Liu, Cindy Y; Zhang, Fengyu; Duan, Xin; Wen, Zhexing; Song, Juan; Feighery, Emer; Lu, Bai; Rujescu, Dan; St Clair, David; Christian, Kimberly; Callicott, Joseph H; Weinberger, Daniel R; Song, Hongjun; Ming, Guo-li

2012-03-02

How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

A case of catatonia in a 14-year-old girl with schizophrenia treated with electroconvulsive therapy.

PubMed

Häßler, Frank; Reis, Olaf; Weirich, Steffen; Höppner, Jacqueline; Pohl, Birgit; Buchmann, Johannes

2013-01-01

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Body Image and Body Experience Disturbances in Schizophrenia: an Attempt to Introduce the Concept of Body Self as a Conceptual Framework.

PubMed

Sakson-Obada, Olga; Chudzikiewicz, Paulina; Pankowski, Daniel; Jarema, Marek

2018-01-01

Disturbances in body experience are described as key schizophrenia symptoms and early disease predictors. In case studies, different disorders relating to body experience are presented, but only a few empirical studies have aimed to distinguish the characteristics of body experience in schizophrenia, and these have been selected arbitrarily and without reference to cohesive theoretical model. To integrate this fragmentary approach, we propose a body self (BS) model, composed of: functions; representations (e.g., body image); and sense of body identity. The aim of the study was to determine whether the BS differentiates schizophrenic patients from healthy controls, and to investigate the relations between aspects of BS and a history of illness and clinical characteristics. The Body Self Questionnaire and the Positive and Negative Syndrome Scale were administered to 63 schizophrenic patients and 63 healthy subjects. The difference was found in the functions of the body-self (perceiving, interpreting, and regulating body experience), in the sense of body identity, and in one of three aspects of body image explored (e.g., acceptance of biological sex). Disturbances in BS were related to positive symptoms and to the number of hospitalizations for other diseases. Together, the results demonstrate that schizophrenia is more body experience than body image disorder, since the negative emotional attitude towards the body and acceptance of fitness were not distinctive for schizophrenia. The link between the disturbances in BS and the number of nonpsychiatric hospitalizations suggests that misinterpretation of body experiences in schizophrenia can promote a search for medical attention.

Dysthymia in male adolescents is associated with increased risk of later hospitalization for psychotic disorders: a historical-prospective cohort study.

PubMed

Weiser, Mark; Lubin, Gad; Caspi, Asaf; Rabinowitz, Jonathan; Shmushkevitz, Mordechai; Yoffe, Rinat; Werbeloff, Nomi; Halperin, Demian; Davidson, Michael

2008-05-01

Retrospective studies indicate that patients with psychotic disorders and schizophrenia often suffer from depressive symptoms before the onset of psychosis. In a historical-prospective design, we studied the association between dysthymia in adolescence and later hospitalization for psychotic disorders and schizophrenia. The Israeli Draft Board screens the entire, unselected population of 16-17 years old male adolescents for psychiatric disorders. These adolescents were followed for hospitalization for psychotic disorders and schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Of 275,705 male adolescents screened, 1267 (0.5%) were hospitalized for psychotic disorders (International Classification of Diseases [ICD]-10 20.0-29.9), and 757 (0.3%) were hospitalized for schizophrenia (ICD-10 20.0-20.9) over the next 1-10 years. Of 275,705 male adolescents screened, 513 (0.2%) were diagnosed as suffering from dysthymia by the Draft Board. Of these adolescents, 10/513 (2.0%) were later hospitalized for psychotic disorders (including schizophrenia, HR=3.967, 95%CI (confidence intervals): 2.129-7.390), and 4/513 (0.8%) were later hospitalized for schizophrenia (HR=2.664, 95%CI: 0.997-7.116). In this population-based cohort of male adolescents, dysthymia was associated with increased risk for future psychotic disorders. Dysthymia in some adolescents might be a prodromal symptom, while in others it might be a risk factor for later psychosis. Clinicians assessing dysthymic adolescents should be aware that these symptoms might be part of the prodrome. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd.

Variants in TERT influencing telomere length are associated with paranoid schizophrenia risk.

PubMed

Rao, Shuquan; Ye, Ning; Hu, Huiling; Shen, Yan; Xu, Qi

2016-04-01

Schizophrenia is one of the most severe psychiatric disorders, with a high heritability of up to 80%. Several studies have reported telomere dysfunction in schizophrenia, and common variants in the telomerase reverse transcriptase (TERT) gene. TERT is a key component of the telomerase complex that maintains telomere length by addition of telomere repeats to telomere ends, and has repeatedly shown association with mean lymphocyte telomere length (LTL). Thus, we hypothesized that TERT may be a novel susceptibility gene for schizophrenia. Using a Taqman protocol, we genotyped eight tag SNPs from the TERT locus in 1,072 patients with paranoid schizophrenia and 1,284 control subjects from a Chinese Han population. We also measured mean LTL in 98 cases and 109 controls using a quantitative PCR-based technique. Chi-square tests showed that two SNPs, rs2075786 (P = 0.0009, OR = 0.76, 95%CI = 0.65-0.90) and rs4975605 (P = 0.0026, OR = 0.73, 95%CI = 0.60-0.90), were associated with a protective effect, while rs10069690 was associated with risk of paranoid schizophrenia (P = 0.0044, OR = 1.23, 95%CI = 1.07-1.42). Additionally, the rs2736118-rs2075786 haplotype showed significant association with paranoid schizophrenia (P = 0.0013). Moreover, mean LTL correlated with rs2075786 genotypes was significantly shorter in the patient group than the control group. The present results suggest that the TERT gene may be a novel candidate involved in the development of paranoid schizophrenia. © 2016 Wiley Periodicals, Inc.

Evaluation of European Schizophrenia GWAS Loci in Asian Populations via Comprehensive Meta-Analyses.

PubMed

Xiao, Xiao; Luo, Xiong-Jian; Chang, Hong; Liu, Zichao; Li, Ming

2017-08-01

Schizophrenia is a severe and highly heritable neuropsychiatric disorder. Recent genetic analyses including genome-wide association studies (GWAS) have implicated multiple genome-wide significant variants for schizophrenia among European populations. However, many of these risk variants were not largely validated in other populations of different ancestry such as Asians. To validate whether these European GWAS significant loci are associated with schizophrenia in Asian populations, we conducted a systematic literature search and meta-analyses on 19 single nucleotide polymorphisms (SNPs) in Asian populations by combining all available case-control and family-based samples, including up to 30,000 individuals. We employed classical fixed (or random) effects inverse variance weighted methods to calculate summary odds ratios (ORs) and 95 % confidence intervals (CIs). Among the 19 GWAS loci, we replicated the risk associations of nine markers (e.g., SNPs at VRK2, ITIH3/4, NDST3, NOTCH4) surpassing significance level (two-tailed P < 0.05), and three additional SNPs in MIR137 and ZNF804A also showed trend associations (one-tailed P < 0.05). These risk associations are in the same directions of allelic effects between Asian replication samples and initial European GWAS findings, and the successful replications of these GWAS loci in a different ethnic group provide stronger evidence for their clinical associations with schizophrenia. Further studies, focusing on the molecular mechanisms of these GWAS significant loci, will become increasingly important for understanding of the pathogenesis to schizophrenia.

Davidoff-Dyke-Masson Syndrome Presenting as Childhood Schizophrenia.

ERIC Educational Resources Information Center

White, James H.; Rust, John B.

1979-01-01

The article presents a case history of a child displaying symptoms of schizophrenia, seizures, and retardation without neurological abnormalities, which were eventually diagnosed as being due to Davidoff-Dyke-Masson syndrome, a condition involving gross anatomical brain pathology. (DLS)

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

PubMed

Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

2017-02-15

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Can interpersonal hypersensitivity under subconscious condition explain paranoid symptom in schizophrenia?

PubMed

Zhu, Yikang; Yang, Zhi; Zhao, Jinping; Li, Ting; Wang, Meijuan; Qian, Jie; Jiang, Yi; Wang, Jijun; Weng, Xuchu; Yu, Dehua; Li, Chunbo

2017-06-01

Interpersonal hypersensitivity is often observed in schizophrenia and has been associated with psychopathological deficits in schizophrenia. Here, we investigated dysfunctions of interpersonal information processing in schizophrenia at both conscious and subconscious levels. The experiment included 143 schizophrenia patients and 59 healthy controls. A continuous flashing suppression approach based on binocular rivalry was employed, which included two modes: invisible (subconscious) and visible (conscious). The accuracy and reaction time of a Gabor patch direction-detection task were assessed under three types of stimuli in both modes: images with no person (type 1), images with two to three noncommunicating persons (type 2), and images with more than three communicating individuals (type 3). In the visible mode, the accuracy of the Gabor patch direction-detection task in the case group was significantly lower than in the control group for the third type of stimuli (P = 0.015). In the invisible mode, however, the accuracy was higher in the case group than in the control group (P = 0.037). The response time difference of the Gabor patch direction-detection task for the third type of images in the invisible mode was negatively correlated with the duration of the illness (P = 0.008). These findings suggest that schizophrenia patients exhibit attentional bias to interpersonal interaction behaviors at both conscious and subliminal levels but toward opposite directions. Our findings shed light on the subconscious deficits under the paranoid symptom in schizophrenia. © 2015 Wiley Publishing Asia Pty Ltd.

Brain antibodies in the cortex and blood of people with schizophrenia and controls

PubMed Central

Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

2017-01-01

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in ‘high’ and ‘low’ proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances. PMID:28786974

Brain antibodies in the cortex and blood of people with schizophrenia and controls.

PubMed

Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

2017-08-08

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in 'high' and 'low' proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances.

Two-year outcome of team-based intensive case management for patients with schizophrenia.

PubMed

Aberg-Wistedt, A; Cressell, T; Lidberg, Y; Liljenberg, B; Osby, U

1995-12-01

Two-year outcomes of patients with schizophrenic disorders who were assigned to an intensive, team-based case management program and patients who received standard psychiatric services were assessed. The case management model featured increased staff contact time with patients, rehabilitation plans based on patients' expressed needs, and patients' attendance at team meetings where their rehabilitation plan was discussed. Forty patients were randomly assigned to either the case management group or the control group that received standard services. Patients' use of emergency and inpatient services, their quality of life, the size of their social networks, and their relatives' burden of care were assessed at assignment to the study groups and at two-year follow-up. Patients in the case management group had significantly fewer emergency visits compared with the two years before the study, and their relatives reported significantly reduced burden of care associated with relationships with psychiatric services over the two-year period. The size of patients' social networks increased for the case management group and decreased for the control group. A team-based intensive case management model is an effective intervention in the rehabilitation of patients with chronic schizophrenia.

Response to benzodiazepines and the clinical course in malignant catatonia associated with schizophrenia: A case report.

PubMed

Ohi, Kazutaka; Kuwata, Aki; Shimada, Takamitsu; Yasuyama, Toshiki; Nitta, Yusuke; Uehara, Takashi; Kawasaki, Yasuhiro

2017-04-01

Malignant catatonia (MC) is a disorder consisting of catatonic symptoms, hyperthermia, autonomic instability, and altered mental status. Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments providing rapid relief from MC. This case study reports a detailed clinical course of a case of MC associated with schizophrenia initially diagnosed as NMS that responded successfully to BZDs but not to dantrolene. A 53-year-old man with schizophrenia was admitted to the psychiatric hospital because of excitement, monologue, muscle rigidity, and insomnia. In the 3 days before admission, the patient had discontinued his medications after his family member's death. He presented with hyperthermia, tachycardia, hypertension, excessive sweating, and an elevated serum creatine phosphokinase (CPK) level. On the basis of these features, he was suspected to have NMS. The patient was treated with dantrolene for 7 days without improvement despite having a normalized serum CPK level. The patient was transferred to our university hospital for an in-depth examination and treatment of his physical status. Infection and pulmonary embolism were excluded as possible causes. To treat his excitement and auditory hallucination, an intravenous drip (IVD) of haloperidol was initiated, but this treatment increased the patient's catatonic and psychotic symptoms, although his serum CPK level had remained within a normal range. As a result, the treatment was changed to diazepam. After an IVD of diazepam, the patient's symptoms rapidly improved, and the IVD was subsequently replaced with oral administration of lorazepam. Eventually, the patient was diagnosed with MC associated with schizophrenia. BZD therapy was dramatically effective. Catatonia, MNS, and MC may be due to a common brain pathophysiology and these conditions may be in a spectrum, although uncertainty in the boundaries among conditions, and the BZD treatment may be useful. Most importantly, catatonia has not been described as a subtype of schizophrenia on the basis of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, and the medications for catatonia and schizophrenia are different. Antipsychotics are not effective in relieving catatonia, or they may induce NMS, whereas BZDs are effective for treating both MC and NMS.

[Delusional misidentification syndromes: A factor associated with violence? Literature review of case reports].

PubMed

Horn, M; Pins, D; Vaiva, G; Thomas, P; Fovet, T; Amad, A

2018-03-23

Delusional misidentification syndromes (DMS) correspond to the delusional belief of misidentification of familiar persons, places or objects and to the conviction that they have been replaced or transformed. Several cases of patients who developed violent behavior while suffering from DMS have been published. This led some authors to consider patients with DMS at risk of violence. However, only a few studies have focused on the potential relationship between violence and DMS. The aim of our study was to explore this relationship with a literature review of published cases of patients having committed violent acts associated to DMS. A systematic literature search was conducted on PubMed up to January 2017 using the following term combination "misidentification" and "violence" Fifteen cases of patients with DMS who had committed violent acts were identified. The data from these descriptions were analyzed and synthetized. Most of the patients were men with a diagnosis of schizophrenia and Capgras syndrome. Acts of violence were severe with a relatively high number of murders or attempted murders. For half of the patients these violent acts were perpetrated with weapons. Victims were regularly the patient's family members and the assaults were usually not planned. Delusional syndromes often progressed for several years. Importantly, substance abuse, which is known to increase the risk of violence in patients with schizophrenia, was only observed in two patients. DMS are associated with several risk factors of violence, such as a diagnosis of schizophrenia, specific delusions including megalomania, persecution, negative affects and identified targets. Despite this risk for severe violence, there are no existing guidelines on how to assess and treat DMS in schizophrenia. Accordingly, we propose (1) the establishment of formal diagnostic criteria, (2) the development of rigorous research on these syndromes and (3) the integration of DMS in assessment of violence risk in schizophrenic patients. Copyright © 2018 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Artificial Sanity: A Case Study for a Class in Introductory Psychology

ERIC Educational Resources Information Center

Quinn, Sheila O'Brien

2005-01-01

Using the story of death row inmate Charles Singleton, who developed paranoid schizophrenia while in prison awaiting execution, this case study explores the relationship between a society's concept of mental illness and its treatment of people who are mentally ill. Students are asked to identify the model of mental illness assumed by each of the…

Behavioral Experiments in the Treatment of Paranoid Schizophrenia: A Single Case Study

ERIC Educational Resources Information Center

Hagen, Roger; Nordahl, Hans M.

2008-01-01

Since the first description of cognitive therapy of paranoid delusions appeared in the literature, the empirical support for cognitive behavioral therapy in treating psychotic symptoms has been widely established. The aim of the present case study is to show how the behavioral experiment can be used as a powerful tool to change delusional thinking…

Dermatoglyphic Profile in 22q Deletion Syndrome

PubMed Central

Martín, B.; Fañanás, L.; Gutiérrez, B.; Chow, E.W.C.; Bassett, A.S.

2011-01-01

A genetic subtype of schizophrenia has been described in 22q11 Deletion syndrome. Previous studies have described an excess of dermatoglyphic alterations in schizophrenia, such as low a–b ridge counts (ABRCs), a high frequency of ridge dissociations, and increased dermatoglyphic fluctuating asymmetry. Little is known however, about the dermatoglyphic profile of 22qDS subjects showing psychotic symptoms and its similarity to the previously reported anomalies in schizophrenia. We studied the palmar dermatoglyphics of 22 subjects with 22qDS of predominantly Caucasian origin, 15 of whom had psychotic illness, and in 84 healthy controls of similar ethnicity. We observed higher values for total ATD angle in cases than in controls (P = 0.04). In addition, there was an excess of radial figures in the hypothenar area in cases, especially in the left hand. Interestingly, greater fluctuating asymmetry, determined by the absolute difference between right and left ABRC, was observed in 22qDS subjects compared to controls (P = 0.05). However, no differences were found for ABRCs and frequency of dissociations. Despite the small sample size, the palmprints analyzed suggest the existence of an altered dermatoglyphic profile in 22qDS, involving: (i) ATD angle amplitude, (ii) presence of radial loops in the hypothenar area, and (iii) an increment of fluctuating asymmetry. The first two features are similar to those found in other genetic syndromes associated with low IQ, while high levels of fluctuating asymmetry have often been reported in schizophrenia. PMID:15211630

California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS).

PubMed

Stone, William S; Mesholam-Gately, Raquelle I; Braff, David L; Calkins, Monica E; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Seidman, Larry J

2015-04-01

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. Copyright © 2014. Published by Elsevier B.V.

Village doctor-assisted case management of rural patients with schizophrenia: protocol for a cluster randomized control trial.

PubMed

Gong, Wenjie; Xu, Dong; Zhou, Liang; Brown, Henry Shelton; Smith, Kirk L; Xiao, Shuiyuan

2014-01-16

Strict compliance with prescribed medication is the key to reducing relapses in schizophrenia. As villagers in China lack regular access to psychiatrists to supervise compliance, we propose to train village 'doctors' (i.e., villagers with basic medical training and currently operating in villages across China delivering basic clinical and preventive care) to manage rural patients with schizophrenia with respect to compliance and monitoring symptoms. We hypothesize that with the necessary training and proper oversight, village doctors can significantly improve drug compliance of villagers with schizophrenia. We will conduct a cluster randomized controlled trial in 40 villages in Liuyang, Hunan Province, China, home to approximately 400 patients with schizophrenia. Half of the villages will be randomized into the treatment group (village doctor, or VD model) wherein village doctors who have received training in a schizophrenia case management protocol will manage case records, supervise drug taking, educate patients and families on schizophrenia and its treatment, and monitor patients for signs of relapse in order to arrange prompt referral. The other 20 villages will be assigned to the control group (case as usual, or CAU model) wherein patients will be visited by psychiatrists every two months and receive free antipsychotic medications under an on-going government program, Project 686. These control patients will receive no other management or follow up from health workers. A baseline survey will be conducted before the intervention to gather data on patient's socio-economic status, drug compliance history, and clinical and health outcome measures. Data will be re-collected 6 and 12 months into the intervention. A difference-in-difference regression model will be used to detect the program effect on drug compliance and other outcome measures. A cost-effectiveness analysis will also be conducted to compare the value of the VD model to that of the CAU group. Lack of specialists is a common problem in resource-scarce areas in China and other developing countries. The results of this experiment will provide high level evidence on the role of health workers with relatively limited medical training in managing severe psychiatric disease and other chronic conditions in developing countries. ChiCTR-TRC-13003263.

Clinical characteristics and premorbid variables in childhood-onset schizophrenia: a descriptive study of twelve cases from a schizophrenia founder population.

PubMed

Maydell, R J; van der Walt, C; Roos, J L; Scribante, L; Ladikos, A

2009-05-01

To analyze clinical and demographic data of childhood-onset (12 years and younger) schizophrenia patients collected for a genetic study in schizophrenia, undertaken nationally in South Africa, using multiple parameters. Patients with an onset of schizophrenia at 12 years or younger, were included. From the Diagnostic Interview for Genetic Studies (DIGS), patients' information and summary report data was tabulated and analyzed. Specific subgroups were further compared. This sub-population of 12 subjects was further compared with a group of the adult sample. Of the 12 patients recruited, prominent results were: male to female ratio of 1:1; all had insidious onset of psychosis; a third had all 3 multidimensional impairment (MDI) symptoms; all patients that received ADHD treatment had ADHD treatment failure; two thirds had milestone delay; 58% had birth complications; a third were predominantly bottle fed; 42% had family history of schizophrenia; a third had family history of other major psychiatric conditions; all patients had at least one non-psychotic deviant behaviour (NPDB); no patient used cannabis; all delusions were paranoid; 92% had school achievement difficulty and a third had treatment resistance. Gender comparison included: earlier onset of psychosis in females; all females had aggression versus a third of males; more females had school achievement difficulty than males; males had more treatment resistance. Patients with MDI, compared to the sample average had: earlier onset of non-psychotic deviant behaviour; lower school drop-out rate; less social difficulty and no treatment resistance. The results compare well to previous research on this topic. The new concepts introduced by the present study require further investigation.

A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation

PubMed Central

2014-01-01

Background Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. Methods 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). Results No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p = .003). A polygenic score analysis found that the Psychiatric GWAS Consortium’s panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 × 10–14) and explained approximately 2% of the phenotypic variance. Conclusions Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through meta-analysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data. PMID:23871474

The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population.

PubMed

Mihaljevic, Marina; Zeljic, Katarina; Soldatovic, Ivan; Andric, Sanja; Mirjanic, Tijana; Richards, Alexander; Mantripragada, Kiran; Pekmezovic, Tatjana; Novakovic, Ivana; Maric, Nadja P

2017-09-01

Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerability-stress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis. The purpose of the present study was to investigate impact of FKBP5 on schizophrenia in Serbian patients and to explore relationship between genetic variants and neuroticism by using the case-sibling-control design. In 158 subjects, we measured psychotic experiences, childhood trauma and neuroticism. Nine single-nucleotide polymorphisms (rs9295158, rs3800373, rs9740080, rs737054, rs6926133, rs9380529, rs9394314, rs2766533 and rs12200498) were genotyped. The genetic influence was modeled using logistic regression, and the relationship between genetic variants and neuroticism was assessed by linear mixed model. Our results revealed genetic main effect of FKBP5 risk alleles (A allele of rs9296158 and T allele of rs3800373) and AGTC "risk" haplotype combination (rs9296158, rs3800373, rs9470080 and rs737054, respectively) on schizophrenia, particularly when childhood trauma was set as a confounding factor. We confirmed strong relationship between neuroticism and psychotic experiences in patients and siblings and further showed relationship between higher levels of neuroticism and FKBP5 risk variants suggesting potential link between biological and psychosocial risk factors. Our data support previous findings that trauma exposure shapes FKBP5 impact on schizophrenia.

Risk of transition to schizophrenia following first admission with substance-induced psychotic disorder: a population-based longitudinal cohort study.

PubMed

Alderson, H L; Semple, D M; Blayney, C; Queirazza, F; Chekuri, V; Lawrie, S M

2017-10-01

The potential for drugs of abuse to induce acute psychotic symptoms is well recognised. However, the likelihood of transition from initial substance-induced psychotic disorder (SIPD) to chronic psychosis is much less well understood. This study investigated the rate of SIPD transition to schizophrenia (F20), the time to conversion and other possible related factors. Using data from the Scottish Morbidity Record, we examined all patients (n = 3486) since their first admission to psychiatric hospital with a diagnosis of SIPD [International Classification of Diseases, Tenth Revision (ICD-10) codes F10-F19, with third digit five] from January 1997 to July 2012. Patients were followed until first episode of schizophrenia (ICD-10 code F20, with any third digit) or July 2012. Any change in diagnosis was noted in the follow-up period, which ranged from 1 day to 15.5 years across the groups. The 15.5-year cumulative hazard rate was 17.3% (s.e. = 0.007) for a diagnosis of schizophrenia. Cannabis, stimulant, opiate and multiple drug-induced psychotic disorder were all associated with similar hazard rates. The mean time to transition to a diagnosis of schizophrenia was around 13 years, although over 50% did so within 2 years and over 80% of cases presented within 5 years of SIPD diagnosis. Risk factors included male gender, younger age and longer first admission. SIPD episodes requiring hospital admission for more than 2 weeks are more likely to be associated with later diagnosis of schizophrenia. Follow-up periods of more than 2 years are needed to detect the majority of those individuals who will ultimately develop schizophrenia.

A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation.

PubMed

Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bruggeman, Richard; Cahn, Wiepke; Chandler, David; Collier, David A; Crespo-Facorro, Benedicto; Dazzan, Paola; de Haan, Lieuwe; Di Forti, Marta; Dragović, Milan; Giegling, Ina; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, René S; Kalaydjieva, Luba; Kravariti, Eugenia; Lawrie, Stephen; Linszen, Don H; Mata, Ignacio; McDonald, Colm; McIntosh, Andrew; Myin-Germeys, Inez; Ophoff, Roel A; Pariante, Carmine M; Paunio, Tiina; Picchioni, Marco; Ripke, Stephan; Rujescu, Dan; Sauer, Heinrich; Shaikh, Madiha; Sussmann, Jessika; Suvisaari, Jaana; Tosato, Sarah; Toulopoulou, Timothea; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Whalley, Heather; Wiersma, Durk; Blackwell, Jenefer M; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A Z; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Lewis, Cathryn M; Murray, Robin M; Donnelly, Peter; Powell, John; Spencer, Chris C A

2014-03-01

Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p = .003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 × 10(-14)) and explained approximately 2% of the phenotypic variance. Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through meta-analysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables.

PubMed

Lee, Ellen E; Hong, Suzi; Martin, Averria Sirkin; Eyler, Lisa T; Jeste, Dilip V

2017-01-01

Inflammation may play a role in the accelerated physical aging reported in schizophrenia, though biomarker findings and associations with demographic and clinical factors are inconsistent. In a cross-sectional, case-control design, 95 outpatients with schizophrenia (mean age ± SD: 48.1 ± 10.2 years) and 95 demographically comparable healthy comparison subjects (HCs) (mean age ± SD: 48.1 ± 12.1 years) were studied. Sociodemographic and clinical data were collected, and plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed. The authors compared cytokine levels, examined demographic and clinical associations, and adjusted for relevant variables with linear models. Individuals with schizophrenia had higher levels of TNF-α and IL-6 but not IFN-γ than HCs. Age was not related to cytokine levels, and age relationships did not differ between diagnostic groups. Women had higher levels of IL-6. TNF-α and IL-6 levels were significantly correlated with depressive symptoms, and adjustment for depression reduced the group effect for both. Within the HCs, TNF-α levels were associated with physical comorbidity and body mass index. IL-6 levels were significantly correlated with body mass index and within schizophrenia patients, with worse mental and physical well-being. Accounting for physical morbidity and mental well-being reduced group differences in TNF-α and IL-6 levels, respectively. Worse positive symptoms were associated with higher IL-6 levels. Higher TNF-α and IL-6 levels in schizophrenia patients were associated with depression, physical comorbidity, and mental well-being. Further longitudinal studies are warranted to assess inflammation as a potential treatment target for a subgroup of schizophrenia. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Allosteric Modulators for the Treatment of Schizophrenia: Targeting Glutamatergic Networks

PubMed Central

Menniti, Frank S.; Lindsley, Craig W.; Conn, P. Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A.

2013-01-01

Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved. PMID:23409764

Association between prenatal exposure to poliovirus infection and adult schizophrenia.

PubMed

Suvisaari, J; Haukka, J; Tanskanen, A; Hovi, T; Lönnqvist, J

1999-07-01

The authors' goal was to determine whether there is an association between prenatal exposure to poliovirus infection and later development of schizophrenia. All Finnish patients born between 1951 and 1969 with discharge diagnoses of schizophrenia (N = 13,559) were identified from the Finnish Hospital Discharge Register. Information on the monthly number of cases of paralytic poliomyelitis was obtained for each province in Finland. The authors analyzed the incidence of births of individuals who later developed schizophrenia by using a Poisson regression model with year and place of birth, age, sex, season of birth, and smoothed incidence of poliomyelitis in different gestational periods as explanatory variables. An association between the incidence of poliomyelitis and the incidence of births 5 months later of individuals who later developed schizophrenia was observed. Without controlling for seasonality, the effect was significant throughout the second trimester. Second-trimester exposure to poliovirus infection may increase the risk for the later development of schizophrenia.

Family caregiver burden in mental illnesses: The case of affective disorders and schizophrenia - a qualitative exploratory study.

PubMed

von Kardorff, Ernst; Soltaninejad, Ali; Kamali, Mohammad; Eslami Shahrbabaki, Mahin

2016-01-01

Caregivers of people with mental illnesses often experience a wide range of burdens. Although many studies have confirmed burdens among family caregivers of mentally ill relatives in general, specific knowledge regarding the concrete everyday hassle and existential sorrows from the caregiverś subjective reasoning perspective is lacking. Furthermore, there is little evidence on the possible different effects of affective disorders and schizophrenia on the quality of burden; this is also true with regard to the role of cultural traditions and lay beliefs. The aim of this study was to explore the specific burdens experienced by caregivers of patients with schizophrenia and affective disorders. A qualitative study was conducted by semi-structured interviews with 45 caregivers of patients with schizophrenia and affective disorders. Data were analysed by qualitative content analysis. Eleven encumbering themes resulted from the interviews including incertitude, unawareness, emotional burden, stigma and blame, financial burden, physical burden, restriction in routine, disruption in routine, dissatisfaction with family, relatives, and acquaintances, troubles with patients' adherence to medication, and problems with health services and governmental support. Caring for a person with mental illness affects caregivers emotionally, financially, physically, and it elicits some restrictions in their routine (daily hassles). Finally, it causes conflicts in family relationships. Despite some differences regarding perceived burden among caregivers of schizophrenia and affective disorders, a common pattern of burden could be identified. Thus, authorities should provide adequate financial, educational, and psychosocial supports for caregivers of mental illnesses.

Predisposing factors for early retirement in patients with schizophrenia in Germany.

PubMed

Schnabel, Reinhard; Friedel, Heiko; Erfurth, Andreas; Angermayer, Matthias; Clouth, Johannes; Eichmann, Florian

2008-08-01

Although early retirement causes major changes in the life of schizophrenic patients and is among the major cost factors to be covered by payers, the causes leading to early retirement of schizophrenic patients have not been investigated in detail. Therefore, the objective of this retrospective non-interventional case-control study was to generate hypotheses on predisposing factors for early retirement in schizophrenia. Logistic regression was used to explore potential predisposing parameters with regard to their effect on the outcome early retirement. As the study results indicate, schizophrenia severity, assistance or care in the patient's everyday life, age and antipsychotic treatment with typical antipsychotics are linked to the occurrence of early retirement. Further research should be planned to confirm or refute the hypotheses determined in this retrospective analysis and to determine whether atypical antipsychotics could help to avoid early retirement and to improve the situation of schizophrenic patients.

Premorbid intellectual functioning and risk of schizophrenia and spectrum disorders.

PubMed

Reichenberg, Abraham; Weiser, Mark; Caspi, Asaf; Knobler, Haim Y; Lubin, Gad; Harvey, Philip D; Rabinowitz, Jonathan; Davidson, Michael

2006-02-01

Evidence from longitudinal studies indicates that lower IQ score in childhood and early adolescence increases risk of schizophrenia and schizophrenia spectrum disorders (SSD). This study investigated the association between premorbid IQ and risk of SSD in a population-based cohort of 17-year-old conscripts. Fifty four thousand males assessed by the Israeli Draft Board during two consecutive years were followed by means of the Israeli National Psychiatric Hospitalization Case Registry for up to 11 years. Tests of verbal and non-verbal reasoning, mathematical knowledge and instructions comprehension and several psychosocial variables were recorded by the Draft Board. Risk for SSD increased with decreasing IQ score. Only poorer non-verbal reasoning conferred a significant increased risk for SSD after taking into account general intellectual ability. IQ was not associated with age of onset. These results confirm the importance of low intellectual functioning as a risk factor for SSD. This is unlikely to be due to prodrome.

Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?

PubMed

Busse, Stefan; Busse, Mandy; Schiltz, Kolja; Bielau, Hendrik; Gos, Tomasz; Brisch, Ralf; Mawrin, Christian; Schmitt, Andrea; Jordan, Wolfgang; Müller, Ulf J; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

2012-11-01

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain's mononuclear phagocyte system (microglial cells) is activated during acute psychosis. Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P=0.047, right: P=0.038; CD20: left: P=0.020, right: P=0.010) and controls (CD3: left: P=0.057, right: P=0.069; CD20: left: P=0.008, right: P=0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P=0.030, right: P=0.012). A similar trend emerged when this group was compared to controls (left: P=0.090, right: P=0.090). BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity. Copyright © 2012 Elsevier Inc. All rights reserved.

Meta-analysis of paternal age and schizophrenia risk in male versus female offspring.

PubMed

Miller, Brian; Messias, Erick; Miettunen, Jouko; Alaräisänen, Antti; Järvelin, Marjo-Riita; Koponen, Hannu; Räsänen, Pirkko; Isohanni, Matti; Kirkpatrick, Brian

2011-09-01

Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. There were 6 cohort studies and 6 case-control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (≥30) compared to a reference paternal age of 25-29, with no gender differences. The relative risk (RR) in the oldest fathers (≥50) was 1.66 [95% confidence interval (95% CI): 1.46-1.89, P < 0.01]. A significant increase in risk was also found for younger fathers (<25) in males (RR = 1.08, 95% CI: 1.02-1.14, P = 0.01) but not females (RR = 1.04, 95% CI: 0.97-1.14, P = 0.28). The population attributable risk percentage (PAR%) was 10% for paternal age ≥30 and 5% for paternal age <25. Both APA (≥30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.

Loss of function studies in mice and genetic association link receptor protein tyrosine phosphatase α to schizophrenia

PubMed Central

Takahashi, Nagahide; Nielsen, Karin Sandager; Aleksic, Branko; Petersen, Steffen; Ikeda, Masashi; Kushima, Itaru; Vacaresse, Nathalie; Ujike, Hiroshi; Iwata, Nakao; Dubreuil, Véronique; Mirza, Naheed; Sakurai, Takeshi; Ozaki, Norio; Buxbaum, Joseph D.; Sap, Jan

2011-01-01

Background Solid evidence links schizophrenia (SZ) susceptibility to neurodevelopmental processes involving tyrosine phosphorylation-mediated signaling. Mouse studies implicate the Ptpra gene, encoding protein tyrosine phosphatase RPTPα, in the control of radial neuronal migration, cortical cytoarchitecture, and oligodendrocyte differentiation. The human gene encoding RPTPα, PTPRA, maps to a chromosomal region (20p13) associated with susceptibility to psychotic illness. Methods We characterized neurobehavioral parameters, as well as gene expression in the central nervous system, of mice with a null mutation in the Ptpra gene. We searched for genetic association between polymorphisms in PTPRA and schizophrenia risk (2 independent cohorts; total of 1420 cases and 1377 controls), and we monitored PTPRA expression in prefrontal dorsolateral cortex of SZ patients (35 cases, 2 control groups of 35 cases) Results We find that Ptpra−/− mice reproduce neurobehavioral endophenotypes of human SZ: sensitization to metamphetamine-induced hyperactivity, defective sensorimotor gating, and defective habituation to a startle response. Ptpra loss of function also leads to reduced expression of multiple myelination genes, mimicking the hypomyelination-associated changes in gene expression observed in post mortem patient brains. We further report that a polymorphism at the PTPRA locus is genetically associated with SZ, and that PTPRA mRNA levels are reduced in post mortem dorsolateral prefrontal cortex of subjects with SZ. Conclusion The implication of this well-studied signaling protein in SZ risk and endophenotype manifestation provides novel entry points into the etiopathology of this disease. PMID:21831360

[Economic evaluation of the demand of medical care for mental health in Mexico: schizophrenia and depression, 1996-2000].

PubMed

Arredondo, Armando; Ramos, René; Zúñiga, Alexis

2003-01-01

Financing protection for both, users and providers of health care services is one of the main objectives of National Program of Health in Mexico, 2001-2006. In fact one of the elements of the present health care reform initiatives is need for the efficient allocation of financial resources, using resource allocation schemes by specific health care demands that combine both the economic, clinical and the epidemiological perspectives. The evaluation of such schemes has been approached in several ways; however, in the case of mental health services, there is dearth of studies that use economic assessment methods. Moreover, such studies are of limited scope, often a response to unmated health needs, disregarding the economic implication for health services production and financing and ensuing medical care market imbalances. This paper presents the results of an evaluative research work aimed to assess the average cost of depression and schizophrenia case management, the financial resources required to meet the health care demands by type of institution, period 1996-2000, in Mexico by type of health care provider. The case management average cost for schizophrenia was $211.00 US, and that for depression was $221.00 US. The demand of services for both conditions in each type of institution showed that the greatest relative demands (96% of the national total for depression and 94% of the national total for schizophrenia) occur in three institutions: IMSS, SSA and ISSSTE. The greatest demand of the health services for the two study condition corresponded to those insured by the IMSS, followed by those uninsured who use the SSA services, and those insured by the ISSSTE. The case management costs for mental conditions are in the middle range between hypertension and diabetes in the upper end, pneumonia and diarrhea in the lower end. The case managment costs of health care demands for the selected tracer conditions differ considerably among institutions for insure populations and those for uninsured populations, with a greater economic impact on-the former. Independent from differences found, these results allow the identification of economic evaluation indicators that could be used to design resource allocation schemes for each of the institutions included in this study.

Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia.

PubMed

Xavier, Rose Mary; Dungan, Jennifer R; Keefe, Richard S E; Vorderstrasse, Allison

2018-06-01

Genetic etiology of psychopathology symptoms and cognitive performance in schizophrenia is supported by candidate gene and polygenic risk score (PRS) association studies. Such associations are reported to be dependent on several factors - sample characteristics, illness phase, illness severity etc. We aimed to examine if schizophrenia PRS predicted psychopathology symptoms and cognitive performance in patients with chronic schizophrenia. We also examined if schizophrenia associated autosomal loci were associated with specific symptoms or cognitive domains. Case-only analysis using data from the Clinical Antipsychotics Trials of Intervention Effectiveness-Schizophrenia trials ( n  = 730). PRS was constructed using Psychiatric Genomics Consortium (PGC) leave one out genome wide association analysis as the discovery data set. For candidate region analysis, we selected 105-schizophrenia associated autosomal loci from the PGC study. We found a significant effect of PRS on positive symptoms at p -threshold ( P T ) of 0.5 ( R 2  = 0.007, p  = 0.029, empirical p  = 0.029) and negative symptoms at P T of 1e-07 ( R 2  = 0.005, p  = 0.047, empirical p  = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive ( p- threshold 0.01, R 2   =  0.007, p =  0.013, empirical p  = 0.167) and negative symptoms ( p- threshold 0.1, R 2   =  0.012, p =  0.004, empirical p  = 0.329). No associations were seen for overall neurocognitive and social cognitive performance tests. Post-hoc analyses revealed that PRS predicted working memory and vigilance performance but did not survive correction. No candidate regions that survived multiple testing corrections were associated with either symptoms or cognitive performance. Our findings point to potentially distinct pathogenic mechanisms for schizophrenia symptoms.

Mitochondrial Mutations in Subjects with Psychiatric Disorders

PubMed Central

Magnan, Christophe; van Oven, Mannis; Baldi, Pierre; Myers, Richard M.; Barchas, Jack D.; Schatzberg, Alan F.; Watson, Stanley J.; Akil, Huda; Bunney, William E.; Vawter, Marquis P.

2015-01-01

A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA. PMID:26011537

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2016-09-01

schizophrenia .    Specifically,   we  used  source-­‐based  morphometry,  a  multivariate...variation  in  the   general  population,  and  verified  its  relevance  to   schizophrenia  in  an  independent  case...it  has  been  linked  to  affective  disorders  and   schizophrenia  in  multiple  populations.  Thus,

Orange juice-induced hyperkalemia in schizophrenia.

PubMed

Berk, David R; Conti, Paul M; Sommer, Barbara R

2004-01-01

Some fruit juices have very high potassium content. However, only several cases of juice-induced hyperkalemia have been reported that involved non-psychiatric, diabetic outpatients with renal compromise. We present a highly unusual case of a 66-year-old non-diabetic, schizophrenic woman with psychogenic polydipsia and normal renal function who developed hyperkalemia secondary to excessive orange juice consumption while an inpatient. In addition to demonstrating this previously undescribed medical comorbidity of schizophrenia, this case highlights the need for careful attention when communicating with both nursing and patients when managing psychogenic polydipsia.

HETEROGENEITY IN PLASMA HOMOVANILLIC ACID LEVELS IN SCHIZOPHRENIFORM DISORDER

PubMed Central

Pradhan, N.; Harihar, C.; Das, P.; Andrade, C.

1992-01-01

Plasma homovanillic acid (pHVA) levels were estimated in 20 cases of schizophreniform disorder, 14 cases of schizophrenia ‘on medication’ and 17 cases of schizophrenia ‘off medication’. A bimodal distribution of pHVA was seen in schizophreniform disorder subjects, suggesting heterogenous groups in terms of dopaminergic function. No significant difference in the pHVA values was seen in the 3 groups, nor was there a relationship between the severity of the illness and the pHVA values; these results suggest plasticity of the dopaminergic system to neuroleptics. PMID:21776112

Heterogeneity in plasma homovanillic Acid levels in schizophreniform disorder.

PubMed

Pradhan, N; Harihar, C; Das, P; Andrade, C

1992-04-01

Plasma homovanillic acid (pHVA) levels were estimated in 20 cases of schizophreniform disorder, 14 cases of schizophrenia 'on medication' and 17 cases of schizophrenia 'off medication'. A bimodal distribution of pHVA was seen in schizophreniform disorder subjects, suggesting heterogenous groups in terms of dopaminergic function. No significant difference in the pHVA values was seen in the 3 groups, nor was there a relationship between the severity of the illness and the pHVA values; these results suggest plasticity of the dopaminergic system to neuroleptics.

Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics: a case-control study.

PubMed

Jorgensen, Anders; Knorr, Ulla; Soendergaard, Mia Greisen; Lykkesfeldt, Jens; Fink-Jensen, Anders; Poulsen, Henrik Enghusen; Jorgensen, Martin Balslev; Olsen, Niels Vidiendal; Staalsø, Jonatan Myrup

2015-04-03

Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA ratio are positively correlated to measures of oxidative stress. We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography. Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology. Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores. Schizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma levels of ADMA were not associated with levels of systemic oxidative stress in vivo.

Testing the association between the incidence of schizophrenia and social capital in an urban area.

PubMed

Kirkbride, J B; Boydell, J; Ploubidis, G B; Morgan, C; Dazzan, P; McKenzie, K; Murray, R M; Jones, P B

2008-08-01

Social capital has been considered aetiologically important in schizophrenia but the empirical evidence to support this hypothesis is absent. We tested whether social capital, measured at the neighbourhood level, was associated with the incidence of schizophrenia (ICD-10 F20). MethodWe administered a cross-sectional questionnaire on social capital to 5% of the adult population in 33 neighbourhoods (wards) in South London (n=16 459). The questionnaire contained items relating to two social capital constructs: social cohesion and trust (SC&T) and social disorganization (SocD). Schizophrenia incidence rates, estimated using data from the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study, provided the outcome. We used multi-level Poisson regression to test our hypothesis while controlling for individual- and neighbourhood-level characteristics. We identified 148 cases during 565 576 person-years at-risk. Twenty-six per cent of the variation in incidence rates was attributable to neighbourhood-level characteristics. Response from the social capital survey was 25.7%. The association between SC&T and schizophrenia was U-shaped. Compared with neighbourhoods with medial levels of SC&T, incidence rates were significantly higher in neighbourhoods with low [incidence rates ratio (IRR) 2.0, 95% confidence interval (CI) 1.2-3.3] and high (IRR 2.5, 95% CI 1.3-4.8) levels of SC&T, independent of age, sex, ethnicity, ethnic density, ethnic fragmentation and socio-economic deprivation. ConclusionNeighbourhood variation in SC&T was non-linearly associated with the incidence of schizophrenia within an urban area. Neighbourhoods with low SC&T may fail to mediate social stress whereas high SC&T neighbourhoods may have greater informal social control or may increase the risk of schizophrenia for residents excluded from accessing available social capital.

Rates of treated schizophrenia and its clinical and cultural features in the population isolate of the Iban of Sarawak: a tri-diagnostic approach.

PubMed

Barrett, Robert; Loa, Peter; Jerah, Edward; Nancarrow, Derek; Chant, David; Mowry, Bryan

2005-02-01

We present results of a study of treated rates of schizophrenia among the Iban of Sarawak, Malaysia. Most Iban live in longhouses, each comprising a kindred group of up to 300 individuals. Cultural practices such as minimal intermarriage with members of adjacent ethnic groups and in-depth genealogical knowledge make them a population suitable for genetic investigation. Iban culture is conducive to a focus on symptoms and illness, and to patterns of treatment-seeking behaviour that are enthusiastic and persistent. We identified all known cases of psychotic disorder within a defined catchment area based on an exhaustive survey of available medical records. From corresponding Malaysian census data (91,056 persons), we report rates of treated schizophrenia in the Iban population, using three diagnostic systems, as well as the demographic and clinical characteristics of these individuals. The most frequent presenting complaints were insomnia and aggression. We found higher treated rates for narrowly defined schizophrenia among males, but no significant gender difference for age of onset. Estimates of treated rates to age 55 years (per 10,000) for narrow schizophrenia were 41.9 (ICD-10), 56.5 (DSM-IV), and 83 (RDC), while the rates for broad schizophrenia were 105.5, 103.2, and 107.5 respectively. Treated rates of schizophrenia were higher than the reported prevalence for many populations at risk, including many small-scale societies, although different methodological approaches may partly explain these findings. Given the cultural patterns of Iban treatment-seeking behaviour, treated rates of schizophrenia reported here may closely approximate the population prevalence of this disorder.

Role of the DLGAP2 Gene Encoding the SAP90/PSD-95-Associated Protein 2 in Schizophrenia

PubMed Central

Li, Jun-Ming; Lu, Chao-Lin; Cheng, Min-Chih; Luu, Sy-Ueng; Hsu, Shih-Hsin; Hu, Tsung-Ming; Tsai, Hsin-Yao; Chen, Chia-Hsiang

2014-01-01

Aberrant synaptic dysfunction is implicated in the pathogenesis of schizophrenia. The DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 (SAPAP2) located at the post-synaptic density of neuronal cells is involved in the neuronal synaptic function. This study aimed to investigate whether the DLGAP2 gene is associated with schizophrenia. We resequenced the putative promoter region and all the exons of the DLGAP2 gene in 523 patients with schizophrenia and 596 non-psychotic controls from Taiwan and conducted a case-control association analysis. We identified 19 known SNPs in this sample. Association analysis of 9 SNPs with minor allele frequency greater than 5% showed no association with schizophrenia. However, we found a haplotype (CCACCAACT) significantly associated with schizophrenia (odds ratio:2.5, p<0.001). We also detected 16 missense mutations and 1 amino acid-insertion mutation in this sample. Bioinformatic analysis showed some of these mutations were damaging or pathological to the protein function, but we did not find increased burden of these mutations in the patient group. Notably, we identified 5 private rare variants in 5 unrelated patients, respectively, including c.−69+9C>T, c.−69+13C>T, c.−69+47C>T, c.−69+55C>T at intron 1 and c.−32A>G at untranslated exon 2 of the DLGAP2 gene. These rare variants were not detected in 559 control subjects. Further reporter gene assay of these rare variants except c.−69+13C>T showed significantly elevated promoter activity than the wild type, suggesting increased DLGAP2 gene expression may contribute to the pathogenesis of schizophrenia. Our results indicate that DLGAP2 is a susceptible gene of schizophrenia. PMID:24416398

Phenotypic characterization and genealogical tracing in an Afrikaner schizophrenia database.

PubMed

Karayiorgou, Maria; Torrington, Marie; Abecasis, Gonçalo R; Pretorius, Herman; Robertson, Brian; Kaliski, Sean; Lay, Stephen; Sobin, Christina; Möller, Natalie; Lundy, S Laura; Blundell, Maude L; Gogos, Joseph A; Roos, J Louw

2004-01-01

Founder populations hold tremendous promise for mapping genes for complex traits, as they offer less genetic and environmental heterogeneity and greater potential for genealogical research. Not all founder populations are equally valuable, however. The Afrikaner population meets several criteria that make it an ideal population for mapping complex traits, including founding by a small number of initial founders that likely allowed for a relatively restricted set of mutations and a large current population size that allows identification of a sufficient number of cases. Here, we examine the potential to conduct genealogical research in this population and present initial results indicating that accurate genealogical tracing for up to 17 generations is feasible. We also examine the clinical similarities of schizophrenia cases diagnosed in South Africa and those diagnosed in other, heterogeneous populations, specifically the US. We find that, with regard to basic sample descriptors and cardinal symptoms of disease, the two populations are equivalent. It is, therefore, likely that results from our genetic study of schizophrenia will be applicable to other populations. Based on the results presented here, the history and current size of the population, as well as our previous analysis addressing the extent of background linkage disequilibrium (LD) in the Afrikaners, we conclude that the Afrikaner population is likely an appropriate founder population to map genes for schizophrenia using both linkage and LD approaches. Copyright 2003 Wiley-Liss, Inc.

Rare variants in the neurotrophin signaling pathway implicated in schizophrenia risk.

PubMed

Kranz, Thorsten M; Goetz, Ray R; Walsh-Messinger, Julie; Goetz, Deborah; Antonius, Daniel; Dolgalev, Igor; Heguy, Adriana; Seandel, Marco; Malaspina, Dolores; Chao, Moses V

2015-10-01

Multiple lines of evidence corroborate impaired signaling pathways as relevant to the underpinnings of schizophrenia. There has been an interest in neurotrophins, since they are crucial mediators of neurodevelopment and in synaptic connectivity in the adult brain. Neurotrophins and their receptors demonstrate aberrant expression patterns in cortical areas for schizophrenia cases in comparison to control subjects. There is little known about the contribution of neurotrophin genes in psychiatric disorders. To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis. We herein report rare missense polymorphisms and novel missense mutations in neurotrophin receptor signaling pathway genes. Furthermore, we observed that several genes have a higher propensity to harbor missense coding variants than others. Based on this initial analysis we suggest that rare variants and missense mutations in neurotrophin genes might represent genetic contributions involved across psychiatric disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Neurological soft signs discriminate schizophrenia from bipolar disorder.

PubMed

Rigucci, Silvia; Dimitri-Valente, Giorgia; Mandarelli, Gabriele; Manfredi, Giovanni; Comparelli, Anna; De Filippis, Sergio; Gherardelli, Simona; Bersani, Giuseppe; Girardi, Paolo; Ferracuti, Stefano

2014-03-01

Although neurological soft signs have been consistently described in patients with schizophrenia, their diagnostic specificity is not well clarified. To test the hypothesis that neurological soft signs are specifically related to schizophrenia, we examined 305 subjects (patients with schizophrenia-spectrum disorder, n=167; patients with bipolar I disorder, n=88; controls, n=50). Neurological soft signs were assessed using the Neurological Evaluation Scale (NES). Multiple logistic regression analysis was used to compute the diagnostic predictive power of neurological soft signs. Patients in the schizophrenia-spectrum disorder group were found to have significantly greater neurological impairment (NES total score=23.9, standard deviation [SD] 11.2) than those in the bipolar disorder group (NES total score=18.2, SD 7.6; p<0.001). Neurological functioning was closely associated with psychopathology (all p<0.001). The NES total score reliably distinguished patients with schizophrenia spectrum disorders from those with bipolar disorder in 68.7% of the cases (p<0.001). Moreover, a particular set of neurological soft signs showed specificity for the schizophrenia-spectrum disorder diagnostic group. Our findings suggest that schizophrenia and bipolar disorder can be distinguished in terms of neurological impairment. Furthermore, we recommend the utility of neurological soft signs as a useful, quantifiable, sensitive, and inexpensive tool for the diagnostic work-up of schizophrenia.

The Use of Electroconvulsive Therapy in Atypical Psychotic Presentations

PubMed Central

Vasu, Devi

2007-01-01

Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial. Case reports have suggested a role for ECT in two specific atypical psychotic disorders: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis. PMID:20428309

The relationship of antisocial personality disorder and history of conduct disorder with crime incidence in schizophrenia

PubMed Central

Maghsoodloo, Safa; Ghodousi, Arash; Karimzadeh, Taghi

2012-01-01

Background: Commission of crime and hostility and their forensic consequences in a patient with schizophrenia can worsen the patient's condition and disturb his family, society, and even the psychiatrist. Based on previous research, patients with schizophrenia are at a higher risk for crime. It is not clear whether this is due to the nature of schizophrenia, comorbidity of antisocial personality disorder, or the history of conduct disorder in childhood. In this study, we investigated this hypothesis. Materials and Methods: In this case-control study, 30 criminal and 30 non-criminal patients with schizophrenia, who had been referred by the court to the Forensic Medicine Center of Isfahan, were evaluated for antisocial personality disorder, history of conduct disorder, and psychopathy checklist-revise (PCL-R) score. Results: Frequency distribution of antisocial personality disorder (73.3%), history of conduct disorder in childhood (86.7%), and score of PCL-R ≥25 (indicating high probability of hostility) in patients (40%) were significantly higher in criminal patients than in non-criminals (10%, 30% and 0%, respectively; P < 0.001). Conclusions: More prevalence of antisocial personality disorder, history of conduct disorder, and high score of PCL-R (≥25) in criminal schizophrenic patients may indicate that in order to control the hostility and for prevention of crime, besides treating acute symptoms of psychosis, patients might receive treatment and rehabilitation for comorbidities too. PMID:23626636

The relationship of antisocial personality disorder and history of conduct disorder with crime incidence in schizophrenia.

PubMed

Maghsoodloo, Safa; Ghodousi, Arash; Karimzadeh, Taghi

2012-06-01

Commission of crime and hostility and their forensic consequences in a patient with schizophrenia can worsen the patient's condition and disturb his family, society, and even the psychiatrist. Based on previous research, patients with schizophrenia are at a higher risk for crime. It is not clear whether this is due to the nature of schizophrenia, comorbidity of antisocial personality disorder, or the history of conduct disorder in childhood. In this study, we investigated this hypothesis. In this case-control study, 30 criminal and 30 non-criminal patients with schizophrenia, who had been referred by the court to the Forensic Medicine Center of Isfahan, were evaluated for antisocial personality disorder, history of conduct disorder, and psychopathy checklist-revise (PCL-R) score. Frequency distribution of antisocial personality disorder (73.3%), history of conduct disorder in childhood (86.7%), and score of PCL-R ≥25 (indicating high probability of hostility) in patients (40%) were significantly higher in criminal patients than in non-criminals (10%, 30% and 0%, respectively; P < 0.001). More prevalence of antisocial personality disorder, history of conduct disorder, and high score of PCL-R (≥25) in criminal schizophrenic patients may indicate that in order to control the hostility and for prevention of crime, besides treating acute symptoms of psychosis, patients might receive treatment and rehabilitation for comorbidities too.

Midbrain dopamine function in schizophrenia and depression: a post-mortem and positron emission tomographic imaging study.

PubMed

Howes, Oliver D; Williams, Matthew; Ibrahim, Kemal; Leung, Garret; Egerton, Alice; McGuire, Philip K; Turkheimer, Federico

2013-11-01

Elevated in vivo markers of presynaptic striatal dopamine activity have been a consistent finding in schizophrenia, and include a large effect size elevation in dopamine synthesis capacity. However, it is not known if the dopaminergic dysfunction is limited to the striatal terminals of dopamine neurons, or is also evident in the dopamine neuron cell bodies, which mostly originate in the substantia nigra. The aim of our studies was therefore to determine whether dopamine synthesis capacity is altered in the substantia nigra of people with schizophrenia, and how this relates to symptoms. In a post-mortem study, a semi-quantitative analysis of tyrosine hydroxylase staining was conducted in nigral dopaminergic cells from post-mortem tissue from patients with schizophrenia (n = 12), major depressive disorder (n = 13) and matched control subjects (n = 13). In an in vivo imaging study, nigral and striatal dopaminergic function was measured in patients with schizophrenia (n = 29) and matched healthy control subjects (n = 29) using (18)F-dihydroxyphenyl-L-alanine ((18)F-DOPA) positron emission tomography. In the post-mortem study we found that tyrosine hydroxylase staining was significantly increased in nigral dopaminergic neurons in schizophrenia compared with both control subjects (P < 0.001) and major depressive disorder (P < 0.001). There was no significant difference in tyrosine hydroxylase staining between control subjects and patients with major depressive disorder, indicating that the elevation in schizophrenia is not a non-specific indicator of psychiatric illness. In the in vivo imaging study we found that (18)F-dihydroxyphenyl-L-alanine uptake was elevated in both the substantia nigra and in the striatum of patients with schizophrenia (effect sizes = 0.85, P = 0.003 and 1.14, P < 0.0001, respectively) and, in the voxel-based analysis, was elevated in the right nigra (P < 0.05 corrected for family wise-error). Furthermore, nigral (18)F-dihydroxyphenyl-L-alanine uptake was positively related with the severity of symptoms (r = 0.39, P = 0.035) in patients. However, whereas nigral and striatal (18)F-dihydroxyphenyl-L-alanine uptake were positively related in control subjects (r = 0.63, P < 0.001), this was not the case in patients (r = 0.30, P = 0.11). These findings indicate that elevated dopamine synthesis capacity is seen in the nigral origin of dopamine neurons as well as their striatal terminals in schizophrenia, and is linked to symptom severity in patients.

Impact of obesity on health-related quality of life in schizophrenia and bipolar disorder.

PubMed

Kolotkin, Ronette L; Corey-Lisle, Patricia K; Crosby, Ross D; Swanson, Jodi M; Tuomari, Anne V; L'italien, Gilbert J; Mitchell, James E

2008-04-01

Studies have reported that up to 60% of individuals with schizophrenia and 68% of those with bipolar disorder are overweight/obese. This paper explores the health-related quality of life (HRQOL) of individuals with schizophrenia or bipolar disorder as a function of obesity status. Two hundred and eleven participants were recruited from four psychiatric programs (outpatient, day treatment, case management, and psychosocial rehabilitation). HRQOL was assessed using both a general measure (Medical Outcomes Study Short-Form-36 (SF-36)) and a weight-related measure (Impact of Weight on Quality of Life-Lite (IWQOL-Lite)). To interpret HRQOL scores obtained by the obese group, we compared scores to those obtained by reference groups from the weight-loss literature. Sixty-three percent of participants with schizophrenia and 68% of those with bipolar disorder were obese. Obese participants were more likely to be women, on mood stabilizers, taking a greater number of psychiatric medications, and to have poorer weight-related and general HRQOL. Weight-related HRQOL in the obese psychiatric sample was more impaired than in outpatient and day treatment samples seeking weight loss but less impaired than in gastric-bypass patients. Several of the physical domains of general HRQOL were more impaired for the obese psychiatric sample than for the outpatient weight-loss sample. However, physical functioning was less impaired for the obese psychiatric sample than for gastric-bypass patients. The presence of obesity among individuals with schizophrenia or bipolar disorder is associated with decreased HRQOL. These results have implications for prevention and management of weight gain in individuals with schizophrenia or bipolar disorder.

Holistic Management of Schizophrenia Symptoms Using Pharmacological and Non-pharmacological Treatment.

PubMed

Ganguly, Pronab; Soliman, Abdrabo; Moustafa, Ahmed A

2018-01-01

Individuals with schizophrenia lead a poor quality of life, due to poor medical attention, homelessness, unemployment, financial constraints, lack of education, and poor social skills. Thus, a review of factors associated with the holistic management of schizophrenia is of paramount importance. The objective of this review is to improve the quality of life of individuals with schizophrenia, by addressing the factors related to the needs of the patients and present them in a unified manner. Although medications play a role, other factors that lead to a successful holistic management of schizophrenia include addressing the following: financial management, independent community living, independent living skill, relationship, friendship, entertainment, regular exercise for weight gained due to medication administration, co-morbid health issues, and day-care programmes for independent living. This review discusses the relationship between different symptoms and problems individuals with schizophrenia face (e.g., homelessness and unemployment), and how these can be managed using pharmacological and non-pharmacological methods. Thus, the target of this review is the carers of individuals with schizophrenia, public health managers, counselors, case workers, psychiatrists, and clinical psychologists aiming to enhance the quality of life of individuals with schizophrenia.

Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

PubMed Central

2011-01-01

Background The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. Methods It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry. Results GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls. Conclusion This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages. PMID:21810251

Partial regimen replacement with aripiprazole reduces serum prolactin in patients with a long history of schizophrenia: A case series.

PubMed

Naono-Nagatomo, Keiko; Naono, Hisao; Abe, Hiroshi; Takeda, Ryuichiro; Funahashi, Hideki; Uchimura, Daisuke; Ishida, Yasushi

2017-02-01

Aripiprazole (ARP) is a popular antipsychotic drug that has demonstrated ameliorative effects on hyperprolactinemia. However, no study to date has studied the utility of ARP in patients with a long history of schizophrenia and antipsychotic treatment. We therefore examined the effect of partial antipsychotic regimen replacement with ARP on hyperprolactinemia induced by chronic antipsychotic use in patients with schizophrenia. Sixteen patients with a schizophrenia diagnosis (F2) based on the International Classification of Diseases (version 10) were recruited. At months 0, 1, 3, and 6 of the study, serum prolactin, body weight, and blood glucose were measured, and QOL and psychotic symptoms were assessed using Global Assessment of Functioning scores and Clinical Global Impressions of Improvement (CGI-I) scores. Nine patients with an average age of 46.7±9.6 years and mean disease duration of 15.9±10.4 years were included in the final analysis. Serum prolactin levels significantly decreased and GAF and CGI-I scores improved significantly over the 6-month period after partial replacement with ARP. Additionally, no changes were observed in body weight or blood glucose over the 6-month period. Partial antipsychotic regimen replacement with ARP improves hyperprolactinemia, and may improve the QOL of patients with a long history of schizophrenia. Japan Medical Association, Center for clinical trials D: JMA-IIA00245. Copyright © 2016 Elsevier B.V. All rights reserved.

Sleep Disturbances and Suicide Risk in an 8-Year Longitudinal Study of Schizophrenia-Spectrum Disorders.

PubMed

Li, Shirley Xin; Lam, Siu Ping; Zhang, Jihui; Yu, Mandy Wai Man; Chan, Joey Wing Yan; Chan, Cassandra Sheung Yan; Espie, Colin A; Freeman, Daniel; Mason, Oliver; Wing, Yun-Kwok

2016-06-01

Disrupted sleep is one of the prominent but often overlooked presenting symptoms in the clinical course of psychotic disorders. The aims of this study were to examine the prevalence of sleep disturbances, particularly insomnia and nightmares, and their prospective associations with the risk of suicide attempts in patients with schizophrenia-spectrum disorders. A naturalistic longitudinal study was conducted in outpatients diagnosed with schizophrenia-spectrum disorders recruited from the psychiatric outpatient clinic of a regional university-affiliated public hospital in Hong Kong. A detailed sleep questionnaire was completed by 388 patients at baseline in May-June 2006. Relevant clinical information was extracted from clinical case notes from June 2007-October 2014. Prevalence of frequent insomnia and frequent nightmares was 19% and 9%, respectively. Baseline frequent insomnia was significantly associated with an increased incidence of suicide attempts during the follow-up period (adjusted hazard ratio = 4.63, 95% confidence interval 1.40-15.36, P < 0.05). Nightmare complaint alone did not predict the occurrence of suicide attempts, but the comorbidity of nightmares and insomnia was associated with the risk of suicide attempt over follow-up (adjusted HR = 11.10, 95% confidence interval: 1.68-73.43, P < 0.05). Sleep disturbances are common in patients with schizophrenia-spectrum disorders. The association between sleep disturbances and suicidal risk underscores the need for enhanced clinical attention and intervention on sleep disturbances in patients with schizophrenia. © 2016 Associated Professional Sleep Societies, LLC.

Substance-induced psychoses converting into schizophrenia: a register-based study of 18,478 Finnish inpatient cases.

PubMed

Niemi-Pynttäri, Jussi A; Sund, Reijo; Putkonen, Hanna; Vorma, Helena; Wahlbeck, Kristian; Pirkola, Sami P

2013-01-01

Despite the clinical importance of substance-induced psychosis (SIP), few studies have examined the course of this condition after its acute manifestation. To investigate the rate of SIP conversion to a schizophrenia spectrum disorder and the length of follow-up needed to catch the majority of these patients whose diagnoses change. In addition to the conversion rate and pattern, we wanted to look for possible related factors. Using the nationwide Finnish Hospital Discharge Register, we followed all patients (N = 18,478) since their first inpatient hospital admission with a diagnosis of SIP (codes 2921 and 2928 in DSM-III-R and codes F10-F19 in ICD-10 with a third digit of 4, 5, or 7) between January 1987 and December 2003 in Finland. Patients (mean age = 43.7 years, standard deviation = 13.5 years) were followed until first occurrence of schizophrenia spectrum disorder, death, or the end of December 2003, whichever took place first. Conversions of discharge diagnoses into schizophrenia spectrum disorders (codes 2951-2959 and 2971 in DSM-III-R and codes F20, F22, and F23 in ICD-10) were recorded at follow-up. Eight-year cumulative risk to receive a schizophrenia spectrum diagnosis was 46% (95% CI, 35%-57%) for persons with a diagnosis of cannabis-induced psychosis and 30% (95% CI, 14%-46%) for those with an amphetamine-induced psychosis. Although alcohol-induced psychosis was the most common type of SIP, 8-year cumulative risk for subsequent schizophrenia spectrum diagnosis was only 5.0% (95% CI, 4.6%-5.5%). No differences were detected with regard to gender, except for amphetamine-induced psychosis, which converted into a schizophrenia spectrum disorder significantly more often in men (P = .04). The majority of conversions to a schizophrenia spectrum diagnosis occurred during the first 3 years following the index treatment period, especially for cannabis-induced psychosis. Substance-induced psychotic disorders predict schizophrenia spectrum disorders to a greater extent than previously thought. The intensity of clinical attention focused on substance-induced psychotic disorders should be increased. © Copyright 2013 Physicians Postgraduate Press, Inc.

Neurocognitive performance in family-based and case-control studies of schizophrenia.

PubMed

Gur, Ruben C; Braff, David L; Calkins, Monica E; Dobie, Dorcas J; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Gur, Raquel E

2015-04-01

Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia.

PubMed

Johnson, Matthew R; Morris, Nicholas A; Astur, Robert S; Calhoun, Vince D; Mathalon, Daniel H; Kiehl, Kent A; Pearlson, Godfrey D

2006-07-01

Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia. We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla. Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results. Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.

[Risk factors for schizophrenia patients with type 2 diabetes: a metaanalysis].

PubMed

Zhou, Min; Xiao, Chuan; Yang, Min; Yuan, Ping; Liu, Yuanyuan

2015-03-01

To investigate risk factors for schizophrenia patients with complication of type 2 diabetes mellitus and to provide scientific evidence for prevention and management of this disease. Relevant studies on schizophrenia with type 2 diabetes mellitus in China were searched through PubMed, Medline, CBM, CNKI and VIP from 1997 to 2014. Meta-analysis was performed using RevMan 5.2 soft ware. A total of 26 studies involving 6 373 participants (including 957 cases and 5 416 controls) were included. The results of Meta-analysis showed that the risk factors for schizophrenic patients with complication of type 2 diabetes mellitus were: gender (female) (OR=1.28, 95%CI: 1.09-1.50), age (≥ 40 year) (OR=6.02, 95%CI: 4.48-8.09), overweight (OR=2.32, 95%CI: 1.52-2.88), family history of diabetes (OR=6.12, 95%CI: 3.16-11.86), duration of schizophrenia (>10 years) (OR=3.60, 95%CI: 2.39-5.41), triglycerides (MD=0.38, 95%CI: 0.05-0.71). Male, old age, overweight, family history of diabetes, longer duration and high level of triglycerides are risk factors for schizophrenic patients with complication of diabetes mellitus.

Psychosocial Acute Treatment in Early-Episode Schizophrenia Disorders

ERIC Educational Resources Information Center

Bola, John R.

2006-01-01

Objective: This article reviews evidence on the treatment of early episode schizophrenia spectrum disorders that contradicts, in some cases, the American Psychiatric Association's generic recommendation of antipsychotic medication treatment for at least a year. Method: Evidence on lack of diagnostic validity, absence of demonstrated long-term…

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

PubMed Central

Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

2017-01-01

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome. PMID:28127577

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.

PubMed

Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

2017-01-01

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.

PubMed

Bernstein, Hans-Gert; Müller, Susan; Dobrowolny, Hendrik; Wolke, Carmen; Lendeckel, Uwe; Bukowska, Alicja; Keilhoff, Gerburg; Becker, Axel; Trübner, Kurt; Steiner, Johann; Bogerts, Bernhard

2017-08-01

The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

PubMed

Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine; Christensen, Anne Marie Raaberg; Nordentoft, Merete; Mortensen, Erik Lykke

2013-10-01

Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms. © 2013 The Scandinavian Psychological Associations.

Symptoms of psychosis in schizophrenia, schizoaffective disorder, and bipolar disorder: A comparison of African Americans and Caucasians in the Genomic Psychiatry Cohort.

PubMed

Perlman, Greg; Kotov, Roman; Fu, Jinmiao; Bromet, Evelyn J; Fochtmann, Laura J; Medeiros, Helena; Pato, Michele T; Pato, Carlos N

2016-06-01

Several studies have reported differences between African Americans and Caucasians in relative proportion of psychotic symptoms and disorders, but whether this reflects racial bias in the assessment of psychosis is unclear. The purpose of this study was to examine the distribution of psychotic symptoms and potential bias in symptoms assessed via semi-structured interview using a cohort of 3,389 African American and 5,692 Caucasian participants who were diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. In this cohort, the diagnosis of schizophrenia was relatively more common, and the diagnosis of bipolar disorder and schizoaffective disorder-bipolar type was less relatively common, among African Americans than Caucasians. With regard to symptoms, relatively more African Americans than Caucasians endorsed hallucinations and delusions symptoms, and this pattern was striking among cases diagnosed with bipolar disorder and schizoaffective-bipolar disorder. In contrast, the relative endorsement of psychotic symptoms was more similar among cases diagnosed with schizophrenia and schizoaffective disorder-depressed type. Differential item function analysis revealed that African Americans with mild psychosis over-endorsed "hallucinations in any modality" and under-endorsed "widespread delusions" relative to Caucasians. Other symptoms did not show evidence of racial bias. Thus, racial bias in assessment of psychotic symptoms does not appear to explain differences in the proportion of symptoms between Caucasians and African Americans. Rather, this may reflect ascertainment bias, perhaps indicative of a disparity in access to services, or differential exposure to risk factors for psychosis by race. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The impact of a short-term cohousing initiative among schizophrenia patients, high school students, and their social context: A qualitative case study

PubMed Central

2018-01-01

Background A number of programs have been developed to promote the contact between adolescents and mentally-ill patients, in order to break the stigma, improve understanding, promote mental health and prevent substance abuse. The aim of this study was to describe the experience of patients with schizophrenia, high school students, and their social context, participating in a short-term cohousing initiative. Methods A qualitative case-study approach was implemented. Patients with schizophrenia from the San Juan de Dios Psychiatric Hospital, female students from Almen High School, and participants from their social context (parents, hospital staff, and teachers) were included, using purposeful sampling. Data were collected from 51 participants (15 patients, nine students, 11 hospital staff, six teachers, 10 parents) via non-participant observation, focus groups, informal interviews, researchers’ field notes and patients’ personal diaries and letters. A thematic analysis was performed. Results The themes identified included a) learning to live together: students and patients participate and learn together; b) the perception of the illness and the mentally-ill: the barrier between health and disease is very slim, and society tends to avoid contact with those who are ill; c) change: a transformation takes place in students, in their self-perception, based on the real and intense nature of the experience; d) a trial and an opportunity: patients test their ability to live outside the hospital; e) discharge and readmission: discharge is experienced as both a liberation and a difficulty, whereas relapse and readmission are experienced as failures. Conclusions Our findings can help us to better understand schizophrenia and encourage a more positive approach towards both the illness and those who suffer from it. These results may be used for the development of cohousing programs in controlled environments. PMID:29324773

The impact of a short-term cohousing initiative among schizophrenia patients, high school students, and their social context: A qualitative case study.

PubMed

Palacios-Ceña, Domingo; Martín-Tejedor, Emilio Andrés; Elías-Elispuru, Ana; Garate-Samaniego, Amaia; Pérez-Corrales, Jorge; García-García, Elena

2018-01-01

A number of programs have been developed to promote the contact between adolescents and mentally-ill patients, in order to break the stigma, improve understanding, promote mental health and prevent substance abuse. The aim of this study was to describe the experience of patients with schizophrenia, high school students, and their social context, participating in a short-term cohousing initiative. A qualitative case-study approach was implemented. Patients with schizophrenia from the San Juan de Dios Psychiatric Hospital, female students from Almen High School, and participants from their social context (parents, hospital staff, and teachers) were included, using purposeful sampling. Data were collected from 51 participants (15 patients, nine students, 11 hospital staff, six teachers, 10 parents) via non-participant observation, focus groups, informal interviews, researchers' field notes and patients' personal diaries and letters. A thematic analysis was performed. The themes identified included a) learning to live together: students and patients participate and learn together; b) the perception of the illness and the mentally-ill: the barrier between health and disease is very slim, and society tends to avoid contact with those who are ill; c) change: a transformation takes place in students, in their self-perception, based on the real and intense nature of the experience; d) a trial and an opportunity: patients test their ability to live outside the hospital; e) discharge and readmission: discharge is experienced as both a liberation and a difficulty, whereas relapse and readmission are experienced as failures. Our findings can help us to better understand schizophrenia and encourage a more positive approach towards both the illness and those who suffer from it. These results may be used for the development of cohousing programs in controlled environments.

Association of IQ Changes and Progressive Brain Changes in Patients With Schizophrenia.

PubMed

Kubota, Manabu; van Haren, Neeltje E M; Haijma, Sander V; Schnack, Hugo G; Cahn, Wiepke; Hulshoff Pol, Hilleke E; Kahn, René S

2015-08-01

Although schizophrenia is characterized by impairments in intelligence and the loss of brain volume, the relationship between changes in IQ and brain measures is not clear. To investigate the association between IQ and brain measures in patients with schizophrenia across time. Case-control longitudinal study at the Department of Psychiatry at the University Medical Center Utrecht, Utrecht, the Netherlands, comparing patients with schizophrenia and healthy control participants between September 22, 2004, and April 17, 2008. Magnetic resonance imaging of the brain and IQ scores were obtained at baseline and the 3-year follow-up. Participants included 84 patients with schizophrenia (mean illness duration, 4.35 years) and 116 age-matched healthy control participants. Associations between changes in IQ and the total brain, cerebral gray matter, cerebral white matter, lateral ventricular, third ventricles, cortical, and subcortical volumes; cortical thickness; and cortical surface area. Cerebral gray matter volume (P = .006) and cortical volume (P = .03) and thickness (P = .02) decreased more in patients with schizophrenia across time compared with control participants. Patients showed additional loss in cortical volume and thickness of the right supramarginal, posterior superior temporal, left supramarginal, left postcentral, and occipital regions (P values were between <.001 and .03 after clusterwise correction). Although IQ increased similarly in patients with schizophrenia and control participants, changes in IQ were negatively correlated with changes in lateral ventricular volume (P = .05) and positively correlated with changes in cortical volume (P = .007) and thickness (P = .004) only in patients with schizophrenia. Positive correlations between changes in IQ and cortical volume and thickness were found globally and in widespread regions across frontal, temporal, and parietal cortices (P values were between <.001 and .03 after clusterwise correction). These findings were independent of symptom severity at follow-up, cannabis use, and the use of cumulative antipsychotic medications during the 3 years of follow-up. Progressive brain tissue loss in schizophrenia is related to relative cognitive decline during the early course of illness.

Going beyond: an adventure- and recreation-based group intervention promotes well-being and weight loss in schizophrenia.

PubMed

Voruganti, Lakshmi N P; Whatham, Jeff; Bard, Eleanor; Parker, Gayle; Babbey, Candice; Ryan, Janet; Lee, Suganya; MacCrimmon, Duncan J

2006-08-01

To undertake a preliminary study to assess the feasibility of clinical implementation and evaluate the effectiveness of a novel adventure- and recreation-based group intervention in the rehabilitation of individuals with schizophrenia. In a 2-year, prospective, case-control study, 23 consecutively referred, clinically stabilized schizophrenia patients received the new intervention over an 8-month period; 31 patients on the wait list, considered the control group, received standard clinical care that included some recreational activities. Symptom severity, self-esteem, self-appraised cognitive abilities, and functioning were documented for both groups with standardized rating scales administered at baseline, on completion of treatment, and at 12 months posttreatment. Treatment adherence was 97%, and there were no dropouts. Patients in the study group showed marginal improvement in perceived cognitive abilities and on domain-specific functioning measures but experienced a significant improvement in their self-esteem and global functioning (P < 0.05), as well as a weight loss of over 12 lb. Improvement was sustained over 1 year with further occupational and social gains. In the context of overcoming barriers to providing early intervention for youth and preventing metabolic problems among older adults with schizophrenia, adventure- and recreation-based interventions could play a useful complementary role.

Gene expression elucidates functional impact of polygenic risk for schizophrenia.

PubMed

Fromer, Menachem; Roussos, Panos; Sieberts, Solveig K; Johnson, Jessica S; Kavanagh, David H; Perumal, Thanneer M; Ruderfer, Douglas M; Oh, Edwin C; Topol, Aaron; Shah, Hardik R; Klei, Lambertus L; Kramer, Robin; Pinto, Dalila; Gümüş, Zeynep H; Cicek, A Ercument; Dang, Kristen K; Browne, Andrew; Lu, Cong; Xie, Lu; Readhead, Ben; Stahl, Eli A; Xiao, Jianqiu; Parvizi, Mahsa; Hamamsy, Tymor; Fullard, John F; Wang, Ying-Chih; Mahajan, Milind C; Derry, Jonathan M J; Dudley, Joel T; Hemby, Scott E; Logsdon, Benjamin A; Talbot, Konrad; Raj, Towfique; Bennett, David A; De Jager, Philip L; Zhu, Jun; Zhang, Bin; Sullivan, Patrick F; Chess, Andrew; Purcell, Shaun M; Shinobu, Leslie A; Mangravite, Lara M; Toyoshiba, Hiroyoshi; Gur, Raquel E; Hahn, Chang-Gyu; Lewis, David A; Haroutunian, Vahram; Peters, Mette A; Lipska, Barbara K; Buxbaum, Joseph D; Schadt, Eric E; Hirai, Keisuke; Roeder, Kathryn; Brennand, Kristen J; Katsanis, Nicholas; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela

2016-11-01

Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ∼20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were ≤ 1.33, and an independent cohort yielded similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases.

A polygenic burden of rare disruptive mutations in schizophrenia

PubMed Central

Purcell, Shaun M.; Moran, Jennifer L.; Fromer, Menachem; Ruderfer, Douglas; Solovieff, Nadia; Roussos, Panos; O’Dushlaine, Colm; Chambert, Kimberly; Bergen, Sarah E.; Kähler, Anna; Duncan, Laramie; Stahl, Eli; Genovese, Giulio; Fernández, Esperanza; Collins, Mark O; Komiyama, Noboru H.; Choudhary, Jyoti S.; Magnusson, Patrik K. E.; Banks, Eric; Shakir, Khalid; Garimella, Kiran; Fennell, Tim; de Pristo, Mark; Grant, Seth G.N.; Haggarty, Stephen; Gabriel, Stacey; Scolnick, Edward M.; Lander, Eric S.; Hultman, Christina; Sullivan, Patrick F.; McCarroll, Steven A.; Sklar, Pamela

2014-01-01

By analyzing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we have demonstrated a polygenic burden primarily arising from rare (<1/10,000), disruptive mutations distributed across many genes. Especially enriched genesets included the voltage-gated calcium ion channel and the signaling complex formed by the activity-regulated cytoskeleton-associated (ARC) scaffold protein of the postsynaptic density (PSD), sets previously implicated by genome-wide association studies (GWAS) and copy-number variation (CNV) studies. Similar to reports in autism, targets of the fragile × mental retardation protein (FMRP, product of FMR1) were enriched for case mutations. No individual gene-based test achieved significance after correction for multiple testing and we did not detect any alleles of moderately low frequency (~0.5-1%) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene mapping paradigms in neuropsychiatric disease. PMID:24463508

Low-level He-Ne laser in intravascular irradiation treatment of schizophrenia

NASA Astrophysics Data System (ADS)

Zhou, Yu-Xue; Fu, Zheng-Hua

1998-11-01

Intravascular low level He-Ne laser irradiation is a new therapy developed in recent years. In our hospital it was applied in the treatment and observation of 220 cases of schizophrenia, among which certain effect was achieved and about which the detail was collated and elaborated.

Sleep in schizophrenia: A systematic review and meta-analysis of polysomnographic findings in case-control studies.

PubMed

Chan, Man-Sum; Chung, Ka-Fai; Yung, Kam-Ping; Yeung, Wing-Fai

2017-04-01

Polysomnographic studies have been performed to examine the sleep abnormalities in schizophrenia, but the results are inconsistent. An updated systematic review, meta-analysis, and moderator analysis was conducted. Major databases were searched without language restriction from 1968 to January 2014. Data were analyzed using the random-effects model and summarized using the Hedges's g. Thirty-one studies with 574 patients and 515 healthy controls were evaluated. Limited by the number of studies and a lack of patient-level data, moderator analysis was restricted to medication status, duration of medication withdrawal, and illness duration. We showed that patients with schizophrenia have significantly shorter total sleep time, longer sleep onset latency, more wake time after sleep onset, lower sleep efficiency, and decreased stage 4 sleep, slow wave sleep, and duration and latency of rapid eye movement sleep compared to healthy controls. The findings on delta waves and sleep spindles were inconsistent. Moderator analysis could not find any abnormalities in sleep architecture in medication-naïve patients. Patients with antipsychotic withdrawal for longer than eight weeks were shown to have less sleep architectural abnormalities, compared to shorter duration of withdrawal, but the abnormalities in sleep continuity were similar. Slow wave sleep deficit was found in patients with schizophrenia for more than three years, while sleep onset latency was increased in medication-naïve, medication-withdrawn, and medicated patients. Our study showed that polysomnographic abnormalities are present in schizophrenia. Illness duration, medication status, and duration of medication withdrawal are several of the clinical factors that contribute to the heterogeneity between studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

CNS changes in Usher's syndrome with mental disorder: CT, MRI and PET findings.

PubMed Central

Koizumi, J; Ofuku, K; Sakuma, K; Shiraishi, H; Iio, M; Nawano, S

1988-01-01

CNS changes in a case of Usher's syndrome associated with schizophrenia-like mental disorder were observed by CT, MRI and PET. The neuro-radiological findings of the case demonstrate the degenerative and metabolic alterations in various regions of cortex, white matter and subcortical areas in the brain. Mental disorder of the case is almost indistinguishable from that of schizophrenia, but the psychotic feature is regarded as an atypical or mixed organic brain syndrome according to the classification in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Images PMID:3264568

DNA pooling: a comprehensive, multi-stage association analysis of ACSL6 and SIRT5 polymorphisms in schizophrenia.

PubMed

Chowdari, K V; Northup, A; Pless, L; Wood, J; Joo, Y H; Mirnics, K; Lewis, D A; Levitt, P R; Bacanu, S-A; Nimgaonkar, V L

2007-04-01

Many candidate gene association studies have evaluated incomplete, unrepresentative sets of single nucleotide polymorphisms (SNPs), producing non-significant results that are difficult to interpret. Using a rapid, efficient strategy designed to investigate all common SNPs, we tested associations between schizophrenia and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5). We initially evaluated the utility of DNA sequencing traces to estimate SNP allele frequencies in pooled DNA samples. The mean variances for the DNA sequencing estimates were acceptable and were comparable to other published methods (mean variance: 0.0008, range 0-0.0119). Using pooled DNA samples from cases with schizophrenia/schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders edition IV criteria) and controls (n=200, each group), we next sequenced all exons, introns and flanking upstream/downstream sequences for ACSL6 and SIRT5. Among 69 identified SNPs, case-control allele frequency comparisons revealed nine suggestive associations (P<0.2). Each of these SNPs was next genotyped in the individual samples composing the pools. A suggestive association with rs 11743803 at ACSL6 remained (allele-wise P=0.02), with diminished evidence in an extended sample (448 cases, 554 controls, P=0.062). In conclusion, we propose a multi-stage method for comprehensive, rapid, efficient and economical genetic association analysis that enables simultaneous SNP detection and allele frequency estimation in large samples. This strategy may be particularly useful for research groups lacking access to high throughput genotyping facilities. Our analyses did not yield convincing evidence for associations of schizophrenia with ACSL6 or SIRT5.

The HLA DQB1 gene locus: Further evidence for an association with schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, X.R.; Rudert, W.A.; Nimgaonkar, L.

A genetic predisposition to schizophrenia is well-established. Immunological abnormalities suggestive of an auto-immune disorder have also been noted. However, no consistent associations with HLA have been detected. A negative association between schizophrenia and HLA DQB1*0602 among African-Americans, but not among Caucasian individuals, was reported recently. The association is plausible, because (i) an association of insulin dependent diabetes mellitus (IDDM) with the HLA DQB1 gene locus is known, and (ii) an inverse relationship between the prevalence of schizophrenia and IDDM has been suggested. In view of the ethnic differences in the above association, a cohort of Chinese ethnicity from Singapore wasmore » examined in the present study. Consenting male inpatients with schizophrenia (n=102, ICD-9 criteria) participated. The controls were male adults undergoing pre-employment checkup (n=111). HLA DQB1 gene polymorphisms were analyzed using a PCR-based reverse dot-blot assay. In case of ambiguity, samples were checked using PCR amplification with sequence-specific primers. In support of the earlier report, a negative association with HLA DQB1*0602 was noted (odds ratio 0.22, C.I. 0.18, 0.83; {chi}{sup 2}=8.0, p<0.005; both analyses uncorrected for multiple comparisons).« less

Treating impaired cognition in schizophrenia: the case for combining cognitive-enhancing drugs with cognitive remediation.

PubMed

Michalopoulou, Panayiota G; Lewis, Shôn W; Wykes, Til; Jaeger, Judith; Kapur, Shitij

2013-08-01

Cognitive impairment is a well-documented feature of schizophrenia and represents a major impediment to the functional recovery of patients. The therapeutic strategies to improve cognition in schizophrenia have either used medications (collectively referred to as 'cognitive-enhancing drugs' in this article) or non-pharmacological training approaches ('cognitive remediation'). Cognitive-enhancing drugs have not as yet been successful and cognitive remediation has shown modest success. Therefore, we may need to explore new therapeutic paradigms to improve cognition in schizophrenia. The optimal approach may require a combination of cognitive-enhancing drugs with cognitive remediation. We review the available data from animal and human studies that provide the conceptual basis, proof-of-concept and illustrations of success of such combination strategies in experimental and clinical paradigms in other conditions. We address the major design issues relevant to the choice of the cognitive-enhancing drugs and cognitive remediation, as well as the timing and the duration of the intervention as will be relevant for schizophrenia. Finally, we address the practical realities of the development and testing of such combined approaches in the real-world clinical situation and conclude that while scientifically attractive, there are several practical difficulties to be overcome for this approach to be clinically feasible. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

[Intervention of Schizophrenia From the Community Model].

PubMed

Taborda Zapata, Eliana María; Montoya González, Laura Elisa; Gómez Sierra, Natalia María; Arteaga Morales, Laura María; Correa Rico, Oscar Andrés

2016-01-01

Schizophrenia is a complex disease for which pharmacological management is an insufficient therapeutic measure to ensure adaptation to the community and restoring the quality of life of the patient, with a multidimensional management and community interventions being necessary. Case report. This case report illustrates a multidisciplinary treatment response, based on a community care model for mental health from Envigado, Colombia. The management of schizophrenia requires multimodal interventions that include community screening, psychoeducation of individuals, their families and society, addressing different areas of operation that allow adaptation of the subject to his social environment. A integrated intervention that can be provided on a Community scale, with the implementation of policies that allow it to be applied. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Blonanserin, a novel antipsychotic, is suitable for treating schizophrenia associated with hyperprolactinemia: a case series.

PubMed

Kawabe, Kentaro; Horiuchi, Fumie; Ueno, Shu-ichi

2013-01-01

Recently, atypical antipsychotic agents have primarily been used in pharmacological treatment of schizophrenia because of the fewer associated adverse effects. Blonanserin is a novel atypical antipsychotic recently introduced to treat patients with schizophrenia in Japan and South Korea. In this study, we examined the efficacy of switching antipsychotic medications to blonanserin monotherapy in patients with chronic schizophrenia with associated hyperprolactinemia. Ten schizophrenic patients (5 males and 5 females) with hyperprolactinemia were recruited. Clinical data before (baseline) and 12 weeks after (end point) switching to blonanserin monotherapy were assessed using the Brief Psychiatric Rating Scale score, Drug-Induced Extrapyramidal Symptoms Scale, and serum prolactin levels. The mean (SD) blonanserin dosage was 14.8 (3.8) mg/d. After switching to blonanserin, there were significant improvements in the Brief Psychiatric Rating Scale in the patients from both sexes. Moreover, serum prolactin levels in the female patients significantly decreased to within reference range. There were no additional adverse effects observed with the blonanserin treatment. Switching to blonanserin can reverse medication-induced prolactin elevations found in female patients- and blonanserin is a suitable antipsychotic for schizophrenic patients.

Cortical grey matter volume reduction in people with schizophrenia is associated with neuro-inflammation

PubMed Central

Zhang, Y; Catts, V S; Sheedy, D; McCrossin, T; Kril, J J; Shannon Weickert, C

2016-01-01

Cortical grey matter volume deficits and neuro-inflammation exist in patients with schizophrenia, although it is not clear whether elevated cytokines contribute to the cortical volume reduction. We quantified cortical and regional brain volumes in fixed postmortem brains from people with schizophrenia and matched controls using stereology. Interleukin (IL)-6, IL-1β, IL-8 and SERPINA3 messenger RNAs (mRNAs) were quantified in the contralateral fresh frozen orbitofrontal cortex. We found a small, but significant reduction in cortical grey matter (1.3% F(1,85)=4.478, P=0.037) and superior frontal gyrus (6.5% F(1,80)=5.700, P=0.019) volumes in individuals with schizophrenia compared with controls. Significantly reduced cortical grey matter (9.2% F(1,24)=8.272, P=0.008) and superior frontal gyrus (13.9% F(1,20)=5.374, P=0.031) volumes were found in cases with schizophrenia and ‘high inflammation' status relative to schizophrenia cases with ‘low inflammation' status in the prefrontal cortex. The expression of inflammatory mRNAs in the orbitofrontal cortex was significantly correlated with those in dorsolateral prefrontal cortex (all r>0.417, all P<0.022), except for IL-8. Moreover, average daily and lifetime antipsychotic intake negatively correlated with cortical grey matter and superior frontal gyrus volumes (all r<−0.362, all P<0.05). The results suggest that the reduction in cortical grey matter volume in people with schizophrenia is exaggerated in those who have high expression of inflammatory cytokines. Further, antipsychotic medication intake does not appear to ameliorate the reduction in brain volume. PMID:27959331

Response to benzodiazepines and the clinical course in malignant catatonia associated with schizophrenia

PubMed Central

Ohi, Kazutaka; Kuwata, Aki; Shimada, Takamitsu; Yasuyama, Toshiki; Nitta, Yusuke; Uehara, Takashi; Kawasaki, Yasuhiro

2017-01-01

Abstract Background: Malignant catatonia (MC) is a disorder consisting of catatonic symptoms, hyperthermia, autonomic instability, and altered mental status. Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments providing rapid relief from MC. This case study reports a detailed clinical course of a case of MC associated with schizophrenia initially diagnosed as NMS that responded successfully to BZDs but not to dantrolene. Case presentation: A 53-year-old man with schizophrenia was admitted to the psychiatric hospital because of excitement, monologue, muscle rigidity, and insomnia. In the 3 days before admission, the patient had discontinued his medications after his family member's death. He presented with hyperthermia, tachycardia, hypertension, excessive sweating, and an elevated serum creatine phosphokinase (CPK) level. On the basis of these features, he was suspected to have NMS. The patient was treated with dantrolene for 7 days without improvement despite having a normalized serum CPK level. The patient was transferred to our university hospital for an in-depth examination and treatment of his physical status. Infection and pulmonary embolism were excluded as possible causes. To treat his excitement and auditory hallucination, an intravenous drip (IVD) of haloperidol was initiated, but this treatment increased the patient's catatonic and psychotic symptoms, although his serum CPK level had remained within a normal range. As a result, the treatment was changed to diazepam. After an IVD of diazepam, the patient's symptoms rapidly improved, and the IVD was subsequently replaced with oral administration of lorazepam. Eventually, the patient was diagnosed with MC associated with schizophrenia. BZD therapy was dramatically effective. Conclusion: Catatonia, MNS, and MC may be due to a common brain pathophysiology and these conditions may be in a spectrum, although uncertainty in the boundaries among conditions, and the BZD treatment may be useful. Most importantly, catatonia has not been described as a subtype of schizophrenia on the basis of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, and the medications for catatonia and schizophrenia are different. Antipsychotics are not effective in relieving catatonia, or they may induce NMS, whereas BZDs are effective for treating both MC and NMS. PMID:28422845

Microduplications of 16p11.2 are Associated with Schizophrenia

PubMed Central

McCarthy, Shane; Makarov, Vladimir; Kirov, George; Addington, Anjene; McClellan, Jon; Yoon, Seungtai; Perkins, Dianna; Dickel, Diane E.; Kusenda, Mary; Krastoshevsky, Olga; Krause, Verena; Kumar, Ravinesh A.; Grozeva, Detelina; Malhotra, Dheeraj; Walsh, Tom; Zackai, Elaine H.; Kaplan, Paige; Ganesh, Jaya; Krantz, Ian D.; Spinner, Nancy B.; Roccanova, Patricia; Bhandari, Abhishek; Pavon, Kevin; Lakshmi, B.; Leotta, Anthony; Kendall, Jude; Lee, Yoon-ha; Vacic, Vladimir; Gary, Sydney; Iakoucheva, Lilia; Crow, Timothy J.; Christian, Susan L.; Lieberman, Jeffrey; Stroup, Scott; Lehtimäki, Terho; Puura, Kaija; Haldeman-Englert, Chad; Pearl, Justin; Goodell, Meredith; Willour, Virginia L.; DeRosse, Pamela; Steele, Jo; Kassem, Layla; Wolff, Jessica; Chitkara, Nisha; McMahon, Francis J.; Malhotra, Anil K.; Potash, James B.; Schulze, Thomas G.; Nöthen, Markus M.; Cichon, Sven; Rietschel, Marcella; Leibenluft, Ellen; Kustanovich, Vlad; Lajonchere, Clara M.; Sutcliffe, James S.; Skuse, David; Gill, Michael; Gallagher, Louise; Mendell, Nancy R.; Craddock, Nick; Owen, Michael J.; O’Donovan, Michael C.; Shaikh, Tamim H.; Susser, Ezra; DeLisi, Lynn E.; Sullivan, Patrick F.; Deutsch, Curtis K.; Rapoport, Judith; Levy, Deborah L.; King, Mary-Claire; Sebat, Jonathan

2010-01-01

Recurrent microdeletions and microduplications of a 600 kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1-3. Here we report the strong association of 16p11.2 microduplications with schizophrenia in two large cohorts. In the primary sample, the microduplication was detected in 12/1906 (0.63%) cases and 1/3971 (0.03%) controls (P=1.2×10-5, OR=25.8). In the replication sample, the microduplication was detected in 9/2645 (0.34%) cases and 1/2420 (0.04%) controls (P=0.022, OR=8.3). For the series combined, microduplication of 16p11.2 was associated with 14.5-fold increased risk of schizophrenia (95% C.I. [3.3, 62]). A meta-analysis of multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. The reciprocal microdeletion was associated only with autism and developmental disorders. Analysis of patient clinical data showed that head circumference was significantly larger in patients with the microdeletion compared with patients with the microduplication (P = 0.0007). Our results suggest that the microduplication of 16p11.2 confers substantial risk for schizophrenia and other psychiatric disorders, whereas the reciprocal microdeletion is associated with contrasting clinical features. PMID:19855392

Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

PubMed Central

2013-01-01

Background In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. Case presentation We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Conclusion Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding. PMID:23648137

Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

PubMed Central

Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

2013-01-01

Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

Minor physical anomalies and craniofacial measures in patients with treatment-resistant schizophrenia.

PubMed

Lin, A-S; Chang, S-S; Lin, S-H; Peng, Y-C; Hwu, H-G; Chen, W J

2015-07-01

Schizophrenia patients have higher rates of minor physical anomalies (MPAs) than controls, particularly in the craniofacial region; this difference lends support to the neurodevelopmental model of schizophrenia. Whether MPAs are associated with treatment response in schizophrenia remains unknown. The aim of this case-control study was to investigate whether more MPAs and specific quantitative craniofacial features in patients with schizophrenia are associated with operationally defined treatment resistance. A comprehensive scale, consisting of both qualitatively measured MPAs and quantitative measurements of the head and face, was applied in 108 patients with treatment-resistant schizophrenia (TRS) and in 104 non-TRS patients. Treatment resistance was determined according to the criteria proposed by Conley & Kelly (2001; Biological Psychiatry 50, 898-911). Our results revealed that patients with TRS had higher MPA scores in the mouth region than non-TRS patients, and the two groups also differed in four quantitative measurements (facial width, lower facial height, facial height, and length of the philtrum), after controlling for multiple comparisons using the false discovery rate. Among these dysmorphological measurements, three MPA item types (mouth MPA score, facial width, and lower facial height) and earlier disease onset were further demonstrated to have good discriminant validity in distinguishing TRS from non-TRS patients in a multivariable logistic regression analysis, with an area under the curve of 0.84 and a generalized R 2 of 0.32. These findings suggest that certain MPAs and craniofacial features may serve as useful markers for identifying TRS at early stages of the illness.

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia

PubMed Central

Yamada, Kazuo; Gerber, David J.; Iwayama, Yoshimi; Ohnishi, Tetsuo; Ohba, Hisako; Toyota, Tomoko; Aruga, Jun; Minabe, Yoshio; Tonegawa, Susumu; Yoshikawa, Takeo

2007-01-01

The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. To replicate and extend our previously reported association between the PPP3CC gene, encoding the calcineurin catalytic γ-subunit, and schizophrenia, we examined 84 SNPs from 14 calcineurin-related candidate genes for genetic association by using 124 Japanese schizophrenic pedigrees. Four of these genes (PPP3CC, EGR2, EGR3, and EGR4) showed nominally significant association with schizophrenia. In a postmortem brain study, EGR1, EGR2, and EGR3 transcripts were shown to be down-regulated in the prefrontal cortex of schizophrenic, but not bipolar, patients. These findings raise a potentially important role for EGR genes in schizophrenia pathogenesis. Because EGR3 is an attractive candidate gene based on its chromosomal location close to PPP3CC within 8p21.3 and its functional link to dopamine, glutamate, and neuregulin signaling, we extended our analysis by resequencing the entire EGR3 genomic interval and detected 15 SNPs. One of these, IVS1 + 607A→G SNP, displayed the strongest evidence for disease association, which was confirmed in 1,140 independent case-control samples. An in vitro promoter assay detected a possible expression-regulatory effect of this SNP. These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene. PMID:17360599

Values in First-Episode Schizophrenia.

PubMed

Agid, Ofer; Mcdonald, Krysta; Fervaha, Gagan; Littrell, Romie; Thoma, Jessica; Zipursky, Robert B; Foussias, George; Remington, Gary

2015-11-01

Functional impairment continues to represent a major challenge in schizophrenia. Surprisingly, patients with schizophrenia report a level of happiness comparable with control subjects, even in the face of the prominent functional deficits, a finding at odds with evidence indicating a positive relation between happiness and level of functioning. In attempting to reconcile these findings, we chose to examine the issue of values, defined as affectively infused criteria or motivational goals used to select and justify actions, people, and the self, as values are related to both happiness and functioning. Fifty-six first-episode patients in remission and 56 healthy control subjects completed happiness and values measures. Statistical analyses included correlations, analysis of variance, structural equation modelling, and smallest space analysis. Results indicated that patients with schizophrenia placed significantly greater priority on the value dimensions of Tradition (P = 0.02) and Power (P = 0.03), and significantly less priority on Self-direction (P = 0.007) and Stimulation, (P = 0.008). Essentially, people with schizophrenia place more emphasis on the customs and ideas that traditional culture or religion provide in conjunction with a decreased interest in change, which is at odds with the expectations of early adulthood. This value difference could be related to functional deficits. To this point, we have assumed that people hold to the same values that guided them before the illness' onset, but this may not be the case. Our study indicates that values differ in people with schizophrenia, compared with control subjects, even early in the illness and in the face of symptomatic remission.

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

PubMed

Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert

2016-12-12

Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm 3 ). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm 3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

Cotard Delusion in the Context of Schizophrenia: A Case Report and Review of the Literature

PubMed Central

Bott, Nicholas; Keller, Corey; Kuppuswamy, Malathy; Spelber, David; Zeier, Joshua

2016-01-01

Background: The Cotard delusion (CD) is one of a variety of narrowly defined monothematic delusions characterized by nihilistic beliefs about the body’s existence or life itself. The presence of CD within the context of schizophrenia is rare (<1%), and remains understudied. Case: ‘Mr. C’ is a 58-year-old veteran with a prior diagnosis of schizophrenia, who presented with CD in the context of significant depression, suicidal ideation, violence, and self-harm behavior. He perseverated in his belief that he was physically dead and possessed by demons for several weeks. This delusion was reinforced by his religious belief that life was an attribute of God, and by inference, he as a human, was dead. His condition gradually improved over the course of treatment with Divalproex and quetiapine with discussions about the rationale for his belief. Upon discharge, Mr. C. demonstrated awareness of his fixation on death and an ability to redirect himself. Discussion: This case highlights the need to better understand the co-occurrence of CD in schizophrenia, their differentiation, the increased risk of violence and self-harm behavior in this presentation, and how specific events and religious factors can influence delusional themes of CD. Pharmacotherapy and aspects of cognitive-behavioral therapy may be effective in ameliorating these symptoms in CD. PMID:27656159

Attitudes and beliefs of the French public about schizophrenia and major depression: results from a vignette-based population survey

PubMed Central

2013-01-01

Background In their study ‘Mental Health in the General Population: Images and Realities’ Jean-Luc Roelandt et al. found a huge divide between the French public’s conceptualizations of insanity and depression. The study aims to examine whether such differences can be replicated using modern operationalized diagnostic criteria for schizophrenia and major depressive disorder. Methods In 2012, an online survey was conducted using a representative sample drawn from the adult French population (N = 1600). After presentation of a case-vignette depicting a person with either schizophrenia or major depressive disorder a fully structured interview was carried out. Results Despite some similarities marked differences between both disorders emerge regarding beliefs and attitudes. While respondents presented with the schizophrenia vignette more frequently defined symptoms as the expression of an illness with a stronger biological component and a less favorable prognosis, demanding psychiatric treatment, respondents presented with the depression vignette considered the occurrence of symptoms more frequently as the consequence of current psychosocial stress, benefitting not only from established but also from alternative treatments. People with schizophrenia were more frequently perceived as unpredictable and dangerous, there was a stronger need to separate one-self from them, they were more frequently met with fear and less frequently reacted to with pro-social feelings, and they also faced more rejection. Conclusions The French public draws a clear line between schizophrenia and major depressive disorder. This applies equally to beliefs about both disorders and to attitudes towards the persons afflicted. There is a need for interventions trying to reduce existing misconceptions in order to improve the care of patients. PMID:24252540

A Common Missense Variant in the Neuregulin1 Gene is associated with Both Schizophrenia and Sudden Cardiac Death

PubMed Central

Huertas-Vazquez, Adriana; Teodorescu, Carmen; Reinier, Kyndaron; Uy-Evanado, Audrey; Chugh, Harpriya; Jerger, Katherine; Ayala, Jo; Gunson, Karen; Jui, Jonathan; Newton-Cheh, Christopher; Albert, Christine M.; Chugh, Sumeet S.

2013-01-01

Background Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD. Objective To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy. Methods From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for association between 17 SNPs mapped to 14 loci previously implicated in schizophrenia and epilepsy using logistic regression, assuming additive, dominant and recessive genetic models. Results The minor allele of the non-synonymous SNP rs10503929 within the Neuregulin 1 gene (NRG1) was associated with SCD under all three investigated models, with the strongest association for the recessive genetic model (recessive P=4.01×10−5, OR= 4.04; additive P=2.84×10−7, OR= 1.9 and dominant P=9.01×10−6, OR= 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P=0.0005, OR= 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown. Conclusions The observed association between a schizophrenia-related NRG1 variant and SCD may represent the first evidence of coexisting genetic susceptibility between two conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD. PMID:23524320

Resequencing of the vesicular glutamate transporter 2 gene (VGLUT2) reveals some rare genetic variants that may increase the genetic burden in schizophrenia.

PubMed

Shen, Yu-Chih; Liao, Ding-Lieh; Lu, Chao-Lin; Chen, Jen-Yeu; Liou, Ying-Jay; Chen, Tzu-Ting; Chen, Chia-Hsiang

2010-08-01

Vesicular glutamate transporters (VGLUT1-3) package glutamate into vesicles in the presynaptic terminal and regulate the release of glutamate. In mesencephalic dopamine neuron culture, the majority of isolated dopamine neurons express VGLUT2, but not VGLUT1 or 3, have been demonstrated. As related to the dysregulated glutamatergic hypothesis of schizophrenia, the gene encoding VGLUT2 is the most plausible candidate involved in the pathogenesis of this illness. We searched for genetic variants in the promoter region and 12 exons (including UTR ends) of the VGLUT2 gene using direct sequencing in a sample of Han Chinese schizophrenic patients (n=375) and non-psychotic controls (n=366) from Taiwan, and conducted a case-control association study. We identified 8 common SNPs in the VGLUT2 gene. SNP and haplotype-based analyses showed no association with schizophrenia. Besides, we identified 9 rare variants in 13 out of 375 patients, including 3 variants located at the promoter region, 2 synonymous variants located at protein coding regions, and 4 variants located at UTR ends. No rare variants were found in the control subjects. Collectively, these rare variants were significantly overrepresented in the patient group (3.5% versus 0, p value of Fisher's exact test=2.3x10(-5)), suggesting they may contribute to the pathogenesis of schizophrenia. Although the functional significance of these rare variants remains to be characterized, our study may lend support to the multiple rare mutations hypothesis of schizophrenia, and may provide genetic clues to indicate the involvement of the glutamate transmission pathway in the pathogenesis of schizophrenia. Copyright 2010 Elsevier B.V. All rights reserved.

No significant association between prenatal exposure poliovirus epidemics and psychosis.

PubMed

Cahill, Matthew; Chant, David; Welham, Joy; McGrath, John

2002-06-01

To examine the association between prenatal exposure to poliovirus infection and later development of schizophrenia or affective psychosis in a Southern Hemisphere psychiatric register. We calculated rates of poliomyelitis cases per 10 000 background population and rates for schizophrenia(n = 6078) and affective psychosis (n = 3707)per 10 000 births for the period 1930-1964. Empirically weighted regression was used to measure the association between a given psychosis birth-rate and a poliomyelitis epidemic during gestation. There was no statistically significant association between exposure to a poliomyelitis epidemic during gestation and subsequent development of schizophrenia or affective psychosis. The lack of a consistent statistically significant association between poliovirus epidemics and schizophrenia suggests that either poliovirus may have a small effect which is only detectable with large data-sets and/or the effect may be modified by location. Further investigation of such inconsistencies may help elucidate candidate risk-modifying factors for schizophrenia.

Exome sequence analysis and follow up genotyping implicates rare ULK1 variants to be involved in susceptibility to schizophrenia

PubMed Central

Al Eissa, Mariam M.; Fiorentino, Alessia; Sharp, Sally I.; O'Brien, Niamh L.; Wolfe, Kate; Giaroli, Giovanni; Curtis, David; Bass, Nicholas J.

2017-01-01

Summary Schizophrenia (SCZ) is a severe, highly heritable psychiatric disorder. Elucidation of the genetic architecture of the disorder will facilitate greater understanding of the altered underlying neurobiological mechanisms. The aim of this study was to identify likely aetiological variants in subjects affected with SCZ. Exome sequence data from a SCZ cas–control sample from Sweden was analysed for likely aetiological variants using a weighted burden test. Suggestive evidence implicated the UNC‐51‐like kinase (ULK1) gene, and it was observed that four rare variants that were more common in the Swedish SCZ cases were also more common in UK10K SCZ cases, as compared to obesity cases. These three missense variants and one intronic variant were genotyped in the University College London cohort of 1304 SCZ cases and 1348 ethnically matched controls. All four variants were more common in the SCZ cases than controls and combining them produced a result significant at P = 0.02. The results presented here demonstrate the importance of following up exome sequencing studies using additional datasets. The roles of ULK1 in autophagy and mTOR signalling strengthen the case that these pathways may be important in the pathophysiology of SCZ. The findings reported here await independent replication. PMID:29148569

Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.

PubMed

Li, Zhiqiang; Chen, Jianhua; Yu, Hao; He, Lin; Xu, Yifeng; Zhang, Dai; Yi, Qizhong; Li, Changgui; Li, Xingwang; Shen, Jiawei; Song, Zhijian; Ji, Weidong; Wang, Meng; Zhou, Juan; Chen, Boyu; Liu, Yahui; Wang, Jiqiang; Wang, Peng; Yang, Ping; Wang, Qingzhong; Feng, Guoyin; Liu, Benxiu; Sun, Wensheng; Li, Baojie; He, Guang; Li, Weidong; Wan, Chunling; Xu, Qi; Li, Wenjin; Wen, Zujia; Liu, Ke; Huang, Fang; Ji, Jue; Ripke, Stephan; Yue, Weihua; Sullivan, Patrick F; O'Donovan, Michael C; Shi, Yongyong

2017-11-01

We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

2015-06-30

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of Parental Age on Treatment Response in Adolescents with Schizophrenia

PubMed Central

Opler, Mark; Malaspina, Dolores; Gopal, Srihari; Nuamah, Isaac; Savitz, Adam J; Singh, Jaskaran; Hough, David

2013-01-01

Background Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. Methods Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT 00518323). Results The mean (SD) paternal age was 29.2 (6.2) years, range (16-50) and maternal age was 26.8 (5.7) years, range (17-42) at childbirth for the 201 adolescents (ages 12-17 years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal age showed significant effects on treatment response (p < 0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents’ ages. Conclusions APA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder. PMID:24144440

Augmentation of clozapine with amisulpride: an effective therapeutic strategy for violent treatment-resistant schizophrenia patients in a UK high-security hospital.

PubMed

Hotham, James E; Simpson, Patrick J D; Brooman-White, Rosalie S; Basu, Amlan; Ross, Callum C; Humphreys, Sharon A; Larkin, Fintan; Gupta, Nitin; Das, Mrigendra

2014-10-01

Clozapine is used in the management of treatment-resistant schizophrenia and is effective in reducing aggression; however a subgroup of patients is poorly responsive. For violent patients in this group, there is limited literature on the use of strategies to augment clozapine with other agents. Here we present a case series of 6 schizophrenia patients, within a high-security hospital, who have a history of serious violence and who were treated with clozapine augmented with amisulpride. We reviewed case notes and health records for evidence of violence/aggression and positive factors such as engagement in activities, and Clinical Global Impression (CGI) scores were formulated. We also examined metabolic parameters before and after augmentation. All 6 of the patients showed clinical improvement in symptoms and a reduction in their risk of violence to others. Five patients had a reduction in number of violent/aggressive incidents, and all patients showed improvement in engagement in occupational, vocational, and/or psychological work. Metabolic parameters were largely unchanged except for 1 patient whose Body Mass Index (BMI) increased. Five patients reported side effects as unchanged or improved. These schizophrenia patients with a history of violence showed clinical improvement and reduced aggression and violence with amisulpride augmentation of clozapine. To our knowledge, this is the first report of an antiaggressive benefit of this combination in forensic psychiatric patients. Further studies are warranted to establish the efficacy and anti-aggressive effects of amisulpride augmentation of clozapine.

[Voice and vibration sensations in the speech forming organs: clinical and theoretical aspects of rare symptoms specific for schizophrenia].

PubMed

Vilela, W; Lolas, F; Wolpert, E

1978-01-01

When studying 750 psychiatric in-patients with psychoses of various diagnostic groups, the symptoms of voice sensations and vibration feelings could only be found among patients with paranoid schizophrenia. In addition, these symptoms were located exclusively in body areas that are involved in the peripheral motor production of voice and speech (areas of head, throat, thorax). In 11 of 15 such cases that could be identified, the sensations of voices and vibrations occurred simultaneously and in identical body parts; in the remaining 4 cases only voices without vibration sensations were reported. Therefore these symptoms can be considered as highly specific for schizophrenia. According to the terminology of Bleuler these two symptoms are because of their rareness to be taken as accessoric symptoms; according to the terminology of Kurt Schneider they have the value of first rank symptoms because of their highly diagnostic specifity for schizophrenia. The pathogenesis of these symptoms is on the one hand discussed under the perspective of language development and the changing function of language for behaviour control; on the other hand, the pathogenesis of these symptoms is discussed from the viewpoint of cybernetic, or neurophysiological-neuroanatomical foundation of speech production and speech control. Both models of explanation have in common that the ideational component of speech is noticed as acustic halluzinations and the motor proprioceptive part of speech is noticed as sensation of vibrations, both in a typically schiphrenic manner, i.e. dissociated and ego-alienated.

Fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia.

PubMed

Rodriguez-Murillo, Laura; Xu, Bin; Roos, J Louw; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2014-03-01

We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32-34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32-34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case-control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation within MYO16 in a second set of Afrikaner families and additional case-control data sets of European descent highlighted a region across introns 2-6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to the genetic liability to schizophrenia.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

PubMed

Berna, F; Misdrahi, D; Boyer, L; Aouizerate, B; Brunel, L; Capdevielle, D; Chereau, I; Danion, J M; Dorey, J M; Dubertret, C; Dubreucq, J; Faget, C; Gabayet, F; Lancon, C; Mallet, J; Rey, R; Passerieux, C; Schandrin, A; Schurhoff, F; Tronche, A M; Urbach, M; Vidailhet, P; Llorca, P M; Fond, G

2015-12-01

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications. Copyright © 2015 Elsevier B.V. All rights reserved.

Voxelwise Correlational Analyses of White Matter Integrity in Multiple Cognitive Domains in Schizophrenia

PubMed Central

Lim, Kelvin O.; Ardekani, Babak A.; Nierenberg, Jay; Butler, Pamela D.; Javitt, Daniel C.; Hoptman, Matthew J.

2007-01-01

Patients with schizophrenia show deficits in several neurocognitive domains. However, the relationship between white matter integrity and performance in these domains is poorly understood. The authors conducted neurocognitive testing and diffusion tensor imaging in 25 patients with schizophrenia. Performance was examined for tests of verbal declarative memory, attention, and executive function. Relationships between fractional anisotropy and cognitive performance were examined by using voxelwise correlational analyses. In each case, better performance on these tasks was associated with higher levels of fractional anisotropy in task-relevant regions. PMID:17074956

Does the increased rate of schizophrenia diagnosis in African-Caribbean men in the UK shown by the AESOP study reflect cultural bias in healthcare?

PubMed

Ngaage, Millie; Agius, Mark

2016-09-01

The UK-based AESOP study conducted over a two-year period in three UK sites simultaneously (London, Nottingham, and Bristol), is the largest study to date to conduct a first contact case-control study of psychosis. The study found that rates of schizophrenia were markedly elevated in both African-Caribbean and Black African people, in both sexes and across all age groups. English language literature published up to 2016 was searched. The initial search included: PubMed, The Cochrane Library, and Web of Science. A second search was conducted using Medical Subject Headings (MeSH) and keywords. Studies selected for retrieval were assessed by two independent reviewers. The search yielded eight results, all of which supported the conclusion of an increased incidence of schizophrenia in Black African and Black Caribbean population in the AESOP study. England is a multicultural landscape; multiplicity of cultures makes diagnosis difficult. The lessons we must learn from the AESOP study is the need for transcultural training and the removal of blinding to ethnicity when a large epidemiological study is conducted - psychiatrists need to be cognisant of cultures and aware of the context of symptoms.

Management of schizophrenia: clinical experience with asenapine.

PubMed

Cortese, Leonardo; Bressan, Rodrigo A; Castle, David J; Mosolov, Sergey N

2013-04-01

Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms (particularly depression and anxiety). The management of schizophrenia requires effective short- and long-term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term. Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults. It has a unique receptor-binding profile and a broad range of therapeutic effects. Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent's efficacy and tolerability under 'real-world' clinical practice conditions is also required. As in clinical trials, real-life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention. It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia. Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters. As such, asenapine is valuable option for the treatment of schizophrenia in adults.

Jack the Giant Tamer: Poetry Writing in the Treatment of Paranoid Schizophrenia.

ERIC Educational Resources Information Center

Silver, Constance

1993-01-01

Provides a brief case report on the use of poetry writing in the treatment of a patient with a diagnosis of paranoid schizophrenia. Notes that, after 23 sessions in which the patient said nothing, the patient brought a poem for the therapist to read at the 24 session. (SR)

Plica neuropathica (polonica) in schizophrenia

PubMed Central

Kumar, P. N. Suresh; Rajmohan, V.

2012-01-01

Plica neuropathica (Polonica) is a common but rarely reported scalp hair condition. In this condition the hairs of scalp in a localized area is compacted into irregularly twisted, irreversibly entangled plaits. Psychological disturbance is a risk factor for plica formation. We report a case of plica neuropathica in an adult female with schizophrenia. PMID:23226861

Nature vs. nurture: two brothers with schizophrenia.

PubMed

Keltner, N L; James, C A; Darling, R J; Findley, L S; Oliver, K

2001-01-01

The nature vs. nurture argument as it pertains to two brothers. To explore the synergistic effects of heritability and environment in the cases of two brothers with schizophrenia. Review of the literature and the authors' clinical experience. The nature vs. nurture dichotomy may not be as relevant as looking at the interaction between these two forces.

Treatment of Paroxysmal Perceptual Alteration in Catatonic Schizophrenia by Switching to Aripiprazole from Risperidone: A Case Report.

PubMed

Yamashita, Satoko; Miyaoka, Tsuyoshi; Nagahama, Michiharu; Ieda, Masa; Tsuchie, Keiko; Wake, Rei; Horiguchi, Jun

2016-01-01

Paroxysmal perceptual alteration (PPA) is the occurrence of brief and recurrent episodes of perceptual changes. It is mainly caused by the treatment of schizophrenia patients with antipsychotics. However, diagnosis of PPA is not very prevalent among psychiatrists, partly due to underrecognition or misunderstanding that it is a worsening of psychiatric symptoms. If psychiatrists do not understand PPA, they cannot treat it appropriately, and the patient's quality of life is impaired. We present a case of PPA in catatonic schizophrenia that was successfully treated by switching to aripiprazole from risperidone. We suggest that the disappearance of PPA in our case was due to both discontinuing risperidone, which completely blocks D2 receptors, and replacing it with aripiprazole, which is characterized as a partial agonist of D2 receptors. Treatment of PPA will improve medication adherence and quality of life. It is important to recognize PPA as a possible side effect of treatment with antipsychotics.

The schizophrenia stigma and mass media: a search for news published by wide circulation media in Brazil.

PubMed

Bevilacqua Guarniero, Francisco; Bellinghini, Ruth Helena; Gattaz, Wagner Farid

2017-06-01

Schizophrenia is the most common illness used today as a metaphor in the media and routinely appears associated with crime and violence with no medical or scientific rigor, reinforcing the stigma against this disorder. Evaluation of the presence of structural stigma in the Brazilian media by means of a survey of printed news and the Internet using the term schizophrenia and its correlates under three aspects: (a) medical and scientific uses, (b) assigning a diagnosis of schizophrenia to crime suspects with little or no medical or scientific rigor, and (c) the metaphorical use. The study was conducted in three stages: search for publications, classification of items found and analysis of the context in which they were published. The survey was conducted in two periods: 2008 and 2011, the first being restricted to the newspaper Folha de S. Paulo and the second extended to the homepage of the main Brazilian print media. We found 229 texts, distributed as follows: 89 (39%) records as science and health, with a tendency to impersonality; 62 (27%) records as crime and violence, in which the 'diagnosis' of schizophrenia is given by lay people and 'supported' by an archeology of the life of the suspect which enlists all sorts of non-standard behavior; and 78 (34%) records of metaphorical use, always with a negative meaning. Most of the texts found (a) does not give voice to people with schizophrenia and their suffering, (b) trivializes the use of this psychiatric illness out of context to describe contradictory or of dubious character political and economic decisions, and (c) reinforces the stigma that lays over the bearer of schizophrenia individualizing them only in rare violent cases with a supposed diagnosis.

Converging evidence that sequence variations in the novel candidate gene MAP2K7 (MKK7) are functionally associated with schizophrenia.

PubMed

Winchester, Catherine L; Ohzeki, Hiromitsu; Vouyiouklis, Demetrius A; Thompson, Rhiannon; Penninger, Josef M; Yamagami, Keiji; Norrie, John D; Hunter, Robert; Pratt, Judith A; Morris, Brian J

2012-11-15

Schizophrenia is a debilitating psychiatric disease with a strong genetic contribution, potentially linked to altered glutamatergic function in brain regions such as the prefrontal cortex (PFC). Here, we report converging evidence to support a functional candidate gene for schizophrenia. In post-mortem PFC from patients with schizophrenia, we detected decreased expression of MKK7/MAP2K7-a kinase activated by glutamatergic activity. While mice lacking one copy of the Map2k7 gene were overtly normal in a variety of behavioural tests, these mice showed a schizophrenia-like cognitive phenotype of impaired working memory. Additional support for MAP2K7 as a candidate gene came from a genetic association study. A substantial effect size (odds ratios: ~1.9) was observed for a common variant in a cohort of case and control samples collected in the Glasgow area and also in a replication cohort of samples of Northern European descent (most significant P-value: 3 × 10(-4)). While some caution is warranted until these association data are further replicated, these results are the first to implicate the candidate gene MAP2K7 in genetic risk for schizophrenia. Complete sequencing of all MAP2K7 exons did not reveal any non-synonymous mutations. However, the MAP2K7 haplotype appeared to have functional effects, in that it influenced the level of expression of MAP2K7 mRNA in human PFC. Taken together, the results imply that reduced function of the MAP2K7-c-Jun N-terminal kinase (JNK) signalling cascade may underlie some of the neurochemical changes and core symptoms in schizophrenia.

The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial: rationale for its methodology and a review of the effectiveness of switching antipsychotics.

PubMed

Leucht, Stefan; Winter-van Rossum, Inge; Heres, Stephan; Arango, Celso; Fleischhacker, W Wolfgang; Glenthøj, Birte; Leboyer, Marion; Leweke, F Markus; Lewis, Shôn; McGuire, Phillip; Meyer-Lindenberg, Andreas; Rujescu, Dan; Kapur, Shitij; Kahn, René S; Sommer, Iris E

2015-05-01

Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia. We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial. We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence. Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report.

PubMed

Matsunaga, Shunji; Koga, Hiroaki; Kawabata, Naoya; Kawamura, Ichiro; Otusji, Masaki; Imakiire, Takanori; Komiya, Setsuro

2008-01-01

The pathogenesis of ossification of the posterior longitudinal ligaments (OPLL) has not been clarified. We here report dizygotic twin sisters with OPLL of the cervical spine and propose a new pathogenesis of OPLL. This is the first report of dizygotic twins with OPLL. The twins suffered from schizophrenia, which might be related to the pathogenesis of OPLL. In addition, we investigated the occurrence of OPLL in 30 patients with schizophrenia who had been admitted to a mental hospital. OPLL of the cervical spine was found in six (20%) of them, with an incidence almost five times higher than the incidence of OPLL among the general population in Japan. Schizophrenia may have a increased susceptibility to OPLL.

Effectiveness of long-acting risperidone in a patient with comorbid intellectual disability, catatonic schizophrenia, and oneiroid syndrome.

PubMed

Serata, Daniele; Rapinesi, Chiara; Kotzalidis, Georgios Demetrios; Alessi, Maria Chiara; Janiri, Delfina; Massolo, Anna Claudia; Ferri, Vittoria Rachele; Criscuolo, Silvia; Callovini, Gemma; Angeletti, Gloria; Girardi, Paolo; Del Casale, Antonio

2015-01-01

A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome. © The Author(s) 2015.

Risk factors for homelessness among women with schizophrenia.

PubMed Central

Caton, C L; Shrout, P E; Dominguez, B; Eagle, P F; Opler, L A; Cournos, F

1995-01-01

A study of risk factors for homelessness among the severely mentally ill was extended to include women, and a case-control study of 100 indigent women with schizophrenia meeting criteria for literal homelessness and 100 such women with no history of homelessness was conducted. Subjects were recruited from shelters, clinics, and inpatient psychiatric programs in New York City. Clinical interviewers used standardized research instruments to probe three domains of risk factors: severity of mental illness, family background, and prior mental health service use. Findings adjusted for ethnicity revealed that homeless women had higher rates of a concurrent diagnosis of alcohol abuse, drug abuse, and antisocial personality disorder. Homeless women also had less adequate family support. PMID:7625518

Facial emotion perception in schizophrenia: Does sex matter?

PubMed

Mote, Jasmine; Kring, Ann M

2016-06-22

To review the literature on sex differences in facial emotion perception (FEP) across the schizophrenia spectrum. We conducted a systematic review of empirical articles that were included in five separate meta-analyses of FEP across the schizophrenia spectrum, including meta-analyses that predominantly examined adults with chronic schizophrenia, people with early (onset prior to age 18) or recent-onset (experiencing their first or second psychotic episode or illness duration less than 2 years) schizophrenia, and unaffected first-degree relatives of people with schizophrenia. We also examined articles written in English (from November 2011 through June 2015) that were not included in the aforementioned meta-analyses through a literature search in the PubMed database. All relevant articles were accessed in full text. We examined all studies to determine the sample sizes, diagnostic characteristics, demographic information, methodologies, results, and whether each individual study reported on sex differences. The results from the meta-analyses themselves as well as the individual studies are reported in tables and text. We retrieved 134 articles included in five separate meta-analyses and the PubMed database that examined FEP across the schizophrenia spectrum. Of these articles, 38 examined sex differences in FEP. Thirty of these studies did not find sex differences in FEP in either chronically ill adults with schizophrenia, early-onset or recently diagnosed people with schizophrenia, or first-degree relatives of people with schizophrenia. Of the eight studies that found sex differences in FEP, three found that chronically ill women outperformed men, one study found that girls with early-onset schizophrenia outperformed boys, and two studies found that women (including first-degree relatives, adults with schizophrenia, and the healthy control group) outperformed men on FEP tasks. In total, six of the eight studies that examined sex differences in FEP found that women outperformed men across the schizophrenia spectrum. Evidence to date suggests few sex differences in FEP in schizophrenia; both men and women across the schizophrenia spectrum have deficits in FEP.

Neurocognitive performance in family-based and case-control studies of schizophrenia

PubMed Central

Gur, Ruben C.; Braff, David L.; Calkins, Monica E.; Dobie, Dorcas J.; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Gur, Raquel E.

2014-01-01

Background Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs. PMID:25432636

Effects of the diagnostic label 'schizophrenia', actively used or passively accepted, on general practitioners' views of this disorder.

PubMed

Magliano, Lorenza; Strino, Antonella; Punzo, Rosanna; Acone, Roberta; Affuso, Gaetana; Read, John

2017-05-01

General practitioners (GPs) play a key role in the care of somatic and psychiatric problems in people diagnosed with schizophrenia (PWS). It is probable that, like other health professionals, GPs are not all free of prejudices toward PWS. In clinical practice, GPs sometimes interact with clients diagnosed with schizophrenia by specialists, passively accepting this diagnosis. Other times, GPs interact with clients having symptoms of schizophrenia but who have not been diagnosed. In this case, GPs are expected to actively make a diagnosis. Giving the key role of GPs in the process of care, it is worthwhile examining whether passive acceptance and active usage of the diagnosis schizophrenia have differential effects on GPs' attitudes toward people with this disorder. To investigate GPs' views of schizophrenia and whether they were influenced by a 'schizophrenia' label, passively accepted or actively used. A total of 430 randomly selected GPs were invited to complete a questionnaire about their views of schizophrenia, either after reading a description of this disorder and making a diagnosis, or without being provided with a description but passively accepting the label 'schizophrenia' given in the questionnaire. The GPs who passively accepted the label schizophrenia ( n = 195) and those who actively identified schizophrenia from the description ( n = 127) had similar views. Compared to the GPs who did not identify schizophrenia in the description ( n = 65), those who used the diagnosis, actively or passively: more frequently reported heredity and less frequently psychosocial factors as causes of the disorder; were more skeptical about recovery; were more convinced of the need for long-term pharmacotherapies; believed more strongly that PWS should be discriminated against when in medical hospital; and perceived PWS as more dangerous and as kept at greater social distance. The diagnosis 'schizophrenia', however used, is associated with pessimistic views. Stigma education should be provided to GPs.

GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

PubMed Central

de Jonge, Jeroen C.; Vinkers, Christiaan H.; Hulshoff Pol, Hilleke E.; Marsman, Anouk

2017-01-01

Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic) neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS) offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course. PMID:28848455

Effectiveness of long-acting injectable risperidone versus oral antipsychotics in the treatment of recent-onset schizophrenia: a case-control study.

PubMed

Barrio, Pablo; Batalla, Albert; Castellví, Pere; Hidalgo, Diego; García, Marta; Ortiz, Ana; Grande, Iria; Pons, Alexandre; Parellada, Eduard

2013-07-01

Long-acting injectable antipsychotics may offer a relevant improvement in treatment adherence in recent-onset psychosis, leading to a decreased rate of hospital readmission, a better rate of clinical remission and improved psychosocial adjustment. The aim of the study was to compare the clinical remission rates, number of hospital readmissions and personal and social functioning after 2 years between patients with recent-onset schizophrenia (<2 years) in treatment with risperidone long-acting injectable (RLAI) and patients with recent-onset schizophrenia receiving oral antipsychotics. This is a case-control study comparing patients with recent-onset schizophrenia who initiated RLAI treatment between 2004 and 2008 (n=26) with a control group matched for age and sex, diagnosed with recent-onset schizophrenia and treated with oral antipsychotics (n=26). Study assessments included sociodemographic variables, the Positive and Negative Syndrome Scale, the Personal and Social Functioning Scale, the number of hospital readmissions and the Andreasen remission criteria. To assess the effect of treatment on each dependent variable, separate generalized estimating equations models were constructed. After 2 years of treatment, and adjusting for educational level, the RLAI group showed a greater reduction in the Positive and Negative Syndrome Scale total scale [mean (SD)=47.7 (12.0) vs. 66.2 (18.5); mean difference =-17.56; 95% confidence interval (CI)=-27.11 to -8.00; P<0.001], as well as in the negative [mean (SD) 14.3 (6.1) vs. 19.4 (6.4); mean difference=-5.02; 95% CI=-8.28 to -1.77; P=0.002] and general psychopathology [mean (SD)=23.4 (6.3) vs. 32.7 (8.1); mean difference=-9.16; 95% CI=-13.3 to -5.03; P<0.001] subscales compared with the oral antipsychotic group. Personal and Social Functioning Scale scores were also higher in the RLAI group [mean (SD)=72.4 (14.8) vs. 59.7 (13.5); mean difference=13.41; 95% CI=5.65-21.18; P<0.001]. Although not statistically significant, there were fewer readmissions (adjusted odds ratio 0.28; 95% CI=0.06-1.35; P=0.114) and more illness remissions (adjusted odds ratio 3.24; 95% CI=0.20-11.93; P=0.077) in the RLAI group. Treatment with RLAI instead of oral antipsychotics in recent-onset schizophrenia might improve clinical symptoms and social functioning. The efficacy of RLAI treatment on remission and readmission rates should be researched further.

Symptom profiles and parental bonding in homicidal versus non-violent male schizophrenia patients.

PubMed

Halmai, Tamás; Tényi, Tamás; Gonda, Xénia

2017-01-30

To compare the intensity and the profile of psychotic symptoms and the characteristics of parental bonding of male schizophrenia patients with a history of homicide and those without a history of violent behaviour. Clinical question - We hypothesized more intense psychotic symptoms, especially positive symptoms as signs of a more severe psychopathology in the background of homicidal behaviour. We also hypothesized a more negatively perceived pattern (less Care more Overprotection) of parental bonding in the case of homicidal schizophrenia patients than in non-violent patients and non-violent healthy controls. Symptom severity and symptom profiles were assessed with the Positive and Negative Syndrome Scale in a group of male schizophrenia patients (n=22) with the history of committed or attempted homicide, and another group (n=19) of male schizophrenia patients without a history of violent behaviour. Care- and Overprotection were assessed using the Parental Bonding Instrument (PBI) in a third group of non-violent healthy controls (n=20), too. Positive, negative and general psychopathology symptoms in the homicidal schizophrenia group were significantly (p<0.005) more severe than in the non-violent schizophrenia group. Non-violent schizophrenia patients scored lower on Care and higher on Overprotection than violent patients and healthy controls. Homicidal schizophrenia patients showed a pattern similar to the one in the healthy control group. It seems imperative to register intense positive psychotic symptoms as predictive markers for later violent behaviour. In the subgroup of male homicidal schizophrenia patients negatively experienced parental bonding does not appear to be major contributing factor to later homicidal behaviour.

One-year follow-up study of psychotic patients treated with blonanserin: a case series.

PubMed

Takahashi, Sakae; Suzuki, Masahiro; Uchiyama, Makoto

2013-09-01

Blonanserin is a relatively new atypical antipsychotic drug, and has been used in Korea and Japan for 1 and 3 years, respectively. Therefore, the clinical characteristics of blonanserin remain unclear. In this study, to clarify the features of blonanserin, we performed prospective and long-term comparative investigations of patients treated with blonanserin. We followed 10 psychiatric patients who were switched to blonanserin from other antipsychotics for 1 year (schizophrenia: 8; mental retardation: 2). In the light of quality of life, we focused on adverse effects of patients during the follow-up. In the long-term follow-up, (i) hyperprolactinemia is more frequently in risperidone than in blonanserin; however, it is more often in blonanserin than in olanzapine; and (ii) weight gain is more common in olanzapine than in blonanserin. We switched to blonanserin from other antipsychotic drugs within the same case, and then followed the case for 1 year. We consider that long-term observations within the same case lead to obvious comparisons among drugs. On the basis of our findings, we conclude that blonanserin may be useful for the maintenance treatment of schizophrenia without inducing hyperprolactinemia and weight gain. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Efficient strategy for detecting gene × gene joint action and its application in schizophrenia.

PubMed

Won, Sungho; Kwon, Min-Seok; Mattheisen, Manuel; Park, Suyeon; Park, Changsoon; Kihara, Daisuke; Cichon, Sven; Ophoff, Roel; Nöthen, Markus M; Rietschel, Marcella; Baur, Max; Uitterlinden, Andre G; Hofmann, A; Lange, Christoph

2014-01-01

We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has reasonable statistical power under most genetic models. We found that the presence of any gene × gene joint action may imply differences in three types of genetic components: the minor allele frequencies and the amounts of Hardy-Weinberg disequilibrium may differ between cases and controls, and between the two genetic loci the degree of linkage disequilibrium may differ between cases and controls. Using Fisher's method, it is possible to combine the different sources of genetic information in an overall test for detecting gene × gene joint action. The proposed statistical analysis is efficient and its simplicity makes it applicable to GWASs. In the current study, we applied the proposed approach to a GWAS on schizophrenia and found several potential gene × gene interactions. Our application illustrates the practical advantage of the proposed method. © 2013 WILEY PERIODICALS, INC.

Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists' survey in India.

PubMed

Gundugurti, Prasad Rao; Nagpal, Rajesh; Sheth, Ashit; Narang, Prashant; Gawande, Sonal; Singh, Vikram

2017-12-01

Schizophrenia is associated with functional challenges for patients; relapses in schizophrenia may lead to increased treatment costs and poor quality of life. This SUSTAIN-I study was conducted to establish psychiatrists' perspective on impact of long-acting injectables (LAIs) antipsychotics on the socio-economic and functional burden of schizophrenia. This cross-sectional, survey-based study was conducted in 5 cities in India. Psychiatrists (≥5years of experience) working in clinics, psychiatric, government hospitals and rehabilitation centers were included and administered a specially designed questionnaire to elicit information on their clinical practice and prescription patterns. Perceived treatment costs for LAI versus oral antipsychotic treatments (OATs) and relapse rates were assessed. Descriptive statistics were used to summarize results. Total 31 physicians completed this survey. In acute phase, OAT prescription was higher whereas chronic patients were treated with either OATs or LAIs. Treatment with LAIs was the preferred treatment in 9% of chronic cases. Reduced relapse rates were observed with LAI treatment: 12% patients on LAIs relapsed as compared with 60% patients on OATs. Monthly medication cost for oral medications was lower ($8-$17) than short-acting injectables ($22-$50). For chronic cases, atypical antipsychotics cost (oral: $11.7-25, LAI: $150-167) was higher than typical antipsychotics (oral: $4-5, LAI: $5-25). Of the total expenses incurred, cost for hospital admissions was the largest component (78%). Despite enhanced treatment adherence and potential to lower risk of rehospitalizations from relapse, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs. Copyright © 2017 Elsevier B.V. All rights reserved.

Left nucleus accumbens atrophy in deficit schizophrenia: A preliminary study.

PubMed

De Rossi, Pietro; Dacquino, Claudia; Piras, Fabrizio; Caltagirone, Carlo; Spalletta, Gianfranco

2016-08-30

A question that remains to be answered is whether schizophrenia can be characterized by a single etiopathophysiology or whether separate sub-syndromes should be differentiated to define specific mechanisms for each sub-type. Individuals affected by the deficit subtype of schizophrenia (DSZ) display avolitional/amotivational features that respond poorly to conventional treatments. Characterizing DSZ from a neuroanatomical point of view may help clarify this issue and develop new treatment strategies. To determine if DSZ is associated with structural alterations in specific deep grey matter structures linked to its key clinical features, 22 DSZ patients, 22 non-deficit schizophrenia (NDSZ) patients and 22 healthy controls (HC) were recruited for a case-control cross-sectional study. High-resolution magnetic resonance imaging was performed in all subjects and volumes of deep grey matter structures were measured using FreeSurfer. DSZ patients displayed smaller left accumbens volumes compared to both NDSZ patients and HC. Moreover, age and duration of illness were significantly associated with lower volume of the left accumbens in DSZ but not in NDSZ. Findings indicate that DSZ is associated with lower volume of the nucleus accumbens in the dominant hemisphere. This is consistent with the psychopathological features and functional impairments present in DSZ and thus indicates a potential mechanism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-brain autoantibodies in the serum of schizophrenic patients: a case-control study.

PubMed

Margari, Francesco; Petruzzelli, Maria Giuseppina; Mianulli, Rossana; Toto, Maddalena; Pastore, Adriana; Bizzaro, Nicola; Tampoia, Marilina

2013-12-30

Schizophrenia is considered a neurodevelopmental disorder with a multifactorial pathogenesis where autoimmune factors may play a significant role. The aim of this study was to verify the presence of anti-brain autoantibodies in the serum of schizophrenic patients compared to healthy controls. Autoantibodies against brain were detected by the immunofluorescence method, utilizing sections of rat hippocampus and hypothalamus and of monkey cerebellum. Three different fluorescence patterns were observed, staining the nucleus-cytoplasm of neurons, the neuroendothelial of blood vessel and the neurofilaments. Search for other organ-specific and non organ-specific autoantibodies was performed in all sera by indirect immunofluorescence method, enzyme linked immunosorbent assay and chemiluminescence immunoassay. Results showed a significant association between schizophrenia and anti-brain autoantibodies against the neuroendothelium of blood vessel in hypothalamus, hippocampus and cerebellum; a significant nuclear and cytoplasmic staining of neurons was assessed only for the hippocampus. No other significant association was found, except between schizophrenia and anti-nuclear autoantibodies on HEp-2 cells. In conclusion, these results support the hypothesis of a significant association between schizophrenia and circulating anti-brain autoantibodies, suggesting a diffuse reactivity against the neuroendothelium of blood vessel and highlighting a nuclear and cytoplasmic staining of the neurons of hippocampus. © 2013 Published by Elsevier Ireland Ltd.

Advancing paternal age at birth is associated with poorer social functioning earlier and later in life of schizophrenia patients in a founder population.

PubMed

Liebenberg, Rudolf; van Heerden, Brigitte; Ehlers, René; Du Plessis, Anna M E; Roos, J Louw

2016-09-30

Consistent associations have been found between advanced paternal age and an increased risk of psychiatric disorders, such as schizophrenia, in their offspring. This increase appears to be linear as paternal age increases. The present study investigates the relationship between early deviant behaviour in the first 10 years of life of patients as well as longer term functional outcome and paternal age in sporadic Afrikaner founder population cases of schizophrenia. This might improve our understanding of Paternal Age-Related Schizophrenia (PARS). Follow-up psychiatric diagnoses were confirmed by the Diagnostic Interview for Genetic Studies (DIGS). An early deviant childhood behaviour semi-structured questionnaire and the Specific Level of Functioning Assessment (SLOF) were completed. From the logistic regression models fitted, a significant negative relationship was found between paternal age at birth and social dysfunction as early deviant behaviour. Additionally, regression analysis revealed a significant negative relationship between paternal age at birth and the SLOF for interpersonal relationships later in life. Early social dysfunction may represent a phenotypic trait for PARS. Further research is required to understand the relationship between early social dysfunction and deficits in interpersonal relationships later in life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function

PubMed Central

Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

2010-01-01

Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package. PMID:20838587

Narrative incoherence in schizophrenia: the absent agent-protagonist and the collapse of internal dialogue.

PubMed

Lysaker, Paul H; Wickett, Amanda M; Wilke, Neil; Lysaker, John

2003-01-01

It is widely known that people with schizophrenia have difficulty telling a coherent story of their lives and that this is linked to impoverished function. But what specifically has gone wrong in the narratives in schizophrenia? Is it the case that some elements of narrative remain intact in schizophrenia while others are uniquely affected? To address these questions, we qualitatively analyze the personal narratives of three persons with schizophrenia, which have emerged in psychotherapy. Based on this analysis we suggest that narratives in schizophrenia uniquely fail to situate agency within the narrator resulting in a story that is missing an agent-protagonist. While the narratives we present contain coherent accounts of how others are connected to one another, they fail to evolve into a story about the self as an agent that others could associate with the narrator. We speculate that this may reflect neuro-cognitively based difficulties maintaining the internal dialogue that propels agency as well as fears that any emergent subjectivity may be appropriated or objectified by others. Implications for psychotherapy are discussed.

Antipsychotic Treatment of Adolescent Dual Diagnosis Patients

PubMed Central

Price, Scott A.; Brahm, Nancy C.

2011-01-01

BACKGROUND A diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients. METHODS A review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms “addiction,” “adolescence,” “childhood,” “dual diagnosis,” “schizophrenia,” and “substance abuse.” Results were limited to English-language articles. RESULTS Seven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events. CONCLUSION There is a great need for more research and use of available data to develop safe and effective treatment guidelines for childhood and adolescent dual diagnosis patients. When appropriate decisions are made regarding treatment of patients with comorbid schizophrenia and chemical dependence, both conditions may benefit with increased remission. PMID:22768007