A Review of Selected Candidate Endophenotypes for Depression

PubMed Central

Goldstein, Brandon L.; Klein, Daniel N.

2014-01-01

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. PMID:25006008

Endophenotype Best Practices

PubMed Central

Iacono, William G.; Malone, Stephen M.; Vrieze, Scott I.

2016-01-01

This review examines the current state of electrophysiological endophenotype research and recommends best practices that are based on knowledge gleaned from the last decade of molecular genetic research with complex traits. Endophenotype research is being oversold for its potential to help discover psychopathology relevant genes using the types of small samples feasible for electrophysiological research. This is largely because the genetic architecture of endophenotypes appears to be very much like that of behavioral traits and disorders: they are complex, influenced by many variants (e.g., tens of thousands) within many genes, each contributing a very small effect. Out of over 40 electrophysiological endophenotypes covered by our review, only resting heart, a measure that has received scant advocacy as an endophenotype, emerges as an electrophysiological variable with verified associations with molecular genetic variants. To move the field forward, investigations designed to discover novel variants associated with endophenotypes will need extremely large samples best obtained by forming consortia and sharing data obtained from genome wide arrays. In addition, endophenotype research can benefit from successful molecular genetic studies of psychopathology by examining the degree to which these verified psychopathology-relevant variants are also associated with an endophenotype, and by using knowledge about the functional significance of these variants to generate new endophenotypes. Even without molecular genetic associations, endophenotypes still have value in studying the development of disorders in unaffected individuals at high genetic risk, constructing animal models, and gaining insight into neural mechanisms that are relevant to clinical disorder. PMID:27473600

The utility of P300 as a schizophrenia endophenotype and predictive biomarker: clinical and socio-demographic modulators in COGS-2.

PubMed

Turetsky, Bruce I; Dress, Erich M; Braff, David L; Calkins, Monica E; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; 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; Light, Gregory

2015-04-01

Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results. Copyright © 2014 Elsevier B.V. All rights reserved.

The Utility of P300 as a Schizophrenia Endophenotype and Predictive Biomarker: Clinical and Socio-Demographic Modulators in COGS-2

PubMed Central

Turetsky, Bruce I.; Dress, Erich M.; Braff, David L.; Calkins, Monica E.; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; 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.; Light, Gregory

2014-01-01

Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 control and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results. PMID:25306203

A review of selected candidate endophenotypes for depression.

PubMed

Goldstein, Brandon L; Klein, Daniel N

2014-07-01

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

Action Monitoring in boys with ADHD, their Nonaffected Siblings and Normal Controls: Evidence for an Endophenotype

PubMed Central

Albrecht, Bjoern; Brandeis, Daniel; Uebel, Henrik; Heinrich, Hartmut; Mueller, Ueli C.; Hasselhorn, Marcus; Steinhausen, Hans-Christoph; Rothenberger, Aribert; Banaschewski, Tobias

2008-01-01

Background Attention deficit/hyperactivity disorder is a very common and highly heritable child psychiatric disorder associated with dysfunctions in fronto-striatal networks that control attention and response organisation. Aim of this study was to investigate whether features of action monitoring related to dopaminergic functions represent endophenotypes which are brain functions on the pathway from genes and environmental risk factors to behaviour. Methods Action monitoring and error processing as indicated by behavioural and electrophysiological parameters during a flanker task were examined in boys with ADHD combined type according to DSM-IV (N=68), their nonaffected siblings (N=18) and healthy controls with no known family history of ADHD (N=22). Results Boys with ADHD displayed slower and more variable reaction-times. Error negativity (Ne) was smaller in boys with ADHD compared to healthy controls, while nonaffected siblings displayed intermediate amplitudes following a linear model predicted by genetic concordance. The three groups did not differ on error positivity (Pe). N2 amplitude enhancement due to conflict (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also displayed intermediate N2 enhancement. Conclusions Converging evidence from behavioural and ERP findings suggests that action monitoring and initial error processing, both related to dopaminergically modulated functions of anterior cingulate cortex, might be an endophenotype related to ADHD. PMID:18339358

Neurocognitive performance as an endophenotype for bipolar disorder.

PubMed

Raust, Aurelie; Daban, Claire; Cochet, Barbara; Henry, Chantal; Bellivier, Frank; Scott, Jan

2014-01-01

Identification of the underlying liability to develop bipolar disorders (BD) is hindered by the genetic complexity and phenotypic heterogeneity of the disease. The use of endophenotypes has been acknowledged as a promising approach that may detect the hidden manifestations of a genetic liability for an illness. One of the most commonly proposed endophenotypes in BD is neurocognitive performance. We identified and examined previously published review articles that had any data pertaining to endophenotypes in BD and combined this with an extensive review of studies of cognitive deficits in BD from 2000 onwards. Using criteria for a valid endophenotype, we identifed that the domains of executive functioning and verbal memory are the most promising candidate endophenotypes for BD. However, they do not meet the criteria for specificity as similar deficits present in schizophrenia and/or severe or psychotic major depressions. Further research is needed as the findings regarding endophenotypes show between-study heterogeneity. In the future, examination of quantitative traits may offer a more promising approach to the study of endophenotypes rather than solely focusing on diagnostic categories.

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.

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.

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: An introduction to this Special Issue of schizophrenia research

PubMed Central

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

2014-01-01

Background The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Methods 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). Results 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. Discussion 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. PMID:25454799

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

PubMed

Beauchaine, Theodore P; Constantino, John N

2017-09-11

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study.

PubMed

Millard, Steven P; Shofer, Jane; Braff, David; Calkins, Monica; Cadenhead, Kristin; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel; Gur, Ruben; Lazzeroni, Laura C; Light, Gregory A; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William S; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Ming; Turetsky, Bruce; Radant, Allen; Tsuang, Debby W

2016-07-01

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially. Published by Elsevier B.V.

Prioritizing Schizophrenia Endophenotypes for Future Genetic Studies: An Example Using Data from the COGS-1 Family Study

PubMed Central

Millard, Steven P.; Shofer, Jane; Braff, David; Calkins, Monica; Cadenhead, Kristin; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel; Gur, Ruben; Lazzeroni, Laura C.; Light, Gregory A.; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Ming; Turetsky, Bruce; Radant, Allen; Tsuang, Debby W.

2016-01-01

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving statistical power of locating genetic regions associated with schizophrenia that may be the easiest to identify initially. PMID:27132484

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

Sustained and selective attention deficits as vulnerability markers to psychosis.

PubMed

Mulet, B; Valero, J; Gutiérrez-Zotes, A; Montserrat, C; Cortés, M J; Jariod, M; Martorell, L; Vilella, E; Labad, A

2007-04-01

The first descriptions of schizophrenia emphasized attention problems patients with schizophrenia have but recent results evidence that other psychotic disorders share them. We compared the performance in sustained and selective attention between psychotic patients (P), their healthy first degree relatives (R) and healthy volunteers (C) to prove whether these alterations could be an endophenotype of vulnerability to psychosis. We also compared the performance of schizophrenic patients (SZP) and that of patients with other functional psychoses (OP) in order to prove whether these alterations are specific of any psychotic disorder. Seventy-six P, 70 R and 39 C were included in the study. A selective attention index, comprising TMT A and B and Stroop Test, and a sustained attention index comprising the Continuous Performance Test were calculated. We conducted an univariant general linear model to compare three group performances in these indexes, with age, sex and years of education as a covariables. We found significant differences between the indexes when we compared P, R and C. No differences in performance were found between SZP and OP. Our data showed that sustained and selective attention alterations could be a vulnerability factor to psychotic disorders in general, but they were not specific of schizophrenia.

Electrophysiological Endophenotypes for Schizophrenia

PubMed Central

Owens, Emily; Bachman, Peter; Glahn, David C; Bearden, Carrie E

2016-01-01

Endophenotypes are quantitative, heritable traits that may help to elucidate the pathophysiologic mechanisms underlying complex disease syndromes, such as schizophrenia. They can be assessed at numerous levels of analysis; here, we review electrophysiological endophenotypes that have shown promise in helping us understand schizophrenia from a more mechanistic point of view. For each endophenotype, we describe typical experimental procedures, reliability, heritability, and reported gene and neurobiological associations. We discuss recent findings regarding the genetic architecture of specific electrophysiological endophenotypes, as well as converging evidence from EEG studies implicating disrupted balance of glutamatergic signaling and GABA-ergic inhibition in the pathophysiology of schizophrenia. We conclude that refining the measurement of electrophysiological endophenotypes, expanding genetic association studies, and integrating datasets are important next steps for understanding the mechanisms that connect identified genetic risk loci for schizophrenia to the disease phenotype. PMID:26954597

The Consortium on the Genetics of Endophenotypes in Schizophrenia: Model Recruitment, Assessment, and Endophenotyping Methods for a Multisite Collaboration

PubMed Central

Calkins, Monica E.; Dobie, Dorcas J.; Cadenhead, Kristin S.; Olincy, Ann; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Light, Gregory A.; Mintz, Jim; Nuechterlein, Keith H.; Radant, Allen D.; Schork, Nicholas J.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2007-01-01

Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health–funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. Methods: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. Results: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). Discussion: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia. PMID:17035358

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

PubMed Central

He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

2016-01-01

Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases. PMID:27790247

Association of Aging-Related Endophenotypes With Mortality in 2 Cohort Studies: the Long Life Family Study and the Health, Aging and Body Composition Study.

PubMed

Singh, Jatinder; Schupf, Nicole; Boudreau, Robert; Matteini, Amy M; Prasad, Tanushree; Newman, Anne B; Liu, YongMei; Christensen, Kaare; Kammerer, Candace M

2015-12-01

One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings.

PubMed

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

2014-09-30

We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes. Published by Elsevier Ireland Ltd.

Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents

PubMed Central

Moseley, R.L.; Ypma, R.J.F.; Holt, R.J.; Floris, D.; Chura, L.R.; Spencer, M.D.; Baron-Cohen, S.; Suckling, J.; Bullmore, E.; Rubinov, M.

2015-01-01

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. PMID:26413477

Nicotine effects on brain function and functional connectivity in schizophrenia.

PubMed

Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar; Pugh, Kenneth R; Skudlarski, Pawel; Krystal, John H

2004-04-15

Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Is there an association between advanced paternal age and endophenotype deficit levels in schizophrenia?

PubMed

Tsuang, Debby; Esterberg, Michelle; Braff, David; Calkins, Monica; Cadenhead, Kristin; Dobie, Dorcas; Freedman, Robert; Green, Michael F; Greenwood, Tiffany; Gur, Raquel; Gur, Ruben; Horan, William; Lazzeroni, Laura C; Light, Gregory A; Millard, Steven P; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine; Swerdlow, Neal; Tsuang, Ming; Turetsky, Bruce; Radant, Allen

2014-01-01

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects' birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.

Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study.

PubMed

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

2016-01-01

The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

Executive functions as a potential neurocognitive endophenotype in anxiety disorders: A systematic review considering DSM-IV and DSM-5 diagnostic criteria classification.

PubMed

Muller, Juliana de Lima; Torquato, Kamilla Irigaray; Manfro, Gisele Gus; Trentini, Clarissa Marceli

2015-01-01

Evidence in the literature indicates that neurocognitive impairments may represent endophenotypes in psychiatric disorders. This study aimed to conduct a systematic review on executive functions as a potential neurocognitive endophenotype in anxiety disorder diagnosis according to the DSM-IV and DSM-5 classifications. A literature search of the LILACS, Cochrane Library, Index Psi Periódicos Técnico-Científicos, PubMed and PsycInfo databases was conducted, with no time limits. Of the 259 studies found, 14 were included in this review. Only studies on obsessive-compulsive disorder (OCD) were found. The executive function components of decision-making, planning, response inhibition, behavioral reversal/alternation, reversal learning and set-shifting/cognitive flexibility were considered to be a neurocognitive endophenotypes in OCD. Further studies on executive functions as a neurocognitive endophenotype in other anxiety disorders are needed since these may have different neurocognitive endophenotypes and require other prevention and treatment approaches.

Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: A genome-wide association study

PubMed Central

VAIDYANATHAN, UMA; MALONE, STEPHEN M.; MILLER, MICHAEL B.; McGUE, MATT; IACONO, WILLIAM G.

2014-01-01

Acoustic startle responses have been studied extensively in relation to individual differences and psychopathology. We examined three indices of the blink response in a picture-viewing paradigm—overall startle magnitude across all picture types, and aversive and pleasant modulation scores—in 3,323 twins and parents. Biometric models and molecular genetic analyses showed that half the variance in overall startle was due to additive genetic effects. No single nucleotide polymorphism was genome-wide significant, but GRIK3 did produce a significant effect when examined as part of a candidate gene set. In contrast, emotion modulation scores showed little evidence of heritability in either biometric or molecular genetic analyses. However, in a genome-wide scan, PARP14 did produce a significant effect for aversive modulation. We conclude that, although overall startle retains potential as an endophenotype, emotion-modulated startle does not. PMID:25387708

Is There an Association between Advanced Paternal Age and Endophenotype Deficit Levels in Schizophrenia?

PubMed Central

Tsuang, Debby; Esterberg, Michelle; Braff, David; Calkins, Monica; Cadenhead, Kristin; Dobie, Dorcas; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany; Gur, Raquel; Gur, Ruben; Horan, William; Lazzeroni, Laura C.; Light, Gregory A.; Millard, Steven P.; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine; Swerdlow, Neal; Tsuang, Ming; Turetsky, Bruce; Radant, Allen

2014-01-01

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects’ birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age–endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia. PMID:24523888

Schizotypal personality disorder inside and outside the schizophrenic spectrum.

PubMed

Torgersen, Svenn; Edvardsen, J; Øien, P A; Onstad, S; Skre, I; Lygren, S; Kringlen, E

2002-03-01

The concept of schizotypal personality disorder has been heavily discussed since its introduction into the official classification of mental disorders in DSM-III. The aim of this study was to investigate the difference between schizotypal personality disorder within and outside the genetic spectrum of schizophrenia. Schizotypals with and without schizophrenic cotwins and first-degree relatives were compared, with individuals with other mental disorders and no mental disorders as controls. It appeared that only inadequate rapport and odd communication were more pronounced among schizotypals within, compared to schizotypals outside the schizophrenic spectrum. Schizotypals outside the schizophrenic spectrum, however, scored higher than schizotypals inside the schizophrenic spectrum on ideas of reference, suspiciousness, paranoia, social anxiety, self-damaging acts, chronic anger, free-floating anxiety and sensitivity to rejection. Interestingly, the four last features are seldom observed among schizotypals inside the schizophrenic spectrum. Monozygotic non-schizophrenic cotwins of schizophrenics score high on inadequate rapport, odd communication, social isolation and delusions/hallucinations. Monozygotic non-schizophrenic cotwins of schizotypals outside the schizophrenic genetic spectrum score high on illusions, depersonalization, derealization and magical thinking. Negative schizotypal features appear to be inside the schizophrenic spectrum, while positive borderline-like features are outside having another genetic endowment.

Endophenotypes for Intelligence in Children and Adolescents

ERIC Educational Resources Information Center

van Leeuwen, Marieke; van den Berg, Stephanie M.; Hoekstra, Rosa A.; Boomsma, Dorret I.

2007-01-01

The aim of this study was to identify promising endophenotypes for intelligence in children and adolescents for future genetic studies in cognitive development. Based on the available set of endophenotypes for intelligence in adults, cognitive tasks were chosen covering the domains of working memory, processing speed, and selective attention. This…

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

Mice Lacking the Circadian Modulators SHARP1 and SHARP2 Display Altered Sleep and Mixed State Endophenotypes of Psychiatric Disorders

PubMed Central

Shahmoradi, Ali; Reinecke, Lisa; Kroos, Christina; Wichert, Sven P.; Oster, Henrik; Wehr, Michael C.; Taneja, Reshma; Hirrlinger, Johannes; Rossner, Moritz J.

2014-01-01

Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2. PMID:25340473

Impressions of Humanness for Android Robot May Represent an Endophenotype for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kumazaki, Hirokazu; Warren, Zachary; Swanson, Amy; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Ishiguro, Hiroshi; Sarkar, Nilanjan; Minabe, Yoshio; Kikuchi, Mitsuru

2018-01-01

Identification of meaningful endophenotypes may be critical to unraveling the etiology and pathophysiology of autism spectrum disorders (ASD). We investigated whether impressions of "humanness" for android robot might represent a candidate characteristic of an ASD endophenotype. We used a female type of android robot with an appearance…

Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains.

PubMed

Blakey, R; Ranlund, S; Zartaloudi, E; Cahn, W; Calafato, S; Colizzi, M; Crespo-Facorro, B; Daniel, C; Díez-Revuelta, Á; Di Forti, M; Iyegbe, C; Jablensky, A; Jones, R; Hall, M-H; Kahn, R; Kalaydjieva, L; Kravariti, E; Lin, K; McDonald, C; McIntosh, A M; Picchioni, M; Powell, J; Presman, A; Rujescu, D; Schulze, K; Shaikh, M; Thygesen, J H; Toulopoulou, T; Van Haren, N; Van Os, J; Walshe, M; Murray, R M; Bramon, E

2018-06-01

A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.

Does Performance on the Standard Antisaccade Task Meet the Co-Familiality Criterion for an Endophenotype?

ERIC Educational Resources Information Center

Levy, Deborah L.; Bowman, Elizabeth A.; Abel, Larry; Krastoshevsky, Olga; Krause, Verena; Mendell, Nancy R.

2008-01-01

The "co-familiality" criterion for an endophenotype has two requirements: (1) clinically unaffected relatives as a group should show both a shift in mean performance and an increase in variance compared with controls; (2) performance scores should be heritable. Performance on the antisaccade task is one of several candidate endophenotypes for…

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.

Temperament and character inventory in homicidal, nonaddicted paranoid schizophrenic patients: a preliminary study.

PubMed

Vandamme, Michel J; Nandrino, Jean-Louis

2004-10-01

This study assessed the personalities of 13 murderer schizophrenics using Cloninger's Temperament and Character Inventory, controlling different factors such as institution, treatment, detention or loss of liberty, and can discriminate between schizophrenic patients involved in homicide, schizophrenics with no past violent behavior, paranoiac murderers, and imprisoned murderers with no psychiatric history. Results show significantly that murderer schizophrenics had significantly higher scores on the subscale, Self-transcendence, than other groups, which suggests that Self-transcendence as measured may be an aggravating factor for schizophrenia and may be found in the personality of schizophrenic subjects who performed homicidal acts. This dimension constitutes a way and an additional element for diagnosis not available with the DSM-IV criteria. It may help understanding and predicting violent behavior among schizophrenic patients.

Subjective Responses to Alcohol Consumption as Endophenotypes: Advancing Behavioral Genetics in Etiological and Treatment Models of Alcoholism

PubMed Central

Ray, Lara A.; MacKillop, James; Monti, Peter M.

2015-01-01

Individual differences in subjective responses to alcohol consumption represent genetically-mediated biobehavioral mechanisms of alcoholism risk (i.e., endophenotype). The objective of this review is three-fold: (1) to provide a critical review the literature on subjective response to alcohol and to discuss the rationale for its conceptualization as an endophenotype for alcoholism; (2) to examine the literature on the neurobiological substrates and associated genetic factors subserving individual differences in subjective response to alcohol; and (3) to discuss the treatment implications of this approach and to propose a framework for conceptualizing, and systematically integrating, endophenotypes into alcoholism treatment. PMID:20590398

The Consortium on the Genetics of Schizophrenia: Neurocognitive Endophenotypes

PubMed Central

Gur, Raquel E.; Calkins, Monica E.; Gur, Ruben C.; Horan, William P.; Nuechterlein, Keith H.; Seidman, Larry J.; Stone, William S.

2007-01-01

The Consortium on the Genetics of Schizophrenia (COGS) is a 7-site collaboration that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia. Here we review the background and rationale for selecting neurocognitive tasks as endophenotypic measures in genetic studies. Criteria are outlined for the potential of measures as endophenotypic vulnerability markers. These include association with illness, state independence (ie, adequate test-retest stability, adequate between-site reliability, impairments in patients not due to medications, impairments observed regardless of illness state), heritability, findings of higher rates in relatives of probands than in the general population, and cosegregation within families. The COGS required that, in addition, the measures be “neurocognitive” and thus linked to neurobiology and that they be feasible in multisite studies. The COGS neurocognitive assessment includes measures of attention, verbal memory, working memory, and a computerized neurocognitive battery that also includes facial processing tasks. Here we describe data demonstrating that these neurobehavioral measures meet criteria for endophenotypic candidacy. We conclude that quantitative neurocognitive endophenotypes need further evidence for efficacy in identifying genetic effects but have the potential of providing unprecedented insight into gene-environment interaction related to dimensions of brain and behavior in health and disease. PMID:17101692

[Structural correlation of schizophrenic thought and language disorders with delusional perception and variations of intentionality].

PubMed

Holm-Hadulla, R

1988-01-01

This study originated from a phenomenological and speech-act theoretical concept of schizophrenic concretism. An experimental study was performed showing a highly significant lack in the schizophrenic patients' ability to use metaphors correctly. Basing on the interpretation of proverbs, the hypothesis is rejected that false interpretations of schizophrenic patients are due to intermingling of personal conflicts. On the other hand, it could be shown that concretistic interpretations of proverbs represent an avoidance of conflicts. The concepts of "substitution" and "transfer" enabled us to measure pathological concreteness and "deconflictualisation". The differentiation between schizophrenic and nonpsychotic patients was found to be highly significant. In a complementary study it could be shown that the chronic schizophrenics' disability to transfer images of proverbs to an interpersonally relevant context does not differ significantly from that of patients with their first schizophrenic episode. Discussing our empirical findings, we try to show that the concretistic reduction of thought and speech is also a paradigma of delusion. The "incorrigibility" of schizophrenic delusion was seen to be based on reification of verbal signs and metaphors. After trying to show a connection between the concretistic "Lebensform" (Wittgenstein) and the disordered intentionality of schizophrenic patients, pointers towards psychotherapeutic implications are given.

Schizophrenic Performance During Interpersonal Competitive Conditions

ERIC Educational Resources Information Center

Anderson, Brent L.

1977-01-01

By assessing the competitive performance of schizophrenics on different types of tasks and by using nonschizophrenic groups, an attempt was made to determine more accurately whether schizophrenics respond differently to competition than nonschizophrenics, and if the effects of competition tend to be task-specific with schizophrenics. (Author/RK)

Doxycycline prevents and reverses schizophrenic-like behaviors induced by ketamine in mice via modulation of oxidative, nitrergic and cholinergic pathways.

PubMed

Ben-Azu, Benneth; Omogbiya, Itivere Adrian; Aderibigbe, Adegbuyi Oladele; Umukoro, Solomon; Ajayi, Abayomi Mayowa; Iwalewa, Ezekiel O

2018-05-01

The involvement of oxidative, nitrergic, cholinergic and inflammatory alterations have been reported to contribute to the pathophysiology of schizophrenia, a debilitating neuropsychiatric disorder. Our previous studies have shown that doxycycline (DOX), a notable member of tetracyclines with proven antioxidant and anti-inflammatory properties, attenuated psychotic-like behaviors induced by apomophine and ketamine (KET) in mice. This present study was designed to further evaluate in detail the ability of DOX and its combination with risperidone (RIS) to prevent and reverse KET-induced schizophrenic-like behaviors and the role of oxidative/nitrergic and cholinergic pathways in mice. In the prevention protocol, mice were treated orally with DOX (25, 50 or 100 mg/kg), RIS (0.5 mg/kg), DOX (50 mg/kg) in combination with RIS, or vehicle for 14 consecutive days. In addition, the animals received intraperitoneal injection of KET (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or vehicle for 14 days prior to DOX, RIS, DOX in-combination with RIS or vehicle treatments. Schizophrenic-like behaviors consisting of positive, negative and cognitive symptoms were evaluated using open field, social interaction, Y-maze and novel object recognition tests. Thereafter, the brain levels of biomarkers of oxidative stress, nitrite and acetylcholinesterase activity were determined. DOX given alone or in combination with RIS attenuated schizophrenic-like behaviors induced by chronic injection of KET in both preventive and reversal treatment protocols. DOX significantly increased glutathione, superoxide dismutase and catalase levels in the brain of chronic KET-treated mice. However, it decreased malonyladehyde, nitrite levels and acetylcholinesterase activity when given alone or in-combination with RIS in both protocols. Taken together, these findings showed that doxycycline ameliorated schizophrenic-like behaviors induced by ketamine in both preventive and reversal treatment protocols in mice via inhibition of oxidative and nitrergic alterations, and acetylcholinesterase activity. Our data further suggests that adjunctive oral administration of doxycycline may augment the therapeutic efficacy of risperidone particularly for the treatment of negative and cognitive symptoms associated with schizophrenia. Copyright © 2018 Elsevier Inc. All rights reserved.

Facial recognition deficits as a potential endophenotype in bipolar disorder.

PubMed

Vierck, Esther; Porter, Richard J; Joyce, Peter R

2015-11-30

Bipolar disorder (BD) is considered a highly heritable and genetically complex disorder. Several cognitive functions, such as executive functions and verbal memory have been suggested as promising candidates for endophenotypes. Although there is evidence for deficits in facial emotion recognition in individuals with BD, studies investigating these functions as endophenotypes are rare. The current study investigates emotion recognition as a potential endophenotype in BD by comparing 36 BD participants, 24 of their 1st degree relatives and 40 healthy control participants in a computerised facial emotion recognition task. Group differences were evaluated using repeated measurement analysis of co-variance with age as a covariate. Results revealed slowed emotion recognition for both BD and their relatives. Furthermore, BD participants were less accurate than healthy controls in their recognition of emotion expressions. We found no evidence of emotion specific differences between groups. Our results provide evidence for facial recognition as a potential endophenotype in BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Factor Structure and Heritability of Endophenotypes in Schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1)

PubMed Central

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

2018-01-01

Background Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. Methods The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003–2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Results Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Conclusions Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. PMID:25682549

Factor structure and heritability of endophenotypes in schizophrenia: findings from the Consortium on the Genetics of Schizophrenia (COGS-1).

PubMed

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

2015-04-01

Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Eye-hand preference in schizophrenia: sex differences and significance for hand function.

PubMed

Liu, Yi-Chia; Yang, Yen Kuang; Lee, I Hui; Lin, Keh-Chung; Jeffries, Keith J; Lee, Li-Ching

2004-06-01

Hand preference and eye dominance were investigated in 73 (30 women, 43 men) schizophrenic patients and 71 (30 women, 41 men) healthy controls. There were significantly more schizophrenic patients and normal controls who were significantly right-hand dominant. However, schizophrenic patients showed a significant excess of left-eye dominance relative to controls (65.8% vs 29.6%; Odds Ratio= 4.75, p< .001). In addition, female schizophrenic patients showed a higher rate of nonright (either left or inconsistent) eye dominance (80%) than male schizophrenic patients (55.8%) and controls (33.3%). Analysis of hand performance on the Purdue Pegboard Test indicated that schizophrenic patients who showed crossed eye-hand dominance scored higher than did patients without crossed eye-hand dominance.

[Cognitive performance in schizophrenia (paranoid vs residual subtype)].

PubMed

Dillon, Carol; Taragano, Fernando; Sarasola, Diego; Iturry, Mónica; Serrano, Cecilia; Raczkowski, Amalia; Allegri, Ricardo

2007-01-01

Several studies refer to the relationship between schizophrenia and cognitive dysfunctions. The most frequent disturbances accepted are the deficits in the executive, memory and verbal tests. However, there are few comparative data about the cognitive functioning of the different subtypes of schizophrenia. Analyze and compare the neuropsychological disturbances present in patients with paranoid and residual schizophrenia. Eleven patients with paranoid schizophrenia, eleven patients with residual schizophrenia (DSM-IV criteria), and thirty one normal subjects matched by age, educational level, and general cognitive level (Mini Mental State Examination (Folstein, 1975), were assessed with a semistructured psychiatric examination and an extensive neuropsychological battery. Significant differences were found in memory, language, and executive functions when schizophrenics were compared with normal subjects. Differences in similarities were found between paranoid and residual schizophrenics. Residual schizophrenics had more disturbances in neuropsychological tests in comparison with paranoid schizophrenics. Schizophrenics demonstrated disturbances in memory, language, executive functions and attention. Residual schizophrenics had more impairment in neuropsychological tests than paranoid schizophrenics.

Psychopathology in children of schizophrenics

PubMed Central

Shah, Sharita; Kamat, Sanjeev; Sawant, Urmila; Dhavale, H.S.

2003-01-01

The higher prevalence of schizophrenia in children of schizophrenics than in the general population has generated an interest in pinpointing those behaviors that may precede the disorder and serve as an index of vulnerability to the disorder. Signs of neurobehavioral dysfunction in areas of neurocognitive functioning and social behavior have been found in school-age children of schizophrenic parents. This study assessed the neurobehavioral functioning, social behavior, cognitive functioning, attention and intelligence in children with a schizophrenic parent and compared the same parameters with children of mentally healthy parents. The children aged 12-15 years, were assessed with a battery of neurobehavioral tests. The children with a schizophrenic parent performed more poorly on the tests as compared to the children of mentally healthy parents. The children with a schizophrenic parent were seen to have more behavioral problems, especially withdrawn behavior and more social problems when compared to the other children in the study. Poor attention, disordered thoughts and lower intelligence were also observed to be more in the children of the schizophrenic parent PMID:21206831

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

PubMed Central

Light, Gregory; Greenwood, Tiffany A.; Swerdlow, Neal R.; Calkins, Monica E.; Freedman, Robert; Green, Michael F.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; 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.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Background: Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes. Methods: Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families. Results: The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively. Conclusions: Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis. PMID:24903414

Contributions from specific and general factors to unique deficits: two cases of mathematics learning difficulties

PubMed Central

Haase, Vitor G.; Júlio-Costa, Annelise; Lopes-Silva, Júlia B.; Starling-Alves, Isabella; Antunes, Andressa M.; Pinheiro-Chagas, Pedro; Wood, Guilherme

2014-01-01

Mathematics learning difficulties are a highly comorbid and heterogeneous set of disorders linked to several dissociable mechanisms and endophenotypes. Two of these endophenotypes consist of primary deficits in number sense and verbal numerical representations. However, currently acknowledged endophenotypes are underspecified regarding the role of automatic vs. controlled information processing, and their description should be complemented. Two children with specific deficits in number sense and verbal numerical representations and normal or above-normal intelligence and preserved visuospatial cognition illustrate this point. Child H.V. exhibited deficits in number sense and fact retrieval. Child G.A. presented severe deficits in orally presented problems and transcoding tasks. A partial confirmation of the two endophenotypes that relate to the number sense and verbal processing was obtained, but a much more clear differentiation between the deficits presented by H.V. and G.A. can be reached by looking at differential impairments in modes of processing. H.V. is notably competent in the use of controlled processing but has problems with more automatic processes, such as nonsymbolic magnitude processing, speeded counting and fact retrieval. In contrast, G.A. can retrieve facts and process nonsymbolic magnitudes but exhibits severe impairment in recruiting executive functions and the concentration that is necessary to accomplish transcoding tasks and word problem solving. These results indicate that typical endophenotypes might be insufficient to describe accurately the deficits that are observed in children with mathematics learning abilities. However, by incorporating domain-specificity and modes of processing into the assessment of the endophenotypes, individual deficit profiles can be much more accurately described. This process calls for further specification of the endophenotypes in mathematics learning difficulties. PMID:24592243

Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study.

PubMed

Light, Gregory; Greenwood, Tiffany A; Swerdlow, Neal R; Calkins, Monica E; Freedman, Robert; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; 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; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2014-11-01

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a "heritability gap" between the diagnosis and related endophenotypes. Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families. The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively. Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2014.

[18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

PubMed Central

Racette, Brad A.; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

2008-01-01

Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field

PubMed Central

Hunsaker, Michael R.

2013-01-01

It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on the FMR1 gene underlying Fragile X-Associated Disorders have reported preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI) mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to the Fmr1 knock-out (KO) mouse model. When combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). PMID:24627796

Neurological Soft Signs in Schizophrenia: A Meta-analysis

PubMed Central

Chan, Raymond C. K.; Xu, Ting; Heinrichs, R. Walter; Yu, Yue; Wang, Ya

2010-01-01

Background: Neurological soft signs (NSS) are hypothesized as candidate endophenotypes for schizophrenia, but their prevalence and relations with clinical and demographic data are unknown. The authors undertook a quantification (meta-analysis) of the published literature on NSS in patients with schizophrenia and healthy controls. A systematic search was conducted for published articles reporting NSS and related data using standard measures in schizophrenia and healthy comparison groups. Method: A systematic search was conducted for published articles reporting data on the prevalence of NSS in schizophrenia using standard clinical rating scales and healthy comparison groups. Meta-analyses were performed using the Comprehensive Meta-analysis software package. Effect sizes (Cohen d) indexing the difference between schizophrenic patients and the healthy controls were calculated on the basis of reported statistics. Potential moderator variables evaluated included age of patient samples, level of education, sample sex proportions, medication doses, and negative and positive symptoms. Results: A total of 33 articles met inclusion criteria for the meta-analysis. A large and reliable group difference (Cohen d) indicated that, on average, a majority of patients (73%) perform outside the range of healthy subjects on aggregate NSS measures. Cognitive performance and positive and negative symptoms share 2%–10% of their variance with NSS. Conclusions: NSS occur in a majority of the schizophrenia patient population and are largely distinct from symptomatic and cognitive features of the illness. PMID:19377058

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.

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

PubMed Central

Archer, Trevor; Oscar-Berman, Marlene; Blum, Kenneth

2011-01-01

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring. PMID:22224195

A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.

PubMed

Mostafavi, Sara; Gaiteri, Chris; Sullivan, Sarah E; White, Charles C; Tasaki, Shinya; Xu, Jishu; Taga, Mariko; Klein, Hans-Ulrich; Patrick, Ellis; Komashko, Vitalina; McCabe, Cristin; Smith, Robert; Bradshaw, Elizabeth M; Root, David E; Regev, Aviv; Yu, Lei; Chibnik, Lori B; Schneider, Julie A; Young-Pearse, Tracy L; Bennett, David A; De Jager, Philip L

2018-06-01

There is a need for new therapeutic targets with which to prevent Alzheimer's disease (AD), a major contributor to aging-related cognitive decline. Here we report the construction and validation of a molecular network of the aging human frontal cortex. Using RNA sequence data from 478 individuals, we first build a molecular network using modules of coexpressed genes and then relate these modules to AD and its neuropathologic and cognitive endophenotypes. We confirm these associations in two independent AD datasets. We also illustrate the use of the network in prioritizing amyloid- and cognition-associated genes for in vitro validation in human neurons and astrocytes. These analyses based on unique cohorts enable us to resolve the role of distinct cortical modules that have a direct effect on the accumulation of AD pathology from those that have a direct effect on cognitive decline, exemplifying a network approach to complex diseases.

Lexical decision as an endophenotype for reading comprehension: An exploration of an association

PubMed Central

NAPLES, ADAM; KATZ, LEN; GRIGORENKO, ELENA L.

2012-01-01

Based on numerous suggestions in the literature, we evaluated lexical decision (LD) as a putative endophenotype for reading comprehension by investigating heritability estimates and segregation analyses parameter estimates for both of these phenotypes. Specifically, in a segregation analysis of a large sample of families, we established that there is little to no overlap between genes contributing to LD and reading comprehension and that the genetic mechanism behind LD derived from this analysis appears to be more complex than that for reading comprehension. We conclude that in our sample, LD is not a good candidate as an endophenotype for reading comprehension, despite previous suggestions from the literature. Based on this conclusion, we discuss the role and benefit of the endophenotype approach in studies of complex human cognitive functions. PMID:23062302

Components of Processing Deficit Among Paranoid and Nonparanoid Schizophrenics

ERIC Educational Resources Information Center

Neufeld, Richard W. J.

1977-01-01

Paranoid and nonparanoid schizophrenics were compared to normals in their performance on a sentence verification task. Results were related to past evidence and hypotheses about central processing performance among schizophrenics. (Editor/RK)

Intermingling and disordered logic as influences on schizophrenic 'thought disorders'.

PubMed

Harrow, M; Prosen, M

1978-10-01

A technique was devised to elicit bizarre or idiosyncratic responses from 30 young schizophrenics, who were then re-interviewed a week later to determine the reasons for each patient's idiosyncratic verbalizations. Taped interviews of the schizophrenics, scored along a series of rating scales, indicated: (1) An overt mechanism involved in bizarre schizophrenic language is a tendency to intermingle into their responses material from their current and past experiences. (2) Careful analysis suggests that the seemingly bizarre intermingled material of schizophrenics usually is close to the original "correct" topic. (3) The bizarre intermingled material is related to the patients' personal lives. (4) The intermingled material does not usually represent a failure to screen out or repress primitive drive dominated sexual or aggressive material. (5) Disordered logic was not a major factor in accounting for bizarre schizophrenic language.

Computer content analysis of schizophrenic speech: a preliminary report.

PubMed

Tucker, G J; Rosenberg, S D

1975-06-01

Computer analysis significantly differtiated the thermatic content of the free speech of 10 schizophrenic patients from that of 10 nonschizophrenic patients and from the content of transcripts of dream material from 10 normal subjects. Schizophrenic patients used the thematic categories in factor 1 (the "schizophrenic factor") 3 times more frequently than the nonschizophrenics and 10 times more frequently than the normal subjects (p smaller than 01). In general, the language content of the schizophrenic patient mirrored an almost agitated attempt to locate oneself in time and space and to defend against internal discomfort and confusion. The authors discuss the implications of this study for future research.

Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

PubMed Central

Huebinger, Ryan M.; Shewale, Shantanu J.; Koenig, Jessica L.; Mitchel, Jeffrey S.; O’Bryant, Sid E.; Waring, Stephen C.; Diaz-Arrastia, Ramon; Chasse, Scott

2015-01-01

Although 24 Alzheimer’s disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel genetic interactions and should be further investigated. PMID:26625115

Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

PubMed

Barber, Robert C; Phillips, Nicole R; Tilson, Jeffrey L; Huebinger, Ryan M; Shewale, Shantanu J; Koenig, Jessica L; Mitchel, Jeffrey S; O'Bryant, Sid E; Waring, Stephen C; Diaz-Arrastia, Ramon; Chasse, Scott; Wilhelmsen, Kirk C

2015-01-01

Although 24 Alzheimer's disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7). Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel genetic interactions and should be further investigated.

Moral Judgment Maturity of Process and Reactive Schizophrenics.

ERIC Educational Resources Information Center

Herron, William G.; And Others

1983-01-01

Premorbid adjustment, paranoid symptomatology, and orientation were examined as major predictors of moral judgment maturity in 40 schizophrenics. Results suggest the importance of cognitive and social skills in the development of schizophrenics' moral judgment maturity. (Author/RH)

Revisiting the association of aggression and suicidal behavior in schizophrenic inpatients.

PubMed

Neuner, Tanja; Hübner-Liebermann, Bettina; Hausner, Helmut; Hajak, Göran; Wolfersdorf, Manfred; Spiessl, Hermann

2011-04-01

Our study investigated the association of aggression and suicidal behavior in schizophrenic inpatients. Eight thousand nine hundred one admissions for schizophrenia (1998-2007) to a psychiatric university hospital were included. Schizophrenic suicides (n = 7)/suicide attempters (n = 40) were compared to suicides (n = 30)/suicide attempters (n = 186) with other diagnoses and to schizophrenic non-attempters regarding aggression. Logistic regression analysis was performed to explore risk factors for attempted suicide. Schizophrenic suicides/suicide attempters did not differ from other suicides/suicide attempters or from schizophrenic non-attempters with regard to aggression. Risk of inpatient suicide attempt was increased for patients with attempted suicide at admission, high school graduation, and disorganized subtype. Aggression could not be found to be a predictor of attempted suicide. Aggression seems to have a minor role for suicidal behavior in schizophrenia. © 2011 The American Association of Suicidology.

Literacy outcomes of children with early childhood speech sound disorders: impact of endophenotypes.

PubMed

Lewis, Barbara A; Avrich, Allison A; Freebairn, Lisa A; Hansen, Amy J; Sucheston, Lara E; Kuo, Iris; Taylor, H Gerry; Iyengar, Sudha K; Stein, Catherine M

2011-12-01

To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills.

Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate

PubMed Central

Mastronardi, C A; Pillai, E; Pineda, D A; Martinez, A F; Lopera, F; Velez, J I; Palacio, J D; Patel, H; Easteal, S; Acosta, M T; Castellanos, F X; Muenke, M; Arcos-Burgos, M

2016-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder. PMID:26598068

Literacy Outcomes of Children With Early Childhood Speech Sound Disorders: Impact of Endophenotypes

PubMed Central

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Hansen, Amy J.; Sucheston, Lara E.; Kuo, Iris; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2012-01-01

Purpose To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Method Children with SSD and their siblings were assessed at early childhood (ages 4–6 years) and followed at school age (7–12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Results Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Conclusions Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills. PMID:21930616

Multivariate synaptic and behavioral profiling reveals new developmental endophenotypes in the prefrontal cortex

PubMed Central

Iafrati, Jillian; Malvache, Arnaud; Gonzalez Campo, Cecilia; Orejarena, M. Juliana; Lassalle, Olivier; Bouamrane, Lamine; Chavis, Pascale

2016-01-01

The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice. Multivariate analysis of bootstrapped datasets revealed subgroups of phenotypic traits specific to each maturational epoch. The preeminence of synaptic AMPA/NMDA receptor content to pre-weaning and juvenile endophenotypes shifts to long-term potentiation and memory renewal during adolescence followed by NMDA-GluN2B synaptic content in adulthood. Strikingly, multivariate analysis shows that pharmacological rehabilitation of reelin haploinsufficient dysfunctions is mediated through induction of new endophenotypes rather than reversion to wild-type traits. By delineating previously unknown developmental endophenotypic sequences, we conceived a promising general strategy to disambiguate the molecular underpinnings of complex psychiatric disorders and for the rational design of pharmacotherapies in these disorders. PMID:27765946

Autism Tendencies and Psychosis Proneness Interactively Modulate Saliency Cost

PubMed Central

Abu-Akel, Ahmad; Apperly, Ian A.; Wood, Stephen J.; Hansen, Peter C.; Mevorach, Carmel

2017-01-01

Atypical responses to salient information are a candidate endophenotype for both autism and psychosis spectrum disorders. The present study investigated the costs and benefits of such atypicalities for saliency-based selection in a large cohort of neurotypical adults in whom both autism and psychosis expressions were assessed. Two experiments found that autism tendencies and psychosis proneness interactively modulated the cost incurred in the presence of a task-irrelevant salient distractor. Specifically, expressions of autism and psychosis had opposing effects on responses to salient information such that the benefits associated with high expressions for autism offset costs associated with high expressions for psychosis. The opposing influences observed on saliency cost may be driven by distinct attentional mechanisms that are differentially affected by expressions for autism and psychosis. PMID:27217269

Family interaction: parental representation in schizophrenic patients.

PubMed

Onstad, S; Skre, I; Torgersen, S; Kringlen, E

1994-01-01

12 monozygotic (MZ) and 19 same-sexed dizygotic (DZ) twin pairs discordant for DSM-III-R schizophrenia completed the Parental Bonding Instrument (PBI). The schizophrenic twins described their parents as less caring and being more overprotective compared to their non-schizophrenic co-twins. These results were independent of age, sex and zygosity. Difference in paternal overprotection was the most important variable discriminating between the schizophrenic probands and their co-twins. Three different hypotheses regarding these findings are discussed.

Radioimmunoassay measurement of creatine kinase bb in the serum of schizophrenic patients

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

Lerner, M.H.; Friedhoff, A.J.

1980-03-03

Brain type creatine kinase (BB) isoenzyme was measured using a highly sensitive and specific radioimmunoassay procedure in two schizophrenic populations. The data would indicate that in the schizophrenic populations examined there is insufficient tissue disruption to cause abnormal build-up of brain creatine kinase levels. However the possibility of a rapid removal of creatine kinase BB from the circulation exists. The elevated creatine kinase reported in acute schizophrenics is most likely not of brain origin.

Inducing Assertive Behavior in Chronic Schizophrenics: A Comparison of Socioenvironmental Desensitization, and Relaxation Therapies

ERIC Educational Resources Information Center

Weinman, Bernard; And Others

1972-01-01

It is concluded that systematic desensitization or relaxation therapy is not effective in inducing assertive behavior in the male chronic schizophrenic. The treatment of choice for the older chronic male schizophrenic remains socioenvironmental therapy. (Author)

Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia.

PubMed

Light, Gregory A; Swerdlow, Neal R; Rissling, Anthony J; Radant, Allen; Sugar, Catherine A; Sprock, Joyce; Pela, Marlena; Geyer, Mark A; Braff, David L

2012-01-01

Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. The majority of neurophysiological and neurocognitive measures exhibited deficits in patients, stability over a 1-year interval and did not demonstrate practice or time effects supporting their use as endophenotypes in neural substrate and genomic studies. These measures hold promise for informing the "gene-to-phene gap" in schizophrenia research.

Characterization of Neurophysiologic and Neurocognitive Biomarkers for Use in Genomic and Clinical Outcome Studies of Schizophrenia

PubMed Central

Light, Gregory A.; Swerdlow, Neal R.; Rissling, Anthony J.; Radant, Allen; Sugar, Catherine A.; Sprock, Joyce; Pela, Marlena; Geyer, Mark A.; Braff, David L.

2012-01-01

Background Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Methods Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Results Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. Conclusions The majority of neurophysiological and neurocognitive measures exhibited deficits in patients, stability over a 1-year interval and did not demonstrate practice or time effects supporting their use as endophenotypes in neural substrate and genomic studies. These measures hold promise for informing the “gene-to-phene gap” in schizophrenia research. PMID:22802938

Nondirective counseling interventions with schizophrenics.

PubMed

Gerwood, J B

1993-12-01

Counseling interventions with paranoid schizophrenics can be daunting. While chemical, directive, and behavioral controls often are considered important, nondirective counseling techniques used by the therapeutic staff may help schizophrenic patients explore their thoughts and feelings. Several nondirective concepts pioneered by Carl Rogers are examined. These methods, which represent basic concepts of the person-centered approach, are empathy, unconditional positive regard, and congruence. A brief illustration of an interaction with a patient diagnosed as paranoid schizophrenic is presented to suggest the effectiveness of Rogerian counseling.

Genetic overlap between polycystic ovary syndrome and bipolar disorder: the endophenotype hypothesis.

PubMed

Jiang, Bowen; Kenna, Heather A; Rasgon, Natalie L

2009-12-01

Polycystic Ovary Syndrome (PCOS) is a polygenic disorder caused by the interaction of susceptible genomic polymorphisms with environmental factors. PCOS, characterized by hyperandrogenism and menstrual abnormalities, has a higher prevalence in women with Bipolar Disorder (BD). Theories explaining this high prevalence have included the effect of PCOS itself or the effect of drugs such as Valproate, which may cause PCOS either directly or indirectly. Incidentally, metabolic abnormalities are observed in both bipolar and PCOS patients. Endophenotypes such as insulin resistance, obesity, and hyperglycemia are common among BD and PCOS patients, suggesting some degree of pathophysiological overlap. Since both BD and PCOS are complex polygenetic diseases, the endophenotype overlap may be the result of common genetic markers. This paper postulates that shared clinical endophenotypes between PCOS and BD indicate common pathophysiological platforms and will review these for the potential of genetic overlap between the two disorders.

Endophenotypes in the personality disorders

PubMed Central

Siever, Larry J.

2005-01-01

The identification of endophenotypes in the personality disorders may provide a basis for the identification of underlying genotypes that influence the traits and dimensions of the personality disorders, as well as susceptibility to major psychiatric illnesses. Clinical dimensions of personality disorders that lend themselves to the study of corresponding endophenotypes include affective instability impulsiwity aggression, emotional information processing, cognitive disorganization, social deficits, and psychosis. For example, the propensity to aggression can be evaluated by psychometric measures, interview, laboratory paradigms, neurochemical imaging, and pharmacological studies. These suggest that aggression is a measurable trait that may be related to reduced serotonergic activity. Hyperresponsiveness of amygdala and other limbic structures may be related to affective instability, while structural and functional brain alterations underlie the cognitive disorganization in psychoticlike symptoms of schizotypal personality disorder. Thus, an endophenotypic approach not only provides clues to underlying candidate genes contributing to these behavioral dimensions, but may also point the way to a better understanding of pathophysiological mechanisms. PMID:16262209

Assessment of the relationship between food addiction and nutritional status in schizophrenic patients.

PubMed

Küçükerdönmez, Özge; Urhan, Murat; Altın, Merve; Hacıraifoğlu, Özge; Yıldız, Burak

2017-10-27

Obesity is one of today's most important public health problems. It is suggested that overeating and substance addiction show similarities, and addiction to food may be an important factor in the obesity epidemic. This study aimed to determine the prevalence of food addiction among schizophrenic patients and to examine the relationship between food addiction and anthropometric measurements and dietary nutrient intake. Study participants included a total of 104 schizophrenic outpatients, 62 females and 42 males. Food addiction was assessed by using the Yale Food Addiction Scale, and the anthropometric measurements of participants and their three-day food consumption were recorded. This study found that more than half of the schizophrenic patients (60.6%) had food addiction, and that female schizophrenic patients had a higher prevalence (62.9%) of food addiction than male patients (57.1%). More than one-third of the schizophrenic patients with food addiction (41.3%) were found to be obese and their BMI, body weight, waist circumference, and body-fat ratio were higher than those of schizophrenic patients who did not have food addiction (P > 0.05). Moreover, the schizophrenic patients with food addiction were found to take significantly more energy, carbohydrate, and fat in their diet (P < 0.05). It was observed that the development of food addiction in schizophrenic patients increased the risk of obesity and cardiovascular diseases, which were found to be at higher levels in these patients. Educational programs should be planned for these patients to acquire health dietary habits and to increase their physical activity levels, and an additional psychosocial support should be provided for patients with food addiction.

Affective Interchange in Families with a Schizophrenic Son.

ERIC Educational Resources Information Center

Angermeyer, Matthias C.; And Others

Sixty half-hour family discussions generated by the "revealed differences technique" were analyzed to determine the emotional intensity and quality (friendliness/attacking) of messages between individuals in families with schizophrenic and "normal" sons. Thirty families in each situation (schizophrenic/normal) were matched for comparison. Both…

Biobehavioral Risk Factors in Children of Schizophrenic Parents.

ERIC Educational Resources Information Center

Erlenmeyer-Kimling, L.; Cornblatt, Barbara

1984-01-01

Research on risk factors for schizophrenia is reviewed with emphasis on children of schizophrenic parents. Four areas of biobehavioral functioning that have been examined in high-risk research are discussed. Three of these are considered compatible with hypothesis neurointegrative defect underlying schizophrenic-proneness. (Author/CL)

Comparison of folic acid levels in schizophrenic patients and control groups

NASA Astrophysics Data System (ADS)

Arthy, C. C.; Amin, M. M.; Effendy, E.

2018-03-01

Folic acid deficiency is a risk factor for schizophrenia through epidemiology, biochemistry and gene-related studies. Compared with healthy people, schizophrenic patients may have high homocysteine plasma values and homocysteine or low levels of folic acid, which seems to correlate with extrapyramidal motor symptoms caused by neuroleptic therapy and with symptoms of schizophrenia. In this present study, we focus on the difference of folic acid level between schizophrenic patient and control group. The study sample consisted of schizophrenic patients and 14 people in the control group and performed blood sampling to obtain the results of folic acid levels. The folic acid level in both groups was within normal range, but the schizophrenic patient group had lower mean folic acid values of 5.00 ng/ml (sb 1.66), compared with the control group with mean folic acid values of 10.75 ng/ml (sb 4.33). there was the group of the control group had a higher value of folic acid than the schizophrenic group.

Somatotypic characteristic of schizophrenic patients.

PubMed

Sivkov, Stefan; Akabaliev, Valentin; Nikolova, Yulia

2005-01-01

Introduction of quantitative metric methods of somatotype assessment in schizophrenic patients to make clinical diagnosis more objective, the diagnosis being otherwise based exclusively on the clinical interview and assessment of the mental status of patients and thus involving certain subjectivity. The study included 67 schizophrenic inpatients (38 men, 29 women) consecutively admitted to the Clinic of Psychiatry in Plovdiv. Their mean age was 31.47 years (SD = 9.43, range 16-56), mean duration of illness 6.86 (SD = 6.09, range 1-27), mean number of hospitalizations 4.22 (SD = 4.08, range 1-19). The patients satisfied DSM-IV criteria for a diagnosis of schizophrenia (American Psychiatric Association, 1994). The control group comprised 69 subjects (36 men, 33 women) with a mean age 39.24 years (SD = 10.18, range 22-68) and socioeconomic background matching that of the patients. The data showed statistically significant differences in the three somatotype component and in almost all somatotypological variables between male schizophrenic patients and control subjects. The somatotype categories were more extensively presented in the schizophrenic patients. There was a tendency to higher frequency of the ectomorphic categories (ectomorphic mesomorph, mesomorphic ectomorph and endomorph-ectomorph). No statistically significant differences were found in the somatotype components and somatotypological variables between the female schizophrenic patients and control subjects. The data of the examination of the somatotype of schizophrenic patients and control subjects evince a definite sexually related body constitution characteristic that differentiates the groups. Schizophrenic patients and control subjects are clearly determined somatotypically only in the group of males.

Depression and Suicide in Schizophrenic Patients.

ERIC Educational Resources Information Center

Salama, Aziz A.

1988-01-01

Identified schizophrenic patients as distinctive subgroup of patients who can suffer from major depressive illness and can commit suicide. Found 22.4 percent of 620 schizophrenics in psychiatric facility showed symptoms of major depressive episode. Seven patients committed suicide during acute phase of illness, 9 attempted suicide while…

Divergent Thinking Abilities across the Schizophrenic Spectrum and Other Psychological Correlates

ERIC Educational Resources Information Center

Rodrigue, Amanda L.; Perkins, David R.

2012-01-01

The literature on the connection between psychopathology and creativity is vast and recent research has focused on the relationship between the schizophrenic spectrum and creativity. The schizophrenic spectrum includes genetically related disorders that share certain symptom features. It has been suggested that schizotypal personality disorder, a…

Revisiting the Association of Aggression and Suicidal Behavior in Schizophrenic Inpatients

ERIC Educational Resources Information Center

Neuner, Tanja; Hubner-Liebermann, Bettina; Hausner, Helmut; Hajak, Goran; Wolfersdorf, Manfred; Spiessl, Hermann

2011-01-01

Our study investigated the association of aggression and suicidal behavior in schizophrenic inpatients. Eight thousand nine hundred one admissions for schizophrenia (1998-2007) to a psychiatric university hospital were included. Schizophrenic suicides (n = 7)/suicide attempters (n = 40) were compared to suicides (n = 30)/suicide attempters (n =…

Family Type as a Prognostic Indicator of Rehabilitation Outcome with Post-Hospitalized Male Schizophrenics

ERIC Educational Resources Information Center

Beres, Barbara Oliver; Frumkin, Robert M.

1973-01-01

A study of 65 male schizophrenic patients at the Bureau of Vocational Rehabilitation Unit, Cleveland Psychiatric Institute, Cleveland, Ohio revealed that family type (conjugal settings, parental settings, living alone) is found to to be a valuable prognosticator of rehabilitation outcome among post-hospitalized schizophrenics. (EA)

Encoding Orientation and the Remembering of Schizophrenic Young Adults

ERIC Educational Resources Information Center

Koh, Soon D.; Peterson, Rolf A.

1978-01-01

This research examines different types of encoding strategies, in addition to semantic and organizational encodings, and their effects on schizophrenics' remembering. Based on Craik and Lockhart (1972), i.e., memory performance is a function of depth of encoding processing, this analysis compares schizophrenics' encoding processing with that of…

SOCIOPATHS AND SCHIZOPHRENICS - A COMPARISON OF FAMILY INTERACTIONS

DTIC Science & Technology

Matched groups of sociopaths and schizophrenics were compared in a military psychiatric hospital. Striking differences in patterns of family...pathological concern. The parents of sociopaths showed conspicuous disinterest, characterized by unconcern or rejection. The parents of...schizophrenics wrote more, visited more, and traveled greater distances than did parents of sociopaths .

Neural Correlates of Three Promising Endophenotypes of Depression: Evidence from the EMBARC Study

PubMed Central

Webb, Christian A; Dillon, Daniel G; Pechtel, Pia; Goer, Franziska K; Murray, Laura; Huys, Quentin JM; Fava, Maurizio; McGrath, Patrick J; Weissman, Myrna; Parsey, Ramin; Kurian, Benji T; Adams, Phillip; Weyandt, Sarah; Trombello, Joseph M; Grannemann, Bruce; Cooper, Crystal M; Deldin, Patricia; Tenke, Craig; Trivedi, Madhukar; Bruder, Gerard; Pizzagalli, Diego A

2016-01-01

Major depressive disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning, and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography. Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5–44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). In contrast, reduced cognitive control correlated with decreased gamma activity in the left dorsolateral prefrontal cortex (dlPFC), decreased theta (6.5–8 Hz) and alpha2 (10.5–12 Hz) activity in the dorsal ACC, and increased alpha2 activity in the right dlPFC. Finally, blunted reward learning correlated with lower OFC and left dlPFC gamma activity. Computational modeling of trial-by-trial reinforcement learning further indicated that lower OFC gamma activity was linked to reduced reward sensitivity. Three putative endophenotypes of depression were found to have partially dissociable resting intracranial EEG correlates, reflecting different underlying neural dysfunctions. Overall, these findings highlight the need to parse the heterogeneity of MDD by focusing on promising endophenotypes linked to specific pathophysiological abnormalities. PMID:26068725

Impact of Life Events on the Relapse of Schizophrenic Patients

ERIC Educational Resources Information Center

Hussein, Hassan Ali; Jacoob, Shirooq; Sharour, Loai Abu

2016-01-01

Objectives: To investigate the relationship between stressful life events at the time of relapse in schizophrenic patients at psychiatric hospitals in Baghdad city. Methodology: A purposive (non-probability) sampling of 50 schizophrenic patients who have relapsed was involved in the present study. Data were collected through the use of the…

Reported Childhood Trauma and Suicide Attempts in Schizophrenic Patients

ERIC Educational Resources Information Center

Roy, Alec

2005-01-01

Childhood traumas are associated with suicidal behavior but this aspect has not been examined in relation to schizophrenia. In this study, 50 chronic schizophrenic patients who had attempted suicide were compared with 50 chronic schizophrenic patients who had never attempted suicide for their scores on the 34-item Childhood Trauma Questionnaire…

Schizophrenia and the paranormal: more psi belief and superstition, and less déjà vu in medicated schizophrenic patients.

PubMed

Shiah, Yung-Jong; Wu, Yi-Zhen; Chen, Yueh-Hua; Chiang, Shih-Kuang

2014-04-01

The present study examined the relation between déjà vu experiences and paranormal beliefs in schizophrenic patients. A total of 522 participants (54.5% female; mean age=33.3, SD=16.02) were recruited, including 422 healthy adults (60.9% female; mean age=29.48, SD=15.07) and 100 medicated adult schizophrenic patients (27.3% female; mean age=48.98, SD=8.57). The Chinese version of the Inventory of Déjà-vu Experiences Assessment was created via back translation. Chinese versions of the Revised Paranormal Belief Scale (CRPB), Beck Anxiety Inventory (CBAI), and Perceived Stress Scale (CPSS) were also used. After controlling for age, gender, education, and anxiety, the results supported the following three hypotheses. Schizophrenic persons have fewer déjà vu experiences than normal persons. These experiences are positively related to paranormal beliefs in healthy adults but not in schizophrenic patients. Schizophrenic patients have higher scores than healthy adults on the psi and superstitious subscales of the CRPB. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive Endophenotypes of Dyslexia

ERIC Educational Resources Information Center

Moll, Kristina; Loff, Ariana; Snowling, Margaret J.

2013-01-01

The study investigated cognitive deficits associated with dyslexia and familial risk of dyslexia (endophenotypes) by comparing children from families with and without a history of dyslexia. Eighty-eight school-aged children were assessed on measures of phonology, language and rapid automatized naming. A series of regression analyses with family…

Genome-wide scans of genetic variants for psychophysiological endophenotypes: a methodological overview.

PubMed

Iacono, William G; Malone, Stephen M; Vaidyanathan, Uma; Vrieze, Scott I

2014-12-01

This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind the steps taken in the molecular genetic study design. The statistical approach included (a) biometric analysis of twin and family data, (b) heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c) genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d) follow-up analyses of candidate SNPs and genes hypothesized to have an association with each endophenotype, (e) rare variant analysis of nonsynonymous SNPs in the exome, and (f) whole genome sequencing association analysis using 27 million genetic variants. These methods were used in the accompanying empirical articles comprising this special issue, Genome-Wide Scans of Genetic Variants for Psychophysiological Endophenotypes. Copyright © 2014 Society for Psychophysiological Research.

Dopamine DRD2/Cys311 is not associated with chronic schizophrenia

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

Crawford, F.; Hoyne, J.; Cai, Xingang

A mutation in the DRD2 receptor gene has been reported in association with schizophrenia in Japanese and Caucasian populations. The variation, Ser to Cys at codon 311, occurs in the third intracellular loop of the receptor and is therefore putatively functional. We report the results of screening US Caucasian schizophrenic and nonschizophrenic populations. We detected the occurrence of the DRD2 Cys311 variant in both schizophrenics and controls. Our data demonstrates no significant difference between the frequency of Cys311 in Caucasian schizophrenic and non-schizophrenic populations, indicating no association with schizophrenia. 8 refs., 1 fig., 1 tab.

[The IPT integrative program of psychological therapy for schizophrenia patients: new perspectives].

PubMed

Pomini, Valentino

2004-04-01

The integrated psychological treatment for schizophrenic patients IPT is composed by six modules that can be implemented either separately or in an articulated way. In that case, the treatment begins with a cognitive remediation phase which is followed by a social skills training phase. In the first phase, exercises specifically focalize on selective attention, memory, logical reasoning, perception and communication skills. The second phase of the program offers three other modules that train other skills: 1) social skills, 2) emotional management, 3) interpersonal problem solving. The IPT program belong to the so called second generation of social skills training programmes. It has been validated by numerous controlled studies, either in its complete form or in partial forms containing only one ore more of its sub-programmes. The results of these studies are globally positive. They show that IPT is an interesting therapeutic contribution for the rehabilitation practice with schizophrenic patients. A third generation of social skills training has been elaborated on the basis of the current IPT program. These new adjunctions to the IPT tend to favour the utilization in the real life of the competencies trained in the sessions, either by adding specific homeworks, in-vivo or booster sessions, or by designating new programmes directed to specific rehabilitation objectives, such as the integration in a apartment, the management of leisure times or the return to a workplace. These new programmes have been studied. They are promising and seem to be a useful complement to the original IPT.

Impressions of Humanness for Android Robot may Represent an Endophenotype for Autism Spectrum Disorders.

PubMed

Kumazaki, Hirokazu; Warren, Zachary; Swanson, Amy; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Ishiguro, Hiroshi; Sarkar, Nilanjan; Minabe, Yoshio; Kikuchi, Mitsuru

2018-02-01

Identification of meaningful endophenotypes may be critical to unraveling the etiology and pathophysiology of autism spectrum disorders (ASD). We investigated whether impressions of "humanness" for android robot might represent a candidate characteristic of an ASD endophenotype. We used a female type of android robot with an appearance similar to that of a real person. Significant differences in overall impressions of 'humanness' for android robot were found between adolescents with ASD and typical development (TD) controls, as well as parents of children with ASD and parents of TD controls. Our current work does suggest robotic systems could potentially play an intelligent role in dissecting ASD heterogeneity.

Subtyping Children with Speech Sound Disorders by Endophenotypes

ERIC Educational Resources Information Center

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2011-01-01

Purpose: The present study examined associations of 5 endophenotypes (i.e., measurable skills that are closely associated with speech sound disorders and are useful in detecting genetic influences on speech sound production), oral motor skills, phonological memory, phonological awareness, vocabulary, and speeded naming, with 3 clinical criteria…

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes.

PubMed

Bas-Hoogendam, Janna Marie; Harrewijn, Anita; Tissier, Renaud L M; van der Molen, Melle J W; van Steenbergen, Henk; van Vliet, Irene M; Reichart, Catrien G; Houwing-Duistermaat, Jeanine J; Slagboom, P Eline; van der Wee, Nic J A; Westenberg, P Michiel

2018-06-01

Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so-called "endophenotypes". These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self-reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD. © 2018 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd.

Visual interaction in recently admitted and chronic long-stay schizophrenic patients.

PubMed

Rutter, D R

1976-09-01

Several reports have suggested that schizophrenic patients engage in very little Looking and eye-contact. However, previous work, much of it methodologically unsatisfactory, has been based almost always on the clinical psychiatric interview, with the result that several important questions remain unanswered. In particular, we do not know how schizophrenic patients behave in free conversation, how their behaviour with another patient may differ from their behaviour with a psychiatrically normal partner, nor even whether they show individual consistency across encounters. The first study was designed to examine these questions, by observing recently admitted schizophrenic patients in two free dyadic conversations, one with a schizophrenic partner and one with a psychiatrically normal partner, and comparing them with three control groups: depressive patients; patients suffering from neurotic or personality disorders; and psychiatrically normal chest patients. The second study went on to test whether the early descriptions of gross abnormality may be more appropriate to chronic long-stay patients than to recently admitted patients, and the design consisted of a comparison between the two groups. The first study revealed a quite unexpected pattern of results. Consistently across their two encounters, schizophrenic subjects behaved similarly for the most part to all three control groups, normal and abnormal alike. Moreover, the few differences which did emerge conflicted sharply with previous findings, including the writer's, and were no more marked in patient-patient than patient-normal encounters. The second study revealed no differences between chronic long-stay and recently admitted schizophrenic patients. It is suggested that the differences in findings between the present two studies and previous reports are most likely to be attributable to differences in verbal content: schizophrenic patients show abnormalities of visual interaction when talking about personal matters, but behave quite normally when the topic is not of immediate personal relevance.

Alpha Asymmetry in Infants at Risk for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Gabard-Durnam, Laurel; Tierney, Adrienne L.; Vogel-Farley, Vanessa; Tager-Flusberg, Helen; Nelson, Charles A.

2015-01-01

An emerging focus of research on autism spectrum disorder (ASD) targets the identification of early-developing ASD endophenotypes using infant siblings of affected children. One potential neural endophenotype is resting frontal electroencephalogram (EEG) alpha asymmetry, a metric of hemispheric organization. Here, we examined the development of…

Revisiting the Suitability of Antisaccade Performance as an Endophenotype in Schizophrenia

ERIC Educational Resources Information Center

Mazhari, Shahrzad; Price, Greg; Dragovic, Milan; Waters, Flavie A.; Clissa, Peter; Jablensky, Assen

2011-01-01

Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in…

[Disorders of emotional control in schizophrenia and unilateral brain damage].

PubMed

Kucharska-Pietura, K; Kopacz, G

2001-01-01

Although, emotions play a crucial role in schizophrenia, the changes in emotional dimension still remain controversial. The aim of our work was: 1) to compare the disorders of emotional control between the examined groups: S--non-chronic schizophrenic patients (n = 50), CS--chronic schizophrenic patients (n = 50), N--healthy controls (n = 50), R--right brain-damaged patients (n = 30), and L--left brain-damaged patients (n = 30), 2) to assess a level of impairment of emotional control, its relation to lateralised hemisphere damage and chronicity of schizophrenic process. All psychiatric subjects were diagnosed as paranoid schizophrenics according to DSM-IV criteria and were scored on the PANSS scale after four weeks of neuroleptic treatment. Brain-damaged patients were included if they experienced single-episode cerebrovascular accidents causing right or left hemisphere damage (confirmed in CT scan reports). The neurological patients were examined at least 3 weeks after the onset of cerebrovascular episode. Emotional control was assessed using Brzeziński Questionnaire of Emotional Control aimed at the evaluation of: 1) control in perception and interpretation of emotive situation, 2) emotional arousal, 3) emotional-rational motivation, and 4) acting caused by emotions. Our results revealed significantly greater impairment of emotional control in schizophrenics (chronic schizophrenics, in particular) compared to healthy volunteers. Chronicity of the schizophrenic process seemed to intensify emotional control impairment. Interestingly, no significant qualitative and quantitative differences in emotional control mechanism between unilateral brain-damaged patients and the control group were found.

Characteristics of the tree-drawing test in chronic schizophrenia.

PubMed

Kaneda, Ayako; Yasui-Furukori, Norio; Saito, Manabu; Sugawara, Norio; Nakagami, Taku; Furukori, Hanako; Kaneko, Sunao

2010-04-01

A tree-drawing test acts as both a projective psychological examination as well as a supplementary psychodiagnostic tool. There is little information relating the characteristics of schizophrenia and the tree-drawing test. The present study compared the structural and morphological differences in the results of the tree-drawing test between schizophrenic patients and healthy individuals, as well as between schizophrenic patients who responded well to treatment and those who responded poorly. The subjects included 202 chronic schizophrenic patients and 113 healthy individuals. The schizophrenic patients were categorized as 'good responders' or 'poor responders' based on their response to medical treatments. The tree-drawing test was performed on all subjects. The tree drawn by each subject was analyzed structurally and morphologically. There were significant differences between the trunk and branches drawn by schizophrenic patients and those drawn by healthy controls. There were no significant differences between the good responders and the poor responders in any aspect of the tree drawings. Multiple regression models showed that the ratio of the tree area to the total area of the drawing paper, the width of the trunk, the trunk base opening, and the size of the branch ends were significantly associated with schizophrenia. The present study suggests that the trees drawn by schizophrenic patients are significantly different from those drawn by healthy individuals, but among schizophrenic patients, it is difficult to distinguish between good responders and poor responders using the tree-drawing test.

Autism Tendencies and Psychosis Proneness Interactively Modulate Saliency Cost.

PubMed

Abu-Akel, Ahmad; Apperly, Ian A; Wood, Stephen J; Hansen, Peter C; Mevorach, Carmel

2017-01-01

Atypical responses to salient information are a candidate endophenotype for both autism and psychosis spectrum disorders. The present study investigated the costs and benefits of such atypicalities for saliency-based selection in a large cohort of neurotypical adults in whom both autism and psychosis expressions were assessed. Two experiments found that autism tendencies and psychosis proneness interactively modulated the cost incurred in the presence of a task-irrelevant salient distractor. Specifically, expressions of autism and psychosis had opposing effects on responses to salient information such that the benefits associated with high expressions for autism offset costs associated with high expressions for psychosis. The opposing influences observed on saliency cost may be driven by distinct attentional mechanisms that are differentially affected by expressions for autism and psychosis. © 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.

Temperament and Character as Endophenotype in Adults with Autism Spectrum Disorders or Attention Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sizoo, Bram B.; van der Gaag, Rutger Jan; van den Brink, Wim

2015-01-01

Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that…

Response Inhibition and ADHD Traits: Correlates and Heritability in a Community Sample

ERIC Educational Resources Information Center

Crosbie, J.; Arnold, P.; Paterson, A.; Swanson, J.; Dupuis, A.; Li, X.; Shan, J.; Goodale, T.; Tam, C.; Strug, L. J.; Schachar, R. J.

2013-01-01

Endophenotypes or intermediate phenotypes are of great interest in neuropsychiatric genetics because of their potential for facilitating gene discovery. We evaluated response inhibition, latency and variability measures derived from the stop task as endophenotypes of ADHD by testing whether they were related to ADHD traits in the general…

Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study

ERIC Educational Resources Information Center

Losh, Molly; Martin, Gary E.; Lee, Michelle; Klusek, Jessica; Sideris, John; Barron, Sheila; Wassink, Thomas

2017-01-01

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of…

A Cognitive Endophenotype of Autism in Families with Multiple Incidence

ERIC Educational Resources Information Center

Nyden, Agneta; Hagberg, Bibbi; Gousse, Veronique; Rastam, Maria

2011-01-01

Twin and family studies have established that there is a strong genetic basis for autism spectrum disorders. To facilitate the identification of susceptibility genes and to study pathways from gene-brain to cognition a more refined endophenotype-based approach may be useful. The purpose of the present study was to examine the neurocognitive…

Interval Timing Deficits Assessed by Time Reproduction Dual Tasks as Cognitive Endophenotypes for Attention-Deficit/Hyperactivity Disorder

PubMed Central

Hwang-Gu, Shoou-Lian; Gau, Susan Shur-Fen

2015-01-01

The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence tests, verbal estimation and time reproduction tasks (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17-second intervals. We found that youths with ADHD tended to overestimate time in verbal estimation more than their unaffected siblings and TD youths, implying that fast subjective internal clock speed might be a characteristic of ADHD, rather than an endophenotype for ADHD. Youths with ADHD and their unaffected siblings were less precise in time reproduction dual tasks than TD youths. The magnitude of estimated errors in time reproduction was greater in youths with ADHD and their unaffected siblings than in TD youths, with an increased time interval at the 17-second interval and with increased task demands on both simple and difficult dual tasks versus the single task. Increased impaired time reproduction in dual tasks with increased intervals and task demands were shown in youths with ADHD and their unaffected siblings, suggesting that time reproduction deficits explained by limited attention capacity might be a useful endophenotype of ADHD. PMID:25992899

Homicide by schizophrenic patients in Israel.

PubMed

Valevski, A; Averbuch, I; Radwan, M; Gur, S; Spivak, B; Modai, I; Weizman, A

1999-04-01

Thirty-three schizophrenic inpatients aged 45.3 +/- 13.5 years who had been found not guilty of homicide by reason of insanity were compared with 28 schizophrenic patients matched for age, sex and duration of disease who had not committed any crime. Statistical analysis revealed a high rate in the study group of individual factors associated with aggression, such as alcohol abuse, previous contact with the police, aggressive behavior and threats (P < 0.05). Significantly more of them were also immigrants (P < 0.05). There was no between-group difference in familial factors. These findings support earlier studies indicating that schizophrenic patients with the profile of alcoholism, aggressiveness and foreign country of origin are at high risk of homicidal behavior.

Psychotherapy with schizophrenics in team groups: a systems model.

PubMed

Beeber, A R

1991-01-01

This paper focuses on the treatment of patients with schizophrenic disorders employing the Team Group model. The advantages and disadvantages of the Team Group are presented. Systems theory and principles of group development are applied as a basis for understanding the dynamics of the group in the context at the acute psychiatric unit. Particular problems encountered in treating patients with schizophrenic disorders in this setting are presented. These include: (1) issues of therapist style and technique, (2) basic psychopathology of the schizophrenic disorders, and (3) phase-specific problems associated with the dynamics of the group. Recommendations for therapist interventions are made that may better integrate these patients into the Team Group.

Visuospatial deficits in schizophrenia: central executive and memory subsystems impairments.

PubMed

Leiderman, Eduardo A; Strejilevich, Sergio A

2004-06-01

Object and spatial visual working memory are impaired in schizophrenic patients. It is not clear if the impairments reside in each memory subsystem alone or also in the central executive component that coordinates these processes. In order to elucidate which memory component is impaired, we developed a paradigm with single spatial and object working memory tasks and dual ones with two different delays (5 and 30 s). Fifteen schizophrenic patients and 14 control subjects performed these tests. Schizophrenic patients had a poorer performance compared to normal controls in all tasks and in all time delays. Both schizophrenics and controls performed significantly worse in the object task than in the spatial task. The performance was even worse in the dual task compared to the singles ones in schizophrenic patients but not in controls. These data suggest that visuospatial performance deficits in schizophrenia are due to both visuospatial memory subsystems impairments and central executive ones. The pattern of deficits observed points to a codification or evocation deficit and not to a maintenance one.

Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

PubMed

Kaminski, R; Powchick, P; Warne, P A; Goldstein, M; McQueeney, R T; Davidson, M

1990-01-01

1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

Effects of fenfluramine on neuropsychological and communicative functioning in treatment-refractory schizophrenic patients.

PubMed

Soper, H V; Elliott, R O; Rejzer, A A; Marshall, B D

1990-06-01

Reported behavioral improvement among autistic patients following feufluramine treatment and a high serotonin level among certain chronic schizophrenic patients suggested that fenfluramine treatment might be beneficial with such schizophrenic patients, especially within the realm of neuropsychological and communicative functioning. A brief neuropsychological battery was administered to eight chronic schizophrenic subjects before, during, and after fenfluramine treatment. Conversations in controlled settings were audiotaped before and during fenfluramine treatment for seven of these subjects and one additional subject. These language samples were analyzed for communicative competence and evidence of thought disorder. Overall, neuropsychological and communicative functioning was worse under the fenfluramine condition, even though blood serotonin levels were about half those at baseline conditions. The results suggest that it is not the higher levels of blood serotonin by themselves that are related to depressed neuropsychological, communicative, and other functioning. In fact, the higher levels of serotonin may well be related to adaptations for maximal level of functioning. These results suggest caution in the use of fenfluramine for other schizophrenic populations.

Discriminant analysis of functional optical topography for schizophrenia diagnosis

NASA Astrophysics Data System (ADS)

Chuang, Ching-Cheng; Nakagome, Kazuyuki; Pu, Shenghong; Lan, Tsuo-Hung; Lee, Chia-Yen; Sun, Chia-Wei

2014-01-01

Abnormal prefrontal function plays a central role in the cognition deficits of schizophrenic patients; however, the character of the relationship between discriminant analysis and prefrontal activation remains undetermined. Recently, evidence of low prefrontal cortex (PFC) activation in individuals with schizophrenia has also been found during verbal fluency tests (VFT) and other cognitive tests with several neuroimaging methods. The purpose of this study is to assess the hemodynamic changes of the PFC and discriminant analysis between schizophrenia patients and healthy controls during VFT task by utilizing functional optical topography. A total of 99 subjects including 53 schizophrenic patients and 46 age- and gender-matched healthy controls were studied. The results showed that the healthy group had larger activation in the right and left PFC than in the middle PFC. Besides, the schizophrenic group showed weaker task performance and lower activation in the whole PFC than the healthy group. The result of the discriminant analysis showed a significant difference with P value <0.001 in six channels (CH 23, 29, 31, 40, 42, 52) between the schizophrenic and healthy groups. Finally, 68.69% and 71.72% of subjects are correctly classified as being schizophrenic or healthy with all 52 channels and six significantly different channels, respectively. Our findings suggest that the left PFC can be a feature region for discriminant analysis of schizophrenic diagnosis.

Pretreatment plasma homovanillic acid in schizophrenia and schizoaffective disorder: the influence of demographic variables and the inpatient drug-free period.

PubMed

Sharma, R P; Javaid, J I; Davis, J M; Janicak, P G

1998-09-15

The relationship between plasma homovanillic acid (pHVA) and schizophrenic symptoms has not been conclusively determined. We reexamine pHVA levels in a new sample of patients with emphasis on demographic variables and the drug-free period. Plasma HVA levels were studied in 54 schizophrenic and schizoaffective-disordered, drug-free inpatients suffering from a psychotic exacerbation. A significant correlation was observed between pHVA levels and the number of inpatient drug-free days in the total sample, as well as the schizophrenic patient subsample. Further, pHVA was significantly and positively correlated with the duration of illness in the schizophrenic patient subsample. Plasma HVA correlations with behavior, as measured by Brief Psychiatric Rating Scale factors (anxiety/depression and hostility/suspiciousness), emerged only when considering schizophrenic patients drug-free for more than 2 weeks. No correlation was found between pHVA and the age of illness onset or the duration of the delay of treatment of the first psychotic episode. The effects of antipsychotic withdrawal on levels of pHVA in clinical populations may have to be examined and controlled for in future studies attempting to study the relationship between this metabolite and behavior in acutely ill, drug-free schizophrenic patients.

Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder.

PubMed

Yang, S D; Yu, J S; Lee, T T; Yang, C C; Ni, M H; Yang, Y Y

1995-09-01

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3 alpha activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.

Are Endophenotypes Based on Measures of Executive Functions Useful for Molecular Genetic Studies of ADHD?

ERIC Educational Resources Information Center

Doyle, Alysa E.; Faraone, Stephen V.; Seidman, Larry J.; Willcutt, Erik G.; Nigg, Joel T.; Waldman, Irwin D.; Pennington, Bruce F.; Peart, Joanne; Biederman, Joseph

2005-01-01

Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or…

Eye Movement Dysfunction in First-Degree Relatives of Patients with Schizophrenia: A Meta-Analytic Evaluation of Candidate Endophenotypes

ERIC Educational Resources Information Center

Calkins, Monica E.; Iacono, William G.; Ones, Deniz S.

2008-01-01

Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit,…

Comorbid Problems in ADHD: Degree of Association, Shared Endophenotypes, and Formation of Distinct Subtypes. Implications for a Future "DSM"

ERIC Educational Resources Information Center

Rommelse, Nanda N. J.; Altink, Marieke E.; Fliers, Ellen A.; Martin, Neilson C.; Buschgens, Cathelijne J. M.; Hartman, Catharina A.; Buitelaar, Jan K.; Faraone, Stephen V.; Sergeant, Joseph A.; Oosterlaan, Jaap

2009-01-01

We aimed to assess which comorbid problems (oppositional defiant behaviors, anxiety, autistic traits, motor coordination problems, and reading problems) were most associated with Attention-Deficit/Hyperactivity Disorder (ADHD); to determine whether these comorbid problems shared executive and motor problems on an endophenotype level with ADHD; and…

COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

PubMed

Zumárraga, Mercedes; Arrúe, Aurora; Basterreche, Nieves; Macías, Isabel; Catalán, Ana; Madrazo, Arantza; Bustamante, Sonia; Zamalloa, María I; Erkoreka, Leire; Gordo, Estibaliz; Arnaiz, Ainara; Olivas, Olga; Arroita, Ariane; Marín, Elena; González-Torres, Miguel A

2016-06-01

We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Neurocognitive Endophenotypes in Schizophrenia: Modulation by Nicotinic Receptor Systems

PubMed Central

Mackowick, Kristen M.; Barr, Mera S.; Wing, Victoria C.; Rabin, Rachel A.; Ouellet-Plamondon, Clairelaine; George, Tony P.

2013-01-01

Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smoking behaviours to remediate symptoms associated with the disorder. Neurocognitive deficits are a core feature of schizophrenia and are present in approximately 80% of patients. Further, these deficits constitute an endophenotype of schizophrenia, as they are stable across disease phases, and heritable. The neurocognitive deficits that are present in schizophrenia are especially debilitating, since they are associated with poor clinical and functional outcomes and community integration. Interestingly, these deficits may also constitute a vulnerability factor towards the initiation and maintenance of tobacco use. Contributing to the potential shared vulnerability between schizophrenia and tobacco dependence is a dysregulation of the nicotinic acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that nicotine affects several neurotransmitter systems, including dopamine (DA), glutamate, and γ-aminobutyric acid (GABA), and certain neuropsychological deficits associated with these neurotransmitters (reaction time, spatial working memory, sustained attention, and sensory gating) are improved after nicotine administration in patients with schizophrenia. These positive effects on neurocognition appear to be more pronounced in smokers with schizophrenia, and may be an important mechanism that explains the co-morbidity of schizophrenia and tobacco dependence. PMID:23871750

Temperament and character as endophenotype in adults with autism spectrum disorders or attention deficit/hyperactivity disorder.

PubMed

Sizoo, Bram B; van der Gaag, Rutger Jan; van den Brink, Wim

2015-05-01

Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that all the endophenotypic impairments that were reviewed in attention deficit/hyperactivity disorder were also present in autism spectrum disorder, suggesting a continuity model with attention deficit/hyperactivity disorder as "a light form of autism spectrum disorder." Using existing data, 75 adults with autism spectrum disorder and 53 with attention deficit/hyperactivity disorder were directly compared on autistic symptoms with the autism spectrum quotient, and on the endophenotypic measure of temperament and character, using the Abbreviated (Dutch: Verkorte) Temperament and Character Inventory. Based on the hypothesis that attention deficit/hyperactivity disorder and autism spectrum disorder are disorders on a continuous spectrum, autism spectrum quotient scores and abbreviated Temperament and Character Inventory scores were expected to be different from normal controls in both disorders in a similar direction. In addition, the autism spectrum quotient and abbreviated Temperament and Character Inventory scores were expected to be closely correlated. These conditions applied to only two of the seven Abbreviated Temperament and Character Inventory scales (harm avoidance and self-directedness), suggesting that temperament and character as an endophenotype of autism spectrum disorder and attention deficit/hyperactivity disorder provides only partial support for the continuity hypothesis of autism spectrum disorder and attention deficit/hyperactivity disorder. © The Author(s) 2014.

'Reading the Mind in the Eyes': an fMRI study of adolescents with autism and their siblings.

PubMed

Holt, R J; Chura, L R; Lai, M-C; Suckling, J; von dem Hagen, E; Calder, A J; Bullmore, E T; Baron-Cohen, S; Spencer, M D

2014-11-01

Mentalizing deficits are a hallmark of the autism spectrum condition (ASC) and a potential endophenotype for atypical social cognition in ASC. Differences in performance and neural activation on the 'Reading the Mind in the Eyes' task (the Eyes task) have been identified in individuals with ASC in previous studies. Performance on the Eyes task along with the associated neural activation was examined in adolescents with ASC (n = 50), their unaffected siblings (n = 40) and typically developing controls (n = 40). Based on prior literature that males and females with ASC display different cognitive and associated neural characteristics, analyses were stratified by sex. Three strategies were applied to test for endophenotypes at the level of neural activation: (1) identifying and locating conjunctions of ASC-control and sibling-control differences; (2) examining whether the sibling group is comparable to the ASC or intermediate between the ASC and control groups; and (3) examining spatial overlaps between ASC-control and sibling-control differences across multiple thresholds. Impaired behavioural performance on the Eyes task was observed in males with ASC compared to controls, but only at trend level in females; and no difference in performance was identified between sibling and same-sex control groups in both sexes. Neural activation showed a substantial endophenotype effect in the female groups but this was only modest in the male groups. Behavioural impairment on complex emotion recognition associated with mental state attribution is a phenotypic, rather than an endophenotypic, marker of ASC. However, the neural response during the Eyes task is a potential endophenotypic marker for ASC, particularly in females.

Drug Treated Schizophrenia, Schizoaffective and Bipolar Disorder Patients Evaluated by qEEG Absolute Spectral Power and Mean Frequency Analysis.

PubMed

Wix-Ramos, Richard; Moreno, Xiomara; Capote, Eduardo; González, Gilbert; Uribe, Ezequiel; Eblen-Zajjur, Antonio

2014-04-01

Research of electroencephalograph (EEG) power spectrum and mean frequency has shown inconsistent results in patients with schizophrenic, schizoaffective and bipolar disorders during medication when compared to normal subjects thus; the characterization of these parameters is an important task. We applied quantitative EEG (qEEG) to investigate 38 control, 15 schizophrenic, 7 schizoaffective and 11 bipolar disorder subjects which remaine under the administration of psychotropic drugs (except control group). Absolute spectral power (ASP), mean frequency and hemispheric electrical asymmetry were measured by 19 derivation qEEG. Group mean values were compared with non parametrical Mann-Whitney test and spectral EEG maps with z-score method at p < 0.05. Most frequent drug treatments for schizophrenic patients were neuroleptic+antiepileptic (40% of cases) or 2 neuroleptics (33.3%). Schizoaffective patients received neuroleptic+benzodiazepine (71.4%) and for bipolar disorder patients neuroleptic+antiepileptic (81.8%). Schizophrenic (at all derivations except for Fp1, Fp2, F8 and T6) and schizoaffective (only at C3) show higher values of ASP (+57.7% and +86.1% respectively) compared to control group. ASP of bipolar disorder patients did not show differences against control group. The mean frequency was higher at Fp1 (+14.2%) and Fp2 (+17.4%) in bipolar disorder patients than control group, but no differences were found in frequencies between schizophrenic or schizoaffective patients against the control group. Majority of spectral differences were found at the left hemisphere in schizophrenic and schizoaffective but not in bipolar disorder subjects. The present report contributes to characterize quantitatively the qEEG in drug treated schizophrenic, schizoaffective or bipolar disorder patients.

A comparative study on long-term evoked auditory and visual potential responses between Schizophrenic patients and normal subjects

PubMed Central

2011-01-01

Background The electrical signals measuring method is recommended to examine the relationship between neuronal activities and measure with the event related potentials (ERPs) during an auditory and a visual oddball paradigm between schizophrenic patients and normal subjects. The aim of this study is to discriminate the activation changes of different stimulations evoked by auditory and visual ERPs between schizophrenic patients and normal subjects. Methods Forty-three schizophrenic patients were selected as experimental group patients, and 40 healthy subjects with no medical history of any kind of psychiatric diseases, neurological diseases, or drug abuse, were recruited as a control group. Auditory and visual ERPs were studied with an oddball paradigm. All the data were analyzed by SPSS statistical software version 10.0. Results In the comparative study of auditory and visual ERPs between the schizophrenic and healthy patients, P300 amplitude at Fz, Cz, and Pz and N100, N200, and P200 latencies at Fz, Cz, and Pz were shown significantly different. The cognitive processing reflected by the auditory and the visual P300 latency to rare target stimuli was probably an indicator of the cognitive function in schizophrenic patients. Conclusions This study shows the methodology of application of auditory and visual oddball paradigm identifies task-relevant sources of activity and allows separation of regions that have different response properties. Our study indicates that there may be slowness of automatic cognitive processing and controlled cognitive processing of visual ERPs compared to auditory ERPs in schizophrenic patients. The activation changes of visual evoked potentials are more regionally specific than auditory evoked potentials. PMID:21542917

Diagnostic consistency and interchangeability of schizophrenic disorders and bipolar disorders: A 7-year follow-up study.

PubMed

Hung, Yen-Ni; Yang, Shu-Yu; Kuo, Chian-Jue; Lin, Shih-Ku

2018-03-01

The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long-term prognoses. In this study, we used a nationwide population-based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders. In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed. In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7-year follow-up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%. Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Reduced Theta-Band Power and Phase Synchrony during Explicit Verbal Memory Tasks in Female, Non-Clinical Individuals with Schizotypal Traits.

PubMed

Choi, Jeong Woo; Jang, Kyoung-Mi; Jung, Ki-Young; Kim, Myung-Sun; Kim, Kyung Hwan

2016-01-01

The study of non-clinical individuals with schizotypal traits has been considered to provide a promising endophenotypic approach to understanding schizophrenia, because schizophrenia is highly heterogeneous, and a number of confounding factors may affect neuropsychological performance. Here, we investigated whether deficits in explicit verbal memory in individuals with schizotypal traits are associated with abnormalities in the local and inter-regional synchrony of brain activity. Memory deficits have been recognized as a core problem in schizophrenia, and previous studies have consistently shown explicit verbal memory impairment in schizophrenic patients. However, the mechanism of this impairment has not been fully revealed. Seventeen individuals with schizotypal traits and 17 age-matched, normal controls participated. Multichannel event-related electroencephalograms (EEGs) were recorded while the subjects performed a continuous recognition task. Event-related spectral perturbations (ERSPs) and inter-regional theta-band phase locking values (TPLVs) were investigated to determine the differences in local and global neural synchrony between the two subject groups. Additionally, the connection patterns of the TPLVs were quantitatively analyzed using graph theory measures. An old/new effect was found in the induced theta-band ERSP in both groups. However, the difference between the old and new was larger in normal controls than in schizotypal trait group. The tendency of elevated old/new effect in normal controls was observed in anterior-posterior theta-band phase synchrony as well. Our results suggest that explicit memory deficits observed in schizophrenia patients can also be found in non-clinical individuals with psychometrically defined schizotypal traits.

The Persistence of Cognitive Deficits in Remitted and Unremitted ADHD: A Case for the State-Independence of Response Inhibition

ERIC Educational Resources Information Center

McAuley, Tara; Crosbie, Jennifer; Charach, Alice; Schachar, Russell

2014-01-01

Background: Response inhibition, working memory, and response variability are possible endophenotypes of ADHD based on their association with the disorder and evidence of heritability. One of the critical although rarely studied criteria for a valid endophenotype is that it persists despite waxing and waning of the overt manifestations of the…

Electrophysiological Endophenotypes and the Error-Related Negativity (ERN) in Autism Spectrum Disorder: A Family Study

ERIC Educational Resources Information Center

Clawson, Ann; South, Mikle; Baldwin, Scott A.; Larson, Michael J.

2017-01-01

We examined the error-related negativity (ERN) as an endophenotype of ASD by comparing the ERN in families of ASD probands to control families. We hypothesized that ASD probands and families would display reduced-amplitude ERN relative to controls. Participants included 148 individuals within 39 families consisting of a mother, father, sibling,…

Literacy Outcomes of Children with Early Childhood Speech Sound Disorders: Impact of Endophenotypes

ERIC Educational Resources Information Center

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Hansen, Amy J.; Sucheston, Lara E.; Kuo, Iris; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2011-01-01

Purpose: To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Method: Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years).…

ω-3 Long-Chain Polyunsaturated Fatty Acids and Fatty Acid Desaturase Activity Ratios as Eventual Endophenotypes for ADHD.

PubMed

Henríquez-Henríquez, Marcela; Solari, Sandra; Várgas, Gisela; Vásquez, Luis; Allende, Fidel; Castañón S, Carla; Tenorio, Marcela; Quiroga Gutiérrez, Teresa

2015-11-01

Epidemiological studies suggest that long-chain polyunsaturated fatty acids (LC-PUFAs) may be suitable as endophenotypes for ADHD. To be appropriated vulnerability traits, endophenotypes should be altered in unaffected relatives of index cases. Serum profiles of LC-PUFAs in unaffected relatives of ADHD patients remain understudied. The main objective of this study was to compare serum LC-PUFAs in ADHD patients, unaffected relatives of index cases, and general-population unaffected participants. LC-PUFA profiles of 72 participants (27 ADHD patients, 27 unaffected relatives, and 18 general-population participants) were obtained by gas chromatography-mass spectrometry (GC-MS). Groups were compared by parametrical statistics. Unaffected females from the general population presented lower Docosapentaenoic acid (DPA; p = .0012) and a-linolenic acid (ALA; p = .0091) levels compared with ADHD females and unaffected relatives. In addition, docosahexaenoic acid (DHA)/ALA and DHA/DPA ratios, addressing desaturase activity, were significantly lower in ADHD patients and unaffected relatives of ADHD patients in the female-subgroup (p = .022 and .04, respectively). DHA/ALA, DHA/DPA, serum DPA, and serum ALA may be suitable as endophenotypes for ADHD women. © The Author(s) 2012.

Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes.

PubMed

Calkins, Monica E; Iacono, William G; Ones, Deniz S

2008-12-01

Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies.

The neuroanatomical basis of panic disorder and social phobia in schizophrenia: a voxel based morphometric study.

PubMed

Picado, Marisol; Carmona, Susanna; Hoekzema, Elseline; Pailhez, Guillem; Bergé, Daniel; Mané, Anna; Fauquet, Jordi; Hilferty, Joseph; Moreno, Ana; Cortizo, Romina; Vilarroya, Oscar; Bulbena, Antoni

2015-01-01

It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus when compared to the control group. Our findings suggest that the comorbidity of schizophrenia with panic disorder and social phobia might be characterized by specific neuroanatomical and clinical alterations that may be related to maladaptive emotion regulation related to anxiety. Even thought our findings need to be replicated, our study suggests that the identification of neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety may lead to an improved diagnosis and management of these conditions.

Nonlinear Analysis of Motor Activity Shows Differences between Schizophrenia and Depression: A Study Using Fourier Analysis and Sample Entropy

PubMed Central

Hauge, Erik R.; Berle, Jan Øystein; Oedegaard, Ketil J.; Holsten, Fred; Fasmer, Ole Bernt

2011-01-01

The purpose of this study has been to describe motor activity data obtained by using wrist-worn actigraphs in patients with schizophrenia and major depression by the use of linear and non-linear methods of analysis. Different time frames were investigated, i.e., activity counts measured every minute for up to five hours and activity counts made hourly for up to two weeks. The results show that motor activity was lower in the schizophrenic patients and in patients with major depression, compared to controls. Using one minute intervals the depressed patients had a higher standard deviation (SD) compared to both the schizophrenic patients and the controls. The ratio between the root mean square successive differences (RMSSD) and SD was higher in the schizophrenic patients compared to controls. The Fourier analysis of the activity counts measured every minute showed that the relation between variance in the low and the high frequency range was lower in the schizophrenic patients compared to the controls. The sample entropy was higher in the schizophrenic patients compared to controls in the time series from the activity counts made every minute. The main conclusions of the study are that schizophrenic and depressive patients have distinctly different profiles of motor activity and that the results differ according to period length analysed. PMID:21297977

The Neuroanatomical Basis of Panic Disorder and Social Phobia in Schizophrenia: A Voxel Based Morphometric Study

PubMed Central

Picado, Marisol; Carmona, Susanna; Hoekzema, Elseline; Pailhez, Guillem; Bergé, Daniel; Mané, Anna; Fauquet, Jordi; Hilferty, Joseph; Moreno, Ana; Cortizo, Romina; Vilarroya, Oscar; Bulbena, Antoni

2015-01-01

Objective It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. Methods Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. Results Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus when compared to the control group. Conclusions Our findings suggest that the comorbidity of schizophrenia with panic disorder and social phobia might be characterized by specific neuroanatomical and clinical alterations that may be related to maladaptive emotion regulation related to anxiety. Even thought our findings need to be replicated, our study suggests that the identification of neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety may lead to an improved diagnosis and management of these conditions. PMID:25774979

Cortical hypoactivation during resting EEG in schizophrenics but not in depressives and schizotypal subjects as revealed by low resolution electromagnetic tomography (LORETA).

PubMed

Mientus, Susanne; Gallinat, Jürgen; Wuebben, Yvonne; Pascual-Marqui, Roberto D; Mulert, Christoph; Frick, Kurt; Dorn, Hans; Herrmann, Werner M; Winterer, Georg

2002-11-30

This study was performed in order to address the question whether the newly introduced technique of low-resolution electromagnetic tomography (LORETA) is able to detect hypofrontality in schizophrenic patients. We investigated resting EEGs of 19 unmedicated schizophrenics and 20 normal subjects. For comparison, we also investigated 19 subjects with schizotypal personality and 30 unmedicated depressive patients. A significant increase of delta activity was found in schizophrenic patients over the whole cortex, most strongly in the anterior cingulate gyrus and temporal lobe (fusiform gyrus). Both schizotypal subjects and depressive subjects showed significantly less delta, theta and beta activity in the anterior cingulum, a decrease of alpha1 activity in the right temporal lobe and a decrease of alpha2 activity in the left temporal lobe. The results suggest general cortical hypoactivation, most pronounced in the anterior cingulate and temporal lobe in schizophrenics, whereas there is evidence for a complex, frequency-dependent spatial pattern of hyperactivation in schizotypal subjects and depressive patients. The results are discussed within a neurophysiological and methodological framework.

Homicide, schizophrenia and substance abuse or dependency.

PubMed

Beaudoin, M N; Hodgins, S; Lavoie, F

1993-10-01

Few studies have extensively studied the aggressive behaviours of mentally disordered offenders. This investigation compared 14 schizophrenics found not guilty of homicide by reason of insanity (NGRI) with 12 schizophrenics convicted of homicide. A comparison group of 15 homicide offenders with no major mental disorder was used. Drug and alcohol consumption, previous history of aggression against others as well as mental health were assessed using standardized, reliable, valid instruments. Significantly more of the inmates with no major mental disorder were diagnosed as having a history of drug or alcohol abuse or dependency (60%) than the NGRI schizophrenics (35.7%). In addition, both groups of convicted homicide offenders were more likely to have committed homicide under the influence of drugs or alcohol than the NGRI group. No significant difference distinguished the groups for the mean number of aggressive incidents. The subjects found NGRI assaulted more often during an acute phase of mental illness than the convicted schizophrenics. Although both groups appeared to have a similar number of hospitalizations, most of the hospitalizations of the convicted schizophrenics occurred after the crime.

Ethnopsychiatric interpretations of schizophrenic illness: the problem of nervios within Mexican-American families.

PubMed

Jenkins, J H

1988-09-01

Among Mexican-American families, the concept of nervios (nerves) serves as a culturally meaningful illness category for a wide range of conditions, including schizophrenic disorders diagnosed according to psychiatric criteria. This article examines the nature and the meaning of nervios as a notion used by Mexican-American families to understand the schizophrenic illness of a relative. Family descriptions of the condition are presented and the emotional and symbolic meanings of the concept are discussed. The complex and somewhat ambiguous nature of folk conceptions is evidenced not only by variations in the description of nervios but also by the finding that nervios is but one way to view schizophrenic illness. It is suggested that a cultural preference for the term nervios is linked to the efforts of family members to reduce the stigma associated with a mental illness while also reinforcing the strength of family bonds and solidarity by fostering tolerant inclusion of the family member within the home. It is argued that the concept of nervios, and the family emotions that surround this folk label, may mediate the course and outcome of schizophrenic disorder.

Schizophrenia and the corpus callosum: developmental, structural and functional relationships.

PubMed

David, A S

1994-10-20

Several empirical and theoretical connections exist between schizophrenia and the corpus callosum: (1) disconnection symptoms resemble certain psychotic phenomena; (2) abnormal interhemispheric transmission could explain typically schizophrenic phenomena; (3) cases of psychosis have been found in association with complete and partial agenesis of the callosum; (4) experimental neuropsychology with schizophrenic patients has revealed abnormal patterns of interhemispheric transfer; (5) studies using magnetic resonance imaging have shown abnormal callosal dimensions in schizophrenic patients. The evidence in support of these links is discussed critically. Novel neuropsychological approaches in the study of information transfer in the visual modality between the cerebral hemispheres, consistent with callosal hyperconnectivity in schizophrenic patients but not matched psychiatric controls are highlighted. Some suggestions for further work including integrating functional and structural measures are offered.

Understanding the symptoms of schizophrenia using visual scan paths.

PubMed

Phillips, M L; David, A S

1994-11-01

This paper highlights the role of the visual scan path as a physiological marker of information processing, while investigating positive symptomatology in schizophrenia. The current literature is reviewed using computer search facilities (Medline). Schizophrenics either scan or stare extensively, the latter related to negative symptoms. Schizophrenics particularly scan when viewing human faces. Scan paths in schizophrenics are important when viewing meaningful stimuli such as human faces, because of the relationship between abnormal perception of stimuli and symptomatology in these subjects.

GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

NASA Technical Reports Server (NTRS)

Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

1995-01-01

The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of schizophrenics, the previously reported upregulation of muscimol binding sites and downregulation of benzodiazepine binding sites in the prefrontal and adjacent cingulate cortex of schizophrenics are possibly due to posttranscriptional modifications of mRNAs and their translated polypeptides.

The Role of Double Dissociation Studies in the Search for Candidate Endophenotypes for the Comorbidity of Attention Deficit Hyperactivity Disorder and Reading Disability

ERIC Educational Resources Information Center

de Jong, Christien G. W.; Oosterlaan, Jaap; Sergeant, Joseph A.

2006-01-01

The neuropsychological underpinnings of Attention Deficit Hyperactivity Disorder (ADHD) and Reading Disability (RD) and their comorbidity may be studied usefully with the double dissociation design. The results of studies using the double dissociation method may be linked to the search for an endophenotype of ADHD and RD and their comorbidity.…

Delta-beta correlation as a candidate endophenotype of social anxiety: A two-generation family study.

PubMed

Harrewijn, Anita; van der Molen, Melle J W; van Vliet, Irene M; Houwing-Duistermaat, Jeanine J; Westenberg, P Michiel

2018-02-01

Social anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation during a social performance task as candidate endophenotype of SAD. Nine families with a target participant (diagnosed with SAD), their spouse and children, as well as target's siblings with spouse and children performed a social performance task in which they gave a speech in front of a camera. EEG was measured during resting state, anticipation, and recovery. Our analyses focused on two criteria for endophenotypes: co-segregation within families and heritability. Co-segregation analyses revealed increased negative delta-low beta correlation during anticipation in participants with (sub)clinical SAD compared to participants without (sub)clinical SAD. Heritability analyses revealed that delta-low beta and delta-high beta correlation during anticipation were heritable. Delta-beta correlation did not differ between participants with and without (sub)clinical SAD during resting state or recovery, nor between participants with and without SAD during all phases of the task. It should be noted that participants were seen only once, they all performed the EEG tasks in the same order, and some participants were too anxious to give a speech. Delta-low beta correlation during anticipation of giving a speech might be a candidate endophenotype of SAD, possibly reflecting increased crosstalk between cortical and subcortical regions. If validated as endophenotype, delta-beta correlation during anticipation could be useful in studying the genetic basis, as well as improving treatment and early detection of persons at risk for developing SAD. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-Instructional Training with an Adolescent Schizophrenic.

ERIC Educational Resources Information Center

Gumaer, Jim; Headspeth, Tanya

1985-01-01

Presents a case study involving the use of self-instructional training with an adolescent schizophrenic boy. Changes initiated in his internal and external dialog with himself improved his self-control and task performance. (JAC)

MMPI Indices in the Discrimination of Brain-Damaged and Schizophrenic Groups

ERIC Educational Resources Information Center

Holland, Terrill R.; And Others

1975-01-01

The results of this investigation support Watson's (1971) hypothesis that his Schizophrenia-Organicity scales might be valid discriminators of braindamaged and schizophrenic patients equated for degree of intellectual deficit. (Author)

Pitting temporal against spatial integration in schizophrenic patients.

PubMed

Herzog, Michael H; Brand, Andreas

2009-06-30

Schizophrenic patients show strong impairments in visual backward masking possibly caused by deficits on the early stages of visual processing. The underlying aberrant mechanisms are not clearly understood. Spatial as well as temporal processing deficits have been proposed. Here, by combining a spatial with a temporal integration paradigm, we show further evidence that temporal but not spatial processing is impaired in schizophrenic patients. Eleven schizophrenic patients and ten healthy controls were presented with sequences composed of Vernier stimuli. Patients needed significantly longer presentation times for sequentially presented Vernier stimuli to reach a performance level comparable to that of healthy controls (temporal integration deficit). When we added spatial contextual elements to some of the Vernier stimuli, performance changed in a complex but comparable manner in patients and controls (intact spatial integration). Hence, temporal but not spatial processing seems to be deficient in schizophrenia.

Evaluation and Socio-occupational Intervention in Bipolar and Schizophrenic Patients within a Multimodal Intervention Program- PRISMA.

PubMed

Díaz Zuluaga, Ana M; Duica, Kelly; Ruiz Galeano, Carlos; Vargas, Cristian; Agudelo Berruecos, Yuli; Ospina, Sigifredo; López-Jaramillo, Carlos

Functional improvement in bipolar and schizophrenic patients is one of the main aims of treatment. Nevertheless, there is no evidence about the effect of socio-occupational intervention within a multimodal intervention (MI) programme. To describe the socio-occupational profile and to evaluate the functional effect of a MI in bipolar I and schizophrenic patients. A prospective, longitudinal, therapeutic-comparative study was performed including 302 subjects (104 schizophrenic and 198 Bipolar Disorder I [BDI] patients), who were randomised into two groups, multimodal (psychiatry, psychology, medicine, occupational therapy, neuropsychology, and family therapy), or traditional intervention (psychiatry and medicine only). Several scales were applied to assess assertiveness, free time management, social abilities, general anxiety, self-care and performance in home, work and community tasks. After performing the longitudinal analysis, it was shown that the multimodal intervention was more effective than traditional intervention in general anxiety scores (P=.026) and development in home tasks (P=.03) in schizophrenic patients. No statistical differences were found in bipolar patients. The other variables showed improvement, however, their effect was similar in both intervention groups. Our study identified functional improvement in home tasks in schizophrenic patients after receiving multimodal intervention. Other variables also showed improvement for both interventions groups. Future studies, applying longer rehabilitation programs and other ecological strategies should be performed to identify the most effective interventions. Copyright © 2017 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Abnormal infant neurodevelopment predicts schizophrenia spectrum disorders.

PubMed

Fish, Barbara; Kendler, Kenneth S

2005-06-01

The aim of this study was to detect infants who carry a schizophrenic genotype and study the development of schizophrenia spectrum disorders (SZSD) from birth. In the 1940s, Bender described uneven maturation in childhood schizophrenics and in 1952 found this in the infant histories of 6 schizophrenic children. We tested a possible index for defective neural integration in infants termed "pandysmaturation" (PDM). This required retarded cranial growth plus retarded and erratic gross motor development on a single exam. Twelve offspring of hospitalized schizophrenic mothers and 12 infants in a "Well Baby Clinic," were examined 10 times between birth and 2 years of age. Psychiatric interviews and psychological testing were done at 10, 15, and 22 years of age, plus follow-up at 27-35 years of age. Six infants had PDM at 2, 6, or 13 months of age. Five individuals have been blindly diagnosed (by KSK) as having lifetime SZSD; all 5 had PDM before 8 months. Chi-square one-tailed tests confirmed the predictions: (1) PDM was related to subsequent SZSD (chi(2) = 11.43; p < 0.0005); (2) schizophrenic mothers had more infants with PDM than nonschizophrenic mothers (chi(2) = 3.28; p < 0.05); and (3) schizophrenic mothers had more SZSD offspring than nonschizophrenic mothers (chi(2) = 6.39; p < 0.0125). These first behavioral observations of aberrant neurodevelopment in pre- SZSD infants support the evidence of early neurodevelopmental disorder seen in studies of brain pathology in SZSD adults.

Different patterns of sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. Results of an investigation by semistructured interview of schizophrenic and neurotic patients and methadone-substituted opiate addicts.

PubMed

Teusch, L; Scherbaum, N; Böhme, H; Bender, S; Eschmann-Mehl, G; Gastpar, M

1995-05-01

Little is known about sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. In the present study schizophrenic patients (n = 45, mostly under neuroleptic treatment), neurotic patients (n = 50, mostly treated without medication), methadone-substituted opiate addicts (n = 37), and normal controls (n = 41) were included. They were interviewed with the aid of a sex-differentiated semistructured questionnaire on sexual function. All the methadone-substituted opiate addicts and nearly all the schizophrenic patients suffered from dysfunctions in at least one criterion. The three clinical groups differed significantly from the controls in sexual interest, emotional arousal, physiological arousal (erectile function/vaginal lubrication), performance (ejaculatory function/vaginism, dyspareunia), and orgasm satisfaction. Characteristic patterns of dysfunction were found in the male patients. The schizophrenic patients had significantly more dysfunctions of interest, physiological arousal, performance, and orgasm than the controls. Emotional arousal, erectile and ejaculatory functions, and orgasm satisfaction were impaired more frequently in the male schizophrenics than in the neurotic patients. Reduced sexual interest, emotional arousal, and orgasm satisfaction were reported more frequently by the methadone-substituted opiate addicts than by the neurotic men. Emotional arousal was even more frequently reduced than in the schizophrenic men. There was no correlation between sexual dysfunction and particular neuroleptics or neuroleptic or methadone dosage. The results are compared with the literature and suggestions made for further investigations.

The effect of stimulus strength on binocular rivalry rate in healthy individuals: Implications for genetic, clinical and individual differences studies.

PubMed

Law, Phillip C F; Miller, Steven M; Ngo, Trung T

2017-11-01

Binocular rivalry (BR) occurs when conflicting images concurrently presented to corresponding retinal locations of each eye stochastically alternate in perception. Anomalies of BR rate have been examined in a range of clinical psychiatric conditions. In particular, slow BR rate has been proposed as an endophenotype for bipolar disorder (BD) to improve power in large-scale genome-wide association studies. Examining the validity of BR rate as a BD endophenotype however requires large-scale datasets (n=1000s to 10,000s), a standardized testing protocol, and optimization of stimulus parameters to maximize separation between BD and healthy groups. Such requirements are indeed relevant to all clinical psychiatric BR studies. Here we address the issue of stimulus optimization by examining the effect of stimulus parameter variation on BR rate and mixed-percept duration (MPD) in healthy individuals. We aimed to identify the stimulus parameters that induced the fastest BR rates with the least MPD. Employing a repeated-measures within-subjects design, 40 healthy adults completed four BR tasks using orthogonally drifting grating stimuli that varied in drift speed and aperture size. Pairwise comparisons were performed to determine modulation of BR rate and MPD by these stimulus parameters, and individual variation of such modulation was also assessed. From amongst the stimulus parameters examined, we found that 8cycles/s drift speed in a 1.5° aperture induced the fastest BR rate without increasing MPD, but that BR rate with this stimulus configuration was not substantially different to BR rate with stimulus parameters we have used in previous studies (i.e., 4cycles/s drift speed in a 1.5° aperture). In addition to contributing to stimulus optimization issues, the findings have implications for Levelt's Proposition IV of binocular rivalry dynamics and individual differences in such dynamics. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative study of clozapine, electroshock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients.

PubMed

Masoudzadeh, A; Khalilian, A R

2007-12-01

The aim of this study was to compare the results of treatment with clozapine alone, Electroshock (ECT) alone and the combination of clozapine with ECT in treatment-resistant schizophrenic patients. Eighteen treatment-resistant schizophrenic patients were assigned to three equal groups: one group was given clozapine; one group was treated with ECT and one group was treated with the combination of clozapine and ECT. The treatment response was evaluated using the PANSS criteria and the data were analyzed with ANOVA. Combination therapy was superior to single modality therapy. The reduction of PANSS scores was 46% in the clozapine group, 40% in the ECT groups and 71% in the combination group, the difference between the combination group and the other groups was statistically significant (p < 0.05). Patients had a quick response to combination treatment, which resulted in a higher cure rate of positive and negative symptoms and improved the patients general performance. There were no significant adverse effects with combination treatment. Combination treatment with clozapine and ECT was safe and effective in treatment-resistant schizophrenic patients. It should be considered for the treatment of treatment-resistant schizophrenic patients.

Tone discrimination performance in schizophrenic patients and normal volunteers: impact of stimulus presentation levels and frequency differences.

PubMed

Holcomb, H H; Ritzl, E K; Medoff, D R; Nevitt, J; Gordon, B; Tamminga, C A

1995-06-29

Psychophysical and cognitive studies carried out in schizophrenic patients show high within-group performance variance and sizable differences between patients and normal volunteers. Experimental manipulation of a target's signal-to-noise characteristics can, however, make a given task more or less difficult for a given subject. Such signal-to-noise manipulations can substantially reduce performance differences between individuals. Frequency and presentation level (volume) changes of an auditory tone can make a sound more or less difficult to recognize. This study determined how the discrimination accuracy of medicated schizophrenic patients and normal volunteers changed when the frequency difference between two tones (high frequency vs. low frequency) and the presentation levels of tones were systematically degraded. The investigators hypothesized that each group would become impaired in its discrimination accuracy when tone signals were degraded by making the frequencies more similar and the presentation levels lower. Schizophrenic patients were slower and less accurate than normal volunteers on tests using four tone levels and two frequency differences; the schizophrenic patient group showed a significant decrement in accuracy when the signal-to-noise characteristics of the target tones were degraded. The benefits of controlling stimulus discrimination difficulty in functional imaging paradigms are discussed.

Neuropsychological dysfunction in schizophrenia and affective disease.

PubMed

Taylor, M A; Redfield, J; Abrams, R

1981-05-01

We used Smith's neuropsychological test battery to study the cortical functioning of 52 patients with affective disorders, 17 schizophrenics, and 8 patients with coarse brain disease (CBD), all diagnosed according to research criteria. Testing and diagnoses were made independently and blindly. After accounting for the variance due to age, sex, handedness, educational level, and psychotropic drugs, we found that on tests of dominant hemisphere function schizophrenics performed significantly worse than patients with affective disorder but were no different from patients with CBD. On tests of nondominant hemisphere function the performance of the schizophrenics was similar to that of the other two groups, which were different from each other in that patients with CBD had poorer performance than affectives. A discriminant function analysis of the test scores applied to a jackknifed classification matrix successfully predicted research diagnosis in 86.5% of the affectively ill patients and 76.5% of the schizophrenics, for an overall hit rate of 84.1%. A canonical plot of the discriminant scores further showed distinct groups, with manics and depressives most alike but quite different from schizophrenics and patients with CBD. These findings are consistent with those derived from other neuropsychological studies, as well as EEG and CT scan studies.

[Acute schizophrenia concept and definition: investigation of a French psychiatrist population].

PubMed

Baylé, F J; Misdrahi, D; Llorca, P M; Lançon, C; Olivier, V; Quintin, P; Azorin, J M

2005-01-01

For schizophrenic disorders, the clinical conception of "acute state" is widely used in clinical settings to assess the effectiveness of therapeutic programs as well as epidemiological studies. Schizophrenic-specific symptomatology modification, need for hospitalization, significant change in care, disturbances in social behavior or suicide attempts were all used to define acute schizophrenic state. The decision to hospitalize is frequently used to define acute state but refers to multiple factors such as mood disorder, suicide attempts, drug abuse or social and environmental problems. Indeed, several and distinct definitions in a criteria basis form are available but no one has reached consensus. Because recognition of acute schizophrenic state remains based on the subjective clinician's advice, epidemiological and therapeutic studies fail in validity and reliability. The aim of the study was to evaluate how a population of French psychiatrists define criteria and therapeutic targets of acute schizophrenic state in their clinical practice. Psychiatrists filled out a self administered interview. At the time the interview was given, clinicians were notified that they were participating in a clinical consensus survey about schizophrenia. Six major indicators for acute state definition based on the literature data were proposed: general schizophrenic symptomatology modification (depression, anxiety, agitation, impulsivity/aggressiveness), specific schizophrenic symptomatology modification (positive symptoms, negative symptoms, disorganization), need for hospitalization, significant change in care, disturbance in social behavior and lastly, suicidal behavior. Minimal duration (1.2 or 4 weeks) of general and specific schizophrenic symptomatology modification required to define acute state were evaluated. The booklet included the 30 PANSS symptoms listed with their definitions. Among this symptom list, clinicians were instructed to select the ten criteria which they estimated best defined the acute state, followed by the ten most important target symptoms to be treated. Out of 2,369 questionnaires, 1,584 were collected on time (66.9%). Among the six majors indicators proposed to define acute state 75% of psychiatrists considered 1 to 3 criteria. Three were more frequently rated, including core schizophrenic symptomatology disturbance (68.4%), general schizophrenic symptomatology disturbance (68.0%) and suicidal behavior (64.9%). The other criteria were rated as follows: need for hospitalization (26.8%), significant change in care (18.3%), and disturbance in social behavior (29.1%). For 53.2% of psychiatrists the definition of acute state requires the presence of specific schizophrenic symptomatology for a minimal duration of one week. Two weeks with general symptomatology was required for 45.5% of psychiatrists to define acute state. Symptoms more often rated within the four first choices for acute state definition included delusions, conceptual disorganization, hallucinatory behavior and excitement. Except for grandiosity, all the PANSS positive subscale items were chosen to be included in the definition (delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution and hostility). Four items, including anxiety, depression, uncontrolled hostility, inner tension from the general psychopathology subscale were chosen as part of the ten most important criteria to define acute state. On the PANSS negative subscale (blunted affect, emotional withdrawal, poor relationships, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity/flow of conversation and stereotyped thinking), no item was rated to be included in the acute state definition. The highest rated symptoms among the four first choices for treatment included delusions, hallucinatory behavior, excitement and anxiety. The ten most important criteria for treatment were the same as for acute state definition with differences in frequency. Excited state, depression and suspiciousness/persecution were more rated for treatment than definition whereas delusion, hostility and conceptual disorganization were less rated as treatment target than definition criteria. In clinical practice, recognition of acute schizophrenic state is underscored by the association of specific schizophrenic symptomatology (positive symptoms, negative symptoms, disorganization) and general symptomatology (impulsivity/aggressiveness, anxiety, depression, agitation) of schizophrenia. For most clinicians, acute state definition requires specific symptom for a minimum of one week and other non-specific indicators such as suicidal behaviour have to be taken into account. With regard to PANSS criteria, most positive schizophrenic symptoms and some general schizophrenic symptoms are necessary for definition and designated as treatment priorities. Negative symptoms were not taken into account. Hallucinatory behavior is the first symptom rated in definition and is considered by psychiatrists as the absolute therapeutic priority. This survey could be a first step in the construction of an operational and consensual definition. This definition is strongly needed as a valid measurement in therapeutic and epidemiological outcome studies, which remain at least partly based on clinician subjective judgment.

Spatial vs. Nonspatial Reasoning Ability in Chronic Schizophrenics

ERIC Educational Resources Information Center

Hartlage, Lawrence C.; Garber, Judy

1976-01-01

Compares spatial with nonspatial reasoning ability within the same patients to determine whether spatial reasoning deficits in schizophrenics are specific to spatial types of tasks or are indicative of generalized reasoning difficulties. (Author/RK)

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes

PubMed Central

Harrewijn, Anita; Tissier, Renaud L.M.; van der Molen, Melle J.W.; van Steenbergen, Henk; van Vliet, Irene M.; Reichart, Catrien G.; Houwing‐Duistermaat, Jeanine J.; Slagboom, P. Eline; van der Wee, Nic J.A.; Westenberg, P. Michiel

2018-01-01

abstract Objectives Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so‐called “endophenotypes”. These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. Methods The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. Results The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. Conclusions By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD. PMID:29700902

[Relaxation to defuse acting out for dangerous schizophrenics].

PubMed

Bogar, Mireille; Bouchard, Jean-Pierre

2015-01-01

Relaxation is often considered as a contraindication in the management of schizophrenics. An experiment carried out with dangerous schizophrenics at the unit for dangerous patients at Cadillac general hospital revealed that, on the contrary, such an opinion is not necessarily valid in all cases. Indeed, for many of these patients, relaxation can have positive effects on their clinical state. As with its other indications, relaxation must be practised by clinicians who have an in-depth knowledge of techniques to use and of mental disorders treated in that way.

Quantification of endocannabinoids in postmortem brain of schizophrenic subjects.

PubMed

Muguruza, Carolina; Lehtonen, Marko; Aaltonen, Niina; Morentin, Benito; Meana, J Javier; Callado, Luis F

2013-08-01

Numerous studies have implicated the endocannabinoid system in the pathophysiology of schizophrenia. Endocannabinoids have been measured in blood and cerebrospinal fluid in schizophrenic patients but, to the date, there are no published reports dealing with measurements of endocannabinoid levels in schizophrenics' brain tissue. In the present study, postmortem brain samples from 19 subjects diagnosed with schizophrenia (DSM-IV) and 19 matched controls were studied. In specific brain regions, levels of four endocannabinoids (2-arachidonoylglycerol (2-AG), arachidonoylethanolamine (anandamide, AEA), dihomo-γ-linolenoylethanolamine (LEA), and docosahexaenoylethanolamine (DHEA)) and two cannabimimetic compounds (palmitoyl-ethanolamine (PEA) and oleoyl-ethanolamine (OEA)) were measured using quantitative liquid chromatography with triple quadrupole mass spectrometric detection. Suffering from schizophrenia significantly affects the brain levels of 2-AG (p<0.001), AEA (p<0.0001), DHEA (p<0.0001), LEA (p<0.01) and PEA (p<0.05). In schizophrenic subjects, the three studied brain regions (cerebellum: 130±18%; p=0.16; hippocampus: 168±28%, p<0.01; prefrontal cortex: 237±45%, p<0.05) showed higher 2-AG levels when compared to matched controls. Conversely, AEA levels were lower in all brain regions of schizophrenic subjects (cerebellum: 66±7%, p<0.01; hippocampus: 66±7%, p<0.01; prefrontal cortex: 75±10%, p=0.07). Statistically significant lower levels of DHEA were also found in cerebellum (60±6%, p<0.001) and hippocampus (68±7%, p<0.05) of schizophrenic subjects. PEA (71±6%, p<0.05) and LEA (72±6%, p<0.05) levels were also found to be lower in cerebellum. No significant differences were found in OEA levels. Our results evidence specific alterations in the levels of some endocannabinoids in different brain regions of schizophrenic subjects. Furthermore, these data evidence the involvement of the endocannabinoid system in the pathophysiology of schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetics of addictive behavior: the example of nicotine dependence.

PubMed

Gorwood, Philip; Le Strat, Yann; Ramoz, Nicolas

2017-09-01

The majority of addictive disorders have a significant heritability-roughly around 50%. Surprisingly, the most convincing association (a nicotinic acetylcholine receptor CHRNA5-A3-B4 gene cluster in nicotine dependence), with a unique attributable risk of 14%, was detected through a genome-wide association study (GWAS) on lung cancer, although lung cancer has a low heritability. We propose some explanations of this finding, potentially helping to understand how a GWAS strategy can be successful. Many endophenotypes were also assessed as potentially modulating the effect of nicotine, indirectly facilitating the development of nicotine dependence. Challenging the involved phenotype led to the demonstration that other potentially overlapping disorders, such as schizophrenia and Parkinson disease, could also be involved, and further modulated by parent monitoring or the existence of a smoking partner. Such a complex mechanism of action is compatible with a gene-environment interaction, most clearly explained by epigenetic factors, especially as such factors were shown to be, at least partly, genetically driven.

A Multidimensional Scaling Analysis of Schizophrenics' and Normals' Perceptions of Verbal Similarity

ERIC Educational Resources Information Center

Neufeld, Richard W. J.

1975-01-01

Twenty-eight schizophrenics (14 paranoid and 14 nonparanoid) were compared with 14 normals on their judgments of similarity among words. The judgments were analyzed using an individual-differences multidimensional scaling procedure. (Editor)

Torque and Schizophrenic Vulnerability: As the World Turns

ERIC Educational Resources Information Center

Blau, Theodore H.

1977-01-01

Based upon reports of parents and guardians, with subjects at an average age of 21 years, it was found that 11 of the youngsters who had exhibited torque had in the interim been diagnosed as schizophrenic. (Author)

[Intensity of negative symptoms, working memory and executive functions disturbances in schizophrenic patients in partial remission period].

PubMed

Hintze, Beata; Borkowska, Alina

2011-01-01

The aim of the study was to assess the correlation between the level of working memory and executive functions impairment in schizophrenic subjects in their partial remission period and the intensity of psychopathological symptoms measured by PANSS scale. 45 patients with schizophrenia were included in the study (28 male and 17 female), aged 18-46 (mean 27 +/- 7) years during partial remission of psychopathological symptoms (PANSS < 70). The control group consisted in 35 age, gender and education matched healthy persons (13 male i 22 female), aged 21-49 (mean 30 +/- 8) years. To assess the intensity of psychopathological symptoms the PANSS scale was used, neuropsychological assessment included the Wisconsin Card Sorting Test (WCST), N-back test and Stroop test from the Vienna Tests Battery. In schizophrenic patients in partial remission period, the significant dysfunctions of working memory and executive functions show association with negative (not positive) schizophrenic symptoms.

Perceptual and conceptual information processing in schizophrenia and depression.

PubMed

Dreben, E K; Fryer, J H; McNair, D M

1995-04-01

Schizophrenic patients (n = 20), depressive patients (n = 20), and normal adults (n = 20) were compared on global vs local analyses of perceptual information using tachistoscopic tasks and on top-down vs bottom-up conceptual processing using card-sort tasks. The schizophrenic group performed more poorly on tasks requiring either global analyses (counting lines when distracting circles were present) or top-down conceptual processing (rule learning) than they did on tasks requiring local analyses (counting heterogeneous lines) or bottom-up processing (attribute identification). The schizophrenic group appeared not to use conceptually guided processing. Normal adults showed the reverse pattern. The depressive group performed similarly to the schizophrenic group on perceptual tasks but closer to the normal group on conceptual tasks, thereby appearing to be less dependent on a particular information-processing strategy. These deficits in organizational strategy may be related to the use of available processing resources as well as the allocation of attention.

[Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

PubMed

Sachs, G; Katschnig, H

2001-03-01

Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

Hypochondriasis and obsessive-compulsive disorder in schizophrenic patients treated with clozapine vs other atypical antipsychotics.

PubMed

Grassi, Giacomo; Poli, Lorenzo; Cantisani, Andrea; Righi, Lorenzo; Ferrari, Gabriella; Pallanti, Stefano

2014-08-01

The aim of the study was to investigate the prevalence rates of obsessive-compulsive disorder (OCD) and hypochondriasis in schizophrenic patients treated with atypical antipsychotics (AAPs) and to investigate the different comorbidity rates of OCD and hypochondriasis between clozapine-treated patients and patients treated with other AAPs. We therefore recruited 60 schizophrenic patients treated with clozapine or other AAPs. We assessed the prevalence rates of OCD or OC symptoms and hypochondriasis or hypochondriac symptoms in the whole group of patients and in clozapine-treated patients versus patients treated with other AAPs. Schizophrenic patients had a higher comorbidity rate of OCD (26.6% vs 1-3%) and hypochondriasis (20% vs 1%) than the general population. These comorbidities were more frequent in schizophrenic patients treated with clozapine versus patients treated with other AAPs (36.7% vs 16.7% and 33.3% vs 6.7%). Clozapine-treated patients showed a higher mean Y-BOCS and HY-BOCS score when compared to patients treated with other AAPs (10.90 vs 5.90, p = .099; 15.40 vs 8.93, p = .166). A statistical significant correlation was found between the Y-BOCS and HY-BOCS scores of the whole group (r = .378, p = 0.03). Furthermore, we found an inverse correlation between the global level of functioning and the diagnosis of hypochondriasis (p = .048) and the severity of hypochondriac symptoms (p = .047). Hypochondriasis could represent an important clinical feature of schizophrenic patients treated with atypical antipsychotics, and further research is needed in this field.

LORETA imaging of P300 in schizophrenia with individual MRI and 128-channel EEG.

PubMed

Pae, Ji Soo; Kwon, Jun Soo; Youn, Tak; Park, Hae-Jeong; Kim, Myung Sun; Lee, Boreom; Park, Kwang Suk

2003-11-01

We investigated the characteristics of P300 generators in schizophrenics by using voxel-based statistical parametric mapping of current density images. P300 generators, produced by a rare target tone of 1500 Hz (15%) under a frequent nontarget tone of 1000 Hz (85%), were measured in 20 right-handed schizophrenics and 21 controls. Low-resolution electromagnetic tomography (LORETA), using a realistic head model of the boundary element method based on individual MRI, was applied to the 128-channel EEG. Three-dimensional current density images were reconstructed from the LORETA intensity maps that covered the whole cortical gray matter. Spatial normalization and intensity normalization of the smoothed current density images were used to reduce anatomical variance and subject-specific global activity and statistical parametric mapping (SPM) was applied for the statistical analysis. We found that the sources of P300 were consistently localized at the left superior parietal area in normal subjects, while those of schizophrenics were diversely distributed. Upon statistical comparison, schizophrenics, with globally reduced current densities, showed a significant P300 current density reduction in the left medial temporal area and in the left inferior parietal area, while both left prefrontal and right orbitofrontal areas were relatively activated. The left parietotemporal area was found to correlate negatively with Positive and Negative Syndrome Scale total scores of schizophrenic patients. In conclusion, the reduced and increased areas of current density in schizophrenic patients suggest that the medial temporal and frontal areas contribute to the pathophysiology of schizophrenia, the frontotemporal circuitry abnormality.

Superior Temporal Gyrus Volume Abnormalities and Thought Disorder in Left-Handed Schizophrenic Men

PubMed Central

Holinger, Dorothy P.; Shenton, Martha E.; Wible, Cynthia G.; Donnino, Robert; Kikinis, Ron; Jolesz, Ferenc A.; McCarley, Robert W.

2010-01-01

Objective Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. Method Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. Results There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. Conclusions These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance. PMID:10553736

Reading in Schizophrenic Subjects and Their Nonsymptomatic First-Degree Relatives

PubMed Central

Roberts, Eryl O.; Proudlock, Frank A.; Martin, Kate; Reveley, Michael A.; Al-Uzri, Mohammed; Gottlob, Irene

2013-01-01

Previous studies have demonstrated eye movement abnormalities during smooth pursuit and antisaccadic tasks in schizophrenia. However, eye movements have not been investigated during reading. The purpose of this study was to determine whether schizophrenic subjects and their nonsymptomatic first-degree relatives show eye movement abnormalities during reading. Reading rate, number of saccades per line, amplitudes of saccades, percentage regressions (reverse saccades), and fixation durations were measured using an eye tracker (EyeLink, SensoMotoric Instruments, Germany) in 38 schizophrenic volunteers, 14 nonaffected first-degree relatives, and 57 control volunteers matched for age and National Adult Reading Test scores. Parameters were examined when volunteers read full pages of text and text was limited to progressively smaller viewing areas around the point of fixation using a gaze-contingent window. Schizophrenic volunteers showed significantly slower reading rates (P = .004), increase in total number of saccades (P ≤ .001), and a decrease in saccadic amplitude (P = .025) while reading. Relatives showed a significant increase in total number of saccades (P = .013) and decrease in saccadic amplitude (P = .020). Limitation of parafoveal information by reducing the amount of visible characters did not change the reading rate of schizophrenics but controls showed a significant decrease in reading rate with reduced parafoveal information (P < .001). Eye movement abnormalities during reading of schizophrenic volunteers and their first-degree relatives suggest that visual integration of foveal and parafoveal information may be reduced in schizophrenia. Reading abnormalities in relatives suggest a genetic influence in reading ability in schizophrenia and rule out confounding effects of medication. PMID:22267532

Chemistry, physiology and neuropsychology of schizophrenia: towards an earlier diagnosis of schizophrenia I.

PubMed

Kornhuber, H H

1983-01-01

Data supporting the glutamate hypothesis of schizophrenia are presented. The glutamate hypothesis is linked to the dopamine hypothesis by the fact that dopamine synapses inhibit the release of glutamate in the striate and mesolimbic system. The glutamate hypothesis of schizophrenia may open a way to find better drugs for treatment. The concept of schizophrenia I is described. It consists of "negative symptoms" such as disconcentration or reduction of energy. Schizophrenia I precedes and follows schizophrenia II with "positive symptoms," e.g. hallucinations and delusions. Schizophrenia I so far cannot be diagnosed as schizophrenia unless schizophrenia II appears. Chemical, physiological or neuropsychological methods for the diagnosis of schizophrenia I would render an earlier treatment of schizophrenia possible and thus make social and occupational rehabilitation more efficient. An objective diagnosis of schizophrenia I may also elucidate the mode of genetic transmission of schizophrenia. Several neuropsychological methods distinguish schizophrenic patients as a group from normals. Some of them are based on a specific disturbance of long term concentration. The EEG also distinguishes schizophrenics from normals when analyzed during voluntary movement. For schizophrenics it takes more effort to initiate a voluntary movement, and there are several features of the EEG correlated to this. Moreover, the longer motor reaction time of schizophrenics is paralleled by a longer duration of the Bereitschaftspotential in schizophrenia. Furthermore, there is a difference in the theta rhythm between schizophrenic patients and normals in a task which requires concentration. Some of the children of schizophrenic parents show a disturbance of concentration in both reaction time tasks and the d 2 test.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

PubMed

Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

2017-05-30

A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

Testing for Neuropsychological Endophenotypes in Siblings Discordant for ADHD

PubMed Central

Bidwell, L. Cinnamon; Willcutt, Erik G.; DeFries, John C.; Pennington, Bruce F.

2007-01-01

Objective Neurocognitive deficits associated with attention deficit-hyperactivity disorder (ADHD) may be useful intermediate endophenotypes for determining specific genetic pathways that contribute to ADHD. Methods This study administered 17 measures from prominent neuropsychological theories of ADHD (executive function, processing speed, arousal regulation and motivation/delay aversion) in dizygotic (DZ) twin pairs discordant for ADHD and control twin pairs (ages 8–18) in order to compare performance between twins affected with ADHD (n = 266), their unaffected co-twins (n = 228), and control children from twin pairs without ADHD or learning difficulties (n = 332). Results ADHD subjects show significant impairment on executive function, processing speed, and response variability measures compared to control subjects. Unaffected cotwins of ADHD subjects are significantly impaired on nearly all the same measures as their ADHD siblings, even when subclinical symptoms of ADHD are controlled. Conclusion Executive function, processing speed, and response variability deficits may be useful endophenotypes for genetic studies of ADHD. PMID:17585884

Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study.

PubMed

Losh, Molly; Martin, Gary E; Lee, Michelle; Klusek, Jessica; Sideris, John; Barron, Sheila; Wassink, Thomas

2017-03-01

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents' childhood records in the domains of language, reading, and math were studied from grades K-12. Results indicated that relatively lower performance and slower development of skills (particularly language related skills), and an uneven rate of development across domains predicted ASD endophenotypes in adulthood for parents, and the severity of clinical symptoms in children with ASD. These findings may mark childhood indicators of genetic liability to ASD in parents, that could inform understanding of the subclinical expression of ASD genetic liability.

Auditory Processing Speed and Signal Detection in Schizophrenia

ERIC Educational Resources Information Center

Korboot, P. J.; Damiani, N.

1976-01-01

Two differing explanations of schizophrenic processing deficit were examined: Chapman and McGhie's and Yates'. Thirty-two schizophrenics, classified on the acute-chronic and paranoid-nonparanoid dimensions, and eight neurotics were tested on two dichotic listening tasks. (Editor)

Computational Approach to Schizophrenia: Disconnection Syndrome and Dynamical Pharmacology

NASA Astrophysics Data System (ADS)

Érdi, Péter; Flaugher, Brad; Jones, Trevor; Ujfalussy, Balázs; Zalányi, László; Diwadkar, Vaibhav A.

2008-07-01

Schizophrenia may be best understood in terms of abnormal interactions between different brain regions. Tasks such as associative learning that engage different brain regions may be ideal for studying altered brain function in the illness. Preliminary data suggest that the hippocampus is involved in the encoding (learning) and the prefrontal cortex in the retrieval of associative memories. Specific changes in the fMRI activities have also been observed based on comparative studies between stable schizophrenia patients and healthy control subjects. Disconnectivity, observed between brain regions in schizophrenic patients could result from abnormal modulation of N-methyl-D-aspartate (NMDA)-dependent plasticity implicated in schizophrenia.

Magical Ideation and Schizophrenia.

ERIC Educational Resources Information Center

George, Leonard; Neufeld, Richard W. J.

1987-01-01

Administered the Eckblad and Chapman (1983) Magical Ideation Scale to groups of paranoid and nonparanoid schizophrenics and control subjects. Schizophrenics scored significantly higher than nonschizophrenic patients (mainly cases of affective disorder) and normal control subjects. Discusses theoretical and prognostic utility of this finding.…

The Schizophrenic Brain: Rewriting the Chapter.

ERIC Educational Resources Information Center

Greenberg, Joel

1979-01-01

Evidence of last two decades indicates schizophrenic disorders related to imbalance of brain chemicals. Recent discovery made of association between chronic schizophrenia and variety of structural abnormalities. Included are frontal lobe reversal and accipital lobe reversal. Computer tomography scans and data presented. (SA)

Ineffectiveness of deanol in tardive dyskinesia: a placebo controlled study.

PubMed

de Montigny, C; Chouinard, G; Annable, L

1979-11-01

In a double-blind placebo-controlled study, deanol acetamidobenzoate, administered in doses up to 1.5 g q.d. for three weeks to chronic schizophrenic patients presenting moderate to severe tardive dyskinesia, failed to alleviate the dyskinetic movements. However, there was a tendency for a significant increase in the schizophrenic symptoms of the deanol-treated group relative to the control group. The ineffectiveness of deanol in alleviating tardive dyskinesia is consistent with its inability to enhance brain acetylcholine synthesis. The worsening of the schizophrenic symptoms may possibly result from an interference by deanol with central cholinergic function.

A controlled comparison of the effects of social skills training and remedial drama on the conversational skills of chronic schizophrenic inpatients.

PubMed

Spencer, P G; Gillespie, C R; Ekisa, E G

1983-08-01

This study compared the effects of social-skills training, remedial drama and group discussion on the conversation skills of chronic schizophrenic patients. After 16 one-hour treatment sessions only the social-skills training resulted in significant improvement, which was maintained at two-month follow-up. Although there was little evidence to support generalisation, the results are seen as indicating the usefulness of social-skills training in improving the performance level of chronic schizophrenic inpatients and in maintaining their social functioning. The implications for future rehabilitation practice are discussed.

[Eyes test performance among unaffected mothers of patients with schizophrenia].

PubMed

Birdal, Seval; Yıldırım, Ejder Akgün; Arslan Delice, Mehtap; Yavuz, Kasım Fatih; Kurt, Erhan

2015-01-01

Theory of Mind (ToM) deficit is a widely accepted feature of schizophrenia. A number of studies have examined ToM deficits of first degree relatives of schizophrenic patients as genetic markers of schizophrenia. Examination of mentalization capacity among mothers of schizophrenia patients may improve our understanding of theory of mind impairments in schizophrenia. The aim of this study is to use Reading Mind in the Eyes test to examine theory of mind capacity among mothers of schizophrenic patients. Performance during the test "Reading the Mind in the Eyes" (Eyes Test) was compared between the mothers of schizophrenic patients (n=47) and mothers whose children have no psychotic mental illness (n=47). Test results were analyzed based on the categorization of test items as positive, negative, and neutral. Mothers of schizophrenic patients displayed poorer performance during the Eyes Test compare to mothers in the control group, particularly in the recognition of positive and neutral mental representations. There was no statistically significant difference in the recognition of negative mental representations between mothers of patients and the control groups. The results of this study indicate that mothers of schizophrenic patients differ in some theory of mind patterns. Theory of mind may be an important developmental or endophenotipic factor in the pathogenesis of schizophrenia and should be further evaluated using other biological markers.

Gender differences in facial emotion recognition in persons with chronic schizophrenia.

PubMed

Weiss, Elisabeth M; Kohler, Christian G; Brensinger, Colleen M; Bilker, Warren B; Loughead, James; Delazer, Margarete; Nolan, Karen A

2007-03-01

The aim of the present study was to investigate possible sex differences in the recognition of facial expressions of emotion and to investigate the pattern of classification errors in schizophrenic males and females. Such an approach provides an opportunity to inspect the degree to which males and females differ in perceiving and interpreting the different emotions displayed to them and to analyze which emotions are most susceptible to recognition errors. Fifty six chronically hospitalized schizophrenic patients (38 men and 18 women) completed the Penn Emotion Recognition Test (ER40), a computerized emotion discrimination test presenting 40 color photographs of evoked happy, sad, anger, fear expressions and neutral expressions balanced for poser gender and ethnicity. We found a significant sex difference in the patterns of error rates in the Penn Emotion Recognition Test. Neutral faces were more commonly mistaken as angry in schizophrenic men, whereas schizophrenic women misinterpreted neutral faces more frequently as sad. Moreover, female faces were better recognized overall, but fear was better recognized in same gender photographs, whereas anger was better recognized in different gender photographs. The findings of the present study lend support to the notion that sex differences in aggressive behavior could be related to a cognitive style characterized by hostile attributions to neutral faces in schizophrenic men.

Smoking in schizophrenic patients: A critique of the self-medication hypothesis

PubMed Central

Manzella, Francesca; Maloney, Susan E; Taylor, George T

2015-01-01

A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments. Roots of the self-medication concept in psychiatry date back at least to the 1980s. Observations that rates of smokers in schizophrenic patients are multiple times the rates for regular smoking in the general population, as well as those with other disorders, proved particularly tempting for a self-medication explanation. Additional evidence came from experiments with animal models exposed to nicotine and the identification of neurobiological mechanisms suggesting self-medication with smoking is a plausible idea. More recently, results from studies comparing smoking and non-smoking schizophrenic patients have led to the questioning of the self-medication hypothesis. Closer examination of the literature points to the possibility that smoking is less beneficial on schizophrenic symptomology than generally assumed while clearly increasing the risk of cancer and other smoking-related diseases responsible for early mortality. It is a good time to examine the evidence for the self-medication concept as it relates to smoking. Our approach is to focus on data addressing direct or implied predictions of the hypothesis in schizophrenic smokers. PMID:25815253

A Review of the Differences in Developmental, Psychiatric, and Medical Endophenotypes Between Males and Females with Autism Spectrum Disorder

PubMed Central

Rubenstein, Eric; Wiggins, Lisa D.; Lee, Li-Ching

2015-01-01

Autism spectrum disorder (ASD) is over four times more prevalent in males compared to females. Increased understanding of sex differences in ASD endophenotypes could add insight into possible etiologies and the assessment and management of the disorder. Consequently, the purpose of this review is to describe current literature regarding sex differences in the developmental, psychiatric, and medical endophenotypes of ASD in order to illustrate current knowledge and areas in need of further research. Our review found that repetitive behaviors and restricted interests are more common in males than females with ASD. Intellectual disability is more common in females than males with ASD. Attention to detail may be more common in males than females with ASD and epilepsy may be more common in females than males with ASD, although limited research in these areas prevent definitive conclusions from being drawn. There does not appear to be a sex difference in other developmental, psychiatric, and medical symptoms associated with ASD, or the research was contradictory or too sparse to establish a sex difference. Our review is unique in that it offers detailed discussion of sex differences in three major endophenotypes of ASD. Further research is needed to better understand why sex differences exist in certain ASD traits and to evaluate whether phenotypic sex differences are related to different pathways of development, assessment, and treatment of the disorder. PMID:26146472

Atypical patterns of respiratory sinus arrhythmia index an endophenotype for depression

PubMed Central

Yaroslavsky, Ilya; Rottenberg, Jonathan; Kovacs, Maria

2015-01-01

Can atypical patterns of parasympathetic nervous system activity serve as endophenotypes for depression? Using respiratory sinus arrhythmia (RSA) as an index of parasympathetic nervous system function, we examined this question in two studies: one involving mothers with and without depression histories and their offspring (at high and low risk for depression, respectively), and a further study of adolescent sibling pairs concordant and discordant for major depression. In both studies, subjects were exposed to sad mood induction; subjects’ RSA was monitored during rest periods and in response to the mood induction. We used Gottesman and Gould’s (2003) criteria for an endophenotype and a priori defined “atypical” and “normative” RSA patterns (combinations of resting RSA and RSA reactivity). We found that atypical RSA patterns (a) predicted current depressive episodes and remission status among women with histories of juvenile onset depression and healthy controls, (b) predicted longitudinal trajectories of depressive symptoms among high- and low-risk young offspring, (c) were concordant across mothers and their juvenile offspring, (d) were more prevalent among never-depressed youth at high risk for depression than their low-risk peers, and (e) were more concordant across adolescent sibling pairs in which both versus only one had a history of major depression. Thus, the results support atypical RSA patterns as an endophenotype for depression. Possible mechanisms by which RSA patterns increase depression risk and their genetic contributors are discussed. PMID:25422965

Visual processing as a potential endophenotype in youths with attention-deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI.

PubMed

Fan, Li-Ying; Shang, Chi-Yung; Tseng, Wen-Yih Isaac; Gau, Susan Shur-Fen; Chou, Tai-Li

2018-05-10

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD. © 2018 Wiley Periodicals, Inc.

Intra-individual reaction time variability based on ex-Gaussian distribution as a potential endophenotype for attention-deficit/hyperactivity disorder.

PubMed

Lin, H-Y; Hwang-Gu, S-L; Gau, S S-F

2015-07-01

Intra-individual variability in reaction time (IIV-RT), defined by standard deviation of RT (RTSD), is considered as an endophenotype for attention-deficit/hyperactivity disorder (ADHD). Ex-Gaussian distributions of RT, rather than RTSD, could better characterize moment-to-moment fluctuations in neuropsychological performance. However, data of response variability based on ex-Gaussian parameters as an endophenotypic candidate for ADHD are lacking. We assessed 411 adolescents with clinically diagnosed ADHD based on the DSM-IV-TR criteria as probands, 138 unaffected siblings, and 138 healthy controls. The output parameters, mu, sigma, and tau, of an ex-Gaussian RT distribution were derived from the Conners' continuous performance test. Multi-level models controlling for sex, age, comorbidity, and use of methylphenidate were applied. Compared with unaffected siblings and controls, ADHD probands had elevated sigma value, omissions, commissions, and mean RT. Unaffected siblings formed an intermediate group in-between probands and controls in terms of tau value and RTSD. There was no between-group difference in mu value. Conforming to a context-dependent nature, unaffected siblings still had an intermediate tau value in-between probands and controls across different interstimulus intervals. Our findings suggest IIV-RT represented by tau may be a potential endophenotype for inquiry into genetic underpinnings of ADHD in the context of heterogeneity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Conformity and Psychopathology: A Comparative Study of Conformity Behaviors in Manic-depressive, Paranoid Schizophrenic and Normal Populations

ERIC Educational Resources Information Center

Marsella, Anthony J.

1975-01-01

The present study investigated the relationship between conformity and psychopathology in male and female manic-depressive (MD), paranoid schizophrenics (PS), and normals (N) on two conformity tasks under conditions of live social pressure. (Author)

Remedying Social Skills Deficits in a Chronic Schizophrenic-Retarded Person.

ERIC Educational Resources Information Center

Jackson, Henry J.; Martin, Rose

1983-01-01

An adult chronic schizophrenic, residual type, with an additional diagnosis of mild-moderate retardation, received social skills training (SST). Videotaped role-play assessments showed change occurred following SST, while a multiple-baseline design demonstrated functional control over the behaviors. (Author/CL)

The Comprehension of Idiomatic Expressions in Schizophrenic Patients

ERIC Educational Resources Information Center

Schettino, Antonio; Lauro, Leonor Romero; Crippa, Franca; Anselmetti, Simona; Cavallaro, Roberto; Papagno, Costanza

2010-01-01

Recent fMRI and TMS studies on idiom comprehension have shown that the prefrontal cortex is involved in idiom processing. Since schizophrenic patients exhibit prefrontal "structural" changes and dysexecutive "behavioural" deficits, we hypothesised an impairment in idiom comprehension, correlating with performance on executive…

Dissociation of emotional decision-making from cognitive decision-making in chronic schizophrenia.

PubMed

Lee, Yanghyun; Kim, Yang-Tae; Seo, Eugene; Park, Oaktae; Jeong, Sung-Hun; Kim, Sang Heon; Lee, Seung-Jae

2007-08-30

Recent studies have examined the decision-making ability of schizophrenic patients using the Iowa Gambling Task (IGT). These studies, however, were restricted to the assessment of emotional decision-making. Decision-making depends on cognitive functions as well as on emotion. The purpose of this study was to examine the performance of schizophrenic patients on the IGT and the Game of Dice Task (GDT), a decision-making task with explicit rules for gains and losses. In addition, it was intended to test whether poor performance on IGT is attributable to impairments in reversal learning within the schizophrenia group using the Simple Reversal Learning Task (SRLT), which is sensitive to measure the deficit of reversal learning following ventromedial prefrontal cortex damage. A group of 23 stable schizophrenic patients and 28 control subjects performed computerized versions of the IGT, GDT, SRLT and Wisconsin Card Sorting Test (WCST). While schizophrenic patients performed poorly on the IGT relative to normal controls, there was no significant difference between the two groups on GDT performance. The performance of the schizophrenia group on the SRLT was poorer than that of controls, but was not related to IGT performance. These data suggest that schizophrenic patients have impaired emotional decision-making but intact cognitive decision-making, suggesting that these two processes of decision-making are different. Furthermore, the impairments in reversal learning did not contribute to poor performance on the IGT in schizophrenia. Therefore, schizophrenic patients have difficulty in making decisions under ambiguous and uncertain situations whereas they make choices easily in clear and unequivocal ones. The emotional decision-making deficits in schizophrenia might be attributable more to another mechanism such as a somatic marker hypothesis than to an impairment in reversal learning.

The planetary positions and relationships at the dates of birth of a cohort of Nigerian schizophrenics.

PubMed

Ohaeri, J U

1997-01-01

Some astrological hypotheses related to predisposition to severe mental illness were tested by analysing the zodiacal signs, the interactions between planetary qualities (aspects), and the occurrence of full and new moon dates, on the dates of birth of 221 schizophrenics, compared with 112 normal subjects. The sun signs of the schizophrenics were significantly more likely to be in the signs associated with introversion, while those of the control population were significantly more likely to be in the outgoing signs. A significantly higher proportion of schizophrenics had their Mars (i.e., symbol of aggressiveness) in the outgoing signs than the normal population. A significantly higher proportion of control subjects fulfilled operational criteria for adequacy of number of aspects between the sun and the other planets. The tendency for a higher proportion of schizophrenics to have "difficult" aspects just failed to reach significance. A significantly higher proportion of control subjects had aspects between the sun and mars; and also a significantly higher proportion of control subjects had "soft" (helpful) aspects between the sun and mars. These findings are in keeping with the well-known oddity of schizophrenia (schiz = split; phren = mind); such that, a group which collectively is characterised by an "introverted" self (i.e. sun sign), has a coexisting aggressive tendency (i.e. strong mars) and poor integration between the elements of the psyche and the self (i.e. inadequacy of aspects between Sun and other planets). However, the findings give only partial support to key astrological postulates because there was a non-significant trend for more schizophrenics to be born in "water" signs and on full moon dates.

EEG theta power and coherence to octave illusion in first-episode paranoid schizophrenia with auditory hallucinations.

PubMed

Zheng, Leilei; Chai, Hao; Yu, Shaohua; Xu, You; Chen, Wanzhen; Wang, Wei

2015-01-01

The exact mechanism behind auditory hallucinations in schizophrenia remains unknown. A corollary discharge dysfunction hypothesis has been put forward, but it requires further confirmation. Electroencephalography (EEG) of the Deutsch octave illusion might offer more insight, by demonstrating an abnormal cerebral activation similar to that under auditory hallucinations in schizophrenic patients. We invited 23 first-episode schizophrenic patients with auditory hallucinations and 23 healthy participants to listen to silence and two sound sequences, which consisted of alternating 400- and 800-Hz tones. EEG spectral power and coherence values of different frequency bands, including theta rhythm (3.5-7.5 Hz), were computed using 32 scalp electrodes. Task-related spectral power changes and task-related coherence differences were also calculated. Clinical characteristics of patients were rated using the Positive and Negative Syndrome Scale. After both sequences of octave illusion, the task-related theta power change values of frontal and temporal areas were significantly lower, and the task-related theta coherence difference values of intrahemispheric frontal-temporal areas were significantly higher in schizophrenic patients than in healthy participants. Moreover, the task-related power change values in both hemispheres were negatively correlated and the task-related coherence difference values in the right hemisphere were positively correlated with the hallucination score in schizophrenic patients. We only tested the Deutsch octave illusion in primary schizophrenic patients with acute first episode. Further studies might adopt other illusions or employ other forms of schizophrenia. Our results showed a lower activation but higher connection within frontal and temporal areas in schizophrenic patients under octave illusion. This suggests an oversynchronized but weak frontal area to exert an action to the ipsilateral temporal area, which supports the corollary discharge dysfunction hypothesis. © 2014 S. Karger AG, Basel.

Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis.

PubMed

Tseng, Ping-Tao; Chen, Yen-Wen; Lin, Pao-Yen; Tu, Kun-Yu; Wang, Hung-Yu; Cheng, Yu-Shian; Chang, Yi-Chung; Chang, Chih-Hua; Chung, Weilun; Wu, Ching-Kuan

2016-01-26

Music therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis. We compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression. The main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course. Our meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity.

Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study.

PubMed

Wilke, M; Kaufmann, C; Grabner, A; Pütz, B; Wetter, T C; Auer, D P

2001-05-01

Voxel-based morphometry has recently been used successfully to detect gray matter volume reductions in schizophrenic patients. The aim of the present study was to confirm the findings on gray-matter changes and to complement these by applying the methodology to CSF-differences. Also, we wanted to determine whether a correlation exists between a clinically defined parameter of disease severity and brain morphology in schizophrenic patients. We investigated 48 schizophrenic patients and compared them with 48 strictly age- and sex-matched controls. High-resolution whole-brain MR-images were segmented and analyzed using SPM99. In a further analysis, the covariate effect of the global assessment of functioning-score (GAF) was calculated. Main findings were (i) left-dominant frontal, temporal, and insular GM-reductions and (ii) GM-increases in schizophrenic patients in the right basal ganglia and bilaterally in the superior cerebellum; (iii) CSF-space increases in patients complementary to some GM-reductions; (iv) a correlation between the GAF-score and local GM-volume in the left inferior frontal and inferior parietal lobe of schizophrenic patients. This study confirms and extends some earlier findings on GM-reduction and detected distinct GM-increases in schizophrenic patients. These changes were corroborated by complementary CSF-increases. Most importantly, a correlation could be established between two particular gray matter-regions and the overall disease severity, with more severely ill patients displaying a local GM-deficit. These findings may be of potentially large importance for both the future interpretation and design of neuroimaging studies in schizophrenia and the further elucidation of possible pathophysiological processes occurring in this disease. Copyright 2001 Academic Press.

Adequate antipsychotic treatment normalizes serum nerve growth factor concentrations in schizophrenia with and without cannabis or additional substance abuse.

PubMed

Jockers-Scherübl, Maria C; Rentzsch, Johannes; Danker-Hopfe, Heidi; Radzei, Nicole; Schürer, Falk; Bahri, Sharif; Hellweg, Rainer

2006-06-12

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important for the development and maintenance of neuron function. Neurodevelopment is thought to be impaired in schizophrenia, and vulnerable schizophrenic brains may be more sensitive to toxic influences. Thus, cannabis as a neurotoxin (and other substances) may be more harmful to schizophrenic brains than to non-schizophrenic brains, when used chronically. In a previous study we demonstrated an earlier disease onset and significantly higher serum NGF concentrations in drug-naïve schizophrenic patients with previous long-term cannabis abuse than in schizophrenics without cannabis abuse or cannabis abusers without schizophrenia. We therefore investigated whether this difference is still observed after treatment. Serum NGF measured in 114 treated schizophrenic patients (schizophrenia alone, n=66; schizophrenia plus cannabis abuse, n=42; schizophrenia plus multiple substance abuse, n=6) no longer differed significantly among those groups and from the control groups (healthy controls, n=51; cannabis controls, n=24; multiple substance controls, n=6). These results were confirmed by an additional prospective study in 28 patients suffering from schizophrenia (S) or schizophrenia with cannabis abuse (SC). Previously elevated serum NGF levels in the drug-naïve state, also differing between the groups (S: 83.44+/-265.25 pg/ml; SC: 246.89+/-310.24 pg/ml, S versus SC: p=0.03) dropped to 10.72+/-14.13 pg/ml (S) and 34.19+/-38.96 pg/ml (SC) (S versus SC, p>0.05), respectively, after adequate antipsychotic treatment. We thus conclude that antipsychotic treatment leads to recovery of neural integrity, as indicated by renormalized NGF values.

Comparisons of methamphetamine psychotic and schizophrenic symptoms: a differential item functioning analysis.

PubMed

Srisurapanont, Manit; Arunpongpaisal, Suwanna; Wada, Kiyoshi; Marsden, John; Ali, Robert; Kongsakon, Ronnachai

2011-06-01

The concept of negative symptoms in methamphetamine (MA) psychosis (e.g., poverty of speech, flatten affect, and loss of drive) is still uncertain. This study aimed to use differential item functioning (DIF) statistical techniques to differentiate the severity of psychotic symptoms between MA psychotic and schizophrenic patients. Data of MA psychotic and schizophrenic patients were those of the participants in the WHO Multi-Site Project on Methamphetamine-Induced Psychosis (or WHO-MAIP study) and the Risperidone Long-Acting Injection in Thai Schizophrenic Patients (or RLAI-Thai study), respectively. To confirm the unidimensionality of psychotic syndromes, we applied the exploratory and confirmatory factor analyses (EFA and CFA) on the eight items of Manchester scale. We conducted the DIF analysis of psychotic symptoms observed in both groups by using nonparametric kernel-smoothing techniques of item response theory. A DIF composite index of 0.30 or greater indicated the difference of symptom severity. The analyses included the data of 168 MA psychotic participants and the baseline data of 169 schizophrenic patients. For both data sets, the EFA and CFA suggested a three-factor model of the psychotic symptoms, including negative syndrome (poverty of speech, psychomotor retardation and flatten/incongruous affect), positive syndrome (delusions, hallucinations and incoherent speech) and anxiety/depression syndrome (anxiety and depression). The DIF composite indexes comparing the severity differences of all eight psychotic symptoms were lower than 0.3. The results suggest that, at the same level of syndrome severity (i.e., negative, positive, and anxiety/depression syndromes), the severity of psychotic symptoms, including the negative ones, observed in MA psychotic and schizophrenic patients are almost the same. Copyright © 2011 Elsevier Inc. All rights reserved.

Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)—a suitable endophenotype of schizophrenia

PubMed Central

Grant, Phillip; Kuepper, Yvonne; Mueller, Eva A.; Wielpuetz, Catrin; Mason, Oliver; Hennig, Juergen

2013-01-01

The concept of schizotypy or “psychosis proneness” captures individual differences in perceptual, cognitive, and affective experiences that may relate to a range of psychotic disorders. The concept is an important way to assess the contribution of pre-existing psychological and genetically based biological features to the development of illnesses such as schizophrenia (so called endophenotypes). The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) is a widely used multi-dimensional measure of the construct and consists of four scales which mirror several groups of psychotic symptoms: Unusual Experiences (UnEx; positive symptoms), Cognitive Disorganization (CogDis; cognitive symptoms), Introvertive Anhedonia (IntAn; negative symptoms), and Impulsive Nonconformity (ImpNon; impulsive and antisocial symptoms). For the purpose of evaluating the suitability of schizotypy as an endophenotype of schizophrenia the current version of the O-LIFE was translated into German: its psychometric properties (including re-test reliability and construct validity) were examined in a large sample (n > 1200) and compared to those of the English original. The German version was both highly reliable and consistent with the original. The study aimed to show that schizotypy as measured by the O-LIFE can indeed be regarded as an endophenotype of schizophrenia in terms of genetic associations regarding relevant dopamine-related candidate polymorphisms of schizotypy [i.e., Val158Met-polymorphism of the COMT gene, uVNTR of the MAOA gene, Taq1A-polymorphism of the DRD2 gene, VNTR of the SLC6A3 (DAT) gene]. We also wanted to compare the genetic associations of the O-LIFE to those published using other operationalizations of schizotypy. Our results show a large number of significant associations and borderline-significant trends between the O-LIFE sub-scales and a range of genes, thereby supporting using the O-LIFE in the search for endophenotypic markers. PMID:23355817

Infant social attention: an endophenotype of ASD-related traits?

PubMed

Jones, Emily J H; Venema, Kaitlin; Earl, Rachel K; Lowy, Rachel; Webb, Sara J

2017-03-01

As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child's environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics. Endophenotypes are quantitative, heritable, trait-related differences that are generally assessed with laboratory-based methods, can be identified in the general population, and may be more closely tied to particular causal chains that have a more restricted set of genetic roots. The most fruitful endophenotypes may be those observed in infancy, prior to the emergence of behavioral symptoms that they are hypothesized to cause. Social motivation is an ASD-related trait that is highly heritable. In this study, we investigate whether infant endophenotypes of social attention relate to familial risk for lower social motivation in the general population. We examined whether infant social attention (measured using habituation, EEG power, and event-related potential tasks previously used in infants/toddlers with ASD) varies quantitatively with parental social motivation in 117 six-month-old and 106 twelve-month-old typically developing infants assessed cross-sectionally. To assess heritable aspects of social motivation, primary caregiver biological parents completed two self-report measures of social avoidance and discomfort that have shown high heritability in previous work. Parents with higher social discomfort and avoidance had infants who showed shorter looks to faces but not objects; reduced theta power during naturalistic social attention; and smaller P400 responses to faces versus objects. Early reductions in social attention are continuously related to lower parental social motivation. Alterations in social attention may be infant endophenotypes of social motivation traits related to ASD. © 2016 Association for Child and Adolescent Mental Health.

Intra-Individual Response Variability Assessed by Ex-Gaussian Analysis may be a New Endophenotype for Attention-Deficit/Hyperactivity Disorder.

PubMed

Henríquez-Henríquez, Marcela Patricia; Billeke, Pablo; Henríquez, Hugo; Zamorano, Francisco Javier; Rothhammer, Francisco; Aboitiz, Francisco

2014-01-01

Intra-individual variability of response times (RTisv) is considered as potential endophenotype for attentional deficit/hyperactivity disorder (ADHD). Traditional methods for estimating RTisv lose information regarding response times (RTs) distribution along the task, with eventual effects on statistical power. Ex-Gaussian analysis captures the dynamic nature of RTisv, estimating normal and exponential components for RT distribution, with specific phenomenological correlates. Here, we applied ex-Gaussian analysis to explore whether intra-individual variability of RTs agrees with criteria proposed by Gottesman and Gould for endophenotypes. Specifically, we evaluated if normal and/or exponential components of RTs may (a) present the stair-like distribution expected for endophenotypes (ADHD > siblings > typically developing children (TD) without familiar history of ADHD) and (b) represent a phenotypic correlate for previously described genetic risk variants. This is a pilot study including 55 subjects (20 ADHD-discordant sibling-pairs and 15 TD children), all aged between 8 and 13 years. Participants resolved a visual Go/Nogo with 10% Nogo probability. Ex-Gaussian distributions were fitted to individual RT data and compared among the three samples. In order to test whether intra-individual variability may represent a correlate for previously described genetic risk variants, VNTRs at DRD4 and SLC6A3 were identified in all sibling-pairs following standard protocols. Groups were compared adjusting independent general linear models for the exponential and normal components from the ex-Gaussian analysis. Identified trends were confirmed by the non-parametric Jonckheere-Terpstra test. Stair-like distributions were observed for μ (p = 0.036) and σ (p = 0.009). An additional "DRD4-genotype" × "clinical status" interaction was present for τ (p = 0.014) reflecting a possible severity factor. Thus, normal and exponential RTisv components are suitable as ADHD endophenotypes.

Infant social attention: an endophenotype of ASD-related traits?

PubMed Central

Jones, Emily J.H.; Venema, Kaitlin; Earl, Rachel K.; Lowy, Rachel; Webb, Sara J.

2018-01-01

Background As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child’s environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics. Endophenotypes are quantitative, heritable, trait-related differences that are generally assessed with laboratory-based methods, can be identified in the general population, and may be more closely tied to particular causal chains that have a more restricted set of genetic roots. The most fruitful endophenotypes may be those observed in infancy, prior to the emergence of behavioral symptoms that they are hypothesized to cause. Social motivation is an ASD-related trait that is highly heritable. In this study, we investigate whether infant endophenotypes of social attention relate to familial risk for lower social motivation in the general population. Methods We examined whether infant social attention (measured using habituation, EEG power, and event-related potential tasks previously used in infants/toddlers with ASD) varies quantitatively with parental social motivation in 117 six-month-old and 106 twelve-month-old typically developing infants assessed cross-sectionally. To assess heritable aspects of social motivation, primary caregiver biological parents completed two self-report measures of social avoidance and discomfort that have shown high heritability in previous work. Results Parents with higher social discomfort and avoidance had infants who showed shorter looks to faces but not objects; reduced theta power during naturalistic social attention; and smaller P400 responses to faces versus objects. Conclusions Early reductions in social attention are continuously related to lower parental social motivation. Alterations in social attention may be infant endophenotypes of social motivation traits related to ASD. PMID:27861851

Size Estimation in Schizophrenic and Nonschizophrenic Subjects

ERIC Educational Resources Information Center

Kopfstein, Joan Held; Neale, John M.

1971-01-01

The results of this study showed no significant differences in the size estimation levels of acute and chronic schizophrenic and nonschizophrenic psychiatric patients. Also, there were no significant differences when these groups were subdivided on the basis of both premorbid adjustment and paranoid status. (Author/CG)

Information Processing by Schizophrenics When Task Complexity Increases

ERIC Educational Resources Information Center

Hirt, Michael; And Others

1977-01-01

The performance of hospitalized paranoid schizophrenics, nonparanoids, and hospitalized controls was compared on motor, perceptual, and cognitive tasks of increasing complexity. The data were examined within the context of comparing differential predictions made by input and central processing theories of information-processing deficit. (Editor)

Comment on Differentiating Paranoid From Nonparanoid Schizophrenics

ERIC Educational Resources Information Center

Calhoun, James F.

1971-01-01

Three methods of differentiating paranoid from nonparanoid schizophrenics were compared using 97 males from a Veterans Administration hospital. Official hospital diagnosis and behavior ratings were found to be significantly correlated, while self-report correlated with neither of the other two techniques. Implications for research are briefly…

Perceived Attitudes of Schizophrenic Inpatients in Relation to Rehospitalization.

ERIC Educational Resources Information Center

Baker, Brian; And Others

1987-01-01

Schizophrenic inpatients who were ready for discharge completed the Influential Relationships Questionnaire, measuring their perceptions of three characteristic attitudes (care, overprotection, and criticism) demonstrated by two influential people in the patients' lives. Readmitted patients rated the second-most influential person higher on the…

The Well Siblings of Schizophrenics.

ERIC Educational Resources Information Center

Samuels, Laurel; Chase, Laura

1979-01-01

Explores the impact of having a schizophrenic sibling. Subjects functioned at high levels of adjustment. Separated from their families, there followed a period of reinvolvement, including responsibility for the ill sibling. Younger siblings expressed guilt over being well, whereas older siblings expressed guilt over earlier sibling rivalry.…

Depressive syndromes among female caregivers of schizophrenic patients in prof. dr. m. ildrem mental hospital medan

NASA Astrophysics Data System (ADS)

Handi, A.; Husada, M. S.; Gultom, D. P.

2018-03-01

Caring for schizophrenic patients can lead to emotional distress. It remains unclear about the level of depressive syndromes among female caregivers of schizophrenic patients. To determine the level of depression among female caregivers of schizophrenic patients. This is a descriptive study with a cross-sectional approach to describe the level of depression of female caregivers in Prof. dr. M. Ildrem Mental Hospital Medan, using HADS instruments. Most age group of caregivers is from age 51-60 years that is 48.15%, caregiver’s work status mostly not works (62.96%), marital status of caregiver mostly is married (59.26%), kinship with most patients are a biological mother (57.41%). Most patient age group is from age below 30 years (50%), work status of most patients is not working (81.48%), marital status of most caregiver is married (83.33%). Mostly of the depressive syndrome is mild depression (42.59%). Mostly of the depressive syndrome is from mild depression.

[Disorders of cognitive activity in schizophrenics].

PubMed

Follin, S; Perrette, J; Sandretto, M

1979-01-01

4 tests are exploring the cognitive activity of 3 groups of persons: normal, mental patients of various types, schizophrenics, homogeneous as far as the I.Q. is concerned (above 110) and education (secondary school, or university). Whereas normal and mental patients give identical results, except that they are worse for the latter, schizophrenics have better success than other patients in two tests of logic-mathematical reasoning and obviously worse in two tests of experimental logic. These results are interpreted in the frame of Piaget's theory as demonstrating the discordance of the very dynamics of schizophrenic thinking whose cognitive activity is at the same time too near to the object by adherence to the perceived structure (too concrete) and too far from it by adherence to formal reasoning schemes acquired under genetic development (too abstract). These results are coherent with clinical features showing that autistic thinking is not only discordant by its contents and its meaning, but also by the formal dynamic patterns of its modus operandi.

Information processing deficits in psychiatric populations: Implications for normal workload assessment

NASA Technical Reports Server (NTRS)

Harvey, Philip D.

1988-01-01

In one study, schizophrenics, bipolar manics, and mentally normal individuals were administered a digit recall task. The total performance of schizophrenics looked much like that of a normal processor under a higher load level. The manics' performance was intermediate. Primary performance was particularly poor among the mentally ill subjects. In a second study, three groups in the same populations as in the first study were asked to shadow and recall verbatim eight descriptive text passages. Distraction effects were found for schizophrenics only in the areas of percentage of words correctly shadowed and recall variables; the two areas were not correlated, however. It appears that, for schizophrenics, distraction disrupts the ability to effectively shadow information to a greater extent than it disrupts the ability to encode information for recall. The two studies imply that capacity-carrying abnormalities that affect the quantity but not the quality of information processing can be useful in pointing to information processing of normal humans under high load conditions.

GABA and homovanillic acid in the plasma of Schizophrenic and bipolar I patients.

PubMed

Arrúe, Aurora; Dávila, Ricardo; Zumárraga, Mercedes; Basterreche, Nieves; González-Torres, Miguel A; Goienetxea, Biotza; Zamalloa, Maria I; Anguiano, Juan B; Guimón, José

2010-02-01

We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research.

Viewing strategies for simple and chimeric faces: an investigation of perceptual bias in normals and schizophrenic patients using visual scan paths.

PubMed

Phillips, M L; David, A S

1997-11-01

Left hemi-face (LHF) perceptual bias of chimeric faces in normal right-handers is well-documented. We investigated mechanisms underlying this by measuring visual scan paths in right-handed normal controls (n = 9) and schizophrenics (n = 8) for simple, full-face photographs and schematic, happy-sad chimeric faces over 5 s. Normals viewed the left side/ LHF first, more so than the right of all stimuli. Schizophrenics viewed the LHF first more than the right of stimuli for which there was a LHF choice of predominant affect. Neither group demonstrated an overall LHF perceptual bias for the chimeric stimuli. Readjustment of the initial LHF bias in controls was probably a result of increased attention to stimulus detail with scanning, whereas the schizophrenics demonstrated difficulty in redirection of the initial focus of attention. The study highlights the role of visual scan paths as a marker of normal and abnormal attentional processes. Copyright 1997 Academic Press.

Long-term outcome of schizoaffective disorder. Are there any differences with respect to schizophrenia?

PubMed

Pinna, Federica; Sanna, Lucia; Perra, Valeria; Pisu Randaccio, Rachele; Diana, Enrica; Carpiniello, Bernardo

2014-01-01

A number of studies suggest that the clinical characteristics and long-term outcome of schizoaffective patients closely resemble those observed in schizophrenia when cases are diagnosed according to DSM criteria. The primary aim was to compare remission and recovery rates in a cohort of chronic schizoaffective and schizophrenic outpatients. A sample of 102 consecutive outpatients, 46 affected by schizophrenia (45.1%, mean age 44.22±9.97 years) and 66 affected by schizoaffective disorder (54.9%, mean age 43.00±9.07 years) was examined in the study. Personal data and psychiatric history were collected according to AMDP system; premorbid assessment was performed by means of PAS. Axis I and II psychiatric diagnosis was confirmed by means of SCID-I and II. Psychopathological status was evaluated by means of PANSS and CGI-SCH scales; neuropsychological evaluation was performed by means of BACS and MMSE; Functioning, subjective well-being and quality of life were respectively evaluated by means of PSP, SWN and WHOQoL-bref. Schizophrenic and schizoaffective patients investigated were characterized by an overlapping age at onset, mean duration of illness, mean duration of untreated psychosis and common sociodemographic characteristics; subjects' cross-sectional psychopathological and neurocognitive profiles were remarkably similar. However, schizoaffective patients are more frequently of the female gender, showing a better social premorbid adjustment and a somewhat more complicated clinical course in terms of more frequent hospitalizations and suicidality; outcome measures are substantially better among schizoaffective patients: rates of clinical remission were 43.5% and 54.5% in schizophrenic and schizoaffective patients, respectively; 13% and 25.8% of schizophrenic and schizoaffective patients, respectively, were considered as functionally remitted; recovery was observed in 6.5% and 22.7% of schizophrenic and schizoaffective patients, respectively; the majority of patients, both schizophrenic and schizoaffective, were taking antipsychotics, mainly atypical, although a significantly higher proportion of schizoaffective subjects were on mood stabilizers, antidepressants and benzodiazepines. Compared to schizophrenic patients, DSM-IV-TR schizoaffective patients may be considered as a subgroup of psychotic patients displaying several specific characteristics in terms of clinical course, clinical and functional outcome and treatment.

Plasma homovanillic acid in schizophrenics: supportive evidence for the two-subtype hypothesis.

PubMed

Chen, T Y; Lee, C F; Lung, F W; Lee, T C; Lin, W L; Hu, W H; Yeh, E K; Chang, W H

1989-06-01

Plasma levels of homovanillic acid (pHVA), a major metabolite of dopamine (DA), were measured in a group of 51 schizophrenic inpatients before and during 6 weeks of neuroleptic treatment. Steady-state plasma drug concentrations were monitored in parallel with pHVA. Good responders (n = 22) had higher pretreatment pHVA levels as compared to poor responders (n = 22). Differential pHVA changes during neuroleptic treatment were also found between each group. The two groups did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, neuroleptic, dose, or plasma drug concentration. Two hypothetical subtypes in the group of schizophrenics were proposed.

Final Report of the Vocational Assessment Project, 1979-80.

ERIC Educational Resources Information Center

Rutgers, The State Univ., New Brunswick, NJ. School of Medicine.

To improve vocational rehabilitation programs for schizophrenic persons, a project sought to design an effective assessment strategy. Inactive records of schizophrenic clients at New Jersey sheltered workshops were examined to determine validity and reliability of assessment instruments being used. General Aptitude Test Battery (GATB) profiles of…

Substance Abuse and Schizophrenia: A Health Maintenance Perspective.

ERIC Educational Resources Information Center

Damron, Susan W.; Simpson, William R.

Abuse of alcohol or other substances by schizophrenic patients seriously undermines effective treatment. To document the extent of substance abuse among schizophrenic patients hospitalized in one Veterans Administration Hospital, medical records of 100 patients were reviewed. The results revealed that 54 patients had recent substance abuse, with…

Hypothesizing dopaminergic genetic antecedents in schizophrenia and substance seeking behavior.

PubMed

Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra D; Palomo, Tomas; Gold, Mark S

2014-05-01

The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta-analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non-SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Smoking improves divided attention in schizophrenia.

PubMed

Ahlers, Eike; Hahn, Eric; Ta, Thi Minh Tam; Goudarzi, Elnaz; Dettling, Michael; Neuhaus, Andres H

2014-10-01

Smoking is highly prevalent in schizophrenia, and there is evidence for beneficial effects on neurocognition. Smoking is therefore hypothesized a self-medication in schizophrenia. Although much effort is devoted to characterize those cognitive domains that potentially benefit from smoking, divided attention has not yet been investigated. The aim of this study was to analyze the interactional effects of diagnosis of schizophrenia and smoking history on divided attention. We investigated behavioral measures of divided attention in a sample of 48 schizophrenic patients and 48 controls (24 current smokers and non-smokers each) carefully matched for age, sex, education, verbal IQ, and smoking status with general linear models. Most important within the scope of this study, significant interactions were found for valid reactions and errors of omission: Performance substantially increased in smoking schizophrenic patients, but not in controls. Further, these interactions were modified by sex, driven by female schizophrenic patients who showed a significant behavioral advantage of smokers over non-smokers, other than male schizophrenic patients or healthy controls who did not express this sex-specific pattern. Results suggest a positive effect of smoking history on divided attention in schizophrenic patients. This study provides first evidence that the complex attention domain of divided attention is improved by smoking, which further substantiates the self-medication hypothesis of smoking in schizophrenia, although this has been shown mainly for sustained and selective attention. Gender-specific effects on cognition need to be further investigated.

Hypothesizing Dopaminergic Genetic Antecedents in Schizophrenia and Substance Seeking Behavior

PubMed Central

Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra; Palomo, Tomas; Gold, Mark S.

2014-01-01

The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta- analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non- SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis.. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. PMID:24636783

Eye movements during the Rorschach test in schizophrenia.

PubMed

Hori, Yasuko; Fukuzako, Hiroshi; Sugimoto, Yoko; Takigawa, Morikuni

2002-08-01

In order to understand relationships between scanning behaviors, characteristics of visual stimuli and the clinical symptoms in schizophrenia, eye movements of 37 schizophrenic patients and 36 controls were recorded using an eye-mark recorder during a free-response period in a Rorschach test. Four cards (I, II, V and VIII) were used. Data were analyzed during 15 s from the presentation of each card. For all cards, the number of eye fixations and the number of eye fixation areas were fewer, and total scanning length and mean scanning length were shorter for schizophrenic patients than for controls. For card II, in the non-popular response group, eye fixation frequency upon area 5 + 6 (red) was higher for schizophrenic patients. For card VIII, in the popular response group, eye fixation frequency upon area 5 + 6 (pink) was lower for schizophrenic patients. For cards II and VIII, the number of eye fixations was inversely correlated with negative symptoms. For card II, total scanning length tended to be inversely correlated with negative symptoms, and mean eye fixation time was correlated with negative symptoms. The number of eye fixation areas was inversely correlated with positive symptoms. For card VIII, eye fixation frequency in a stimulative area tended to be correlated with positive symptoms. Scanning behaviors in schizophrenic patients are affected by characteristics of visual stimuli, and partially by clinical symptoms.

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

PubMed Central

Pineda, David A.; Lopera, Francisco; Puerta, Isabel C.; Trujillo-Orrego, Natalia; Aguirre-Acevedo, Daniel C.; Hincapié-Henao, Liliana; Arango, Clara P.; Acosta, Maria T.; Holzinger, Sandra I.; Palacio, Juan David; Pineda-Alvarez, Daniel E.; Velez, Jorge I.; Martinez, Ariel F.; Lewis, John E.

2014-01-01

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association. PMID:21779842

Interference Effects in Schizophrenic Short-Term Memory

ERIC Educational Resources Information Center

Bauman, Edward; Kolisnyk, Eugene

1976-01-01

Assesses the effects of input and output interference on schizophrenic recall. Input interference is the interference resulting from the interpolation of items between presentation and recall of the probed item. Output interference is the interference resulting from the interpolation of responses between the presentation and recall of the probed…

HIGH SCHOOL STUDENTS WHO LATER BECAME SCHIZOPHRENIC.

ERIC Educational Resources Information Center

BOWER, ELI M.; AND OTHERS

THE STUDY IDENTIFIED A GROUP OF 44 INSTITUTIONALIZED MALE SCHIZOPHRENIC PATIENTS AGED 19 TO 26 AND SURVEYED DESCRIPTIONS OF THEIR HIGH SCHOOL BEHAVIOR FOR PREDICTIVE SYMPTOMS. INTERVIEWS USING AN 18-ITEM BEHAVIOR RATING FORM WERE CONDUCTED WITH THE PATIENTS' FORMER HIGH SCHOOL TEACHERS. CONTROL SUBJECTS WERE ALSO RATED. ADDITIONAL DATA WERE…

A Study of Childhood Social Competence, Adult Premorbid Competence, and Psychiatric Outcome in Three Schizophrenic Subtypes

ERIC Educational Resources Information Center

Lewine, R. J.; And Others

1978-01-01

School and hospital records were used to examine childhood social competence, adult premorbid competence, and psychiatric outcome in adult schizoaffective, paranoid, and undifferentiated schizophrenics. A significant difference existed in childhood interpersonal competence and adult social competence among the subtypes. Results reflect…

Schizophrenics for Whom Phenothiazines May Be Contraindicated or Unnecessary.

ERIC Educational Resources Information Center

Rappaport, Maurice; And Others

In this study of young male schizophrenic patients who reported they were not taking antipsychotic medication at follow-up, those treated with placebos in contrast to those treated with chlorpromazine while hospitalized showed significantly greater long term clinical improvement, less pathology at follow-up, fewer rehospitalizations and better…

Schizophrenia: A Cognitive Model and Its Implications for Psychological Intervention.

ERIC Educational Resources Information Center

Hemsley, David R.

1996-01-01

Proposes a cognitive model of schizophrenia stating that schizophrenic behavior is caused by a disturbance in sensory input and stored material integration. Cites research to support this model. Outlines the manner in which a disturbance in sensory input integration relates to schizophrenic symptoms and discusses the model's relevance for…

Work History of Schizophrenics and Alcoholics

ERIC Educational Resources Information Center

Gregory, Caesar C.; Downie, N. M.

1970-01-01

Data were obtained from 308 alcoholic and 297 schizophrenics on the following variables: age, hospitalizations, funds, education, number and quality of jobs, time longest job held, placement related to past work, and marital status. Results pointed to new insights into the working behavior and social adjustment of the two groups. (Author)

Sensory Integration and Ego Development in a Schizophrenic Adolescent Male.

ERIC Educational Resources Information Center

Pettit, Karen A.

1987-01-01

A retrospective study compared hours spent by a schizophrenic adolescent in "time out" before and after initiation of treatment. The study evaluated the effects of sensory integrative treatment on the ability to handle anger and frustration. Results demonstrate the utility of statistical analysis versus visual comparison to validate effectiveness…

Multiple Group Counseling with Discharged Schizophrenic Adolescents and their Parents.

ERIC Educational Resources Information Center

Lurie, Abraham; Harold, Ron

Discharged adolescent schizophrenics (17) and their families participated in a pilot program of multiple group counseling, planned to help ex-patients reintegrate into the community. Patients were selected prior to discharge and randomly divided into three multiple-family groups. Each participating family had had a severe breakdown in the…

Referent Communication in Chronic Schizophrenia

ERIC Educational Resources Information Center

Kantorowitz, David A.; Cohen, Bertram D.

1977-01-01

Thirty chronic schizophrenics (15 process and 15 reactive) and 15 normal control speakers described colors displayed in three-chip sets containing a referent and two nonreferent colors. Concludes that poor communication accuracy in long-term schizophrenics results from failure to include a self-editing stage as a part of the communication process.…

Recognition of facial emotion and affective prosody in children with ASD (+ADHD) and their unaffected siblings.

PubMed

Oerlemans, Anoek M; van der Meer, Jolanda M J; van Steijn, Daphne J; de Ruiter, Saskia W; de Bruijn, Yvette G E; de Sonneville, Leo M J; Buitelaar, Jan K; Rommelse, Nanda N J

2014-05-01

Autism is a highly heritable and clinically heterogeneous neuropsychiatric disorder that frequently co-occurs with other psychopathologies, such as attention-deficit/hyperactivity disorder (ADHD). An approach to parse heterogeneity is by forming more homogeneous subgroups of autism spectrum disorder (ASD) patients based on their underlying, heritable cognitive vulnerabilities (endophenotypes). Emotion recognition is a likely endophenotypic candidate for ASD and possibly for ADHD. Therefore, this study aimed to examine whether emotion recognition is a viable endophenotypic candidate for ASD and to assess the impact of comorbid ADHD in this context. A total of 90 children with ASD (43 with and 47 without ADHD), 79 ASD unaffected siblings, and 139 controls aged 6-13 years, were included to test recognition of facial emotion and affective prosody. Our results revealed that the recognition of both facial emotion and affective prosody was impaired in children with ASD and aggravated by the presence of ADHD. The latter could only be partly explained by typical ADHD cognitive deficits, such as inhibitory and attentional problems. The performance of unaffected siblings could overall be considered at an intermediate level, performing somewhat worse than the controls and better than the ASD probands. Our findings suggest that emotion recognition might be a viable endophenotype in ASD and a fruitful target in future family studies of the genetic contribution to ASD and comorbid ADHD. Furthermore, our results suggest that children with comorbid ASD and ADHD are at highest risk for emotion recognition problems.

Neuropsychological Endophenotype Approach to Genome-wide Linkage Analysis Identifies Susceptibility Loci for ADHD on 2q21.1 and 13q12.11

PubMed Central

Rommelse, Nanda N.J.; Arias-Vásquez, Alejandro; Altink, Marieke E.; Buschgens, Cathelijne J.M.; Fliers, Ellen; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Sergeant, Joseph A.; Oosterlaan, Jaap; Franke, Barbara

2008-01-01

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores ≥ 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders. PMID:18599010

Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission

PubMed Central

Scoriels, L; Salek, R M; Goodby, E; Grainger, D; Dean, A M; West, J A; Griffin, J L; Suckling, J; Nathan, P J; Lennox, B R; Murray, G K; Bullmore, E T; Jones, P B

2015-01-01

Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders. PMID:25826115

Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models

PubMed Central

Carmen Arenas, M.; Aguilar, María A.; Montagud-Romero, Sandra; Mateos-García, Ana; Navarro-Francés, Concepción I.; Miñarro, José; Rodríguez-Arias, Marta

2016-01-01

Novelty seeking (NS), defined as a tendency to pursue novel and intense emotional sensations and experiences, is one of the most relevant individual factors predicting drug use among humans. High novelty seeking (HNS) individuals present an increased risk of drug use compared to low novelty seekers. The NS endophenotype may explain some of the differences observed among individuals exposed to drugs of abuse in adolescence. However, there is little research about the particular response of adolescents to drugs of abuse in function of this endophenotype, and the data that do exist are inconclusive. The present work reviews the literature regarding the influence of NS on psychostimulant reward, with particular focus on adolescent subjects. First, the different animal models of NS and the importance of this endophenotype in adolescence are discussed. Later, studies that have used the most common animal models of reward (self-administration, conditioned place preference paradigms) to evaluate how the NS trait influences the rewarding effects of psychostimulants are reviewed. Finally, possible explanations for the enhanced risk of developing substance dependence among HNS individuals are discussed. In conclusion, the studies referred to in this review show that the HNS trait is associated with: (1) increased initial sensitivity to the rewarding effects of psychostimulants, (2) a higher level of drug craving when the subject is exposed to the environmental cues associated with the drug, and (3) enhanced long-term vulnerability to relapse to drug consumption after prolonged abstinence. PMID:26391743

Motor sequencing deficit as an endophenotype of speech sound disorder: a genome-wide linkage analysis in a multigenerational family.

PubMed

Peter, Beate; Matsushita, Mark; Raskind, Wendy H

2012-10-01

The aim of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were carried out using a genome-wide panel of 404 microsatellites. In seven of the 10 family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect the component traits of language impairment. The results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification.

Motor sequencing deficit as an endophenotype of speech sound disorder: A genome-wide linkage analysis in a multigenerational family

PubMed Central

Peter, Beate; Matsushita, Mark; Raskind, Wendy H.

2012-01-01

Objectives The purpose of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. Methods In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were conducted using a genome-wide panel of 404 microsatellites. Results In seven of the ten family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect component traits of language impairment. Conclusions Results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification. PMID:22517379

A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity.

PubMed

Wang, Lien; Alachkar, Amal; Sanathara, Nayna; Belluzzi, James D; Wang, Zhiwei; Civelli, Olivier

2015-05-19

Modulating the methylation process induces broad biochemical changes, some of which may be involved in schizophrenia. Methylation is in particular central to epigenesis, which is also recognized as a factor in the etiology of schizophrenia. Because methionine administration to patients with schizophrenia has been reported to exacerbate their psychotic symptoms and because mice treated with methionine exhibited social deficits and prepulse inhibition impairment, we investigated whether methionine administration could lead to behavioral changes that reflect schizophrenic symptoms in mice. l-Methionine was administered to mice twice a day for 7 days. We found that this treatment induces behavioral responses that reflect the 3 types of schizophrenia-like symptoms (positive, negative, or cognitive deficits) as monitored in a battery of behavioral assays (locomotion, stereotypy, social interaction, forced swimming, prepulse inhibition, novel object recognition, and inhibitory avoidance). Moreover, these responses were differentially reversed by typical haloperidol and atypical clozapine antipsychotics in ways that parallel their effects in schizophrenics. We thus propose the l-methionine treatment as an animal model recapitulating several symptoms of schizophrenia. We have established the face and predictive validity for this model. Our model relies on an essential natural amino acid and on an intervention that is relatively simple and time effective and may offer an additional tool for assessing novel antipsychotics. © The Author 2015. Published by Oxford University Press on behalf of CINP.

The face and its emotion: right N170 deficits in structural processing and early emotional discrimination in schizophrenic patients and relatives.

PubMed

Ibáñez, Agustín; Riveros, Rodrigo; Hurtado, Esteban; Gleichgerrcht, Ezequiel; Urquina, Hugo; Herrera, Eduar; Amoruso, Lucía; Reyes, Migdyrai Martin; Manes, Facundo

2012-01-30

Previous studies have reported facial emotion recognition impairments in schizophrenic patients, as well as abnormalities in the N170 component of the event-related potential. Current research on schizophrenia highlights the importance of complexly-inherited brain-based deficits. In order to examine the N170 markers of face structural and emotional processing, DSM-IV diagnosed schizophrenia probands (n=13), unaffected first-degree relatives from multiplex families (n=13), and control subjects (n=13) matched by age, gender and educational level, performed a categorization task which involved words and faces with positive and negative valence. The N170 component, while present in relatives and control subjects, was reduced in patients, not only for faces, but also for face-word differences, suggesting a deficit in structural processing of stimuli. Control subjects showed N170 modulation according to the valence of facial stimuli. However, this discrimination effect was found to be reduced both in patients and relatives. This is the first report showing N170 valence deficits in relatives. Our results suggest a generalized deficit affecting the structural encoding of faces in patients, as well as the emotion discrimination both in patients and relatives. Finally, these findings lend support to the notion that cortical markers of facial discrimination can be validly considered as vulnerability markers. © 2011 Elsevier Ireland Ltd. All rights reserved.

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

PubMed Central

Fineberg, Naomi A; Potenza, Marc N; Chamberlain, Samuel R; Berlin, Heather A; Menzies, Lara; Bechara, Antoine; Sahakian, Barbara J; Robbins, Trevor W; Bullmore, Edward T; Hollander, Eric

2010-01-01

Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field. PMID:19940844

[Development of a proverb test for assessment of concrete thinking problems in schizophrenic patients].

PubMed

Barth, A; Küfferle, B

2001-11-01

Concretism is considered an important aspect of schizophrenic thought disorder. Traditionally it is measured using the method of proverb interpretation, in which metaphoric proverbs are presented with the request that the subject tell its meaning. Interpretations are recorded and scored on concretistic tendencies. However, this method has two problems: its reliability is doubtful and it is rather complicated to perform. In this paper, a new version of a multiple choice proverb test is presented which can solve these problems in a reliable and economic manner. Using the new test, it is has been shown that schizophrenic patients have greater deficits in proverb interpretation than depressive patients.

Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.

PubMed

Chen, Rui; Davis, Lea K; Guter, Stephen; Wei, Qiang; Jacob, Suma; Potter, Melissa H; Cox, Nancy J; Cook, Edwin H; Sutcliffe, James S; Li, Bingshan

2017-01-01

Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown. In this study, pursuing the hypothesis that de novo variants (DNVs) and rare risk alleles acting in a recessive mode may play an important role in predisposition of hyperserotonemia in people with ASD, we carried out whole exome sequencing (WES) in 116 ASD parent-proband trios with most (107) probands having 5-HT measurements. Combined with published ASD DNVs, we identified USP15 as having recurrent de novo loss of function mutations and discovered evidence supporting two other known genes with recurrent DNVs ( FOXP1 and KDM5B ). Genes harboring functional DNVs significantly overlap with functional/disease gene sets known to be involved in ASD etiology, including FMRP targets and synaptic formation and transcriptional regulation genes. We grouped the probands into High-5HT and Normal-5HT groups based on normalized serotonin levels, and used network-based gene set enrichment analysis (NGSEA) to identify novel hyperserotonemia-related ASD genes based on LoF and missense DNVs. We found enrichment in the High-5HT group for a gene network module (DAWN-1) previously implicated in ASD, and this points to the TGF-β pathway and cell junction processes. Through analysis of rare recessively acting variants (RAVs), we also found that rare compound heterozygotes (CHs) in the High-5HT group were enriched for loci in an ASD-associated gene set. Finally, we carried out rare variant group-wise transmission disequilibrium tests (gTDT) and observed significant association of rare variants in genes encoding a subset of the serotonin pathway with ASD. Our study identified USP15 as a novel gene implicated in ASD based on recurrent DNVs. It also demonstrates the potential value of 5-HT as an effective endophenotype for gene discovery in ASD, and the effectiveness of this strategy needs to be further explored in studies of larger sample sizes.

A Weight-Reduction Program for Schizophrenic Patients on a Token Economy Unit: Two Case Studies

ERIC Educational Resources Information Center

Upper, Dennis; Newton, Judith G.

1971-01-01

Overweight patients on a token economy psychiatric ward were reinforced with tokens, off ward privileges and social approval for meeting a weight loss criterion of three pounds per week. The progress of two subjects, both chronic paranoid schizophrenics, is described. The procedure appears to be effective. (Author)

Context, Cortex, and Dopamine: A Connectionist Approach to Behavior and Biology in Schizophrenia.

ERIC Educational Resources Information Center

Cohen, Jonathan D.; Servan-Schreiber, David

1992-01-01

Using a connectionist framework, it is possible to develop models exploring effects of biologically relevant variables on behavior. The ability of such models to explain schizophrenic behavior in terms of biological disturbances is considered, and computer models are presented that simulate normal and schizophrenic behavior in an attentional task.…

Therapeutic Relationship of A-B Therapists as Perceived by Client and Therapist

ERIC Educational Resources Information Center

Bednar, Richard L.

1970-01-01

Analysis of variance was employed to evaluate the therapeutic relationship offered to schizophrenic and psychoneurotic patients by A-B type therapists. Results are discussed in context of the Whitehorn-Betz original claim that the differential therapeutic success of A-B type therapists with schizophrenic and psychoneurotic clients are a function…

Schizophrenia--A High-Risk Factor for Suicides: Clues to Risk Reduction.

ERIC Educational Resources Information Center

Caldwell, Constance B.; Gottesman, Irving I.

1992-01-01

Notes that suicide is chief cause of premature death among schizophrenic persons, with lifetime incidence of suicide for patients with schizophrenia at 10-13% compared to general population estimate of 1%. Discusses salient risk factors for suicide in schizophrenics and types of especially vulnerable patients identified by research. Notes that…

Internalized Stigma of Mental Illness among Schizophrenic Patients and Their Families (Comparative Study)

ERIC Educational Resources Information Center

Mahmoud, Sahar; Zaki, Rania A.

2015-01-01

This study was a comparative study aiming to assess the extent of internalized stigma of mental illness among patients with schizophrenia & identify stigma as perceived by family members caring schizophrenic patients. The study was conducted in two settings 1st clinic was outpatient clinic for psychiatric patient affiliated to Abbasia…

Dysfluent Handwriting in Schizophrenic Outpatients.

PubMed

Gawda, Barbara

2016-04-01

Taking into account findings in the literature, the author aimed to test whether specific graphical characteristics of handwriting can distinguish patients diagnosed with schizophrenic disorders from healthy controls. Handwriting samples (one sample from each person) from 60 outpatients (29 women, 31 men; age M = 28.5, SD = 5.4) with paranoid schizophrenia were analyzed by three documents examiners and were compared to samples from 60 controls (30 men, 30 women, age M = 28.0, SD = 3.0) without psychiatric disorders. Document examiners assessed 32 graphical features potentially related to schizophrenia. The comparisons between groups revealed that only 7 out of 32 handwriting properties were significantly different in the handwriting of schizophrenic outpatients from controls: the calligraphic forms of letters, loops in ovals, lacking of dots, tremor, sinusoidal baseline, and irregularities size of lower zone. These findings are discussed in terms of motor disturbances in schizophrenia and in relation to the previous research on handwriting of other mental disorders. Similarities between the graphical patterns of handwriting of schizophrenic patients and those of other mental disorders and/or other mental states have been demonstrated. © The Author(s) 2016.

The relationship between intelligence and cognitive function in schizophrenic

NASA Astrophysics Data System (ADS)

Catherine; Amin, M. M.; Effendy, E.

2018-03-01

The most common of psychotic disorders is schizophrenia. While evaluating the cognitive function with a standardized test, the intelligence test is by using the IQ test. For schizophrenic patients, intelligence is usually reported to be lower than average. This research is an analytical study that commenced in January and ended in March 2014. Primary criteria are schizophrenics who are in-patients in Prof. dr. M. Ildrem Mental Hospital, aged between 15 to 55 years old, with the highest qualification of secondary high school. The secondary criteria are those patients with other psychotic disorders, head injuries and other neurological disorders, endocrine disorders. The total sample is 100 subjects. From this study, the correlation value is 0.876 shows a very strong correlation. And the p-value 0.001.The results of this study show that there is a direct correlation (p=0.001) and a correlation (r=0.876) between intelligence and cognitive function on schizophrenic. And it is also necessary to do more researches by using other rating scales and examination to measure the relationship between intelligence and cognitive function, and other factors that may affect results.

Exploratory eye movements to pictures in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

PubMed

Karatekin, C; Asarnow, R F

1999-02-01

We investigated exploratory eye movements to thematic pictures in schizophrenic, attention-deficit/hyperactivity disorder (ADHD), and normal children. For each picture, children were asked three questions varying in amount of structure. We tested if schizophrenic children would stare or scan extensively and if their scan patterns were differentially affected by the question. Time spent viewing relevant and irrelevant regions, fixation duration (an estimate of processing rate), and distance between fixations (an estimate of breadth of attention) were measured. ADHD children showed a trend toward shorter fixations than normals on the question requiring the most detailed analysis. Schizophrenic children looked at fewer relevant, but not more irrelevant, regions than normals. They showed a tendency to stare more when asked to decide what was happening but not when asked to attend to specific regions. Thus, lower levels of visual attention (e.g., basic control of eye movements) were intact in schizophrenic children. In contrast, they had difficulty with top-down control of selective attention in the service of self-guided behavior.

Maoa and Maob polymorphisms and personality traits in suicide attempters and healthy controls: a preliminary study.

PubMed

Balestri, Martina; Calati, Raffaella; Serretti, Alessandro; Hartmann, Annette M; Konte, Bettina; Friedl, Marion; Giegling, Ina; Rujescu, Dan

2017-03-01

Serotonergic neurotransmission dysfunctions have been well documented in patients with suicidal behaviour. We investigated monoamine oxidase A (MAOA: rs2064070, rs6323, rs909525) and B (MAOB: rs1799836, rs2311013, rs2205655) genetic modulation of personality traits (Temperament and Character Inventory, TCI) as endophenotype for suicidal behaviour. 108 suicide attempters and 286 healthy controls of German origin were screened. Among females, allelic analyses revealed associations between MAOA rs6323 A allele and higher Harm Avoidance in suicide attempters and MAOB rs2205655 A allele and higher Cooperativeness scores in healthy controls. Among males, MAOA rs909525 A allele was associated with higher Reward Dependence in suicide attempters. Multivariate analyses controlling for age and educational level mainly confirmed results. Case-control analyses in this subsample do not differ from our previously reported one. Despite of the small sample size, a possible involvement of these genes in the modulation of personality traits closely related to suicidal behaviour cannot be excluded. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Implicit and explicit learning in schizophrenics treated with olanzapine and with classic neuroleptics.

PubMed

Stevens, Andreas; Schwarz, Jürgen; Schwarz, Benedikt; Ruf, Ilona; Kolter, Thomas; Czekalla, Joerg

2002-03-01

Novel and classic neuroleptics differ in their effects on limbic striatal/nucleus accumbens (NA) and prefrontal cortex (PFC) dopamine turnover, suggesting differential effects on implicit and explicit learning as well as on anhedonia. The present study investigates whether such differences can be demonstrated in a naturalistic sample of schizophrenic patients. Twenty-five inpatients diagnosed with DSM-IV schizophrenic psychosis and treated for at least 14 days with the novel neuroleptic olanzapine were compared with 25 schizophrenics taking classic neuroleptics and with 25 healthy controls, matched by age and education level. PFC/NA-dependent implicit learning was assessed by a serial reaction time task (SRTT) and compared with cerebellum-mediated classical eye-blink conditioning and explicit visuospatial memory. Anhedonia was measured with the Snaith-Hamilton-Pleasure Scale (SHAPS). Implicit (SRTT) and psychomotor speed, but not explicit (visuospatial) learning were superior in the olanzapine-treated group as compared to the patients on classic neuroleptics. Compared to healthy controls, olanzapine-treated schizophrenics showed similar implicit learning, but reduced explicit (visuospatial) memory performance. Acquisition of eyeblink conditioning was not different between the three groups. There was no difference with regard to anhedonia and SANS scores between the patients. Olanzapine seems to interfere less with unattended learning and motor speed than classical neuroleptics. In daily life, this may translate into better adaptation to a rapidly changing environment. The effects seem specific, as in explicit learning and eyeblink conditioning no difference to classic NL was found.

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

PubMed

Emri, Miklós; Glaub, Teodóra; Berecz, Roland; Lengyel, Zsolt; Mikecz, Pál; Repa, Imre; Bartók, Eniko; Degrell, István; Trón, Lajos

2006-05-01

Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory "oddball" paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [15O]-butanol activity changes in the PET camera was recorded. Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area - BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area - and consequently a larger variety of neuronal networks--is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.

Impairment of perception and recognition of faces, mimic expression and gestures in schizophrenic patients.

PubMed

Berndl, K; von Cranach, M; Grüsser, O J

1986-01-01

The perception and recognition of faces, mimic expression and gestures were investigated in normal subjects and schizophrenic patients by means of a movie test described in a previous report (Berndl et al. 1986). The error scores were compared with results from a semi-quantitative evaluation of psychopathological symptoms and with some data from the case histories. The overall error scores found in the three groups of schizophrenic patients (paranoic, hebephrenic, schizo-affective) were significantly increased (7-fold) over those of normals. No significant difference in the distribution of the error scores in the three different patient groups was found. In 10 different sub-tests following the movie the deficiencies found in the schizophrenic patients were analysed in detail. The error score for the averbal test was on average higher in paranoic patients than in the two other groups of patients, while the opposite was true for the error scores found in the verbal tests. Age and sex had some impact on the test results. In normals, female subjects were somewhat better than male. In schizophrenic patients the reverse was true. Thus female patients were more affected by the disease than male patients with respect to the task performance. The correlation between duration of the disease and error score was small; less than 10% of the error scores could be attributed to factors related to the duration of illness. Evaluation of psychopathological symptoms indicated that the stronger the schizophrenic defect, the higher the error score, but again this relationship was responsible for not more than 10% of the errors. The estimated degree of acute psychosis and overall sum of psychopathological abnormalities as scored in a semi-quantitative exploration did not correlate with the error score, but with each other. Similarly, treatment with psychopharmaceuticals, previous misuse of drugs or of alcohol had practically no effect on the outcome of the test data. The analysis of performance and test data of schizophrenic patients indicated that our findings are most likely not due to a "non-specific" impairment of cognitive function in schizophrenia, but point to a fairly selective defect in elementary cognitive visual functions necessary for averbal social communication. Some possible explanations of the data are discussed in relation to neuropsychological and neurophysiological findings on "face-specific" cortical areas located in the primate temporal lobe.

CHRONIC SCHIZOPHRENIA—A PSYCHOPHARMACOLOGICAL APROACH1

PubMed Central

Ban, Thomas A.; Guy, William; Prakash, Rudra

1984-01-01

SUMMARY Our work suggests that the Leonhard classification system holds much pron.ise as a framework for future neurological development. One might speculate along biochemical lines that the nonsystematic subpopulation of schizophrenics may suffer from altered dopamine β-hydroxylase activity which results in an excess of dopamine, This would eeplain why this class responds so well to dopamine receptor blocking agent when other patient do not. One might also speculate tint we are dealing with a number of diseases-each with different courses and progressing to different end states, but all with common pattern during the acute stage, e.g., increased dopamine levels or receptor sensitivity levels. This is probably why the acute stage can usually be controlled by the administration of a dopamine receptor blocking agent. A further speculation concerns the catatonic patient- who had begun to respond to psychosocial and milieu treatment prior to the introduction of neuroleptics. This particular group of patients do not seem to benefit from prophylactic treatment with neuroleptics. If, by activating a patient, catecholamines are released, it is hypothesized that the Catatonics are a completely separate subpopulation-not just clinically-but also biochemically. Completely different types of drugs may be helpful for the different schizophrenic subpopulations. Among the various substances, propranolol should be considered. Obviously, this drug will not be effective in all schizophrenics; but there arc certain types of patients who respond to β-blockers. There is also increasing evidence that clordine (which stimulates alpha-adrenergic receptors) may also have an effect on certain schizophrenics The most recent findings is that cholecystokinin-thought for Some time to be an exclusively peripheral substance-appears to be present in the brain and available in the form of ceulotide, a neuropeptide which is a dopamine agonist. This susbtance, also, seems to be effective in the treatment of certain schizophrenics. Chronic schizophrenia requires re-evaluation and it should be recognized that different drugs are effective in different types of patients. There is renewed interest in the various schizophrenic conditions and their end states. We must hope that the pharmacologists, provided with sufficient information, will search for new drugs with differentiated activities that will meaningfully influence the end states of schizophrenic disorders and/or prevent their development. PMID:21966007

Partial Genetic Deletion of Neuregulin 1 Modulates the Effects of Stress on Sensorimotor Gating, Dendritic Morphology, and HPA Axis Activity in Adolescent Mice

PubMed Central

Chohan, Tariq W.; Boucher, Aurelie A.; Spencer, Jarrah R.; Kassem, Mustafa S.; Hamdi, Areeg A.; Karl, Tim; Fok, Sandra Y.; Bennett, Maxwell R.; Arnold, Jonathon C.

2014-01-01

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence. PMID:24442851

Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

PubMed Central

Knorr, Ulla; Vinberg, Maj; Klose, Marianne; Feldt-Rasmussen, Ulla; Hilsted, Linda; Gade, Anders; Haastrup, Eva; Paulson, Olaf; Wetterslev, Jørn; Gluud, Christian; Gether, Ulrik; Kessing, Lars

2009-01-01

Background Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention. Methods The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group. Trial registration Local Ethics Committee: H-KF 307413 Danish Medicines Agency: 2612-3162. EudraCT: 2006-001750-28. Danish Data Agency: 2006-41-6737. ClinicalTrials.gov: NCT 00386841 PMID:19671139

Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science.

PubMed

Viswanath, Biju; Rao, Naren P; Narayanaswamy, Janardhanan C; Sivakumar, Palanimuthu T; Kandasamy, Arun; Kesavan, Muralidharan; Mehta, Urvakhsh Meherwan; Venkatasubramanian, Ganesan; John, John P; Mukherjee, Odity; Purushottam, Meera; Kannan, Ramakrishnan; Mehta, Bhupesh; Kandavel, Thennarasu; Binukumar, B; Saini, Jitender; Jayarajan, Deepak; Shyamsundar, A; Moirangthem, Sydney; Vijay Kumar, K G; Thirthalli, Jagadisha; Chandra, Prabha S; Gangadhar, Bangalore N; Murthy, Pratima; Panicker, Mitradas M; Bhalla, Upinder S; Chattarji, Sumantra; Benegal, Vivek; Varghese, Mathew; Reddy, Janardhan Y C; Raghu, Padinjat; Rao, Mahendra; Jain, Sanjeev

2018-04-18

There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer's dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository. The identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo whole exome sequencing. We hope to identify unique and overlapping brain endophenotypes for major psychiatric syndromes. In a proportion of subjects, we expect these neuro-endophenotypes to progress over time and to predict treatment outcome. Similarly, cellular assays could differentiate cell lines derived from such groups. The repository of biomaterials as well as digital datasets of clinical parameters, will serve as a valuable resource for the broader scientific community who wish to address research questions in the area.

Interactional Patterns of Schizophrenic, Depressed and Well Mothers and Their Young Children.

ERIC Educational Resources Information Center

Musick, Judith S.; And Others

This study analyzes the interaction patterns and behavioral characteristics of mentally ill and well mothers and their young children. The children were between 1 and 4 years of age. The group of mentally ill mothers was comprised of 18 schizophrenic and psychotically depressed women each with a history of at least one psychiatric hospitalization.…

Weight reduction in schizophrenics by molindone.

PubMed

Gardos, G; Cole, J O

1977-03-01

The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month. The mechanism producing this weight loss is uncertain, but a central anorexigenic effect may be an important factor.

[Hölderlin--or the question of the meaning of psychosis].

PubMed

Gonther, U; Schlimme, J E

2009-03-01

Friedrich Hölderlin (1770-1843) is one of the most important German poets. Actual research into his life and work has shown new aspects in his thinking concerning questions about subjectivity, sense of life and psychosis. We follow these lines using a hermeneutical method. In his late poems the experience of schizophrenic alienation appears metaphorically speaking like an ebbing of a former plenitude of meanings or as if he were decentered from his own life. Hölderlin names it an "uninvolved" view onto the ordinary life. Hölderlin invites and enables us via his offer for an innerperspective understanding of the schizophrenic experience of alienation to deal fairly and respectfully with schizophrenic patients as if we were "alienists" (E. Straus).

Integrating Behavioral Economics and Behavioral Genetics: Delayed Reward Discounting as an Endophenotype for Addictive Disorders

PubMed Central

MacKillop, James

2013-01-01

Delayed reward discounting is a behavioral economic index of impulsivity, referring to how much an individual devalues a reward based on its delay in time. As a behavioral process that varies considerably across individuals, delay discounting has been studied extensively as a model for self-control, both in the general population and in clinical samples. There is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders (i.e., a heritable mechanism partially responsible for conferring genetic risk). This review assembles and critiques the evidence supporting this hypothesis. Via numerous cross-sectional studies and a small number of longitudinal studies, there is considerable evidence that impulsive discounting is associated with addictive behavior and appears to play an etiological role. Moreover, there is increasing evidence from diverse methodologies that impulsive delay discounting is temporally stable, heritable, and that elevated levels are present in nonaffected family members. These findings suggest that impulsive discounting meets the criteria for being considered an endophenotype. In addition, recent findings suggest that genetic variation related to dopamine neurotransmission is significantly associated with variability in discounting preferences. A significant caveat, however, is that the literature is modest in some domains and, in others, not all the findings have been supportive or consistent. In addition, important methodological considerations are necessary in future studies. Taken together, although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation. PMID:23344986

Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.

PubMed

Glahn, David C; Almasy, Laura; Barguil, Marcela; Hare, Elizabeth; Peralta, Juan Manuel; Kent, Jack W; Dassori, Albana; Contreras, Javier; Pacheco, Adriana; Lanzagorta, Nuria; Nicolini, Humberto; Raventós, Henriette; Escamilla, Michael A

2010-02-01

Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes. To adjudicate neurocognitive endophenotypes for bipolar disorder. All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status. Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas. Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia. Neurocognitive test performance. Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory. This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.

Temperament and character as schizophrenia-related endophenotypes in non-psychotic siblings.

PubMed

Smith, Matthew J; Cloninger, C Robert; Harms, Michael P; Csernansky, John G

2008-09-01

Quantitative endophenotypes are needed to better understand the pathogenesis of schizophrenia. The psychobiological model of temperament and character suggests that personality traits are heritable and regulated by brain systems influencing schizophrenia susceptibility. Thus, measures of temperament and character may serve as schizophrenia-related endophenotypes in individuals with schizophrenia and their non-psychotic siblings. Individuals with schizophrenia (n=35), their non-psychotic siblings (n=34), controls (n=63), and their siblings (n=56) participated in a study of the clinical, neurocognitive and neuromorphological characteristics of schizophrenia. A mixed-model approach assessed group differences on the Temperament and Character Inventory (TCI). Neurocognitive deficits and psychopathology were correlated with the TCI. Configurations of TCI domains were examined using a generalized linear model. Individuals with schizophrenia and their non-psychotic siblings had higher harm avoidance than controls and their siblings. Individuals with schizophrenia had lower self-directedness and cooperativeness, and higher self-transcendence than their non-psychotic siblings, controls, and the siblings of controls. Neurocognition was not related to temperament and character in individuals with schizophrenia or either control group. In non-psychotic siblings, self-directedness and cooperativeness were correlated with working memory and crystallized IQ. Evidence supports harm avoidance as a schizophrenia-related endophenotype. An increased risk of schizophrenia may be associated with asociality (configured as high harm avoidance and low reward dependence), schizotypy (configured as low self-directedness, low cooperativeness, and high self-transcendence), and neurocognitive deficits (poor executive functioning, working/episodic memory, attention, and low IQ). The non-psychotic siblings demonstrated features of a mature character profile including strong crystallized IQ, which may confer protection against psychopathology.

The role of selective estrogen receptor modulators in the treatment of schizophrenia.

PubMed

Bratek, Agnieszka; Krysta, Krzysztof; Drzyzga, Karolina; Barańska, Justyna; Kucia, Krzysztof

2016-09-01

Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention - the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects.

Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.

PubMed

Di Pietro, N C; Seamans, J K

2007-12-01

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study.

PubMed

Kosaka, H; Omori, M; Murata, T; Iidaka, T; Yamada, H; Okada, T; Takahashi, T; Sadato, N; Itoh, H; Yonekura, Y; Wada, Y

2002-09-01

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion. Copyright 2002 Elsevier Science B.V.

Effectiveness of gratitude disposition promotion program on depression and quality of life of chronic schizophrenic patients.

PubMed

Jung, Miran; Han, Kuemsun

2017-01-01

Gratitude intervention is expectedly an effective intervention to reduce depression and improve the quality of life in schizophrenic patients, but there is a lack of literature on it. We attempted to develop and test the effectiveness of the gratitude disposition promotion program for chronic schizophrenic patients in Korea. Nonequivalent control group pre- and post-test design was used in two mental health centers located at Gyeonggi-do in South Korea. This paper was a quasi-experimental study and the participants who took part in the gratitude disposition promotion program were 17 of experimental group and 15 of control group. Gratitude disposition (the short gratitude, resentment, and appreciation test), depression (Beck Depression Inventory), and quality of life (developed by Kook) of chronic schizophrenic patients were measured before and after an intervention, as compared to the control. Chi-square test, Fisher's exact test, and t -test were performed for prehomogeneity testing for variables related to the general characteristics. Testing for the effectiveness of gratitude disposition promotion program and hypothesis testing for its effect on depression and quality of life were by ANCOVA and t -test, as verified to significance level of P < 0.05. The participants who received the gratitude disposition promotion program showed significant improvements in gratitude disposition ( F = 18.740, P < 0.0001) and in quality of life ( F = 9.800, P = 0.004), but no significant difference in depression ( F = 3.870, P = 0.059). The gratitude disposition promotion program was an effective clinical intervention program for enhancing gratitude disposition and quality of life of chronic schizophrenic patients in community.

Effect of age and disease on bone mass in Japanese patients with schizophrenia.

PubMed

Sugawara, Norio; Yasui-Furukori, Norio; Umeda, Takashi; Tsuchimine, Shoko; Fujii, Akira; Sato, Yasushi; Saito, Manabu; Furukori, Hanako; Danjo, Kazuma; Matsuzaka, Masashi; Takahashi, Ippei; Kaneko, Sunao

2012-02-20

There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. We recruited patients (n = 362), aged 48.8 ± 15.4 (mean ± SD) years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI) was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community. Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males. Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.

MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function

PubMed Central

Miller, Brooke H.; Zeier, Zane; Xi, Li; Lanz, Thomas A.; Deng, Shibing; Strathmann, Julia; Willoughby, David; Kenny, Paul J.; Elsworth, John D.; Lawrence, Matthew S.; Roth, Robert H.; Edbauer, Dieter; Kleiman, Robin J.; Wahlestedt, Claes

2012-01-01

Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects. The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects. Consistent with NMDA-mediated hypofunction observed in schizophrenic subjects, administration of an NMDA antagonist to adult mice results in miR-132 down-regulation in the prefrontal cortex. Furthermore, miR-132 expression in the murine prefrontal cortex exhibits significant developmental regulation and overlaps with critical neurodevelopmental processes during adolescence. Adult prefrontal expression of miR-132 can be down-regulated by pharmacologic inhibition of NMDA receptor signaling during a brief postnatal period. Several key genes, including DNMT3A, GATA2, and DPYSL3, are regulated by miR-132 and exhibited altered expression either during normal neurodevelopment or in tissue from adult schizophrenic subjects. Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia. PMID:22315408

BDNF (brain-derived neurotrophic factor) serum levels in schizophrenic patients with cognitive deficits

NASA Astrophysics Data System (ADS)

Utami, N.; Effendy, E.; Amin, M. M.

2018-03-01

Schizophrenia is a complex neurodevelopmental disorder with cognitive impairment as the main part. BDNF regulates aspects of developmental plasticity in the brain and is involved in cognitive function. Cognitive functions include capabilities such as attention, executive functioning, assessing, monitoring and evaluating. The aim of the study was to know the BDNF levels in schizophrenic patients with cognitive deficits. The study was held in October 2016 - March 2017, and was the first in Indonesia, especially in North Sumatra. The study was approved by the medical ethics committee of the University of North Sumatera. The study is descriptive based on a retrospective method with cross-sectional approach. The subject is 40 male schizophrenia. Cognitive deficits were assessed by MoCA-Ina. BDNF serum levels were analyzed using the quantitative sandwich enzyme immunoassay. The average MoCA-Ina score is 21.03±5.21. This suggests that there is a cognitive function deficit in schizophrenic patients. The mean serum BDNF level was 26629±6762. MoCA-Ina scores in schizophrenic patients <26 who experienced a deficit of 77.5% and serum BDNF levels with normal values ranging from 6.186 to 42.580pg/ml.

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

Subverting Space: An Exploration of a Dance Therapy Workshop Apparatus for Schizophrenics.

PubMed

Lippi, Silvia; Petit, Laetitia

2017-04-01

The authors created a dance workshop for schizophrenic patients designed to address their singular experience of space, in which the categories of interior and exterior do not function as limits. The space of the workshop, which, paradoxically, is thought in terms of the psychic space of schizophrenic patients by playing on its borderless quality, creates a continuity between the psychiatric hospital and the external world, and thus helps to prevent the segregation and isolation of such patients. This continuity is established on the basis of both the physical architecture of the workshop setting and the practice of dancing itself. The authors explore the hypothesis that, inside the particular space made possible by the apparatus of the workshop, schizophrenic patients benefit from the experience of movement, beginning with the pulse of rhythm, which establishes a consistency in time. By means of its repetitive character, the beat of music, like movement, accompanies and promotes the experience of continuity, which is the condition for any possible form of symbolizing. Two brief clinical illustrations show how this approach to dance therapy allows a moribund jouissance to be overturned and transformed into the aesthetic jouissance that characterizes the experience of dance.

Performance of the Italian version of the subjective well-being under neuroleptic (SWN) scale in schizophrenic outpatients.

PubMed

Balestrieri, M; Giaroli, G; Mazzi, M; Bellantuono, C

2006-05-01

Several studies indicate that subjective experience toward antipsychotic drugs (APs) in schizophrenic patients is a key factor in ensuring a smooth recovery from the illness. The principal aim of this study was to establish the psychometric performance of the Subjective Well-being Under Neuroleptic (SWN) scale in its Italian version and to assess, through the SWN scale, the subjective experience of stabilized psychotic outpatients in maintenance with APs. The original short version of SWN, consisting of 20 items, was back translated, and a focus group was also conducted to better improve the comprehension of the scale. The results showed a good performance of the Italian version of the SWN as documented by the internal consistency (Cronbach's alpha; 0.85). A satisfactory subjective experience was reported in the sample of schizophrenic outpatients interviewed (SWN mean total score: 84.95, SD: 17.5). The performance of the SWN scale in the present study was very similar to that reported by Naber et al. in the original validation study. Large multi-center studies are needed to better establish differences in the subjective experience of schizophrenic patients treated with first- and second-generation APs.

Intact figure-ground segmentation in schizophrenia.

PubMed

Herzog, Michael H; Kopmann, Sabine; Brand, Andreas

2004-11-30

As revealed by backward masking studies, schizophrenic patients show strong impairments of early visual processing. However, the underlying temporal mechanisms are not yet well understood. To shed light on the exact timing of these deficits, we employed a paradigm in which two masks follow each other. We investigated 16 medicated schizophrenic patients and a matched group of 14 controls with a new backward masking technique, shine-through. In accordance with other masking studies, schizophrenic patients require a dramatically longer processing time to reach a predefined performance level compared with healthy subjects. However, patients are surprisingly sensitive to subtle differences in the timing of the two masks, revealing good temporal resolution. This good temporal resolution indicates intact and fast perceptual grouping and figure-ground segmentation in spite of high susceptibility to masking procedures in schizophrenia.

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.

Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.

PubMed

Khan, R S; Amin, F; Powchik, P; Knott, P; Goldstein, M; Apter, S; Kerman, B; Jaff, S; Davidson, M

1990-01-01

1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

Why Some People Discount More than Others: Baseline Activation in the Dorsal PFC Mediates the Link between COMT Genotype and Impatient Choice

PubMed Central

Gianotti, Lorena R. R.; Figner, Bernd; Ebstein, Richard P.; Knoch, Daria

2012-01-01

Individuals differ widely in how steeply they discount future rewards. The sources of these stable individual differences in delay discounting (DD) are largely unknown. One candidate is the COMT Val158Met polymorphism, known to modulate prefrontal dopamine levels and affect DD. To identify possible neural mechanisms by which this polymorphism may contribute to stable individual DD differences, we measured 73 participants’ neural baseline activation using resting electroencephalogram (EEG). Such neural baseline activation measures are highly heritable and stable over time, thus an ideal endophenotype candidate to explain how genes may influence behavior via individual differences in neural function. After EEG-recording, participants made a series of incentive-compatible intertemporal choices to determine the steepness of their DD. We found that COMT significantly affected DD and that this effect was mediated by baseline activation level in the left dorsal prefrontal cortex (DPFC): (i) COMT had a significant effect on DD such that the number of Val alleles was positively correlated with steeper DD (higher numbers of Val alleles means greater COMT activity and thus lower dopamine levels). (ii) A whole-brain search identified a cluster in left DPFC where baseline activation was correlated with DD; lower activation was associated with steeper DD. (iii) COMT had a significant effect on the baseline activation level in this left DPFC cluster such that a higher number of Val alleles was associated with lower baseline activation. (iv) The effect of COMT on DD was explained by the mediating effect of neural baseline activation in the left DPFC cluster. Our study thus establishes baseline activation level in left DPFC as salient neural signature in the form of an endophenotype that mediates the link between COMT and DD. PMID:22586360

Early social enrichment provided by communal nest increases resilience to depression-like behavior more in female than in male mice.

PubMed

D'Andrea, Ivana; Gracci, Fiorenza; Alleva, Enrico; Branchi, Igor

2010-12-20

Early experiences produce persistent changes in behavior and brain function. Being reared in a communal nest (CN), consisting of a single nest where three mouse mothers keep their pups together and share care-giving behavior from birth to weaning, provides an highly stimulating social environment to the developing pup since both mother-offspring and peer-to-peer interactions are markedly increased. Here we show that being reared in a CN affects adult behavior of CD-1 mice in a gender-dependent fashion, with reduced depression-like responses in females and increased anxiety-like behavior in males. In particular, CN females showed higher sucrose preference at baseline condition, drinking more sweet solution compared to female mice reared in a standard laboratory condition (SN). In the isolation test, both SN and CN females showed a reduction in sucrose preference after exposure to isolation stress. However, after 24h, only CN females significantly recovered. Finally, in the forced swim test, compared to SN, CN females spent longer time floating, a behavioral response that in the CN model has been inversely associated with display of endophenotypes of depression. With regard to the emotional response, CN males displayed an increased anxiety-like behavior in comparison to SN, spending less time in the open arms and displaying reduced head-dippings in the elevated plus-maze test. No difference was found in females. Overall, our findings show that gender and early experiences interact in modulating adult behavior. In particular, we show that early experiences modified developmental trajectories shaping adult endophenotypes of depression more markedly in females than in males. Copyright 2010 Elsevier B.V. All rights reserved.

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.

PubMed

Chen, Andrew C H; Tang, Yongqiang; Rangaswamy, Madhavi; Wang, Jen C; Almasy, Laura; Foroud, Tatiana; Edenberg, Howard J; Hesselbrock, Victor; Nurnberger, John; Kuperman, Samuel; O'Connor, Sean J; Schuckit, Marc A; Bauer, Lance O; Tischfield, Jay; Rice, John P; Bierut, Laura; Goate, Alison; Porjesz, Bernice

2009-04-05

Evidence suggests the P3 amplitude of the event-related potential and its underlying superimposed event-related oscillations (EROs), primarily in the theta (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3-q32.1 under the peak region where we previously identified significant linkage (peak LOD = 3.5) using a genome-wide linkage scan of the same phenotype (event-related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The family-based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event-related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event-related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders. (c) 2008 Wiley-Liss, Inc.

Group II Metabotropic Glutamate Receptors as Targets for Novel Antipsychotic Drugs

PubMed Central

Muguruza, Carolina; Meana, J. Javier; Callado, Luis F.

2016-01-01

Schizophrenia is a chronic psychiatric disorder which substantially impairs patients’ quality of life. Despite the extensive research in this field, the pathophysiology and etiology of schizophrenia remain unknown. Different neurotransmitter systems and functional networks have been found to be affected in the brain of patients with schizophrenia. In this context, postmortem brain studies as well as genetic assays have suggested alterations in Group II metabotropic glutamate receptors (mGluRs) in schizophrenia. Despite many years of drug research, several needs in the treatment of schizophrenia have not been addressed sufficiently. In fact, only 5–10% of patients with schizophrenia successfully achieve a full recovery after treatment. In recent years mGluRs have turned up as novel targets for the design of new antipsychotic medications for schizophrenia. Concretely, Group II mGluRs are of particular interest due to their regulatory role in neurotransmission modulating glutamatergic activity in brain synapses. Preclinical studies have demonstrated that orthosteric Group II mGluR agonists exhibit antipsychotic-like properties in animal models of schizophrenia. However, when these compounds have been tested in human clinical studies with schizophrenic patients results have been inconclusive. Nevertheless, it has been recently suggested that this apparent lack of efficacy in schizophrenic patients may be related to previous exposure to atypical antipsychotics. Moreover, the role of the functional heterocomplex formed by 5-HT2A and mGlu2 receptors in the clinical response to Group II mGluR agonists is currently under study. PMID:27242534

Neurocognitive Endophenotypes for Bipolar Disorder Identified in Multiplex Multigenerational Families

PubMed Central

Glahn, David C.; Almasy, Laura; Barguil, Marcela; Hare, Elizabeth; Peralta, Juan Manuel; Kent, Jack W.; Dassori, Alabana; Contreras, Javier; Pacheco, Adriana; Lanzagorta, Nuria; Nicolini, Humberto; Raventós, Henriette; Escamilla, Michael A.

2012-01-01

Context Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, one strategy for identifying risk genes is the use of quantitative endophenotypes. Objective The goal of the current study is to adjudicate neurocognitive endophenotypes for bipolar disorder. Design, Setting, and Participants 709 Latino individuals from the central valley of Costa Rica, Mexico City, Mexico, or San Antonio, Texas participated in the study. 660 of these persons were members of extended pedigrees with at least two siblings diagnosed with bipolar disorder (n=230). The remaining subjects were community controls drawn from each site and without personal or family history of bipolar disorder or schizophrenia. All subjects received psychodiagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which tests are impaired in affected individuals, sensitive to genetic liability for the illness and genetically correlated with affection status. Main Outcome Measures The main outcome measure was neurocognitive test performance. Results Two of the 21 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 of these cognitive measures compared to non-related healthy subjects. Non-bipolar first-degree relatives were impaired on five of these and three tests were genetically correlated with affection status: digit symbol coding, object delayed response, and immediate facial memory. Conclusions This large-scale extended pedigree study of cognitive functioning in bipolar disorder identified measures of processing speed, working memory and declarative (facial) memory as candidate endophenotypes for bipolar disorder. PMID:20124116

Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder?

PubMed

Van Eylen, Lien; Boets, Bart; Cosemans, Nele; Peeters, Hilde; Steyaert, Jean; Wagemans, Johan; Noens, Ilse

2017-03-01

Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided. For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions. © 2016 Association for Child and Adolescent Mental Health.

Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study.

PubMed

Korgaonkar, Mayuresh S; Ram, Kaushik; Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M

2014-08-01

The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders. Copyright © 2014 Wiley Periodicals, Inc.

Heart rate variability as candidate endophenotype of social anxiety: A two-generation family study.

PubMed

Harrewijn, A; Van der Molen, M J W; Verkuil, B; Sweijen, S W; Houwing-Duistermaat, J J; Westenberg, P M

2018-09-01

Social anxiety disorder (SAD) is the extreme fear and avoidance of one or more social situations. The goal of the current study was to investigate whether heart rate variability (HRV) during resting state and a social performance task (SPT) is a candidate endophenotype of SAD. In this two-generation family study, patients with SAD with their partner and children, and their siblings with partner and children took part in a SPT (total n = 121, 9 families, 3-30 persons per family, age range: 8-61 years, 17 patients with SAD). In this task, participants had to watch and evaluate the speech of a female peer, and had to give a similar speech. HRV was measured during two resting state phases, and during anticipation, speech and recovery phases of the SPT. We tested two criteria for endophenotypes: co-segregation with SAD within families and heritability. HRV did not co-segregate with SAD within families. Root mean square of successive differences during the first resting phase and recovery, and high frequency power during all phases of the task were heritable. It should be noted that few participants were diagnosed with SAD. Results during the speech should be interpreted with caution, because the duration was short and there was a lot of movement. HRV during resting state and the SPT is a possible endophenotype, but not of SAD. As other studies have shown that HRV is related to different internalizing disorders, HRV might reflect a transdiagnostic genetic vulnerability for internalizing disorders. Future research should investigate which factors influence the development of psychopathology in persons with decreased HRV. Copyright © 2018 Elsevier B.V. All rights reserved.

Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

PubMed

Kimmich, Okka; Molloy, Anna; Whelan, Robert; Williams, Laura; Bradley, David; Balsters, Joshua; Molloy, Fiona; Lynch, Tim; Healy, Daniel G; Walsh, Cathal; O'Riordan, Seán; Reilly, Richard B; Hutchinson, Michael

2014-05-01

The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society.

Identification of two heritable cross-disorder endophenotypes for Tourette Syndrome

PubMed Central

Darrow, Sabrina M.; Hirschtritt, Matthew E.; Davis, Lea K.; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L.; Cath, Danielle C.; Greenberg, Erica; Lyon, Gholson J.; Yu, Dongmei; McGrath, Lauren M.; McMahon, William M.; Lee, Paul C.; Delucchi, Kevin L.; Scharf, Jeremiah M.; Mathews, Carol A.

2016-01-01

Objective Phenotypic heterogeneity in Tourette syndrome (TS) is partly due to complex genetic relationships between TS, obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Method 3494 individuals recruited for genetic studies were assessed for TS, OCD, and ADHD symptoms. Symptom-level factor and latent class analyses were conducted in TS families and replicated in an independent sample. Classes were characterized by comorbidity rates and proportion of parents. Heritability and TS-, OCD-, and ADHD-associated polygenic load were estimated. Results We identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high (disinhibition factor= 0.35, SE=0.03, p= 4.2 ×10−34; symmetry factor= 0.39, SE=0.03, p= 7.2 ×10−31; symmetry class=0.38, SE=0.10, p=0.001). Mothers of TS probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a TS genome-wide association study (GWAS) were associated with symmetry (p= 0.02), while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were associated with disinhibition (p =0.03), while TS and ADHD risk scores were not. Conclusions We identified two heritable TS-related endophenotypes that cross traditional diagnostic boundaries. The symmetry phenotype correlated with TS polygenic load, and was present in otherwise “TS-unaffected” mothers, suggesting that this phenotype may reflect additional TS (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses. PMID:27809572

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

PubMed

Darrow, Sabrina M; Hirschtritt, Matthew E; Davis, Lea K; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L; Cath, Danielle C; Greenberg, Erica; Lyon, Gholson J; Yu, Dongmei; McGrath, Lauren M; McMahon, William M; Lee, Paul C; Delucchi, Kevin L; Scharf, Jeremiah M; Mathews, Carol A

2017-04-01

Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated. The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not. The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

Temperament and Character as Schizophrenia-Related Endophenotypes in Non-psychotic Siblings

PubMed Central

Smith, Matthew J.; Cloninger, C. Robert; Harms, Michael P.; Csernansky, John G.

2008-01-01

Background Quantitative endophenotypes are needed to better understand the pathogenesis of schizophrenia. The psychobiological model of temperament and character suggests that personality traits are heritable and regulated by brain systems influencing schizophrenia susceptibility. Thus, measures of temperament and character may serve as schizophrenia-related endophenotypes in individuals with schizophrenia and their non-psychotic siblings. Methods Individuals with schizophrenia (n=35), their non-psychotic siblings (n=34), controls (n=63), and their siblings (n=56) participated in a study of the clinical, cognitive and neuromorphological characteristics of schizophrenia. A mixed-model approach assessed group differences on the Temperament and Character Inventory (TCI). Neurocognitive deficits and psychopathology were correlated with the TCI. Configurations of TCI domains were examined using a generalized linear model. Results Individuals with schizophrenia and their siblings had higher harm avoidance than controls and their siblings. Individuals with schizophrenia had lower self-directedness and cooperativeness, and higher self-transcendence than their non-psychotic siblings, controls, and the siblings of controls. Neurocognition was not related to temperament and character in individuals with schizophrenia or either control group. In non-psychotic siblings, self-directedness and cooperativeness were correlated with working memory and crystallized IQ. Conclusion Evidence supports harm avoidance as a schizophrenia-related endophenotype. An increased risk of schizophrenia may be associated with asociality (configured as high harm avoidance and low reward dependence), schizotypy (configured as low self-directedness, low cooperativeness, and high self-transcendence), and neurocognitive deficits (poor executive functioning, working/episodic memory, attention, and low IQ). The non-psychotic siblings demonstrated features of a mature character profile including strong crystallized IQ, which may confer protection against psychopathology. PMID:18718739

Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia

PubMed Central

Neuhoff, Nina; Bruder, Jennifer; Bartling, Jürgen; Warnke, Andreas; Remschmidt, Helmut; Müller-Myhsok, Bertram; Schulte-Körne, Gerd

2012-01-01

Dyslexia affects 5–10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore “unaffected” despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/−/ba/contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300–700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia. PMID:22606227

P300 and LORETA: comparison of normal subjects and schizophrenic patients.

PubMed

Winterer, G; Mulert, C; Mientus, S; Gallinat, J; Schlattmann, P; Dorn, H; Herrmann, W M

2001-01-01

It was the aim of the present study 1) to investigate how many cortical activity maxima of scalp-recorded P300 are detected by Low Resolution Electromagentic Tomography (LORETA) when analyses are performed with high time-resolution, 2) to see if the resulting LORETA-solution is in accordance with intracortical recordings as reported by others and 3) to compare the given pattern of cortical activation maxima in the P300-timeframe between schizophrenic patients and normal controls. Current density analysis was performed in 3-D Talairach space with high time resolution i.e. in 6 ms steps. This was done during an auditory choice reaction paradigm separately for normal subjects and schizophrenic patients with subsequent group comparisons. In normal subjects, a sequence of at least seven cortical activation maxima was found between 240-420ms poststimulus: the prefrontal cortex, anterior or medial cingulum, posterior cingulum, parietal cortex, temporal lobe, prefrontal cortex, medial or anterior cingulum. Within the given limits of spatial resolution, this sequential maxima distribution largely met the expectations from reports on intracranial recordings and functional neuroimaging studies. However, localization accuracy was higher near the central midline than at lateral aspects of the brain. Schizophrenic patients less activated their cortex in a widespread area mainly in the left hemisphere including the prefrontal cortex, posterior cingulum and the temporal lobe. From these analyses and comparsions with intracranial recordings as reported by others, it is concluded that LORETA correctly localizes P300-related cortical activity maxima on the basis of 19 electrodes except for lateral cortical aspects which is most likely an edge-phenomenon. The data further suggest that the P300-deficit in schizophrenics involves an extended cortical network of the left hemisphere at several steps in time during the information processing stream.

Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid.

PubMed

Ando, Masazumi; Amayasu, Hideaki; Itai, Takahiro; Yoshida, Hisahiro

2017-01-01

Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. The blood ammonia level was positively correlated with the serum glutamate concentration ( r  = 0.44, p  < 0.01) but negatively correlated with glutamine ( r  = -0.41, p  = 0.01), citrulline ( r  = -0.42, p  = 0.01), and glycine concentrations ( r  = -0.54, p  < 0.01). It was also revealed that the concomitant administration of the mood stabilizers ( p  = 0.04) risperidone ( p  = 0.03) and blonanserin ( p  < 0.01) was positively associated with the elevation of the blood ammonia level. We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.

[Evoked potentials N200/P300 disorders and clinical phenotype in Cuban families with paranoid schizophrenia: a family-based association study].

PubMed

Guerra López, Seidel; Martín Reyes, Migdyrai; Pedroso Rodríguez, María de Los Ángeles; Reyes Berazain, Adnelys; Mendoza Quiñones, Raúl; Bravo Collazo, Tania Martha; Días de Villarvilla, Thais; Machado Cano, María Julia; Bobés León, María Antonieta

2015-04-01

N200 and P300 event-related evoked potentials provide sensitive measurements of sensory and cognitive function and have been used to study information processing in patients with schizophrenia and their unaffected first-degree relatives. Reduced amplitude and increased latency of N200 and P300 potentials have been consistently reported in schizophrenia. Thus, event-related evoked potentials abnormalities are promising possible biological markers for genetic vulnerability to schizophrenia. To assess the association of changes in latency, amplitude and topographic distribution of potentials N200 and P300 of patients with paranoid schizophrenia and their healthy first-degree relatives, in families with schizophrenia multiplex. We measured latency and amplitude of the N200 and P300 component of evoked potentials using an auditory odd-ball paradigm in 25 schizophrenic patients (probands) from 60 families multiply affected with paranoid schizophrenia, 23 of their non-schizophrenic first-degree relatives and 25 unrelated healthy controls, through a study of family association. Schizophrenic patients and their relatives showed significant latency prolongation and amplitude reduction of the N200 and P300 waves compared to controls. Left-temporal as compared to right-temporal N200 and P300 were significantly smaller in schizophrenic patients and their non-schizophrenic first-degree relatives than in controls. Our results suggest that event-related evoked potentials abnormalities may serve as markers of genetic vulnerability in schizophrenia. Confirming results of other researchers, this present study suggests that latency prolongation and amplitude reduction of the N200 and P300 waves and an altered topography at temporal sites may be a trait “marker” of paranoid schizophrenia.

Opposite differential risks for autism and schizophrenia based on maternal age, paternal age, and parental age differences

PubMed Central

Boomsma, Jacobus J.

2016-01-01

Abstract Background and objectives: Effects of maternal and paternal age on offspring autism and schizophrenia risks have been studied for over three decades, but inconsistent risks have often been found, precluding well-informed speculation on why these age-related risks might exist. Methodology: To help clarify this situation we analysed a massive single population sample from Denmark including the full spectrum of autistic and schizophrenic disorders (eliminating between-study confounding), used up to 30 follow-up years, controlled for over 20 potentially confounding factors and interpret the ultimate causation of the observed risk patterns using generally accepted principles of parent-offspring conflict and life-history theory. Results: We evaluated the effects of paternal age, maternal age and parental age difference on offspring mental disorders and found consistently similar risk patterns for related disorders and markedly different patterns between autistic and schizophrenic disorders. Older fathers and mothers both conferred increased risk for autistic but not schizophrenic disorders, but autism risk was reduced in younger parents and offspring of younger mothers had increased risk for many schizophrenic disorders. Risk for most disorders also increased when parents were more dissimilarly aged. Monotonically increasing autism risk is consistent with mutation accumulation as fathers’ age, but this explanation is invalid for schizophrenic disorders, which were not related to paternal age and were negatively correlated with maternal age. Conclusions and implications: We propose that the observed maternally induced risk patterns ultimately reflect a shifting ancestral life-history trade-off between current and future reproduction, mediated by an initially high but subsequently decreasing tendency to constrain foetal provisioning as women proceed from first to final pregnancy. PMID:27637201

Further data on the effects of subliminal symbiotic stimulation on schizophrenics.

PubMed

Kaplan, R; Thornton, P; Silverman, L

1985-11-01

This investigation further examined the effects of activating unconscious symbiotic fantasies in schizophrenics. One hundred twenty-eight hospitalized schizophrenic men who qualified as "relatively differentiated" on the Adjective Rating Scale were randomly assigned to four groups. Each group was assessed for pathological thinking, pathological nonverbal behavior, and self-esteem before and after the subliminal exposure of an experimental and control stimulus. The control stimulus for all groups was the message PEOPLE ARE WALKING and the experimental stimuli were the messages MOMMY AND I ARE ONE, MOMMY IS ALWAYS WITH ME, MOMMY FEEDS ME WELL, and I CANNOT HURT MOMMY (one for each group). One half of each group was subliminally exposed to verbal messages only and one half to verbal messages accompanied by congruent pictures. The first stimulus (MOMMY AND I ARE ONE) was intended to activate unconscious symbiotic fantasies that in a number of prior studies reduced pathology in groups of relatively differentiated schizophrenics. The other stimuli were intended to activate reassuring unconscious fantasies about "mommy" that were not specifically symbiosis-related. Only the MOMMY AND I ARE ONE stimulus led to more adaptive behavior and did so on all three dependent variables. This supported the supposition, also borne out in two other studies, that it is specifically symbiosis-related gratifications that are ameliorative for schizophrenics. The above results were considerably stronger for the subgroup that was exposed to a picture accompanying the MOMMY AND I ARE ONE message. This was viewed as probably the result of the pictorial representation serving as a concretization of the more abstract verbal message and as such being more relevant to the relatively primitive mode of thinking in schizophrenia.

Effectiveness of gratitude disposition promotion program on depression and quality of life of chronic schizophrenic patients

PubMed Central

Jung, Miran; Han, Kuemsun

2017-01-01

Context: Gratitude intervention is expectedly an effective intervention to reduce depression and improve the quality of life in schizophrenic patients, but there is a lack of literature on it. Aims: We attempted to develop and test the effectiveness of the gratitude disposition promotion program for chronic schizophrenic patients in Korea. Settings and Design: Nonequivalent control group pre- and post-test design was used in two mental health centers located at Gyeonggi-do in South Korea. Materials and Methods: This paper was a quasi-experimental study and the participants who took part in the gratitude disposition promotion program were 17 of experimental group and 15 of control group. Gratitude disposition (the short gratitude, resentment, and appreciation test), depression (Beck Depression Inventory), and quality of life (developed by Kook) of chronic schizophrenic patients were measured before and after an intervention, as compared to the control. Statistical Analysis: Chi-square test, Fisher's exact test, and t-test were performed for prehomogeneity testing for variables related to the general characteristics. Testing for the effectiveness of gratitude disposition promotion program and hypothesis testing for its effect on depression and quality of life were by ANCOVA and t-test, as verified to significance level of P < 0.05. Results: The participants who received the gratitude disposition promotion program showed significant improvements in gratitude disposition (F = 18.740, P < 0.0001) and in quality of life (F = 9.800, P = 0.004), but no significant difference in depression (F = 3.870, P = 0.059). Conclusions: The gratitude disposition promotion program was an effective clinical intervention program for enhancing gratitude disposition and quality of life of chronic schizophrenic patients in community. PMID:28827866

Duration of untreated illness (DUI) and schizophrenia sub-types: a collaborative study between the universities of Milan and Moscow.

PubMed

Buoli, Massimiliano; Dell'osso, Bernardo; Zaytseva, Yuliya; Gurovich, Isaac Ya; Movina, Larisa; Dorodnova, Anna; Shmuckler, Alexander; Altamura, A Carlo

2013-12-01

Several studies show an association between a long duration of untreated illness (DUI) and poor outcome in schizophrenic patients. DUI, in turn, may be influenced by different variables including specific illness-related factors as well as access to local psychiatric services. The purposes of the present study were to detect differences in terms of DUI among schizophrenics coming from different geographic areas and to evaluate differences in DUI across diagnostic sub-types. One hundred and twenty-five (125) schizophrenic patients of the Psychiatric Clinic of Milan (n = 51) and Moscow (n = 74) were enrolled. SCID-I was administered to all patients and information about DUI was obtained by consulting clinical charts and health system databases, and by means of clinical interviews with patients and their relatives. DUI was defined as the time between the onset of illness and the administration of the first antipsychotic drug. One-way analyses of variance (ANOVAs) were performed to find eventual differences in terms of DUI across diagnostic sub-types. Italian patients showed a longer DUI (M = 4.14 years, SD = 4.95) than Russians (M = 1.16 years, SD = 1.43) (F = 24.03, p < .001). DUI was found to be longer in paranoid schizophrenics (M = 3.47 years, SD = 4.19) compared to catatonic patients (M = 0.96 years, SD = 0.94) (F = 3.56, p = .016). The results of the present study suggest that the different schizophrenic sub-types may differ in terms of DUI, likely due to different clinical severity and social functioning. Studies with larger samples are needed to confirm the data of the present study.

[Tolerance of ambiguity, art therapy and psychiatric illness].

PubMed

Grube, Michael

2002-11-01

Tolerance of ambiguity means the ability to tolerate contradictory and incalculable informations. There is the hypothesis that a high degree of tolerance of ambiguity correlates with creativity. It is unclear how various psychiatric illnesses and psychopathological conditions affect tolerance of ambiguity. Therefore we carried out a study concerning the tolerance of ambiguity: 154 persons were systematically investigated with a standardized questionnaire (31 schizophrenic in-patients, 41 neurotic in-patients, 49 members of the staff as control group, 33 artists as control group). In addition we examined the degree of depression in the neurotic group, the anancasm score and the well-being in general. In the schizophrenic group we assessed psychotic symptoms, the positive and negative symptoms, medication, anancasm and depression. Tolerance of ambiguity decreased in the following sequence: artists - members of the staff - neurotic in-patients - schizophrenic in-patients. It became evident that in the schizophrenic group negative symptoms negatively correlates with tolerance of ambiguity. The results seem to confirm the hypothesis that there is a positive correlation between tolerance of ambiguity and creativity. In addition, the higher degree of intolerance of ambiguity in schizophrenic patients may represent a protective mechanism. Intolerance of ambiguity possibly protects from too many contradictory informations. Furthermore the necessity is confirmed that creative therapy methods should be carefully chosen to avoid irritation on the one hand and not to neglect the required training of creative basic functions on the other hand. Although our results weaken the thesis that psychiatric illness is generally associated with an increase of creativity they don't exclude that highly creative performances in some individuals are possible who are especially talented in spite of or even because of their emotional suffering.

Psychopathology of Lived Time: Abnormal Time Experience in Persons With Schizophrenia.

PubMed

Stanghellini, Giovanni; Ballerini, Massimo; Presenza, Simona; Mancini, Milena; Raballo, Andrea; Blasi, Stefano; Cutting, John

2016-01-01

Abnormal time experience (ATE) in schizophrenia is a long-standing theme of phenomenological psychopathology. This is because temporality constitutes the bedrock of any experience and its integrity is fundamental for the sense of coherence and continuity of selfhood and personal identity. To characterize ATE in schizophrenia patients as compared to major depressives we interviewed, in a clinical setting over a period of 15 years, 550 consecutive patients affected by schizophrenic and affective disorders. Clinical files were analyzed by means of Consensual Qualitative Research (CQR), an inductive method suited to research that requires rich descriptions of inner experiences. Of the whole sample, 109 persons affected by schizophrenic (n = 95 acute, n = 14 chronic) and 37 by major depression reported at least 1 ATE. ATE are more represented in acute (N = 109 out of 198; 55%) than in chronic schizophrenic patients (N = 14 out of 103; 13%). The main feature of ATE in people with schizophrenia is the fragmentation of time experience (71 out of 109 patients), an impairment of the automatic and prereflexive synthesis of primal impression-retention-protention. This includes 4 subcategories: disruption of time flowing, déjà vu/vecu, premonitions about oneself and the external world. We contrasted ATE in schizophrenia and in major depression, finding relevant differences: in major depressives there is no disarticulation of time experience, rather timelessness because time lacks duration, not articulation. These core features of the schizophrenic pheno-phenotype may be related to self-disorders and to the manifold of characteristic schizophrenic symptoms, including so called bizarre delusions and verbal-acoustic hallucinations. © 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.

Correlates of positive and negative schizophrenic syndromes in Nigerian patients.

PubMed

Gureje, O

1989-11-01

The two-syndrome concept of schizophrenia was investigated in a sample of 70 Nigerian schizophrenic patients. The positive and negative syndromes were studied in relation to demographic, historical, neurological and psychometric measures. The negative syndrome was associated with cognitive impairment, behavioural deterioration and left eye dominance, and also with poor pre-morbid educational achievement and longer length of current stay in hospital. The positive syndrome was unrelated to any of the independent variables. The two syndromes were not significantly related, supporting the view that they represent relatively independent dimensions of pathology. This provides further support for the validity of the Type I-Type II subtyping of schizophrenia in populations of patients from different cultural backgrounds, and suggests that the negative syndrome is related to the presence of neurodevelopmental deficits that possibly antedate the schizophrenic illness.

A New Approach of Personality and Psychiatric Disorders: A Short Version of the Affective Neuroscience Personality Scales

PubMed Central

Pingault, Jean-Baptiste; Falissard, Bruno; Côté, Sylvana; Berthoz, Sylvie

2012-01-01

Background The Affective Neuroscience Personality Scales (ANPS) is an instrument designed to assess endophenotypes related to activity in the core emotional systems that have emerged from affective neuroscience research. It operationalizes six emotional endophenotypes with empirical evidence derived from ethology, neural analyses and pharmacology: PLAYFULNESS/joy, SEEKING/interest, CARING/nurturance, ANGER/rage, FEAR/anxiety, and SADNESS/separation distress. We aimed to provide a short version of this questionnaire (ANPS-S). Methodology/Principal Findings We used a sample of 830 young French adults which was randomly split into two subsamples. The first subsample was used to select the items for the short scales. The second subsample and an additional sample of 431 Canadian adults served to evaluate the psychometric properties of the short instrument. The ANPS-S was similar to the long version regarding intercorrelations between the scales and gender differences. The ANPS-S had satisfactory psychometric properties, including factorial structure, unidimensionality of all scales, and internal consistency. The scores from the short version were highly correlated with the scores from the long version. Conclusions/Significance The short ANPS proves to be a promising instrument to assess endophenotypes for psychiatrically relevant science. PMID:22848510

Cognitive endophenotypes of attention deficit/hyperactivity disorder and intra-subject variability in patients with autism spectrum disorder.

PubMed

Biscaldi, M; Bednorz, N; Weissbrodt, K; Saville, C W N; Feige, B; Bender, S; Klein, C

2016-07-01

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have previously been studied mainly in isolation from each other. However the two conditions may be aetiologically related and thus show overlap in aetiologically relevant functions. In order to address this question of potential aetiological overlap between ADHD and ASD, the present study set out to investigate putative endophenotypes of ADHD in N=33 typically developing (TD) children and N=28 patients with ASD that were (ASD+) or were not (ASD-) co-morbid for ADHD. With regard to both the cognitive endophenotype candidates (working memory, inhibition, temporal processing) and intra-subject variability (ISV) the pattern of abnormalities was inconsistent. Furthermore, the overall profile of ASD-TD differences was extremely similar to the pattern of differences between the ASD+ and ASD- sub-groups, suggesting that any abnormalities found were due to the comorbid ASD subgroup. This held in particular for ISV, which did not show in patients with ASD the task-general increase that is common in ADHD samples. Altogether, the present results do not support the hypothesis of aetiological overlap between ASD and ADHD. Copyright © 2016 Elsevier B.V. All rights reserved.

Altered Reward Reactivity as a Behavioural Endophenotype in Eating Disorders: A Pilot Investigation in Twins.

PubMed

Kanakam, Natalie; Krug, Isabel; Collier, David; Treasure, Janet

2017-05-01

Altered reward reactivity is a potential risk endophenotype for eating disorders (EDs). The aim of this study was to examine reward reactivity in female twins with EDs and compare it with a twin control group. A sample of 112 twins [n = 51 met lifetime DSM-IV ED criteria (anorexia nervosa n = 26; bulimic disorders n = 24), n = 19 unaffected cotwins and n = 42 control twins] was administered measures assessing reward reactivity, including the Game of Dice Task, the Behavioural Inhibition/Activation (BIS/BAS) Scales and the Appetitive Motivation Scale (AMS). Within pair, correlations for monozygotic and dizygotic twins were calculated and generalised estimating equations compared probands with non-ED cotwins and controls. The BAS and the AMS were reduced in EDs and negatively associated with restrictive symptoms. In addition, monozygotic twins pairs demonstrated significant within pair similarity for the BAS and AMS. Conversely, there was less evidence to support the BIS or risky decision-making as measured by the Game of Dice Task as an endophenotype in EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Vitamin D, parathyroid hormone, serum calcium and phosphorus in patients with schizophrenia and major depression.

PubMed

Jamilian, Hamidreza; Bagherzadeh, Kamran; Nazeri, Zeinab; Hassanijirdehi, Marzieh

2013-02-01

Vitamin D deficiency has been associated with an increased risk of depression and schizophrenia. The aim was to compare serum levels of vitamin D, calcium, phosphorus and parathyroid hormone in schizophrenics, depressed patients and healthy subjects in an Iranian population. In a cross-sectional study, 100 patients with schizophrenia and 100 with major depression were enrolled. A questionnaire was filled by using medical records of patients. After that a serum sample was taken and levels of vitamin D, calcium, phosphorus and parathyroid hormone were assessed and then compared between the three groups. Post-hoc analysis of Tukey showed that vitamin D level in healthy participants was significantly higher than depressed patients and schizophrenics while there was no significant difference between vitamin D level in depressed and schizophrenic patients. The findings suggest that vitamin D affects the brain independent of hormonal pathways which regulate serum level of calcium. Non-significant difference in the serum level of vitamin D between the schizophrenics and the depressed patients suggests that the independent effect of vitamin D in brain is a general effect and is not specialized to a specific region or pathway in the brain; however, differences between psychiatric and non-psychiatric patients might be resulted from differences in psychosocial backgrounds.

The impact of antipsychotics on psychomotor performance with regards to car driving skills.

PubMed

Brunnauer, Alexander; Laux, Gerd; Geiger, Elisabeth; Möller, Hans-Jürgen

2004-04-01

Cognitive and psychomotor impairments are a core feature of most patients with schizophrenia and may have an important influence on driving ability. The present study investigated the effects of neuroleptic monotherapy on psychomotor functions related to car driving skills in schizophrenic patients. Consecutively admitted schizophrenic inpatients (n = 120) were tested under steady state plasma level conditions before discharge to outpatient treatment. Patients met the International Classification of Diseases, Tenth Revision criteria for schizophrenia. The study followed a naturalistic nonrandomized design. Data were collected with the computerized Act & React Testsystem and were analyzed according to medication, severity of illness, and age. Only 32.5% of the schizophrenic inpatients passed the tests without major impairments. Patients treated with atypical neuroleptics or clozapine showed a better test performance on skills related to driving ability when compared with patients on typical neuroleptics. Differences were most pronounced in measures of divided attention, stress tolerance, and attention. Data also suggest that treatment with clozapine had an overall positive impact on measures of reactivity and stress tolerance. These results show that even under steady state pharmacologic conditions psychomotor functions of most schizophrenic patients partly remitted must be considered as impaired. To evaluate these effects, a systematic neuropsychologic examination is recommended.

Further association study on dopamine D2 receptor variant S311C in Schizophrenia and affective disorders

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

Arinami, Tadao; Hamaguchi, Hideo; Itokawa, Masanari

The dopamine D2 receptor gene is a candidate gene for schizophrenia because the potency of certain neuroleptics correlates with their affinity for this receptor. Case-control studies in 291 schizophrenics, 78 patients with affective disorders, and 579 controls on an association of a molecular variant of S311C of the dopamine D2 receptor with psychiatric disorders were conducted. The frequency of individuals with S311C was significantly higher in schizophrenics with the absence of negative symptoms (17.1%, P < 0.00001), but similar in schizophrenics with the presence of negative symptoms (5.7%, P = 0.46) when compared with the controls (4.1%). The frequency ofmore » S311C was significantly higher in familiar schizophrenics from one local area but not in those from other areas. It was significant that S311C was frequently present in patients with mood-incongruent psychotic affective disorders (33.3%, P < 0.0001), but not in those with other affective disorders. These data suggest that S311C might be one of the genetic factors for symptomatic dimensions of delusions and hallucinations and might be involved in underlying clinical heterogeneity in schizophrenia and affective disorders. 48 refs., 3 tabs.« less

Constitutive heterochromatin of chromosome 1 and Duffy blood group alleles in schizophrenia

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

Kosower, N.S.; Gerad, L.; Goldstein, M.

1995-04-24

Cytogenetic analysis was carried out in unrelated schizophrenic patients, unrelated controls and patients and family members in multiplex families. The size-distribution of chromosome 1 heterochromatic region (1qH, C-band variants) among 21 unrelated schizophrenic patients was different from that found in a group of 46 controls. The patient group had 1qH variants of smaller size than the control group (P < 0.01). Incubation of phytohemagglutinin-treated blood lymphocytes with 5-azacytidine (which causes decondensation and extension of the heterochromatin) led to a lesser degree of heterochromatin decondensation in a group of patients than in the controls (7 schizophrenic, 9 controls, P < 0.01).more » The distribution of phenotypes of Duffy blood group system (whose locus is linked to the 1qH region) among 28 schizophrenic patients was also different from that in the general population. Cosegregation of schizophrenia with a 1qH (C-band) variant and Duffy blood group allele was observed in one of six multiplex families. The overall results suggest that alterations within the Duffy/1qH region are involved in schizophrenia in some cases. This region contains the locus of D5 dopamine receptor pseudogene 2 (1q21.1), which is transcribed in normal lymphocytes. 33 refs., 1 fig., 2 tabs.« less

Abnormal Sense of Agency in Patients with Schizophrenia: Evidence from Bimanual Coupling Paradigm

PubMed Central

Garbarini, Francesca; Mastropasqua, Angela; Sigaudo, Monica; Rabuffetti, Marco; Piedimonte, Alessandro; Pia, Lorenzo; Rocca, Paola

2016-01-01

A fruitful approach to the understanding the human awareness of action is the study of those pathologies in which some aspects of it are altered. Previous evidences showed that patients with schizophrenia tend to attribute someone else’ actions to their own, as internally, rather than externally, generated. Here, we asked whether schizophrenics have an “excessive” sense of agency, while observing others’ movements. We took advantage from the circles-lines task, known to show bimanual interferences. Twenty schizophrenics and 20 age-matched healthy controls were administered: (a) the bimanual version of the task: drawing lines with one hand and circles with the other; and (b) a modified version: drawing lines while observing the examiner drawing circles. In the bimanual version, patients and controls showed a comparable interference effect. In the observation version, schizophrenics, compared to controls, showed a significantly greater interference effect of the examiners’ hand drawing circles on the own hand drawing lines. This effect was significantly correlated to the strength of the positive symptoms (hallucinations and delusions) and to the alteration of the sense of agency, reported during the task. These findings suggest that an altered sense of agency, as shown by schizophrenics, can induce objective consequences on the motor system. PMID:27014005

A STUDY OF THOUGHT, LANGUAGE AND COMMUNICATION (T.L.C) DISORDERS IN SCHIZOPHRNIA*

PubMed Central

Mazumdar, Pralay Kumar; Chaturvedi, S.K.; Gopinath, P.S.

1988-01-01

SUMMARY This study examines in detail - i) the magnitude, nature and severity of thought disorder in schizophrenia, ii) the correlations between type and severity of thought disorder with socio-demographic and clinical variables, and iii) differences between different subtypes of schizophrenia. Forty five schizophrenics (Research Diagnostic Criteria) were assessed by ‘live’ interview as well as tape recorded interviews. Instruments used for assessment were (a) Scale for assessment of Thought, Language and Communication (Andreasen 1978), (b) Brief Psychiatric Rating Scale (Overall & Gorham 1962), (c) Mini Mental State (Folstein 1975), and (d) Clinical and demographic data recording proforma. The Schizophrenic patients were subdivided as (i) Acute and chronic (R.D.C.), (ii) Paranoid and non-paranoid; and (iii) Negative, positive, mixed (Andreasen's criteria) and intragroup and intergroup differences were computed. Poverty of speech, tangentiality, derailment, loss of goal, perseveration were found to be the commonest thought disorders. Positive and negative thought disorders were seen in equiproportion in both positive and negative schizophrenics. Significant differences were noted between thought disorders and education as well as habitat. Rural patients more often had negative formal thought disorders. Literates had more often clanging, neologism, circumstantiality and echolalia. This study provides ample information on the nature of thought disorder in Indian schizophrenic subjects. PMID:21927321

[Face recognition in patients with schizophrenia].

PubMed

Doi, Hirokazu; Shinohara, Kazuyuki

2012-07-01

It is well known that patients with schizophrenia show severe deficiencies in social communication skills. These deficiencies are believed to be partly derived from abnormalities in face recognition. However, the exact nature of these abnormalities exhibited by schizophrenic patients with respect to face recognition has yet to be clarified. In the present paper, we review the main findings on face recognition deficiencies in patients with schizophrenia, particularly focusing on abnormalities in the recognition of facial expression and gaze direction, which are the primary sources of information of others' mental states. The existing studies reveal that the abnormal recognition of facial expression and gaze direction in schizophrenic patients is attributable to impairments in both perceptual processing of visual stimuli, and cognitive-emotional responses to social information. Furthermore, schizophrenic patients show malfunctions in distributed neural regions, ranging from the fusiform gyrus recruited in the structural encoding of facial stimuli, to the amygdala which plays a primary role in the detection of the emotional significance of stimuli. These findings were obtained from research in patient groups with heterogeneous characteristics. Because previous studies have indicated that impairments in face recognition in schizophrenic patients might vary according to the types of symptoms, it is of primary importance to compare the nature of face recognition deficiencies and the impairments of underlying neural functions across sub-groups of patients.

Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs

PubMed Central

Ersan, Etem Erdal; Aydin, Hüseyin; Erdoğan, Serpil; Erşan, Serpil; Alişik, Murat; Bakir, Sevtap; Erel, Özcan; Koç, Derya

2018-01-01

Objective Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. Methods Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. Results The TAS (p=0.001), total thiol, and native thiol levels (p<0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p<0.001). Conclusion These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. PMID:29397665

Plasma 3-methoxy-4-hydroxyphenylglycol and homovanillic acid measurements in deficit and nondeficit forms of schizophrenia.

PubMed

Thibaut, F; Ribeyre, J M; Dourmap, N; Ménard, J F; Dollfus, S; Petit, M

1998-01-01

Discrepancies in the biochemical research on negative symptoms in schizophrenia may be ascribed to the lack of differentiation into primary and secondary negative symptoms. We have used Carpenter's criteria to define the deficit syndrome of schizophrenia as the presence of enduring and primary negative symptoms and measured catecholaminergic parameters in deficit as compared with nondeficit schizophrenics. We have investigated plasma homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG) concentrations in 34 DSM-III-R neuroleptic-treated schizophrenic patients who were classified into deficit (n = 14) and nondeficit (n = 20) forms of schizophrenia. All these patients were in a stable clinical and therapeutic status for the preceding 12 months. The 14 deficit schizophrenic patients had lower plasma levels of pHVA and higher plasma concentrations of pMHPG from 9 AM to 12 AM as compared with the 20 nondeficit schizophrenic patients. The two groups did not differ on any demographic, therapeutic, or clinical variable considered. Our data are consistent with the postulated distinct pathophysiological basis for the deficit syndrome of schizophrenia and suggest that opposite alterations in the pHVA or pMHPG levels may reflect specific changes in noradrenergic and dopaminergic functions in these deficit patients.

A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics.

PubMed

Phillips, M L; Williams, L; Senior, C; Bullmore, E T; Brammer, M J; Andrew, C; Williams, S C; David, A S

1999-11-08

Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

Knowledge-driven binning approach for rare variant association analysis: application to neuroimaging biomarkers in Alzheimer's disease.

PubMed

Kim, Dokyoon; Basile, Anna O; Bang, Lisa; Horgusluoglu, Emrin; Lee, Seunggeun; Ritchie, Marylyn D; Saykin, Andrew J; Nho, Kwangsik

2017-05-18

Rapid advancement of next generation sequencing technologies such as whole genome sequencing (WGS) has facilitated the search for genetic factors that influence disease risk in the field of human genetics. To identify rare variants associated with human diseases or traits, an efficient genome-wide binning approach is needed. In this study we developed a novel biological knowledge-based binning approach for rare-variant association analysis and then applied the approach to structural neuroimaging endophenotypes related to late-onset Alzheimer's disease (LOAD). For rare-variant analysis, we used the knowledge-driven binning approach implemented in Bin-KAT, an automated tool, that provides 1) binning/collapsing methods for multi-level variant aggregation with a flexible, biologically informed binning strategy and 2) an option of performing unified collapsing and statistical rare variant analyses in one tool. A total of 750 non-Hispanic Caucasian participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort who had both WGS data and magnetic resonance imaging (MRI) scans were used in this study. Mean bilateral cortical thickness of the entorhinal cortex extracted from MRI scans was used as an AD-related neuroimaging endophenotype. SKAT was used for a genome-wide gene- and region-based association analysis of rare variants (MAF (minor allele frequency) < 0.05) and potential confounding factors (age, gender, years of education, intracranial volume (ICV) and MRI field strength) for entorhinal cortex thickness were used as covariates. Significant associations were determined using FDR adjustment for multiple comparisons. Our knowledge-driven binning approach identified 16 functional exonic rare variants in FANCC significantly associated with entorhinal cortex thickness (FDR-corrected p-value < 0.05). In addition, the approach identified 7 evolutionary conserved regions, which were mapped to FAF1, RFX7, LYPLAL1 and GOLGA3, significantly associated with entorhinal cortex thickness (FDR-corrected p-value < 0.05). In further analysis, the functional exonic rare variants in FANCC were also significantly associated with hippocampal volume and cerebrospinal fluid (CSF) Aβ 1-42 (p-value < 0.05). Our novel binning approach identified rare variants in FANCC as well as 7 evolutionary conserved regions significantly associated with a LOAD-related neuroimaging endophenotype. FANCC (fanconi anemia complementation group C) has been shown to modulate TLR and p38 MAPK-dependent expression of IL-1β in macrophages. Our results warrant further investigation in a larger independent cohort and demonstrate that the biological knowledge-driven binning approach is a powerful strategy to identify rare variants associated with AD and other complex disease.

[Efficacy and tolerance of PDE-5 in the treatment of erectile dysfunction in schizophrenic patients: A literature review].

PubMed

Bacconi, L; Gressier, F

2017-02-01

Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients. This literature review aimed to summarize the current data on the efficacy and tolerability of PDE-5 inhibitors in the erectile dysfunction in schizophrenic patients. PubMed, PsycInfo and Cochrane databases were searched for studies published until August 2014. Only 6 studies met the inclusion criteria. Three were randomized, double-blind, cross-over, placebo-controlled trials and three were open studies. Various scales were used to measure erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, quality of life and intensity of schizophrenic symptoms. In the 3 randomized studies (one with sildenafil 25-50 mg, one with lodenafil carbonate 80 mg/j and the last one with tadalafil 10 mg), the rate of participants who completed the trial was high (around 95 %). All three included patients with schizophrenia or schizophrenia spectrum disorders. Patients reported significant improvement on sexual dysfunction. However, no statistical difference was reported between lodenafil and placebo, on different scales, suggesting a very important placebo effect in patients with schizophrenia. All three found a good tolerance of PDE-5 inhibitors. Side effects were rare and were mainly nasal congestion, headaches, nausea and dizziness. There were no major side effects or drug interactions. Considering the 3 open studies, 2 involved sildenafil and one tadalafil. All concluded in improved erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

EFFICACY OF PROPRANOLOL ON SCHIZOPHRENIC THOUGHT DISORDER

PubMed Central

Sethi, B. B.; Dube, Sanjay

1981-01-01

SUMMARY 15 schizophrenic patients were treated with dl-propranolol in a 4 week open study. Dosage was gradually increased over a period of 17 days to 1920 mg/day. Improvements were rated on Thought Disorder Scores (A & B) of the MBPRS and GPRS subscale for schizophrenia. Majority of the patients showed a 50% improvement in terms of their residual scores by the 4th week of treatment and the side effects experienced were minimal. PMID:22064778

Obsessive-compulsive symptoms in clozapine-treated schizophrenic patients.

PubMed

Ertugrul, Aygun; Anil Yagcioglu, A Elif; Eni, Nurhayat; Yazici, Kâzim M

2005-04-01

The aim of the present study was to assess the occurrence of obsessive-compulsive symptoms (OCS) in schizophrenic patients treated with clozapine, and to examine the relationship between OCS and other clinical variables. The results support earlier findings which suggest that clozapine produces or unmasks OCS. In addition, the severity of OCS was not related to other dimensions of psychopathology, severity of illness, clinical improvement or dose and duration of clozapine treatment.

[Schizophrenia and cannabis consumption: epidemiology and clinical symptoms].

PubMed

Jockers-Scherübl, Maria C

2006-01-01

More and more young people consume cannabis in sometimes high dosage at an age when their brain is not yet fully developed and reacts particularly sensitive to toxic influences. Cannabis can induce and exacerbate psychotic symptoms and it can deteriorate the disease process in schizophrenic patients. First-episode schizophrenic patients with long-term cannabis consumption were significantly younger at disease-onset, mostly male and suffered more often from paranoid schizophrenia (with a better prognosis) than those without cannabis consumption in our investigation. The significance of higher serum neurotrophin levels in cannabis consuming schizophrenics as compared to those without cannabis consumption remains equivocal so far. The cognitive functions of this patient group are at least not worse than in those with schizophrenia alone. Taken together, the effect of cannabis on the brain vulnerable to schizophrenia is not yet completely understood; besides the undoubtedly deleterious effects, there may also be some neuroprotective effects.

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.

A combined cICA-EEMD analysis of EEG recordings from depressed or schizophrenic patients during olfactory stimulation

NASA Astrophysics Data System (ADS)

Götz, Th; Stadler, L.; Fraunhofer, G.; Tomé, A. M.; Hausner, H.; Lang, E. W.

2017-02-01

Objective. We propose a combination of a constrained independent component analysis (cICA) with an ensemble empirical mode decomposition (EEMD) to analyze electroencephalographic recordings from depressed or schizophrenic subjects during olfactory stimulation. Approach. EEMD serves to extract intrinsic modes (IMFs) underlying the recorded EEG time. The latter then serve as reference signals to extract the most similar underlying independent component within a constrained ICA. The extracted modes are further analyzed considering their power spectra. Main results. The analysis of the extracted modes reveals clear differences in the related power spectra between the disease characteristics of depressed and schizophrenic patients. Such differences appear in the high frequency γ-band in the intrinsic modes, but also in much more detail in the low frequency range in the α-, θ- and δ-bands. Significance. The proposed method provides various means to discriminate both disease pictures in a clinical environment.

The Genetic Basis of Thought Disorder and Language and Communication Disturbances in Schizophrenia

PubMed Central

Levy, Deborah L.; Coleman, Michael J.; Sung, Heejong; Ji, Fei; Matthysse, Steven; Mendell, Nancy R.; Titone, Debra

2009-01-01

Thought disorder as well as language and communication disturbances are associated with schizophrenia and are over-represented in clinically unaffected relatives of schizophrenics. All three kinds of dysfunction involve some element of deviant verbalizations, most notably, semantic anomalies. Of particular importance, thought disorder characterized primarily by deviant verbalizations has a higher recurrence in relatives of schizophrenic patients than schizophrenia itself. These findings suggest that deviant verbalizations may be more penetrant expressions of schizophrenia susceptibility genes than schizophrenia. This paper reviews the evidence documenting the presence of thought, language and communication disorders in schizophrenic patients and in their first-degree relatives. This familial aggregation potentially implicates genetic factors in the etiology of thought disorder, language anomalies, and communication disturbances in schizophrenia families. We also present two examples of ways in which thought, language and communication disorders can enrich genetic studies, including those involving schizophrenia. PMID:20161689

Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid concentration in normal subjects.

PubMed

Zemishlany, Z; Davidson, M

1996-08-15

The present study was undertaken to investigate if acute anxiety can affect plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels have been associated with severity of schizophrenic symptoms, the results of this study will help determine if the pHVA elevations are directly related to psychosis or if anxiety is also a contributory factor. Anxiety was provoked in 10 young normal subjects by a combined paradigm of mental arithmetic task and threat of electrical shock. A significant increase in self-ratings of anxiety, blood pressure, and plasma levels of norepinephrine, 3-methoxy-4-hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used was effective in provoking anxiety; however, anxiety did not affect pHVA concentrations. The results may support the notion that increased pHVA levels in severely ill schizophrenic patients are related to the schizophrenic pathophysiology rather than to anxiety.

Abnormal visual scan paths: a psychophysiological marker of delusions in schizophrenia.

PubMed

Phillips, M L; David, A S

1998-02-09

The role of the visual scan path as a psychophysiological marker of visual attention has been highlighted previously (Phillips and David, 1994). We investigated information processing in schizophrenic patients with severe delusions and again when the delusions were subsiding using visual scan path measurements. We aimed to demonstrate a specific deficit in processing human faces in deluded subjects by relating this to abnormal viewing strategies. Scan paths were measured in six deluded and five non-deluded schizophrenics (matched for medication and negative symptoms), and nine age-matched normal controls. Deluded subjects had abnormal scan paths in a recognition task, fixating non-feature areas significantly more than controls, but were equally accurate. Re-testing after improvement in delusional conviction revealed fewer group differences. The results suggest state-dependent abnormal information processing in schizophrenics when deluded, with reliance on less-salient visual information for decision-making.

Taking cognizance of mental illness in schizophrenics and its association with crime and substance-related diagnoses.

PubMed

Munkner, R; Haastrup, S; Jørgensen, T; Andreasen, A H; Kramp, P

2003-02-01

To analyse how committed crimes and substance-related diagnoses are associated with the age on the first contact with the psychiatric hospital system and the age at diagnosing of schizophrenia among schizophrenics. In a register-based study including all Danes diagnosed with schizophrenia born after November 1, 1963, data on criminality, substance-related diagnoses and contacts with the psychiatric hospital system were analysed. Compared with the non-convicted schizophrenics the convicted were older on first contact with the psychiatric hospital system and older when the diagnosis of schizophrenia was first given. In contrast, having a substance-related diagnosis was associated with a younger age on first contact but did not influence the age at which the diagnosis of schizophrenia was given. It is important that both psychiatrists and the judicial system are aware of possible psychotic symptoms in criminal and abusing individuals to enable earlier detection and treatment.

OBSESSIVE-COMPULSIVE SYMPTOMS IN CHRONIC SCHIZOPHRENIA: A NEW IDEA OR AN OLD BELIEF?

PubMed Central

Jaydeokar, Sujeet; Gore, Yogita; Diwan, Pradnya; Deshpande, Prasad; Desai, Neena

1997-01-01

Obsessive-compulsive (OC) symptoms during the course of schizophrenia have been reported, yet the incidence and significance of this finding is still unclear. This study was undertaken to determine the prevalence of OC symptoms among chronic schizophrenic patients and to systematically identify them. 101 patients satisfying DSM-IV diagnosis of chronic schizophrenia were assessed for OC symptoms. All patients were also rated on the Yale-Brown Obsessive Compulsive Scale for the severity of their symptoms. The study revealed that 26.7% of the chronic schizophrenic patients had significant OC symptoms with a high prevalence in the age group below 35 years. OC symptoms were more severe in patients with duration of illness more than 5 years. The OC symptoms were more prevalent among paranoid schizophrenics with the frequent obsessions being that of contamination, sexual and aggressive thoughts and frequent compulsion was need to ask or confess. PMID:21584101

[Homicide, schizophrenia and substance abuse: a complex interaction].

PubMed

Richard-Devantoy, S; Bouyer-Richard, A I; Jollant, F; Mondoloni, A; Voyer, M; Senon, J-L

2013-08-01

The prevalence of homicide perpetrators with a diagnosis of schizophrenia is 6% in Western countries populations. The relationship between schizophrenia and homicide is complex and cannot be reduced to a simple causal link. The aim of this systematic review was to clarify the role of substance abuse in the commission of murder in people suffering from schizophrenia. A systematic English-French Medline and EMBASE literature search of cohort studies, case-control studies and transversal studies published between January 2001 and December 2011 was performed, combining the MeSH terms "schizophrenia", "psychotic disorders", "homicide", "violence", "substance use disorder", and the TIAB term "alcohol". Abstract selection was based on the STROBE and PRISMA checklist for observational studies and systematic and meta-analysis studies, respectively. Of the 471 selected studies, eight prospective studies and six systematic reviews and meta-analysis studies met the selection criteria and were included in the final analysis. Homicide committed by a schizophrenic person is associated with socio-demographic (young age, male gender, low socioeconomic status), historical (history of violence against others), contextual (a stressful event in the year prior to the homicide), and clinical risk factors (severe psychotic symptoms, long duration of untreated psychosis, poor adherence to medication). In comparison to the general population, the risk of homicide is increased 8-fold in schizophrenics with a substance abuse disorder (mainly alcohol abuse) and 2-fold in schizophrenics without any comorbidities. A co-diagnosis of substance abuse allows us to divide the violent schizophrenics into "early-starters" and "late-starters" according to the age of onset of their antisocial and violent behavior. The violence of the "early-starters" is unplanned, usually affects an acquaintance and is not necessarily associated with the schizophrenic symptoms. Substance abuse is frequent and plays an important role in the homicide commission. In addition, the risk of reoffending is high. In the "late-starters", the violence is linked to the psychotic symptoms and is directed to a member of the family. The reoffence risk is low and it depends on the pursuit of care or not. Defining subgroups of violent schizophrenic patients would avoid stigmatization and would help to prevent the risk of homicide by offering a multidisciplinary care which would take into account any substance abuse. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Neurophysiology and neuropsychology of recognition confabulation in hospitalized schizophrenic patients].

PubMed

Salazar Fraile, J; Tabarés Seisdedos, R; Selva Vera, G; Balanzá Martínez, V; Leal Cercós, C; Vilela Soler, C; Vallet Mas, M

1998-01-01

Recognition confabulation was studied in 16 schizoprhenic patients and 16 normal controls. Half of the schizophrenics presented recognition confabulation, while the remaining 8 and 16 controls did not. This type of confabulation was associated to attentional deficiency, difficulties in perceptual follow-up and perceptive changes. These test satisfactorily discriminated confabulating schizoprhenics and both ill and healthy non-confabulating subjects. The possible mechanisms underlying this type of confabulation are discussed, in relation to the deficiences observed.

Schizophrenia and neurotrophin-3 alleles.

PubMed

Jŏnsson, E; Brené, S; Zhang, X R; Nimgaonkar, V L; Tylec, A; Schalling, M; Sedvall, G

1997-05-01

Studies of brain anatomy and premorbid functioning indicate that schizophrenia may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3 (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located in the promoter region was found to be associated with schizophrenia in a Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association with schizophrenic patients with a putative neurodevelopmental form of the disease. We examined Swedish schizophrenic patients (n = 109) and control subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent exonic polymorphism (at Pro55). No significant difference was found between the two groups. However, in a meta-analysis including the present and previous studies of Caucasian subjects, the A3/147-bp allele frequency was found to be significantly higher in the schizophrenic patients. In the present study, carriers of the A3/147 bp allele tended to have an earlier age of onset and to display more extrapyramidal symptoms. In the silent exonic polymorphism (at Pro55), female schizophrenic patients had higher adenine and lower guanine allele frequencies than control female subjects. Together with previous studies, the results provide some support for an association between the NT-3 gene and certain forms of schizophrenia. This warrants further investigation of NT-3 and other neurotrophic factors with additional polymorphisms and larger patient samples.

[Comparison of Criminal Characteristics in Depression Patients and Schizophrenics with Homicide Behavior].

PubMed

Wang, J; Fu, P X; Gao, Y L; Zhu, M X; Shi, T T

2017-06-01

To explore the criminal characteristics of forensic psychiatry expertise in depression patients and schizophrenics with homicide behavior. A total of 40 depression （depressive episode） patients and 50 schizophrenics with homicide behavior were randomly assigned into the study group and control group, respectively. Data of demographic and criminal characteristic of the two groups were collected by a self-designed questionnaire, and then were compared. There were no statistical differences in age, education level and career between study and control groups （ P >0.05）. Compared with the control group, the victims in the study group were mainly the patient's children and parents, and most offenders had suicidal behavior after homicide （70%）. In study group, the motives of crime were mainly extended suicide and indirect suicide, and most offenders had attempted suicide （85%） and diminished capacity of criminal responsibility （70%）, which in control group had no capacity of criminal responsibility （56%）. Except for criminal site, there were statistical differences in other criminal characteristics between two groups （ P <0.05）. There are different criminal characteristics between depression patients and schizophrenics with homicide behavior in forensic psychiatry, and these characteristics should be considered when these two diagnoses are distinguished in forensic psychiatry expertise. Copyright© by the Editorial Department of Journal of Forensic Medicine

Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study.

PubMed

Donlon, P T; Swaback, D O; Osborne, M L

1977-02-01

In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients.

[Efficacy of family intervention in management of schizophrenic patients in China: a meta-analysis].

PubMed

Chen, Nan; An, Jing-huan; Yang, Min; Liu, Yuan-yuan

2015-11-01

To assess the efficacy of family intervention in management of schizophrenic patients in China. Chinese databases CNKI, VIP, WANFANG, CBM and English databases OVID Medline, Science Direct, Web of science, EBSCO were searched systematically from inception to January 2015. Quantitative and empirical studies on the outcomes of social disability screening scale (SDSS), brief psychiatric rating scale (BPRS) and positive and negative syndrome scale (PANSS) of family intervention for Chinese schizophrenic patients were selected. The effect size was derived from the standardized mean difference (SMD), and meta-analysis was conducted to compare effects of family intervention by intervention types, time of intervention, durations of illness and severity of schizophrenia. The study included 57 articles that met inclusion criteria. SDSS and PANSS scores revealed that the effect was positively associated with the length of intervention time (P<0.0001, P=0.0025); the effect of single family intervention was better than that of combined single and multiple family intervention (P<0.0001, P=0.0131); the effect was better for patients with severe conditions than those with less severe conditions (P<0.0001, P=0.0280). The SDSS showed that the effect was better for patients with shorter disease duration (P<0.0001). The results suggest that the long single family intervention would benefit to schizophrenic patients, particularly for severe patients with short disease duration.

Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain.

PubMed

Stefanis, N C; Bresnick, J N; Kerwin, R W; Schofield, W N; McAllister, G

1998-01-01

The D4 dopamine (DA) receptor has been proposed to be a target for the development of a novel antipsychotic drug based on its pharmacological and distribution profile. There is much interest in whether D4 DA receptor levels are altered in schizophrenia, but the lack of an available receptor subtype-specific radioligand made this difficult to quantitate. In this study, we examined whether D4 mRNA levels are altered in different brain regions of schizophrenics compared to controls. Ribonuclease protection assays were carried out on total RNA samples isolated postmortem from frontal cortex and caudate brain regions of schizophrenics and matched controls. 32P-labelled RNA probes to the D4 DA receptor and to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), were hybridised with the RNA samples, digested with ribonucleases to remove unhybridised probe, and separated on 6% sequencing gels. Densitometer analysis on the subsequent autoradiogams was used to calculate the relative optical density of D4 mRNA compared to G3PDH mRNA. Statistical analysis of the data revealed a 3-fold higher level (P<0.011) of D4 mRNA in the frontal cortex of schizophrenics compared to controls. No increase was seen in caudate. D4 receptors could play a role in mediating dopaminergic activity in frontal cortex, an activity which may be malfunctioning in schizophrenia.

Reduced event-related current density in the anterior cingulate cortex in schizophrenia.

PubMed

Mulert, C; Gallinat, J; Pascual-Marqui, R; Dorn, H; Frick, K; Schlattmann, P; Mientus, S; Herrmann, W M; Winterer, G

2001-04-01

There is good evidence from neuroanatomic postmortem and functional imaging studies that dysfunction of the anterior cingulate cortex plays a prominent role in the pathophysiology of schizophrenia. So far, no electrophysiological localization study has been performed to investigate this deficit. We investigated 18 drug-free schizophrenic patients and 25 normal subjects with an auditory choice reaction task and measured event-related activity with 19 electrodes. Estimation of the current source density distribution in Talairach space was performed with low-resolution electromagnetic tomography (LORETA). In normals, we could differentiate between an early event-related potential peak of the N1 (90-100 ms) and a later N1 peak (120-130 ms). Subsequent current-density LORETA analysis in Talairach space showed increased activity in the auditory cortex area during the first N1 peak and increased activity in the anterior cingulate gyrus during the second N1 peak. No activation difference was observed in the auditory cortex between normals and patients with schizophrenia. However, schizophrenics showed significantly less anterior cingulate gyrus activation and slowed reaction times. Our results confirm previous findings of an electrical source in the anterior cingulate and an anterior cingulate dysfunction in schizophrenics. Our data also suggest that anterior cingulate function in schizophrenics is disturbed at a relatively early time point in the information-processing stream (100-140 ms poststimulus). Copyright 2001 Academic Press.

The neuropathological study of myelin oligodendrocyte glycoprotein in the temporal lobe of schizophrenia patients.

PubMed

Marui, Tomoyasu; Torii, Youta; Iritani, Shuji; Sekiguchi, Hirotaka; Habuchi, Chikako; Fujishiro, Hiroshige; Oshima, Kenichi; Niizato, Kazuhiro; Hayashida, Shotaro; Masaki, Katsuhisa; Kira, Junichi; Ozaki, Norio

2018-03-22

Recent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients. Myelin oligodendrocyte glycoprotein (MOG) was evaluated in the cortex of the superior temporal gyrus (STG) and the hippocampus in 10 schizophrenic and nine age- and sex-matched normal control postmortem brains. The expression of MOG was significantly lower in the middle layer of the neocortex of the STG and stratum lucidum of CA3 in the hippocampus in the long-term schizophrenic brains (patients with ≥30 years of illness duration) than in the age-matched controls. Furthermore, the thickness of MOG-positive fibre-like structures was significantly lower in both regions of the long-term schizophrenic brains than in the age-matched controls. These findings suggest that a long duration of illness has a marked effect on the expression of MOG in these regions, and that myelin-oligodendrocyte abnormalities in these regions may be related to the progressive pathophysiology of schizophrenia.

Frequency and severity of obsessive-compulsive symptoms/disorders, violence and suicidal in schizophrenic patients.

PubMed

Hosseini, S H; Zarghami, M; Moudi, S; Mohammadpour, A R

2012-06-01

This study determined the prevalence and severity of obsessive-compulsive symptoms/disorder (OCS/OCD), aggression and suicidal in schizophrenic patients. Also we compared the prevalence and severity of aggression and suicidal in schizophrenic patients with and without OCS/OCD considering anxiety, depression and substance abuse as confounding factors. During 2007 and 2008, 100 schizophrenic patients were evaluated with Yale-Brown Obsessive Compulsive Scale, Positive and Negative Syndrome Scale, Beck Depression Inventory, Spilberger State/Trait Anxiety Inventory, Beck Scale for suicide Ideation, and Overt Aggression Scale. OCS/OCD and suicidal attempts were seen in 33%, 10% and 12% of patients respectively. The most common form of aggression was against others (55%), and aggressive obsessions were seen in 10% of the patients. Comparing patients with and without OCS/OCD, there were no significant differences in the severity of schizophrenia, suicidal and overt aggression. The severity of overt aggression was related to the patients' age and education reversely. Also, there was a relationship between their suicidal thoughts and residence in the cities. High rate of aggressive obsessions and lack of relationship between severity of aggression and presence of OCD indicated that these patients did not act on these thoughts. The risk of suicide was more serious in patients living in the cities, and risk of violence was more serious in younger and less educated patients.

Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: findings from the Consortium on the Genetics of Schizophrenia (COGS).

PubMed

Stone, William S; Giuliano, Anthony J; Tsuang, Ming T; Braff, David L; Cadenhead, Kristin S; Calkins, Monica E; Dobie, Dorcas J; Faraone, Stephen V; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Mintz, Jim; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Roe, Andrea H; Schork, Nicholas J; Siever, Larry J; Silverman, Jeremy M; Swerdlow, Neal R; Thomas, Alison R; Tsuang, Debby W; Turetsky, Bruce I; Seidman, Larry J

2011-05-01

Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n=305), their full biological siblings (n=449) and parents (n=232), and in community comparison subjects (CCS; n=509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

Neural markers of errors as endophenotypes in neuropsychiatric disorders

PubMed Central

Manoach, Dara S.; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach. PMID:23882201

[Posttraumatic stress disorder endophenotypes: several clinical dimensions for specific treatments].

PubMed

Auxéméry, Y

2012-01-01

Posttraumatic stress disorder is a syndrome with a very complex clinical that it is useful to describe according to a multidimensional approach. Following a critical review of the international literature, we have been able to highlight the genetic supports of posttraumatic stress disorder in the perspective of returning to the source of the clinical of this syndrome in order to steer its treatment better. We consider in succession the neuromodulation pathways involving dopamine, serotonine and noradrenaline to describe the hyperdomaminergic, hyposerotoninergic and hypernoradrenergic endophenotypes of posttraumatic stress disorder. Neurogenetic studies have affirmed two essential proposals. On the one hand, the pharmacological treatment of psychotraumatic disorders can be very closely adjusted to the different endophenotypes. On the other hand, the psychotherapeutic approach retains all its importance in the sense that it is the subjective implication that generated the trauma, subjectivity interacting with a genetic heritage and environmental factors integrating a social context. The changing definition of posttraumatic stress disorder over time comes from scientific exploration in part determined by a sociocultural context and, reciprocally, the psychic trauma is caused by the collapse of reassuring social values which were considered as immutable. The clinical is not developed according to fixed references: the evolution of neurogenetic techniques changes our perception of psychic traumas and the therapeutic possibilities.

Neurocognitive functioning in parents of schizophrenia patients: Attentional and executive performance vary with genetic loading.

PubMed

Schulze-Rauschenbach, Svenja; Lennertz, Leonhard; Ruhrmann, Stephan; Petrovsky, Nadine; Ettinger, Ulrich; Pukrop, Ralf; Dreher, Jan; Klosterkötter, Joachim; Maier, Wolfgang; Wagner, Michael

2015-12-30

Neuropsychological deficits are candidate endophenotypes of schizophrenia which can assist to explain the neurocognitive impact of genetic risk variants. The identification of endophenotypes is often based on the familiality of these phenotypes. Several studies demonstrate neuropsychological deficits in unaffected biological relatives of schizophrenia patients without differentiating between genetic and non-genetic factors underlying these deficits. We assessed N=129 unaffected biological parents of schizophrenia patients, N=28 schizophrenia patients (paranoid subtype), and N=143 controls without a family history of schizophrenia with an extensive neuropsychological test battery. Direct comparison of N=22 parents with an ancestral history of schizophrenia (more likely carriers, MLC) and N=17 of their spouses without such a history (less likely carriers, LLC) allowed the separation of genetic and non-genetic aspects in cognition. Overall, parents showed significant deficits in neuropsychological tasks from all cognitive domains with medium effect sizes. Direct comparisons of MLC- and LLC-parents showed that attentional and executive tasks were most strongly affected by genetic loading. To conclude, unaffected parents of schizophrenia patients showed modest yet significant impairments in attention, memory, and executive functioning. In particular, attentional and executive impairments varied most strongly with genetic loading for schizophrenia, prioritising these dysfunctions for genotype-endophenotype analyses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neural markers of errors as endophenotypes in neuropsychiatric disorders.

PubMed

Manoach, Dara S; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

Disentangling the adult attention-deficit hyperactivity disorder endophenotype: parametric measurement of attention.

PubMed

Finke, Kathrin; Schwarzkopf, Wolfgang; Müller, Ulrich; Frodl, Thomas; Müller, Hermann J; Schneider, Werner X; Engel, Rolf R; Riedel, Michael; Möller, Hans-Jürgen; Hennig-Fast, Kristina

2011-11-01

Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The decomposition of endophenotypes by means of experimental neuro-cognitive assessment has the potential to improve diagnostic assessment, evaluation of treatment response, and disentanglement of genetic and environmental influences. We assessed four parameters of attentional capacity and selectivity derived from simple psychophysical tasks (verbal report of briefly presented letter displays) and based on a "theory of visual attention." These parameters are mathematically independent, quantitative measures, and previous studies have shown that they are highly sensitive for subtle attention deficits. Potential reductions of attentional capacity, that is, of perceptual processing speed and working memory storage capacity, were assessed with a whole report paradigm. Furthermore, possible pathologies of attentional selectivity, that is, selection of task-relevant information and bias in the spatial distribution of attention, were measured with a partial report paradigm. A group of 30 unmedicated adult ADHD patients and a group of 30 demographically matched healthy controls were tested. ADHD patients showed significant reductions of working memory storage capacity of a moderate to large effect size. Perceptual processing speed, task-based, and spatial selection were unaffected. The results imply a working memory deficit as an important source of behavioral impairments. The theory of visual attention parameter working memory storage capacity might constitute a quantifiable and testable endophenotype of ADHD.

Is attention to detail a similarly strong candidate endophenotype for anorexia nervosa and bulimia nervosa?

PubMed

Roberts, Marion E; Tchanturia, Kate; Treasure, Janet L

2013-08-01

To investigate whether attention to detail is a similarly strong candidate endophenotype of anorexia (AN) and bulimia nervosa (BN), and to explore the incidence and clinical correlates of attention to detail. A total of 266 women (including AN, BN, recovered AN, unaffected sisters of AN/BN & control women) undertook a thorough clinical assessment and were administered two neuropsychological measures of attention to detail (Group Embedded Figure Test; Rey-Osterrieth Complex Figure). Superior attention to detail was found across all AN groups including recovered AN and unaffected AN sisters. Those with BN and their unaffected sisters showed a profile more consistent with poor global integration. The combined effect of superior attention to detail and poor global integration ("weak coherence") was present in 42.3% of active cases and corresponded with a more severe illness, elevated obsessive-compulsive symptoms, and a higher likelihood of comorbid clinical anxiety and self-harm. Attention to detail is a stronger candidate endophenotype of AN compared to BN, where poor global integration may be more relevant. The unique contribution of both aspects of weak coherence (superior attention to detail/poor global integration) requires further exploration and understanding in both eating disorders. Integrating cognitive remediation of these traits into treatment for the subset of patients it is relevant for may improve outcome.

Suicide risk in schizophrenia: learning from the past to change the future.

PubMed

Pompili, Maurizio; Amador, Xavier F; Girardi, Paolo; Harkavy-Friedman, Jill; Harrow, Martin; Kaplan, Kalman; Krausz, Michael; Lester, David; Meltzer, Herbert Y; Modestin, Jiri; Montross, Lori P; Mortensen, Preben Bo; Munk-Jørgensen, Povl; Nielsen, Jimmi; Nordentoft, Merete; Saarinen, Pirjo Irmeli; Zisook, Sidney; Wilson, Scott T; Tatarelli, Roberto

2007-03-16

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5-13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures. This review paper is the result of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophrenia patients.

Effects of weight loss diet therapy on anthropometric measurements and biochemical variables in schizophrenic patients.

PubMed

Urhan, Murat; Ergün, Can; Aksoy, Meral; Ayer, Ahmet

2015-07-01

Prevalence of obesity in schizophrenic patients is two to three times higher than in the general population and unhealthy dietary patterns, a sedentary lifestyle and antipsychotic medication use may contribute to the higher levels of obesity among schizophrenic patients. We evaluated the effects of diet therapy on weight loss, anthropometric and biochemical variables in overweight or obese (body mass index, BMI ≥ 27 kg/m(2)) female schizophrenic patients who use antipsychotic medications and in healthy volunteers. Primary demographic variables were collected via questionnaire; blood samples and anthropometric measurements were obtained. Personalized diet recipes were prepared and nutritional education was shared. We logged the physical activity of the patients and maintained food consumption records at 3-day intervals. Participants were weighed every week; anthropometric measurements and blood samples were collected at the end of the first and second months. At the end of the study, reductions in body weight and other anthropometric measurements were statistically significant (P < 0.05). Reductions in body weight and BMI values for patient group were - 4.05 ± 1.73 kg and - 1.62 ± 0.73 kg/m(2) and for the control group were - 6.79 ± 1.80 kg and - 2.55 ± 0.64 kg/m(2), respectively. When compared with the patient group, reductions in the anthropometric variables of the control group were statistically significant (P < 0.05). Fasting glucose, blood lipids, albumin and leptin levels were decreased; insulin and homeostatic model assessment-measured insulin resistance (HOMA-IR) levels were increased insignificantly. Increases in the blood ghrelin levels for both groups were statistically significant (P < 0.05). Improvements to the diets of schizophrenic patient led to improvements in anthropometric measurements and biochemical variables and reduced the health risks caused by antipsychotic medications. Furthermore, we hypothesize that antipsychotic medications do not have any direct effect on leptin and ghrelin metabolism, and that changes in hormone metabolism may be attributable to changes in body weight.

[Evaluating work-personality insufficiency of schizophrenic patients; an assessment of employability in psychiatric rehabilitation].

PubMed

Nozu, M

1995-01-01

Work-Personality means a person's motivation, values and attitude toward labor, general abilities which make his/her work performance efficient, which can be grasped through observation of behavior patterns in working situations. Problems connected with Work-Personality may cause schizophrenics some vocational difficulties. The author made out a "Work-Personality Insufficiency (WPI) Rating Scale" with 15 items, in order to estimate the employability of schizophrenics, and examined its inter-rater reliability by means of ANOVA-ICC and the results were sufficient enough. Then, WPI was applied to 71 schizophrenic outpatients of Tokyo Metropolitan Chubu Comprehensive Mental Health Center (Occupational Training Unit). Also positive and negative symptoms were estimated at admission, and some indicies of historical data were collected. These data were examined statistically as shown below. (1) Construct validity was verified through factor analysis of scores at admission. (2) By comparison of admission scores between two groups of employed and unemployed at discharge, the average score of employed was significantly low (p < 0.01), and the correlation between the discharge state and the total WPI score was significantly high (r = 0.472, p < 0.01), which proved predict validity. (3) The total score of negative symptoms correlated to WPI scores. Also the total score of positive symptoms correlated to some components of WPI scores. (4) By comparison of WPI scores between at admission and at discharge, reduction of disability was seen mainly in interpersonal area, which meant the improvement of patients' adaptability to work situation. Work performance in the narrow sense, however, seemed to make little development, which meant the limited effect of prevocational training with limited time. (5) Indicies of historical data had no relations to outcome and WPI, which showed the difficulty of predicting vocational prognosis from these variables directly. From above, the author concluded that WPI could be utilized to the vocational issues of prolonged schizophrenic patients, and discussed the predictors of vocational prognosis.

[Expressed Emotions, Burden and Family Functioning in Schizophrenic and Bipolar I Patients of a Multimodal Intervention Program: PRISMA].

PubMed

Ramírez, Alexandra; Palacio, Juan David; Vargas, Cristian; Díaz-Zuluaga, Ana María; Duica, Kelly; Agudelo Berruecos, Yuli; Ospina, Sigifredo; López-Jaramillo, Carlos

Bipolar disorder and schizophrenia are causes of major suffering in patients. Nevertheless, they also affect family and caregiver functioning. This is important because the participation and involvement of families and caregivers is essential to achieve an optimal treatment. To describe the level of expressed emotions, burden, and family functioning of bipolar and schizophrenic patients and, to evaluate the efficacy of the multimodal intervention (MI) versus traditional intervention (TI) in family functioning and its perception by patients and caregivers. A prospective, longitudinal, therapeutic-comparative study was conducted with 302 patients (104 schizophrenic and 198 bipolar patients) who were randomly assigned to a MI or TI groups of a multimodal intervention program PRISMA. MI group received care from psychiatry, general medicine, neuropsychology, family therapy, and occupational therapy. TI group received care from psychiatry and general medicine. Hamilton, Young and SANS, SAPS scales were applied to bipolar and schizophrenic patients, respectively. The EEAG, FEICS, FACES III and ECF were also applied at the initial and final time. There were statistically significant differences in socio- demographic and clinical variables in schizophrenia vs bipolar group: 83% vs 32.2% were male, 37 vs 43 mean age, 96% vs 59% were single, 50% vs 20% unemployed, and 20% vs 40% had college studies. In addition, 2 vs 2.5 numbers of hospitalisations, 18 vs 16 mean age of substance abuse onset and, 55 vs 80 points in EEAG. There were no statistically significant differences in family scales after conducting a multivariate analysis on thr initial and final time in both groups. This study did not show changes in variables of burden and family functioning between bipolar and schizophrenic groups that were under TI vs MI. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

[Impact of a Multimodal Intervention on the Psychological Profile of Schizophrenic and Bipolar I Patients: A Study of PRISMA Program].

PubMed

Díaz-Zuluaga, Ana María; Vargas, Cristian; Duica, Kelly; Richard, Shanel; Palacio, Juan David; Agudelo Berruecos, Yuli; Ospina, Sigifredo; López-Jaramillo, Carlos

Bipolar Disorder (BD) and schizophrenia are included in the group of severe mental illness and are main causes of disability and morbidity in the local population due to the bio-psycho-social implications in patients. In the last 20 years or so, adjunctive psychological interventions been studied with the purpose of decreasing recurrences, stabilising the course of the disease, and improving the functionality in these patients. To analyse the psychological effect of a multimodal intervention (MI) vs a traditional intervention (TI) program in BD I and schizophrenic patients. A prospective, longitudinal, therapeutic-comparative study was conducted with 302 patients (104 schizophrenic and 198 bipolar patients) who were randomly assigned to the MI or TI groups of a multimodal intervention program PRISMA. The MI group received care from psychiatry, general medicine, neuropsychology, family therapy, and occupational therapy. The TI group received care from psychiatry and general medicine. The Hamilton and Young scales, and the Scales for the Assessment of Negative Symptoms (SANS) and Postive Symptoms (SAPS) were used on bipolar and schizophrenic patients, respectively. The scales AQ-12, TEMPS-A, FAST, Zuckerman sensation seeking scale, BIS-11, SAI-E and EEAG were applied to measure the psychological variables. The scales were performed before and after the interventions. The psychotherapy used in this study was cognitive behavioural therapy. There were statistically significant differences in socio-demographic and clinical variables in the schizophrenia and bipolar disorder group. There were no statistically significant differences in the psychological scales after conducting a multivariate analysis between the intervention groups and for both times (initial and final). This study did not show any changes in variables of psychological functioning variables between bipolar and schizophrenic groups, who were subjected to TI vs MI (who received cognitive behavioural therapy). Further studies are needed with other psychological interventions or other psychometric scales. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

QLiS--development of a schizophrenia-specific quality-of-life scale.

PubMed

Franz, Michael; Fritz, Michael; Gallhofer, Bernd; Meyer, Thorsten

2012-06-07

The aim of the project was to develop an instrument for the assessment of subjective quality of life specific to schizophrenic persons on the basis of patients' views on their own life and on sound psychometric principles. The project applied a six-step multiphase development process with six distinct studies. (1) The elicitation of schizophrenic persons' views on their quality of life was based on open-ended interviews with interviewees from different settings (acute ward inpatients, long-term care patients, community care patients; n = 268). (2) A cross-sectional study with schizophrenic and healthy persons was conducted to quantify the relative importance of the various aspect of quality of life that emerged from the qualitative study (n = 143). (3) We conducted an empirical comparison of response formats with schizophrenic persons (n = 32). (4) A scale construction- and reliability-testing study was performed (n = 203) as well as (5) a test-retest reliability study (n = 49). (6) The final questionnaire (QLiS, quality of life in schizophrenia) was tested in an additional study on convergent and discriminant validity (n = 135). The QLiS comprises 52 items (plus 2 optional items related to work) in 12 subscales: social contacts, appreciation by others, relationship to family, appraisal of pharmacotherapy, appraisal of psychopathological symptoms, cognitive functioning, abilities to manage daily living, appraisal of accommodation/housing, financial situation, leading a 'normal' life, confidence, general life-satisfaction. An item response format with four response categories was preferred by the schizophrenic persons. The mean values of the subscales clustered around the theoretical mean of the subscales and only minimal ceiling effects were found. The reliability (test-retest-reliability and internal consistency) was with one exception > .70 for all subscales. Taking the low numbers of items per subscale into account, the QLiS can be regarded as an accurate assessment instrument of subjective quality of life in schizophrenia with good content validity.

Suicide risk in schizophrenia: learning from the past to change the future

PubMed Central

Pompili, Maurizio; Amador, Xavier F; Girardi, Paolo; Harkavy-Friedman, Jill; Harrow, Martin; Kaplan, Kalman; Krausz, Michael; Lester, David; Meltzer, Herbert Y; Modestin, Jiri; Montross, Lori P; Bo Mortensen, Preben; Munk-Jørgensen, Povl; Nielsen, Jimmi; Nordentoft, Merete; Saarinen, Pirjo Irmeli; Zisook, Sidney; Wilson, Scott T; Tatarelli, Roberto

2007-01-01

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures. This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients. PMID:17367524

Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.

PubMed

Marchese, Maria; Conti, Valerio; Valvo, Giulia; Moro, Francesca; Muratori, Filippo; Tancredi, Raffaella; Santorelli, Filippo M; Guerrini, Renzo; Sicca, Federico

2014-02-27

With a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly. We analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly. Among 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with "extreme" macrocephaly, autism, intellectual disability and seizures. We did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with "extreme" macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical endophenotypes might be of help to address genetic studies and establish actual causative correlations in autism-epilepsy.

[Machinery and mechanical eroticism. A study on the phenomenology of schizophrenia in two painters' artworks in the Reuter Collection (Pecs)].

PubMed

Simon, Mária

2010-01-01

In this essay, I introduce two schizophrenic artists from the Reuter's Psychopathological Art Collection (Pecs, Hungary), who had been treated in the 1920es.One artist drew a number of sketches of machines; the other created a serial of mechanically erotic pictures. Pictures are analyzed from an intersubjective-phenomenological perspective. Schizophrenic patients' subjective experiences i.e. the experience of reification as well as the intrusivity and uncontrollability of sexuality are particularly emphasized.

Cytomegalovirus Antibody in Cerebrospinal Fluid of Schizophrenic Patients Detected by Enzyme Immunoassay

NASA Astrophysics Data System (ADS)

Fuller Torrey, E.; Yolken, Robert H.; Winfrey, C. Jack

1982-05-01

By means of enzyme immunoassay techniques to detect the presence of antibody to cytomegalovirus, the cerebrospinal fluid of 178 patients with schizophrenia, 17 patients with bipolar disorders, and 11 other psychiatric patients was compared with that of 79 neurological patients and 41 normal control subjects. The cerebrospinal fluid of 20 of the schizophrenic patients and 3 of the patients with bipolar disorders showed significant increases in immunoglobulin M antibody to cytomegalovirus; no difference was found in patients on or off psychotropic medications.

Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

PubMed

Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

1987-12-01

Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

Suggested posthypnotic amnesia in psychiatric patients and normals.

PubMed

Frischholz, Edward J; Lipman, Laurie S; Braun, Bennett G; Sachs, Roberta

2015-01-01

The present study examined both quantitative and qualitative hypnotizability differences among four psychiatric patient groups (dissociative disorder (n = 17), schizophrenic (n = 13), mood disorder (n = 14), and anxiety disorder (n = 14) patients), and normals (college students (n = 63)). Dissociative disorder patients earned significantly higher corrected total scores on the Stanford Hypnotic Susceptibility Scale, Form C (mean = 7.94), than all other groups. Likewise, dissociative disorder patients initially recalled significantly fewer items when the posthypnotic amnesia suggestion was in effect (mean = .41) and reversed significantly more items when the suggestion was canceled (mean = 3.82) than all other groups. In contrast, schizophrenic patients recalled significantly fewer items when the amnesia suggestion was in effect (mean = 1.85) and reversed significantly fewer items when it was canceled (mean = .77) than the remaining groups. This qualitative difference between schizophrenic patients and the other groups on the suggested posthypnotic amnesia item was observed even though there were no significant quantitative differences between groups in overall hypnotic responsivity.

Plasma HVA in psychiatric patients: longitudinal studies.

PubMed

Javaid, J I; Sharma, R P; Janicak, P G; Davis, J M

1990-01-01

Plasma homovanillic acid (pHVA) was measured in 40 inpatients (25 schizophrenic and 15 nonschizophrenic patients) who underwent up to 3 weeks of drug washout. Schizophrenic patients were then treated with trifluoperazine for 4 weeks, and weekly behavioral and pHVA measures were obtained. The baseline pHVA had no relationship to age, sex, washout period, diagnosis, or behavioral rating scores. In schizophrenic patients, the baseline pHVA did not differ significantly from any value obtained during 4 weeks of treatment. Although there was significant improvement in clinical symptoms, this was not related to changes in pHVA. Further, changes in any of the four Brief Psychiatric Rating Scale (BPRS) factors (i.e., positive symptoms, negative symptoms, hostility/suspicion, or anxiety/depression) were not correlated with changes in pHVA. Although other studies have reported a positive correlation between pHVA and psychotic symptoms, results of this study suggest that any observed relationship between pHVA and psychosis must be carefully interpreted.

[Visual and motor functions in schizophrenic patients].

PubMed

Del Vecchio, S; Gargiulo, P A

1992-12-01

In the present work, visual and motor functions have been explored in 26 chronic schizophrenic patients, and 7 acute schizophrenic patients, compared with 26 normal controls, by means of the Bender-Gestalt Test. Parameters under consideration were: Form distortion, rotation, integration, perseveration, use of space, subtle motricity, score (global parameter), and time employed. As regards distortion and rotation there have been highly significant differences between chronic patients and control group. Among acute patients, it was observed that perseveration was also highly significant. Conversely, integration and use of space did not differ significantly among the three groups involved. The global score, resulting from all the above mentioned parameters showed important differences between both patient groups on the one hand, and control group on the other hand. Taking into account that patients were being administered neuroleptic drugs, it can safely be said, however, that the Bender-Gestalt Test allows to recognize alteration in perceptual closure consistent with a loss of the objective structure of perceived phenomena, in both chronic and acute patients.

Associations of oxidative stress status parameters with traditional cardiovascular disease risk factors in patients with schizophrenia.

PubMed

Vidović, Bojana; Stefanović, Aleksandra; Milovanović, Srđan; Ðorđević, Brižita; Kotur-Stevuljević, Jelena; Ivanišević, Jasmina; Miljković, Milica; Spasić, Slavica

2014-04-01

The purpose of this study was to assess oxidative stress status parameters and their possible associations with traditional cardiovascular risk factors in patients with schizophrenia, as well as their potential for patient-control discrimination. Fasting glucose, lipid profile and oxidative stress status parameters were assessed in 30 schizophrenic patients with atypical antipsychotic therapy and 60 control subjects. Malondialdehyde (MDA), pro-oxidant/antioxidant balance (PAB) and total anti-oxidant status (TAS) were significantly higher whereas total sulfhydryl (SH) groups were significantly lower in schizophrenic patients vs. control group. Higher serum PAB values showed an independent association with schizophrenia. The addition of PAB to conventional risk factors improved discrimination between healthy control subjects and patients. Increased oxidative stress and changed lipid profile parameters are associated in schizophrenic patients and may indicate risk for atherosclerosis. The serum PAB level may reflect the levels of oxidative stress in schizophrenia and improve discrimination of patients from controls.

Saccadic abnormalities in psychotic patients. I. Neuroleptic-free psychotic patients.

PubMed

Crawford, T J; Haeger, B; Kennard, C; Reveley, M A; Henderson, L

1995-05-01

Most of the previous research reporting abnormalities of rapid re-fixation eye movements (saccades) in patients with schizophrenia has used patients receiving neuroleptic medication. In this study non-neuroleptically medicated schizophrenics were compared with other psychiatric patients using a variety of saccadic paradigms to determine the specificity of saccadic dysfunction. The patient groups consisted of schizophrenics (N = 18), bipolar affectives (N = 18), anxiety neurotics (N = 10) and normal controls (N = 31), none of whom had received neuroleptic medication for the preceding 6 months. Four behavioural paradigms, reflexive, predictive, remembered and ANTI were used to elicit saccades. The primary abnormality in the schizophrenic group was a significantly increased rate of distractibility in the ANTI (saccades made towards the target rather than in an opposite direction) and REM (saccades made prior to the imperative cue) paradigms. The major neuropsychological variable predictive of these errors was Wisconsin card sort perseverative errors. These data, in conjunction with findings from previous neurological research, would seem to provide converging evidence towards dysfunction of prefrontal cortex in schizophrenia.

Decreased cytochrome-c oxidase activity and lack of age-related accumulation of mitochondrial DNA deletions in the brains of schizophrenics

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

Cavelier, L.; Jazin, E.E.; Eriksson, I.

1995-09-01

Defects in mitochondrial energy production have been implicated in several neurodegenerative disorders, such as Parkinson disease and amyotrophic lateral sclerosis. To study the contribution of mitochondrial defects to Alzheimer disease and schizophrenia, cytochrome-c oxidase (COX) activity and levels of the mtDNA{sup 4977} deletion in postmortem brain tissue specimens of patients were compared with those of asymptomatic age-matched controls. No difference in COX activity was observed between Alzheimer patients and controls in any of five brain regions investigated. In contrast, schizophrenic patients had a 63% reduction of the COX activity in the nucleus caudatus (P<0.0001) and a 43% reduction in themore » cortex gyrus frontalis (P<0.05) as compared to controls. The average levels of the mtDNA{sup 4977} deletion did not differ significantly between Alzheimer patients and controls, and the deletion followed similar modes of accumulation with age in the two groups. In contrast, no age-related accumulation of mtDNA deletions was found in schizophrenic patients. The reduction in COX activity in schizophrenic patients did not correlate with changes in the total amount of mtDNA or levels of the mtDNA{sup 4977} deletion. The lack of age-related accumulation of the mtDNA{sup 4977} deletion and reduction in COX activity suggest that a mitochondrial dysfunction may be involved in the pathogenesis of schizophrenia. 41 refs., 3 figs., 1 tab.« less

Anterior cingulate dysfunction during choice anticipation in schizophrenia.

PubMed

Quintana, Javier; Wong, Tiffany; Ortiz-Portillo, Elena; Marder, Stephen R; Mazziotta, John C

2004-12-15

The anterior cingulate cortex (ACGC) participates in selective attention, working memory (WM), anticipation, and behavioral monitoring. Subjects with schizophrenia exhibit deficits in these mechanisms during selective attention and WM tasks. However, ACGC dysfunctions have not been specifically investigated during behavioral anticipation, whose deficits may relate to salient schizophrenic features such as foresight abnormalities and impaired social functioning and behavior. We thus studied ACGC function in relation to two aspects of WM, remembering information and anticipating responses, in control and schizophrenic subjects. We measured brain activation in eight subjects with schizophrenia and eight healthy volunteers using functional magnetic resonance imaging. All subjects performed stimulus-response delay tasks with color dots or facial expression diagrams as cues and either 50% or 100% response predictability, which emphasized demands on remembering the cues or anticipating the response for correct performance, respectively. We found a double dissociation of ACGC activation between subject groups and task type. In controls, the ACGC became intensely activated during response anticipation (more extensively and bilaterally when the cues were colors than when they were facial diagrams) but remained at resting activity levels during remembering. In schizophrenic patients, significant ACGC activation was seen only when remembering a percept (more extensively and bilaterally when it was a facial diagram than when it was a color) but not when anticipating a response. These results reveal an ACGC dysfunction during choice anticipation in schizophrenia and suggest that it might underlie the foresight deficits seen in schizophrenic patients.

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics.

PubMed

Lan, T H; Loh, E W; Wu, M S; Hu, T M; Chou, P; Lan, T Y; Chiu, H-J

2008-12-01

Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neuro-fuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.

Neural changes associated with appetite information processing in schizophrenic patients after 16 weeks of olanzapine treatment

PubMed Central

Stip, E; Lungu, O V; Anselmo, K; Letourneau, G; Mendrek, A; Stip, B; Lipp, O; Lalonde, P; Bentaleb, L A

2012-01-01

There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation. PMID:22714121

Which community care for patients with schizophrenic disorders? Packages of care provided by Departments of Mental Health in Lombardy (Italy).

PubMed

Lora, Antonio; Cosentino, Ugo; Gandini, Anna; Zocchetti, Carlo

2007-01-01

The treatment of schizophrenic disorders is the most important challenge for community care. The analysis focuses on packages of care provided to 23.602 patients with a ICD-10 diagnosis of schizophrenic disorder and treated in 2001 by the Departments of Mental Health in Lombardy, Italy. Packages of care refer to a mix of treatments provided to each patient during the year by different settings. Direct costs of the packages were calculated. Linear Discriminant Analysis has been used to link socio-demographic and diagnostic sub-groups of the patients to packages of care. People with schizophrenic disorders received relatively few care packages: only four packages involved more than 5%. Two thirds of the patients received only care provided by Community Mental Health Centres. In the other two packages with a percentage over 5%, the activity was provided by CMHCs, jointly with General Hospitals or Day Care Facilities. Complex care packages were rare (only 6%). As well as the intensity, also the variety of care provided by CMHCs increased with the complexity of care packages. In Lombardy more than half of the resources were spent for schizophrenia. The range of the costs per package was very wide. LDA failed to link characteristics of the patients to packages of care. Care packages are useful tools to understand better how mental health system works, how resources have been spent and to point out problems in the quality of care.

Neural bases of different cognitive strategies for facial affect processing in schizophrenia.

PubMed

Fakra, Eric; Salgado-Pineda, Pilar; Delaveau, Pauline; Hariri, Ahmad R; Blin, Olivier

2008-03-01

To examine the neural basis and dynamics of facial affect processing in schizophrenic patients as compared to healthy controls. Fourteen schizophrenic patients and fourteen matched controls performed a facial affect identification task during fMRI acquisition. The emotional task included an intuitive emotional condition (matching emotional faces) and a more cognitively demanding condition (labeling emotional faces). Individual analysis for each emotional condition, and second-level t-tests examining both within-, and between-group differences, were carried out using a random effects approach. Psychophysiological interactions (PPI) were tested for variations in functional connectivity between amygdala and other brain regions as a function of changes in experimental conditions (labeling versus matching). During the labeling condition, both groups engaged similar networks. During the matching condition, schizophrenics failed to activate regions of the limbic system implicated in the automatic processing of emotions. PPI revealed an inverse functional connectivity between prefrontal regions and the left amygdala in healthy volunteers but there was no such change in patients. Furthermore, during the matching condition, and compared to controls, patients showed decreased activation of regions involved in holistic face processing (fusiform gyrus) and increased activation of regions associated with feature analysis (inferior parietal cortex, left middle temporal lobe, right precuneus). Our findings suggest that schizophrenic patients invariably adopt a cognitive approach when identifying facial affect. The distributed neocortical network observed during the intuitive condition indicates that patients may resort to feature-based, rather than configuration-based, processing and may constitute a compensatory strategy for limbic dysfunction.

Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

PubMed

Mo, Christina; Hannan, Anthony J; Renoir, Thibault

2015-05-01

Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity. Copyright © 2015. Published by Elsevier Ltd.

Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice.

PubMed

Chohan, Tariq W; Boucher, Aurelie A; Spencer, Jarrah R; Kassem, Mustafa S; Hamdi, Areeg A; Karl, Tim; Fok, Sandra Y; Bennett, Maxwell R; Arnold, Jonathon C

2014-11-01

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Creativity and antipsychotic drugs].

PubMed

Murry, P; Torrecuadrada, J L

1997-09-01

For the authors, the creative abilities of a schizophrenic patient are indicators of the therapeutic efficacy of an antipsychotic treatment and the incidence of adverse effects. The new antipsychotic drugs available, unlike conventional neuroleptics, show enhanced efficacy and do not exacerbate the negative symptoms. They may even alleviate them. With regard to clozapine, the authors illustrate the foregoing by two examples of a favorable course in two patients. Clozapine induced an indisputable clinical improvement and hence the opportunity for undeniable artistic activity. Lastly, the new antipsychotics contribute to changing the image that we have of schizophrenic patients.

Nasal cycle dominance and hallucinations in an adult schizophrenic female.

PubMed

Shannahoff-Khalsa, David; Golshan, Shahrokh

2015-03-30

Nasal dominance, at the onset of hallucinations, was studied as a marker of both the lateralized ultradian rhythm of the autonomic nervous system and the tightly coupled ultradian rhythm of alternating cerebral hemispheric dominance in a single case study of a schizophrenic female. Over 1086 days, 145 hallucination episodes occurred with left nostril dominance significantly greater than the right nostril dominant phase of the nasal cycle. A right nostril breathing exercise, that primarily stimulates the left hemisphere, reduces symptoms more quickly for hallucinations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

REJECTION OF CHRONIC SCHIZOPHRENIC PATIENTS : SOME PRELIMINARY OBSERVATIONS FROM KERALA

PubMed Central

Manickam, L. Sam S.; Chandran, Satheesh R.

1998-01-01

A study was conducted on 57 relatives (34 male and 23 female) of 57 (32 male and 25 female) schizophrenic patients in Kerala. The rejection response was found to be related to gender of patients and relatives, being significantly higher in males. The test reliability alpha of the Patient Rejection Scale was found to be 0.93 and it is higher than English and German version of the scale. Compared to the German and New York sample, the present sample tend to have high rejection feeling. PMID:21494484

Genomewide Association Scan of a Mortality Associated Endophenotype for a Long and Healthy Life in the Long Life Family Study.

PubMed

Singh, Jatinder; Minster, Ryan L; Schupf, Nicole; Kraja, Aldi; Liu, YongMei; Christensen, Kaare; Newman, Anne B; Kammerer, Candace M

2017-10-01

Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. Using data from the Long Life Family Study, we performed genomewide association analyses on an endophenotype construct, LF1, comprising a linear combination of traits across health domains. LF1 primarily reflected traits from the pulmonary and physical activity domains. We detected a significant association between LF1 and a locus on chromosome 10p15 (p-value = 4.65 × 10-8) and suggestive evidence (p-value < 5 × 10-6) for association on chromosomes 1, 2, 8, 12, 15, 18, and 22. Using data from the Health, Aging and Body Composition Study, we subsequently replicated the association for the 1p13 region near the NBPF6 locus (p-value = 3.65 × 10-4). Our analyses indicate that loci influencing a healthy aging endophenotype construct predominantly comprised of pulmonary and physical function domains may be located on chromosome 1p13 near the NBPF6 locus. Further investigation of this possible locus and other suggestive loci may reveal novel biological pathways that influence healthy aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence.

PubMed

Ersche, Karen D; Turton, Abigail J; Chamberlain, Samuel R; Müller, Ulrich; Bullmore, Edward T; Robbins, Trevor W

2012-09-01

Not everyone who takes drugs becomes addicted, but the likelihood of developing drug addiction is greater in people with a family history of drug or alcohol dependence. Relatively little is known about how genetic risk mediates the development of drug dependence. By comparing the phenotypic profile of individuals with and without a family history of addiction, the authors sought to clarify the extent to which cognitive dysfunction and personality traits are shared by family members--and therefore likely to have predated drug dependence--and which aspects are specific to drug-dependent individuals. The authors assessed cognitive function and personality traits associated with drug dependence in stimulant-dependent individuals (N=50), their biological siblings without a history of drug dependence (N=50), and unrelated healthy volunteers (N=50). Cognitive function was significantly impaired in the stimulant-dependent individuals across a range of domains. Deficits in executive function and response control were identified in both the stimulant-dependent individuals and in their non-drug-dependent siblings. Drug-dependent individuals and their siblings also exhibited elevated anxious-impulsive personality traits relative to healthy comparison volunteers. Deficits in executive function and response regulation as well as anxious-impulsive personality traits may represent endophenotypes associated with the risk of developing cocaine or amphetamine dependence. The identification of addiction endophenotypes may be useful in facilitating the rational development of therapeutic and preventive strategies.

Profiles of executive function in parents and siblings of individuals with autism spectrum disorders.

PubMed

Wong, D; Maybery, M; Bishop, D V M; Maley, A; Hallmayer, J

2006-11-01

Delineation of a cognitive endophenotype for autism is useful both for exploring the genetic mechanisms underlying the disorder and for identifying which cognitive traits may be primary to it. This study investigated whether first-degree relatives of individuals with autism spectrum disorders (ASDs) demonstrate a specific profile of performance on a range of components of executive function (EF), to determine whether EF deficits represent possible endophenotypes for autism. Parents and siblings of ASD and control probands were tested on EF tasks measuring planning, set-shifting, inhibition and generativity. ASD parents showed poorer performance than control parents on a test of ideational fluency or generativity, and ASD fathers demonstrated a weakness in set-shifting to a previously irrelevant dimension. ASD siblings revealed a mild reduction in ideational fluency and a weakness in non-verbal generativity when compared with control siblings. Neither ASD parents nor siblings displayed significant difficulties with planning or inhibition. These results indicated that the broad autism phenotype may not be characterized primarily by impairments in planning and cognitive flexibility, as had been previously proposed. Weaknesses in generativity emerged as stronger potential endophenotypes in this study, suggesting that this aspect of EF should play a central role in cognitive theories of autism. However, discrepancies in the EF profile demonstrated by parents and siblings suggest that factors related to age or parental responsibility may affect the precise pattern of deficits observed.

Cognitive Characteristics of Children with Genetic Syndromes

PubMed Central

Simon, Tony J.

2008-01-01

The cognitive profile of several different populations of children, each with a distinct neurogenetic disorder that has been described as fitting the pattern of a “nonverbal learning disorder”, is examined. In particular, this paper presents the view that a cognitive endophenotype, specified in terms of specific cognitive processes involving the spatial, temporal and attentional domains, can be used to generate an explanation of the neurocognitive foundation of the common impairments found in these disorders. Methods for evaluating cognitive impairments are first compared and contrasted and the concept of “nonverbal learning disorders” is described. The paper then examines data from experimental tests of spatiotemporal and executive cognitive function acquired from children with one of several disorders to determine whether such a cognitive endophenotype holds promise for moving from descriptions of to explanations for the impairments observed and whether prescriptions for therapeutic interventions might flow from such an account. Synopsis This paper presents the cognitive profile observed in children with one of several common genetic syndromes associated with “nonverbal learning disorders”. It introduces the concept of a cognitive endophenotype in order to help explain the similar pattern of impairments across the syndromes. It explores the explanation of diverse impairments in higher-order visual, spatial, temporal, numerical and executive cognitive competencies deriving from origins in more basic attentional and spatial cognitive dysfunctions. The importance of a developmental approach to understanding dysfunction is stressed. PMID:17562581

Multivariate modelling of endophenotypes associated with the metabolic syndrome in Chinese twins.

PubMed

Pang, Z; Zhang, D; Li, S; Duan, H; Hjelmborg, J; Kruse, T A; Kyvik, K O; Christensen, K; Tan, Q

2010-12-01

The common genetic and environmental effects on endophenotypes related to the metabolic syndrome have been investigated using bivariate and multivariate twin models. This paper extends the pairwise analysis approach by introducing independent and common pathway models to Chinese twin data. The aim was to explore the common genetic architecture in the development of these phenotypes in the Chinese population. Three multivariate models including the full saturated Cholesky decomposition model, the common factor independent pathway model and the common factor common pathway model were fitted to 695 pairs of Chinese twins representing six phenotypes including BMI, total cholesterol, total triacylglycerol, fasting glucose, HDL and LDL. Performances of the nested models were compared with that of the full Cholesky model. Cross-phenotype correlation coefficients gave clear indication of common genetic or environmental backgrounds in the phenotypes. Decomposition of phenotypic correlation by the Cholesky model revealed that the observed phenotypic correlation among lipid phenotypes had genetic and unique environmental backgrounds. Both pathway models suggest a common genetic architecture for lipid phenotypes, which is distinct from that of the non-lipid phenotypes. The declining performance with model restriction indicates biological heterogeneity in development among some of these phenotypes. Our multivariate analyses revealed common genetic and environmental backgrounds for the studied lipid phenotypes in Chinese twins. Model performance showed that physiologically distinct endophenotypes may follow different genetic regulations.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.

PubMed

van der Velde, Jorien; Gromann, Paula M; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

2015-05-01

Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

Recent considerations in the use of recombinant interferon gamma for biological therapy of atopic dermatitis.

PubMed

Brar, Kanwaljit; Leung, Donald Y M

2016-01-01

Atopic dermatitis (AD) is the most common inflammatory skin disease in the general population. There are different endophenotypes of AD that likely have a unique immune and molecular basis, such as those who are predisposed to eczema herpeticum, or Staphylococcus aureus infections. In this review, we highlight the endophenotypes of AD where reduced interferon gamma expression may be playing a role. Additionally, we review the potential role of recombinant interferon gamma therapy in the treatment of atopic dermatitis and the particular phenotypes that may benefit from this treatment. Recombinant interferon gamma treatment will likely benefit the pediatric population with AD, as well as those with susceptibilities for skin infections. Future studies are needed to elucidate whether IFN-γ may reduce the prevalence of skin infection in AD.

Differences in Neural Correlates of Speech Perception in 3 Month Olds at High and Low Risk for Autism Spectrum Disorder.

PubMed

Edwards, Laura A; Wagner, Jennifer B; Tager-Flusberg, Helen; Nelson, Charles A

2017-10-01

In this study, we investigated neural precursors of language acquisition as potential endophenotypes of autism spectrum disorder (ASD) in 3-month-old infants at high and low familial ASD risk. Infants were imaged using functional near-infrared spectroscopy while they listened to auditory stimuli containing syllable repetitions; their neural responses were analyzed over left and right temporal regions. While female low risk infants showed initial neural activation that decreased over exposure to repetition-based stimuli, potentially indicating a habituation response to repetition in speech, female high risk infants showed no changes in neural activity over exposure. This finding may indicate a potential neural endophenotype of language development or ASD specific to females at risk for the disorder.

A role for D-aspartate oxidase in schizophrenia and in schizophrenia-related symptoms induced by phencyclidine in mice

PubMed Central

Errico, F; D'Argenio, V; Sforazzini, F; Iasevoli, F; Squillace, M; Guerri, G; Napolitano, F; Angrisano, T; Di Maio, A; Keller, S; Vitucci, D; Galbusera, A; Chiariotti, L; Bertolino, A; de Bartolomeis, A; Salvatore, F; Gozzi, A; Usiello, A

2015-01-01

Increasing evidence points to a role for dysfunctional glutamate N-methyl-D-aspartate receptor (NMDAR) neurotransmission in schizophrenia. D-aspartate is an atypical amino acid that activates NMDARs through binding to the glutamate site on GluN2 subunits. D-aspartate is present in high amounts in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-aspartate oxidase (DDO). The agonistic activity exerted by D-aspartate on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for some of the NMDAR-related alterations observed in schizophrenia. Consistently, substantial reductions of D-aspartate and NMDA were recently observed in the postmortem prefrontal cortex of schizophrenic patients. Here we show that DDO mRNA expression is increased in prefrontal samples of schizophrenic patients, thus suggesting a plausible molecular event responsible for the D-aspartate imbalance previously described. To investigate whether altered D-aspartate levels can modulate schizophrenia-relevant circuits and behaviors, we also measured the psychotomimetic effects produced by the NMDAR antagonist, phencyclidine, in Ddo knockout mice (Ddo−/−), an animal model characterized by tonically increased D-aspartate levels since perinatal life. We show that Ddo−/− mice display a significant reduction in motor hyperactivity and prepulse inhibition deficit induced by phencyclidine, compared with controls. Furthermore, we reveal that increased levels of D-aspartate in Ddo−/− animals can significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico–hippocampal connectivity networks potentially involved in schizophrenia. Collectively, the present results suggest that altered D-aspartate levels can influence neurodevelopmental brain processes relevant to schizophrenia. PMID:25689573

Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

PubMed

Laviolette, Steven R

2007-07-01

The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.

Stimulation of nicotinic acetylcholine alpha7 receptors rescue schizophrenia-like cognitive impairments in rats.

PubMed

Potasiewicz, Agnieszka; Nikiforuk, Agnieszka; Hołuj, Małgorzata; Popik, Piotr

2017-02-01

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction plays an important role in schizophrenia. Positive allosteric modulators of α7 nAChR have emerged as a promising therapeutic approach to manage cognitive deficits that are inadequately treated in schizophrenic patients. The aim of the present study was to evaluate the ability of type I (CCMI) and type II (PNU120596) α7 nAChR positive allosteric modulators to counteract MK-801-induced cognitive and sensorimotor gating deficits. The activity of these compounds was compared with the action of the α7 nAChR agonist A582941. CCMI, PNU120596 and A582941 reversed the sensorimotor gating impairment evoked by MK-801 based on the prepulse inhibition of the startle response. Additionally, no MK-801-evoked working memory deficits were observed with α7 nAChR ligand pretreatment as assessed in a discrete paired-trial delayed alternation task. However, these compounds did not affect the rats' attentional performances in the five-choice serial reaction time test. The α7 nAChR agents demonstrated a beneficial effect on sensorimotor gating and some aspects of cognition tested in a rat model of schizophrenia. Therefore, these results support the use of α7 nAChR positive allosteric modulators as a potential treatment strategy in schizophrenia.

Validation of the French version of the BACS (the brief assessment of cognition in schizophrenia) among 50 French schizophrenic patients.

PubMed

Bralet, Marie-Cécile; Falissard, Bruno; Neveu, Xavier; Lucas-Ross, Margaret; Eskenazi, Anne-Marie; Keefe, Richard S E

2007-09-01

Schizophrenic patients demonstrate impairments in several key dimensions of cognition. These impairments are correlated with important aspects of functional outcome. While assessment of these cognition disorders is increasingly becoming a part of clinical and research practice in schizophrenia, there is no standard and easily administered test battery. The BACS (Brief Assessment of Cognition in Schizophrenia) has been validated in English language [Keefe RSE, Golberg TE, Harvey PD, Gold JM, Poe MP, Coughenour L. The Brief Assessment of Cognition in Schizophrenia: reliability, sensibility, and comparison with a standard neurocognitive battery. Schizophr. Res 2004;68:283-97], and was found to be as sensitive to cognitive dysfunction as a standard battery of tests, with the advantage of requiring less than 35 min to complete. We developed a French adaptation of the BACS and this study tested its ease of administration and concurrent validity. Correlation analyses between the BACS (version A) and a standard battery were performed. A sample of 50 stable schizophrenic patients received the French Version A of the BACS in a first session, and in a second session a standard battery. All the patients completed each of the subtests of the French BACS . The mean duration of completion for the BACS French version was 36 min (S.D.=5.56). A correlation analysis between the BACS (version A) global score and the standard battery global score showed a significant result (r=0.81, p<0.0001). The correlation analysis between the BACS (version A) sub-scores and the standard battery sub-scores showed significant results for verbal memory, working memory, verbal fluency, attention and speed of information processing and executive functions (p<0.001) and for motor speed (p<0.05). The French Version of the BACS is easier to use in French schizophrenic patients compared to a standard battery (administration shorter and completion rate better) and its good psychometric properties suggest that the French Version of the BACS may be a useful tool for assessing cognition in schizophrenic patients with French as their primary language.

Effects of hormones on cognition in schizophrenic male patients--preliminary results.

PubMed

Bratek, Agnieszka; Koźmin-Burzyńska, Agnieszka; Krysta, Krzysztof; Cierpka-Wiszniewska, Katarzyna; Krupka-Matuszczyk, Irena

2015-09-01

Schizophrenia is a prevalent neurodevelopmental disorder of an unknown etiology and a variable phenotypic expression. In the recent years, the impact of hormones on the course of schizophrenia has been investigated. This study is aimed at assessing the level of correlating serum levels of hormones in schizophrenic male patients with their cognitive functioning measured with neuropsychological tests. In the index group there were 15 medicated male schizophrenic patients. In the control group there were 15 age and education matched healthy men. All subjects underwent analysis of serum hormones level (TSH, testosterone, estradiol, FSH, LH, progesterone and prolactin) and a battery of tests (Trail Making Test A and B, Stroop Test, Verbal and Semantic Fluency Test). The mean serum levels of the following hormones were higher in the index group than in the control group: TSH (1.76 mIU/L vs 1.58 mIU/L; p=0.66), progesterone (0.85 ng/ml vs 0.69 ng/ml; p=0.22) and prolactin (558.71 uIU/ml vs 181 uIU/ml; p=0.025). The mean levels of estradiol (24.36 pg/ml vs 25.40 ng/ml; p=0.64), FSH (3.17 mIU/ml vs 5.72 mIU/ml; p=0.019), LH (3.85 mIU/ml vs 5.77 mIU/ml; p=0.056) and testosterone (2.90 ng/ml vs 5.38 ng/ml; p=0.003) were higher in the control group. In the index group there were significant negative correlations between FSH and semantic fluency (ρ=-0.678606), progesterone and: TMT B (ρ=-0.586763), Stroop 1 (ρ=-0.701880) and Stroop 2 (ρ=-0.601074) and prolactin and TMT A (ρ=-0.579607). The preliminary results of our study show that serum levels of FSH and testosterone are significantly lower, whereas the level of prolactin is markedly higher, in schizophrenic male patients than in healthy men. There is an inverse correlation between serum levels of progesterone, FSH and prolactin and the results of certain cognitive functioning tests in schizophrenic men.

Use of general medical services among Medicaid patients with severe and persistent mental illness.

PubMed

Salsberry, Pamela J; Chipps, Esther; Kennedy, Carol

2005-04-01

The aim of this study was to examine patterns of use of general medical services among persons with a severe and persistent mental illness enrolled in Medicaid from 1996 to 1998. A total of 669 persons with a severe and persistent mental illness were identified by using statewide clinical criteria. A three-year database of Medicaid claims was developed to examine service use. The main outcome measures were use of outpatient services for a general medical problem, use of dental and vision services, and use of screening tests for women. Service use was examined by primary psychiatric diagnosis (schizophrenic, affective, paranoid, and anxiety disorders), and analyses controlled for the presence of a chronic medical condition, age, race, and sex. This study found high levels of service use for outpatient services but very low levels for primary and preventive services. Although 78 percent of persons with a schizophrenic disorder had an office-based visit during the three-year period, all persons with an anxiety disorder had such a visit. Sixty-nine percent of persons with a schizophrenic disorder had at least one emergency department visit, whereas 83 percent of those with an anxiety disorder had such a visit. Dental and vision visits and the use of mammograms and pap tests followed the same pattern; persons with a schizophrenic disorder had fewer visits and had less overall use than the other diagnostic groups. The use patterns across the four groups were significantly different in outpatient service use, dental and vision service use, and screening tests for women. Compared with persons with a schizophrenic disorder, those with an anxiety disorder were more likely to have had an office-based visit and to have received vision services, those with a paranoid disorder were more likely to have used dental services or received a mammogram, and those with an affective disorder were more likely to have had a pap test. Although this group of Medicaid patients with severe and persistent mental illness had access to providers, they received an unacceptably low level of preventive care. Use of health services for general medical problems differed somewhat by primary psychiatric illness.

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

PubMed Central

Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

2015-01-01

Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

Posttraumatic growth and its correlates in primary caregivers of schizophrenic patients

PubMed Central

Balaban, Ozlem Devrim; Yazar, Menekse Sila; Aydin, Erkan; Agachanli, Ruken; Yumrukcal, Huseyin

2017-01-01

Context: The concept of posttraumatic growth (PTG) is important to focus on positive outcomes of a challenging process like caregiving. Aims: The aim of the present study is to investigate the factors inclusively considered to be related to PTG in primary caregivers of schizophrenic patients. Settings and Design: This cross-sectional study was conducted with caregivers of patients with schizophrenia between January 2013 and February 2014 at a mental health hospital. Materials and Methods: The study was carried out on 109 schizophrenic patients followed up at Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, and 109 family members who are the primary caregivers of the patients. All caregivers were evaluated with Posttraumatic Growth Inventory, Multidimensional Scale of Perceived Social Support, Ways of Coping Inventory, and the Basic Personality Traits Inventory and Religious Orientation Scale. Statistical Analysis: Kruskal–Wallis and Mann–Whitney U-test were used in quantitative analysis of data. Spearman's correlation analysis was used in the determination of correlation between variables. Linear regression analysis was used in the determination of predictors of PTG. Results: Optimistic and problem-focused coping, perceived social support (total and all three - family, friends, significant others - domains), personality traits such as extraversion, conscientiousness, and openness to experience, and religiousness were found to be related with PTG. Religiousness, perceived social support, and openness to experience were independent predictors of PTG. Conclusions: Interventions to caregivers of schizophrenic patients on the domains of social support and coping strategies may contribute to caring process in a positive change. PMID:29497186

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

PubMed Central

2010-01-01

Background Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia. Methods For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected. Results The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail. Conclusions The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes. PMID:21067598

Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects.

PubMed

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-06-15

Studies in schizophrenic patients have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus, and cortex that have been related to positive symptoms and cognitive impairments. [(18)F]fallypride positron emission tomography studies were performed in off-medication or never-medicated schizophrenic subjects (n = 11, 6 men, 5 women; mean age of 30.5 +/- 8.0 [SD] years; 4 drug-naive) and age-matched healthy subjects (n = 11, 5 men, 6 women, mean age of 31.6 +/- 9.2 [SD]) to examine dopamine D(2) receptor (DA D(2)r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. In schizophrenic subjects, increased DA D(2)r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with ROI data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex ROI (r = .94, p = .0001), which remained significant after correction for multiple comparisons (p < .03). Correlations of symptoms with parametric images of DA D(2)r levels revealed no significant clusters of correlations with negative symptoms but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. The results of this study demonstrate abnormal DA D(2)r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D(2)r mediate positive symptoms.

Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

PubMed

Peitl, Vjekoslav; Štefanović, Mario; Karlović, Dalibor

2017-07-03

Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of apolipoprotein A5 (APOA5) polymorphisms on serum triglyceride levels in schizophrenic patients under long-term atypical antipsychotic treatment.

PubMed

Hong, Chen-Jee; Chen, Tzu-Ting; Bai, Ya Mei; Liou, Ying-Jay; Tsai, Shih-Jen

2012-01-01

Schizophrenic patients treated with clozapine or olanzapine often develop hypertriglyceridemia. The apolipoprotein A5 gene (APOA5), which affects VLDL production and lipolysis, has been implicated in the triglyceride (TG) metabolism. This study examined the association of common APOA5 genetic variants and TG levels in chronically institutionalized schizophrenic patients, on a stable dose of atypical antipsychotic (clozapine, olanzapine or risperidone. The TG levels in 466 schizophrenic patients treated with clozapine (n = 182), olanzapine (n = 89) or risperidone (n = 195) were measured. Patients were genotyped for the three APOA5 single nucleotide polymorphisms (SNPs) rs662799 (-1131T > C), rs651821 (3A > G) and rs2266788 (1891T > C). A gene × drug interaction with TG levels was observed. In single-marker-based analysis, the minor alleles of the two polymorphisms (-1131C and -3G) were observed to be associated with increased TGs in patients treated with risperidone, but not with clozapine or olanzapine. Haplotype analysis further revealed that carriers of the haplotype constructed with the three minor alleles had higher TG levels than those who did not carry this haplotype in patients taking risperidone (CGC((+/+)) vs. = 125.4 ± 59.1 vs. 82.2 ± 65.8, P = 0.015; CGC((-/+ )) vs. CGC((-/-)) = 113.7 ± 80.4 vs. 82.2 ± 65.8, P = 0.012). Our findings extend and add new information to the existing data regarding the association between APOA5 and TG regulation during long-term atypical antipsychotic treatment.

Speech graphs provide a quantitative measure of thought disorder in psychosis.

PubMed

Mota, Natalia B; Vasconcelos, Nivaldo A P; Lemos, Nathalia; Pieretti, Ana C; Kinouchi, Osame; Cecchi, Guillermo A; Copelli, Mauro; Ribeiro, Sidarta

2012-01-01

Psychosis has various causes, including mania and schizophrenia. Since the differential diagnosis of psychosis is exclusively based on subjective assessments of oral interviews with patients, an objective quantification of the speech disturbances that characterize mania and schizophrenia is in order. In principle, such quantification could be achieved by the analysis of speech graphs. A graph represents a network with nodes connected by edges; in speech graphs, nodes correspond to words and edges correspond to semantic and grammatical relationships. To quantify speech differences related to psychosis, interviews with schizophrenics, manics and normal subjects were recorded and represented as graphs. Manics scored significantly higher than schizophrenics in ten graph measures. Psychopathological symptoms such as logorrhea, poor speech, and flight of thoughts were grasped by the analysis even when verbosity differences were discounted. Binary classifiers based on speech graph measures sorted schizophrenics from manics with up to 93.8% of sensitivity and 93.7% of specificity. In contrast, sorting based on the scores of two standard psychiatric scales (BPRS and PANSS) reached only 62.5% of sensitivity and specificity. The results demonstrate that alterations of the thought process manifested in the speech of psychotic patients can be objectively measured using graph-theoretical tools, developed to capture specific features of the normal and dysfunctional flow of thought, such as divergence and recurrence. The quantitative analysis of speech graphs is not redundant with standard psychometric scales but rather complementary, as it yields a very accurate sorting of schizophrenics and manics. Overall, the results point to automated psychiatric diagnosis based not on what is said, but on how it is said.

The Dream as a Model for Psychosis: An Experimental Approach Using Bizarreness as a Cognitive Marker

PubMed Central

Scarone, Silvio; Manzone, Maria Laura; Gambini, Orsola; Kantzas, Ilde; Limosani, Ivan; D'Agostino, Armando; Hobson, J. Allan

2008-01-01

Many previous observers have reported some qualitative similarities between the normal mental state of dreaming and the abnormal mental state of psychosis. Recent psychological, tomographic, electrophysiological, and neurochemical data appear to confirm the functional similarities between these 2 states. In this study, the hypothesis of the dreaming brain as a neurobiological model for psychosis was tested by focusing on cognitive bizarreness, a distinctive property of the dreaming mental state defined by discontinuities and incongruities in the dream plot, thoughts, and feelings. Cognitive bizarreness was measured in written reports of dreams and in verbal reports of waking fantasies in 30 schizophrenics and 30 normal controls. Seven pictures of the Thematic Apperception Test (TAT) were administered as a stimulus to elicit waking fantasies, and all participating subjects were asked to record their dreams upon awakening. A total of 420 waking fantasies plus 244 dream reports were collected to quantify the bizarreness features in the dream and waking state of both subject groups. Two-way analysis of covariance for repeated measures showed that cognitive bizarreness was significantly lower in the TAT stories of normal subjects than in those of schizophrenics and in the dream reports of both groups. The differences between the 2 groups indicated that, under experimental conditions, the waking cognition of schizophrenic subjects shares a common degree of formal cognitive bizarreness with the dream reports of both normal controls and schizophrenics. Though very preliminary, these results support the hypothesis that the dreaming brain could be a useful experimental model for psychosis. PMID:17942480

An Investigation of Factors Increasing the Risk of Aggressive Behavior among Schizophrenic Inpatients

PubMed Central

Lejoyeux, Michel; Nivoli, Fabrizia; Basquin, Anne; Petit, Aymeric; Chalvin, Florence; Embouazza, Houcine

2013-01-01

Aim of the study: This study tried to identify risk factors of aggressive behavior in a population of schizophrenic inpatients. We tested the association between aggressive behavior and socio-demographic characteristics, addictive disorders, history of suicide attempt, and sexual violence, impulsivity, and sensation seeking. Methods: All consecutive schizophrenic inpatients (100) were assessed during 6 months. Aggressive behavior was quantified with a standardized scale, the Overt Aggression Scale (OAS). We studied socio-demographic characteristics and the history of suicide attempt and sexual violence with a specific standardized questionnaire. Addictive disorders were identified with the Fagerström and CAGE questionnaires and with the DSM-IV-R diagnostic criteria for nicotine, alcohol, cannabis opiates, and cocaine abuse and dependence disorders. Lastly, we studied sensation seeking with the Zuckerman scale and impulsivity with the Barratt scale. Results: Linear regression identified four factors associated with aggressive behavior: male gender (odd ratio = 12.8), history of sexual violence (odd ratio = 3.6), Fagerström score (odd ratio = 1.3), number of cigarettes smoked each day (odd ratio = 1.16). Patients with nicotine use or dependence had significantly higher levels of OAS scores. This difference was not observed between patients with or without alcohol dependence. OAS scores were correlated to the number of cigarettes smoked each day and to Fagerström scores. Patients with a higher level of sensation seeking and impulsivity also had higher OAS scores. Conclusion: A typical schizophrenic patient at risk of showing aggressive behavior is a man, who smokes and presents a history of sexual violence. PMID:24027539

No association of dopamine D2 receptor molecular variant Cys311 and schizophrenia in Chinese patients

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

Chia-Hsiang Chen; Shih-Hsiang Chien; Hai-Gwo Hwu

A serine-to-cysteine mutation of dopamine D2 receptor at codon 311 (Cys311) was found to have higher frequency in schizophrenic patients than in normal controls in Japanese by Arinami et al. The Cys311 allele was found to be associated with patients with younger age-of-onset, positive family history, and more positive symptoms. To investigate the possible involvement of Cys311 in schizophrenia in the Chinese population, 114 unrelated Taiwanese Chinese schizophrenic patients with positive family history and 88 normal controls were genotyped for Cys311. Four patients and 5 normal controls were heterozygotes of Ser311/Cys311; no homozygotes of Cys311 were identified in either group.more » The allele frequencies of Cys311 in Chinese schizophrenic patients and normal controls were 2% and 3%, respectively. No significant difference was detected between the two groups. Our results do not support the argument that the Cys311 allele of DRD2 poses a genetic risk for certain types of schizophrenia in Chinese populations. 18 refs.« less

Association study between schizophrenia and dopamine D3 receptor gene polymorphism

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

Tanaka, Toshihisa; Takahashi, Makoto; Maeda, Masaya

Crocq et al. reported the existence of an association between schizophrenia and homozygosity of a BalI polymorphism in the first exon of the dopamine D3 receptor (DRD3) gene. In response to this report, further studies were conducted; however, these studies yielded conflicting results. In the present study, we examined 100 unrelated Japanese schizophrenics and 100 normal controls to determine any association between this polymorphism and schizophrenia. Results suggest that neither allele nor genotype frequencies of the DRD3 gene in the schizophrenics as a whole are significantly different from those of the controls. Further, we found no association between any allelemore » or genotype and any clinical subtype based on family history of schizophrenia and age-at-onset. A significantly high frequency of homozygosity of a dopamine D3 receptor gene allele was not observed in the schizophrenics as a whole, or in clinical subtypes. Our results suggest that an association between the dopamine D3 receptor gene and schizophrenia is unlikely to exist. 26 refs., 1 tab.« less

[Negative symptoms in patients with non schizophrenic psychiatric disorders].

PubMed

Donnoli, Vicente F; Moroni, María V; Cohen, Diego; Chisari Rocha, Liliana; Marleta, María; Sepich Dalmeida, Tomás; Bonani, Matías; D'Alessio, Luciana

2011-01-01

The presence of negative symptoms (NS) in different clinical entities other than schizophrenia, with a dimensional approach of negative symptoms, was considered in this work. Determine the presence and distribution of NS, in a population of patients with non schizophrenic psychiatric disorders attending ambulatory treatment at public hospitals. Patients with define DSM IV diagnosis criteria for different disorders; affective, alimentary, substance abuse, anxiety, personality disorders and patients with ILAE diagnoses criteria for temporal lobe epilepsy were included. All patients underwent the subscale PANNS for negative symptoms of schizophrenia. Student T test was calculated to determine the differences of frequency for NS among psychiatric disorders. 106 patients were included; 60 women, 46 men, 38 years +/- 12.1. The 90% of patients have a low score of NS. Media 11.6, Max/min 9.38 -14.29. Emotional withdrawal and passive social withdrawal were more frequent in alimentary disorders than in affective disorder and than in epilepsy. Emotional withdrawal was more frequent in substance disorders than epilepsy. According this study, negative symptoms are present in a low to moderate intensity in non schizophrenic psychiatry entities and in the temporal lobe epilepsy.

Familial transmission of risk factors in the first-degree relatives of schizophrenic people.

PubMed

Waldo, M C; Adler, L E; Leonard, S; Olincy, A; Ross, R G; Harris, J G; Freedman, R

2000-02-01

Schizophrenia is a complex illness with multiple pathophysiologic factors that contribute to its psychopathology. One strategy to identify these factors is to observe them in isolation from each other, by characterizing their expression in the relatives of schizophrenic probands. By Mendel's second law, each genetic factor should be independently distributed in a sibship, so that each can be observed by itself, uncomplicated by the general problems of the illness. Such independently distributed phenotypes are obviously useful for genetic analyses; however, they can also be considered together, to model how various brain dysfunctions may combine to produce psychoses. In addition to a sensory gating deficit linked to the alpha 7-nicotinic acetylcholine receptor locus, schizophrenics and their families have a number of other deficits, including decreased hippocampal volume on magnetic resonance images and increased plasma levels of the dopamine metabolite homovanillic acid. Although such research is far from complete, a heuristic model combining a sensory gating deficit, decreased hippocampal neuron capacity, and increased dopaminergic neurotransmission is consonant with current understanding of the neuropsychology of schizophrenia.

Visual scan paths are abnormal in deluded schizophrenics.

PubMed

Phillips, M L; David, A S

1997-01-01

One explanation for delusion formation is that they result from distorted appreciation of complex stimuli. The study investigated delusions in schizophrenia using a physiological marker of visual attention and information processing, the visual scan path-a map tracing the direction and duration of gaze when an individual views a stimulus. The aim was to demonstrate the presence of a specific deficit in processing meaningful stimuli (e.g. human faces) in deluded schizophrenics (DS) by relating this to abnormal viewing strategies. Visual scan paths were measured in acutely-deluded (n = 7) and non-deluded (n = 7) schizophrenics matched for medication, illness duration and negative symptoms, plus 10 age-matched normal controls. DS employed abnormal strategies for viewing single faces and face pairs in a recognition task, staring at fewer points and fixating non-feature areas to a significantly greater extent than both control groups (P < 0.05). The results indicate that DS direct their attention to less salient visual information when viewing faces. Future paradigms employing more complex stimuli and testing DS when less-deluded will allow further clarification of the relationship between viewing strategies and delusions.

Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis.

PubMed

Heekeren, K; Neukirch, A; Daumann, J; Stoll, M; Obradovic, M; Kovar, K-A; Geyer, M A; Gouzoulis-Mayfrank, E

2007-05-01

Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

A depressive endophenotype of mild cognitive impairment and Alzheimer's disease.

PubMed

Johnson, Leigh A; Hall, James R; O'Bryant, Sid E

2013-01-01

Alzheimer's disease (AD) is a devastating public health problem that affects over 5.4 million Americans. Depression increases the risk of Mild Cognitive Impairment (MCI) and AD. By understanding the influence of depression on cognition, the potential exists to identify subgroups of depressed elders at greater risk for cognitive decline and AD. The current study sought to: 1) clinically identify a sub group of geriatric patients who suffer from depression related cognitive impairment; 2) cross validate this depressive endophenotype of MCI/AD in an independent cohort. Data was analyzed from 519 participants of Project FRONTIER. Depression was assessed with the GDS30 and cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to create the Depressive endophenotype of MCI and AD (DepE). DepE was significantly negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37, p<0.001), visuospatial skills (B=-1.11, SE=0.26, p<0.001), Language (B=-1.03, SE=0.21, p<0.001), Attention (B=-2.56, SE=0.49, p<0.001), and Delayed Memory (B=-1.54, SE = 037, p<0.001), and higher DepE scores were related to poorer executive functioning (EXIT25; B=0.65, SE=0.19, p=0.001). DepE scores significantly increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69). Data from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium) were analyzed for cross-validation of findings in an independent cohort. The DepE was significantly related to poorer scores on all measures, and a significantly predicted of cognitive change over 12- and 24-months. The current findings suggest that a depressive endophenotype of MCI and AD exists and can be clinically identified using the GDS-30. Higher scores increased risk for MCI and was cross-validated by predicting AD in the TARCC. A key purpose for the search for distinct subgroups of individuals at risk for AD and MCI is to identify novel treatment and preventative opportunities.

A unified explanation for the diverse structural deviations reported for adult schizophrenics with disrupted speech.

PubMed

Chaika, E

1982-06-01

This paper attempts a unified explanation for the diverse manifestations of deviant speech considered pathognomic for schizophrenia. Examination of the structure of such speech shows that what appear to be diverse errors are really manifestations of two problems: apparently random or erroneous triggering of sounds and words coupled with inappropriate perseverations. These are shown to be different manifestations of the same problem, possibly a schizophrenic dysfunction in neurotransmitters in the brain.. Studies of hemispheric asymetry in schizophrenia, involuntary eyetracking, and the probable action of antipsychotic medication confirm the linguistic data.

[Autogenic training within the therapeutic scope of schizophrenic patients].

PubMed

Starke, H

1976-06-01

The author calls the reader's attention to the rather strange fact that autogenic training, in spite of worldwide recognition and extensive uses of the method in various disciplines of medicine and spheres of live, has not so far been finding wide application in the medical specialty dealing with mental disorders. After discussing some possible causes of this situation and commenting on first signs of a necessary change in attitude toward autogenic training, he reports his own experience in the treatment of schizophrenic patients with this psychotherapeutic method, emphasizing the need for including psychotherapy in a complex concept of the treatment of psychoses.

Decreased energy demanding processes in the frontal lobes of schizophrenics due to neuroleptics? A 31P-magneto-resonance spectroscopic study.

PubMed

Volz, H P; Rzanny, R; Rössger, G; Hübner, G; Kreitschmann-Andermahr, I; Kaiser, W A; Sauer, H

1997-12-30

In the present investigation on 31P-magneto-resonance spectroscopic parameters in the frontal lobe, we found phosphocreatine levels and the ratio phosphocreatine/adenosine triphosphate to be increased (12.62 +/- 1.98% resp. 0.31 +/- 0.06) in 50 neuroleptic-treated schizophrenics, whereas no differences were detected in 10 neuroleptic-free patients (11.66 +/- 2.57% resp. 0.29 +/- 0.08) compared to 36 controls (11.37 +/- 1.45 resp. 0.29 +/- 0.04). This result points to a major role of neuroleptics in the metabolism of high-energy phosphates.

Animal models to improve our understanding and treatment of suicidal behavior.

PubMed

Gould, T D; Georgiou, P; Brenner, L A; Brundin, L; Can, A; Courtet, P; Donaldson, Z R; Dwivedi, Y; Guillaume, S; Gottesman, I I; Kanekar, S; Lowry, C A; Renshaw, P F; Rujescu, D; Smith, E G; Turecki, G; Zanos, P; Zarate, C A; Zunszain, P A; Postolache, T T

2017-04-11

Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic-pituitary-adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

PubMed Central

van der Velde, Jorien; Gromann, Paula M.; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

2015-01-01

Background Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. Methods We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. Results We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. Limitations The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. Conclusion These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia. PMID:25768029

[On the improvement of everyday life behavior of chronic schizophrenic patients; from the viewpoint of "play-like behavior"].

PubMed

Maruta, N

2000-01-01

In this study, the author examined the behavioral patterns of chronic schizophrenic inpatients to follow the process of the amelioration of abulic symptoms such as loss of interest, poverty of thought, lack of sociality, and poor communication. In everyday life in the ward, abulic patients had difficulties in accomplishing not only the basic habitual acts such as getting up or going to bed regularly, exchanging greetings, cleaning teeth, bathing, and washing clothes, but also their assigned duties on the ward. Furthermore, they were unable to behave according to the rules for inpatients, express their emotions appropriately, or build normal interpersonal relationship. The author found that five inpatients achieved some spontaneous behaviors of their own choices in the process of improvement in the above-mentioned habitual acts. As these spontaneous behaviors proceeded through several phases, obvious improvements in their behavioral patterns in everyday life were also observed. The initial phase of transient spontaneous behavior was followed by the second phase of continual spontaneous behavior. Finally, in the interview sessions, the patients became to express pleasurable emotions and physical feelings when they performed their own acts of continual spontaneous behavior. This phenomenon seemed valuable in the therapeutic context because schizophrenic patients are considered seldom capable of having positive feelings toward their own experiences. Therefore, these pleasurable continual spontaneous behaviors may be called "play-like behavior", as confirmed by comparison with the properties of "play" as defined by Caillois. In considering schizophrenic autism, Minkowski described "activité autiste" as an intrinsic quality of the way of life in schizophrenic patients. The manifestation of such quality in spontaneous behaviors can be regarded as having two meanings; an aspect of pathological acting out and a sign of recovery to realistic behaviors. Therapists should consider both aspects when conducting therapies. Although the patients regained the habits and norms of everyday life during hospitalization, the rules involved in "play-like" behavior seemed to contradict some rules in the habitual acts or assigned duties in their daily lives because within "play-like" behavior, freedom predominates over rules. The rules in "play-like" behavior are acquired mostly by mimicking other people. These rules are not fixed laws with penalties but are changeable rules depending on the circumstances of the behavioral process. From this viewpoint, "play-like" behavior allows the patients to acquire practical rules and to understand the relative nature of the rules. Most of the "play-like" behaviors originate from the preferences of the individual patients, which may be something that they have already experienced, something that they have longed for, or something that gives them self-fulfillment. These qualities contribute to the acquisition of experiences that they find pleasurable. For the patients, recalling each "play-like" behavior in the interview sessions enables them to grasp the whole picture of their behaviors, to reinforce their attachment to these behaviors as their own experiences, and to promote the dynamic process between behavior and thought. In this sense, psychotherapy incorporating the aspect of "play-like" behavior seems to prepare the schizophrenic patients to improve their way of thinking. To nurture "play-like" behavior helps the chronic schizophrenic patients to recover will power, independence and sociality, and contributes to the improvement of clinical symptoms and of daily life activities.

The Effect of Yoga on Functional Recovery Level in Schizophrenic Patients.

PubMed

Kavak, Funda; Ekinci, Mine

2016-12-01

The objective of this study is to determine the effect of yoga on functional recovery level in schizophrenic patients. The study was conducted in quasi-experimental design with pretest-posttest control group. The population of the study consisted of schizophrenic patients with registered in Malatya and Elazığ Community Mental Health Centers and regularly going to these centers. The sample group of the study consisted of totally 100 patients including 50 patients in the experimental group and 50 patients in the control group who were specified through power analysis and chosen by using random sampling method from this population. The data were collected between April 2015 and August 2015. 'Patient Description Form' and 'FROGS' were used to collect the data. Yoga was applied to patients in the experimental group. Any intervention was not made to patients in the control group. Percentage distribution, arithmetic mean, standard deviation, chi-square, independent samples t test, and paired t test were used to assess the data. Patients in the control and experimental group pretest subscale and the total means scores of FROGS was found to be low. In the posttest subscale and total means scores of FROGS in the experimental group were higher than in the control group and the differences between them were found to be statistically significant (p<0.05). In the experimental group pretest and posttest subscale and total means scores of FR0GS was determined to be statistically significant (p<0.05). Yoga that applied to schizophrenic patients it was determined to increased the level of functional recovery. It can be suggested that yoga should be used as an complementary method in nursing practise in order to increase the effectiveness of the treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

PubMed

Haralanov, Svetlozar; Haralanova, Evelina; Milushev, Emil; Shkodrova, Diana; Claussen, Claus-Frenz

2018-04-17

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives. © 2018 John Wiley & Sons, Ltd.

F45. THE EFFICACY AND SAFETY OF BLONASERIN AFTER SWITCHING FROM OTHER ATYPICAL ANTIPSYCHOTICS IN SCHIZOPHRENIC INPATIENTS: AN OPEN-LABEL, MULTI-CENTER TRIAL

PubMed Central

Yoon, Bo-Hyun; Bahk, Won-Myong; Kwon, Young Joon; Lee, Sang-Yeol; Lee, Kwanghun; Kim, Moon Doo; Park, Sung-Yong; Song, Min-Kyu

2018-01-01

Abstract Background The aim of this study was to investigate the efficacy and safety of blonanserin treatment after switching from other atypical antipsychotics in schizophrenic inpatients who showed inadequate efficacy and poor tolerability. Methods A total of 63 schizophrenic inpatients (inadequate response group=45 and poor tolerability group=18) were included in this study. They were already treated with atypical antipsychotics except blonanserin and not favored due to inadequate responses or intolerable adverse effects. Blonanserin was administered during 12 weeks after switching from their previous antispsychotics. Treatment response was evaluated with Brief Psychiatric Rating Scale (BPRS) and CGI-S, and safety profile were measured with Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Extrapyramidal Side effects Scale (SAR)S and Barnes Akathisia Rating Scale (BARS). Drug Attitude Inventory (DAI-10) and Subjective Well-being Under Neuroleptic Treatment (SWN) were used for subjective estimates. Assessments were done at baseline, 1, 2, 4, 8 and 12 weeks after blonanserin treatment. Repeated measures of ANOVA were done to analyze the group (inadequate vs. intolerable group) and time effects. Results CGI and BPRS were showed significant treatment responses after switching to Blonaserin. Time effects were significant at 2, 4, 8, 12 weeks after switching and group by time effect were also significant at that time. Mean changes of AIMS, SARS and BARS scores were not significant throughout test trial. Although SWN was significantly improved after switching to Blonaserin, it was not found significant group by time effect. Discussion The results suggest that blonanserin may be effective and well tolerable in schizophrenic patients who showed inadequate treatment response or poor tolerability.

Dopamine D2 Receptor Levels in Striatum, Thalamus, Substantia Nigra, Limbic Regions, and Cortex in Schizophrenic Subjects

PubMed Central

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-01-01

Background Studies in schizophrenics have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus and cortex which have been related to positive symptoms and cognitive impairments. Methods [18F]fallypride PET studies were performed in off medication or never medicated schizophrenic subjects [N = 11, 6 M, 5 F; mean age of 30.5 ± 8.0 (S.D.); 4 drug naive] and age matched healthy subjects [N = 11, 5M, 6F, mean age of 31.6 ± 9.2 (S.D.)] to examine dopamine D2 receptor (DA D2r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. Results In schizophrenic subjects increased DA D2r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with region of interest data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex region of interest (r = 0.94, P = 0.0001) which remained significant after correction for multiple comparisons (P<0.03). Correlations of symptoms with parametric images of DA D2r levels revealed no significant clusters of correlations with negative symptoms, but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. Conclusions The results of this study demonstrate abnormal DA D2r mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D2r mediate positive symptoms. PMID:19251247

The Dynamics of a Periodically Forced Cortical Microcircuit, With an Application to Schizophrenia

NASA Astrophysics Data System (ADS)

Vierling-Claassen, Dorea; Kopell, Nancy

2009-01-01

Synchronous neural activity in the brain in the gamma and beta frequency bands (50-70 Hz)is thought to be important for sensory processing and is altered in schizophrenia. In a previous study, gamma/beta click-train auditory stimuli were used to probe cortical oscillatory activity in control and schizophrenic subjects. We found that control subjects exhibited preferential 40 Hz responses to both 20 and 40 Hz stimulations, while schizophrenic subjects had enhanced 20 Hz responses to the same stimuli [D. Vierling-Claassen, P. Siekmeier, S. Stufflebeam, and N. Kopell, J. Neurophysiol., 99 (2008), p. 2656]. High-dimensional computational network models constructed previously, which were based on evidence of altered inhibition in schizophrenia, numerically generated the entrainment behaviors observed experimentally. However, questions regarding the dynamic origin of model behaviors remained. It was not clear that the 20 Hz response to 40 Hz drive in the schizophrenic network was robust to parameter changes, which would be necessary for the predicted mechanism to explain data from a heterogeneous subject population. In the schizophrenic network we observed 30 Hz drive responses with a frequency component below 30 Hz, for which no analogue appeared in experimental data, and wondered if these were dynamically distinct from the modeled 20 Hz response to 40 Hz drive. We also wished to explore the role of background noise in model behavior. To address these questions, we consider a system of two mutually coupled oscillators representative of neural cells, driven periodically in the gamma/beta frequency band. We show that there is a one-parameter family of discontinuous discrete maps, whose dynamics clarifies issues of robustness, classifies entrainment patterns, and provides insight into the role of excitatory noise.

Finger patterns and age of onset for the determination of the parent-of-origin in the transmission of schizophrenia

PubMed Central

Ponnudurai, R.; Jayakar, J.

2015-01-01

Summary: Dermatoglyphic traits which are reported to be largely determined by genes could be considered as phenotypic characterestics and if the same are expressed through generations in schizophrenic families it can be speculated to serve as genetic markers for schizophrenia. Another factor that might be influenced by genes is the age of onset of the illness in the offspring and the parent of origin. Objective: This study was aimed to elucidate the occurrence of identical finger patterns in the schizophrenic patients and their affected parents. The other objective was to assess the age of onset of the illness in them. Methods: Forty six schizophrenic patients in whom one of the parents was also affected with schizophrenia or related disorders were recruited. Of these pairs 29 were taken up for finger patterns analysis, with an equal number of control group pairs. 35 proband and parent pairs were investigated for the age of onset of the illness. Results: The frequency of occurrence of identical patterns in the right thumbs of proband and their affected mother pairs was significantly more than between the proband and their affected father pairs. Additionally, the number of identical patterns was also more in the right thumbs of proband and their affected mother pairs compared with the control group. The difference between the mean age of onset of the illness in the probands and their affected fathers was more than between the probands and their affected mothers. Conclusion: The genetic association of schizophrenic patients with the affected maternal side appear to be more stronger than with the paternal side. PMID:25657454

Development of the caregivers attitude scale on home care of schizophrenics (CASHS)

PubMed Central

Balasubramanian, N; Sathyanarayana Rao, T. S.; D’Sa, Juliana Linnette

2014-01-01

Background: Schizophrenia is a severe mental disorder that elicits feelings of strangeness and discomfort, which may create stigma and lead to the social exclusion of the mentally ill and of the people relating with them. In the past decade, there has been an increase in the number of research studies on attitudes toward mental disorders. Materials and Methods: An instrument was developed to assess the attitude of primary caregivers on home care of schizophrenics. This article describes the development of a Likert scale, the Caregivers Attitude Scale on Home Care of Schizophrenics CASHS, which is a 31-item self-reported instrument that quantifies three aspects of home care, that is, attitude towards patient, towards treatment, and towards social interaction. The steps involved in its development are the review of literature, development of items, content validation, translation and language validity, pretesting, and reliability. Results: After establishing the content validity, the CASHS was pretested with five subjects. To establish the reliability of the CASHS, 21 primary caregivers were recruited through purposive sampling technique. In order to measure the stability between scores obtained, a test-retest reliability was computed using Karl Pearson correlation coefficient and the r value was 0.78. The internal consistency was measured using Cronbach's alpha and item-total correlation and the r value was 0.789. The item discrimination analysis was also computed and the value was of above 0.35. These statistical measurements indicate that the CASHS was reliable. Conclusions: The CASHS is a valid and reliable tool that can be utilized for assessing the attitude of primary caregivers on home care of schizophrenics. PMID:24574561

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

PubMed

Woodruff, P W; Wright, I C; Bullmore, E T; Brammer, M; Howard, R J; Williams, S C; Shapleske, J; Rossell, S; David, A S; McGuire, P K; Murray, R M

1997-12-01

The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Self psychology conceptualization of postpsychotic depression and recovery among paranoid schizophrenic patients.

PubMed

Potik, David

2014-01-01

Many psychoanalysts have offered innovative ideas on the treatment of schizophrenic patients, but none on postpsychotic depression. The author presents a psychoanalytic conceptualization of postpsychotic depression based on Kohut's ideas regarding the development of normal and pathological grandiosity. The main premise is that postpsychotic depression stems from the loss of psychotic grandiosity, and that it is the psychological reaction to the loss of omnipotent identity whose role it is to provide an alternative reality. Through near-experience connectedness, clinicians and practitioners in the psychiatric rehabilitation field can facilitate an empathic milieu in which new mental constructs can be established and new behavioral skills can be learned.

[Functionality as a goal in the treatment of schizophrenia].

PubMed

García, Bousoño

2002-01-01

Rational use of new atypical antipsychotics have allowed clinicians to have a more optimistic view, on functional outcome in Schizophrenia. Functional outcome is revised here as an essential concept to be kept in mind in the treatment and control of schizophrenic symptoms. This view allows for a better evaluation of the clinical meaning of symptoms and signs, and the impact on daily functioning of unwelcome side effects of some antipsychotics; and finally the impact of all these upon social functioning and may allow the clinician to implement some interventions in the clinical setting taking into account the ultimate and realistic goal in the treatment of schizophrenic patients: their functional outcome.

ALE Meta-Analysis of Schizophrenics Performing the N-Back Task

NASA Astrophysics Data System (ADS)

Harrell, Zachary

2010-10-01

MRI/fMRI has already proven itself as a valuable tool in the diagnosis and treatment of many illnesses of the brain, including cognitive problems. By exploiting the differences in magnetic susceptibility between oxygenated and deoxygenated hemoglobin, fMRI can measure blood flow in various regions of interest within the brain. This can determine the level of brain activity in relation to motor or cognitive functions and provide a metric for tissue damage or illness symptoms. Structural imaging techniques have shown lesions or deficiencies in tissue volumes in schizophrenics corresponding to areas primarily in the frontal and temporal lobes. These areas are currently known to be involved in working memory and attention, which many schizophrenics have trouble with. The ALE (Activation Likelihood Estimation) Meta-Analysis is able to statistically determine the significance of brain area activations based on the post-hoc combination of multiple studies. This process is useful for giving a general model of brain function in relation to a particular task designed to engage the affected areas (such as working memory for the n-back task). The advantages of the ALE Meta-Analysis include elimination of single subject anomalies, elimination of false/extremely weak activations, and verification of function/location hypotheses.

Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.

PubMed

Papageorgiou, C; Kontaxakis, V P; Havaki-Kontaxaki, B J; Stamouli, S; Vasios, C; Asvestas, P; Matsopoulos, G K; Kontopantelis, E; Rabavilas, A; Uzunoglu, N; Christodoulou, G N

2001-09-17

Deficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.

The role of serotonin in schizophrenia.

PubMed

Iqbal, N; van Praag, H M

1995-01-01

The hypothesis that the LSD psychosis and by inference schizophrenic psychoses are related to dysfunctions in central serotonergic systems, formulated by Woolley and Shaw in the early 1950s was the first testable theory of modern biological psychiatry. Initially, it did not get the scientific attention it deserved. First, because LSD fell into disrepute and was to all intents and purposes banned from human experimentation. Secondly, the antipsychotics were discovered in the same period, and it became clear that these compounds block dopaminergic transmission and hence for many years thereafter the dopaminergic system occupied center stage in biological schizophrenia research. Presently, interest in the relation between serotonin and schizophrenia has been revived, due to the development of serotonin-blocking agents that appear to exert therapeutic effects in schizophrenia. In this paper the evidence for and against a link between serotonergic defects and schizophrenia psychopathology is critically discussed. The conclusion to be reached is threefold. (1) Interruption of certain serotonergic circuits represents an antipsychotic principle. (2) Tentative evidence suggests the involvement of serotonergic dysfunctions in the pathogenesis of schizophrenic psychoses. (3) It is not yet known whether serotonergic lesions contribute directly to the occurrence of schizophrenic psychopathology or via alterations in the dopaminergic system.

[The Influence of Threatening Stimuli on the Component P200 in Patients with Paranoid Schizophrenia].

PubMed

Strelets, V B; Arkhipov, A Yu

2015-01-01

We studied schizophrenic patients with the dominance of pseudohallucinations. As is well known, pseudohallucinations are the main syndrome of schizophrenia, the so-called first rank syndrome. Pseudohallucinations are defined as a disorder of sense (affective) perception. This disorder is mainly diagnosed from the clinical picture or by pathopsychologichal observations. We investigated the evoked potentials (EP) of brain after neutral and emotionally meaningful (threatening) visual stimuli in order to specify the neurophysiological disorders of affective perception in schizophrenic patients with severe paranoid-hallucinatory syndrome who did not receive neuroleptic therapy. The analysis of P200 component in healthy subjects showed an increase in the amplitude and shortening of the latency of this wave in response to thretaning stimuli, as compared to neutral stimuli. In the group of patients with schizophrenia, the analysis showed the same increase in the level of excitation in response to emotionally threatening stimuli. However, in schizophrenic patients there were also found certain areas where the amplitude and latency decreased or increased at the same time. The results show that patients with schizophrenia have the pathological effect of having parameters typical of the processes of both excitation and inhibition.

ZNF804A Variation May Affect Hippocampal-Prefrontal Resting-State Functional Connectivity in Schizophrenic and Healthy Individuals.

PubMed

Zhang, Yuyanan; Yan, Hao; Liao, Jinmin; Yu, Hao; Jiang, Sisi; Liu, Qi; Zhang, Dai; Yue, Weihua

2018-06-01

The ZNF804A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity (RSFC) between the hippocampus and the dorsolateral prefrontal cortex (DLPFC) in both schizophrenic patients and healthy controls. The homozygous ZNF804A rs1344706 genotype (AA) conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC (F(2,165) = 13.43, P < 0.001). The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804A rs1344706 on hippocampal-prefrontal RSFC associated with schizophrenia.

Functional abnormalities in the cortical processing of sound complexity and musical consonance in schizophrenia: evidence from an evoked potential study

PubMed Central

2013-01-01

Background Previous studies have demonstrated functional and structural temporal lobe abnormalities located close to the auditory cortical regions in schizophrenia. The goal of this study was to determine whether functional abnormalities exist in the cortical processing of musical sound in schizophrenia. Methods Twelve schizophrenic patients and twelve age- and sex-matched healthy controls were recruited, and participants listened to a random sequence of two kinds of sonic entities, intervals (tritones and perfect fifths) and chords (atonal chords, diminished chords, and major triads), of varying degrees of complexity and consonance. The perception of musical sound was investigated by the auditory evoked potentials technique. Results Our results showed that schizophrenic patients exhibited significant reductions in the amplitudes of the N1 and P2 components elicited by musical stimuli, to which consonant sounds contributed more significantly than dissonant sounds. Schizophrenic patients could not perceive the dissimilarity between interval and chord stimuli based on the evoked potentials responses as compared with the healthy controls. Conclusion This study provided electrophysiological evidence of functional abnormalities in the cortical processing of sound complexity and music consonance in schizophrenia. The preliminary findings warrant further investigations for the underlying mechanisms. PMID:23721126

Impaired preparatory re-mapping of stimulus-response associations and rule-implementation in schizophrenic patients--the role for differences in early processing.

PubMed

Finke, Mareike; Barceló, Francisco; Garolera, Maite; Cortiñas, Miriam; Garrido, Gemma; Pajares, Marta; Escera, Carles

2011-07-01

An accurate representation of task-set information is needed for successful goal directed behavior. Recent studies point to disturbances in the early processing stages as plausible causes for task-switching deficits in schizophrenia. A task-cueing protocol was administered to a group of schizophrenic patients and compared with a sample of age-matched healthy controls. Patients responded slower and less accurate compared with controls in all conditions. The concurrent recording of event-related brain potentials to contextual cues and target events revealed abnormalities in the early processing of both cue-locked and target-locked N1 potentials. Abnormally enhanced target-locked P2 amplitudes were observed in schizophrenic patients for task-switch trials only, suggesting disrupted stimulus evaluation and memory retrieval processes. The endogenous P3 potentials discriminated between task conditions but without further differences between groups. These results suggest that the observed impairments in task-switching behavior were not specifically related to anticipatory set-shifting, but derived from a deficit in the implementation of task-set representations at target onset in the presence of irrelevant and conflicting information. Copyright © 2011 Elsevier B.V. All rights reserved.

FT-IR spectroscopy and multivariate analysis as an auxiliary tool for diagnosis of mental disorders: Bipolar and schizophrenia cases

NASA Astrophysics Data System (ADS)

Ogruc Ildiz, G.; Arslan, M.; Unsalan, O.; Araujo-Andrade, C.; Kurt, E.; Karatepe, H. T.; Yilmaz, A.; Yalcinkaya, O. B.; Herken, H.

2016-01-01

In this study, a methodology based on Fourier-transform infrared spectroscopy and principal component analysis and partial least square methods is proposed for the analysis of blood plasma samples in order to identify spectral changes correlated with some biomarkers associated with schizophrenia and bipolarity. Our main goal was to use the spectral information for the calibration of statistical models to discriminate and classify blood plasma samples belonging to bipolar and schizophrenic patients. IR spectra of 30 samples of blood plasma obtained from each, bipolar and schizophrenic patients and healthy control group were collected. The results obtained from principal component analysis (PCA) show a clear discrimination between the bipolar (BP), schizophrenic (SZ) and control group' (CG) blood samples that also give possibility to identify three main regions that show the major differences correlated with both mental disorders (biomarkers). Furthermore, a model for the classification of the blood samples was calibrated using partial least square discriminant analysis (PLS-DA), allowing the correct classification of BP, SZ and CG samples. The results obtained applying this methodology suggest that it can be used as a complimentary diagnostic tool for the detection and discrimination of these mental diseases.

Three-year recovery outcomes for long-term patients with co-occurring schizophrenic and substance use disorders.

PubMed

Xie, Haiyi; McHugo, Gregory J; Helmstetter, Barbara S; Drake, Robert E

2005-06-15

Little is known about the expected treatment outcomes of patients with co-occurring schizophrenic and substance use disorders. This paper reports 3-year outcomes for 152 patients with schizophrenia or schizoaffective disorder and substance use disorders, all of whom received integrated dual disorders treatments in the New Hampshire Dual Diagnosis Study. Outcomes are defined as positive coping behaviors identified by consumers as indicators of recovery. Participants improved steadily in terms of controlling symptoms of schizophrenia, actively attaining remissions from substance abuse, increasing competitive employment, increasing social contacts with non-substance abusers, and improving life satisfaction. Though successful in reducing hospitalization and homelessness, they did not increase time in independent living situations. Outcomes were only weakly interrelated, suggesting that recovery is a multidimensional concept. Neither psychotic diagnosis (schizophrenia vs. schizoaffective disorder) nor substance abuse diagnosis (alcohol vs. other drug disorder vs. both) was related to outcomes. However, these patients with co-occurring schizophrenic and substance use disorders did significantly less well than patients with co-occurring bipolar and substance use disorders in terms of hospitalization, independent living, and quality of life. Overall, the findings provide a hopeful long-term perspective for dual diagnosis patients.

Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action.

PubMed

Xuan, Jiekun; Pan, Guihua; Qiu, Yunping; Yang, Lun; Su, Mingming; Liu, Yumin; Chen, Jian; Feng, Guoyin; Fang, Yiru; Jia, Wei; Xing, Qinghe; He, Lin

2011-12-02

Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium.

PubMed

Lee, Byung Dae; Park, Je Min; Lee, Young Min; Moon, Eunsoo; Jeong, Hee Jeong; Chung, Young In; Yi, Young Mi

2016-05-31

Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and Character Inventory (TCI) to measure personality and symptomatic dimensions. The heritability of personality dimensions in a total of 472 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). To measure familiality, we compared the personality dimensions of family members with those of 336 healthy unrelated controls using analysis of variance (ANOVA) analysis. Three of the seven TCI variables were significantly heritable and were included in subsequent analyses. The three groups (control, unaffected first-degree relative, case) were found to significantly differ from one another, with the expected order of average group scores, for all heritable dimensions. Despite several study limitations with respect to family recruitment and phenotyping, our results show that aberrations in several personality dimensions related to genetic-environment coactions or interactions may underlie the complexity of the schizophrenic syndrome.

The vulnerability to schizophrenia mainstream research paradigms and phenomenological directions.

PubMed

Stanghellini, Giovanni; Fusar-Poli, Paolo

2012-01-01

Early psychopathological attempts to characterize the vulnerability to schizophrenia were based on the phenomenological method. From the beginning, phenomenologically-oriented psychopathologists have searched the basic vulnerability underlying schizophrenic phenomena in two main domains: depersonalization and derealisation/desocialization. Schizophrenic persons undergo a special kind of depersonalisation: the living body becomes a functioning body, a thing-like mechanism in which feelings, perceptions, and actions take place as if they happened in an outer space. They also endure a special kind of derealisation/de-socialization: the interpersonal scene becomes like a theatre stage, pervaded with a sense of unreality, on which the main actor is unaware of the plot, out of touch with the role he is acting and unable to make sense of the objects he encounters and of what the other people are doing. Many years later, the mainstream research paradigms employed to investigate the vulnerability concept in schizophrenic psychosis have included genetic studies, birth cohort studies, psychosis proneness, and clinical high risk. We will review these studies and conclude with an outline of future research directions focusing on three main features of the psychopathology of early schizophrenia: anomalies of the pre-reflexive self and of the social self (intersubjectivity), and existential re-orientation.

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

PubMed

Akiyama, K; Tsuchida, K; Kanzaki, A; Ujike, H; Hamamura, T; Kondo, K; Mutoh, S; Miyanagi, K; Kuroda, S; Otsuki, S

1995-11-15

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Drama therapy as a means of rehabilitation for schizophrenic patients: our impressions.

PubMed

Bielańska, A; Cechnicki, A; Budzyna-Dawidowski, P

1991-10-01

The authors describe the development of drama therapy and its place in the system of psychosocial treatment of schizophrenic patients. Organizational and therapeutic elements are illustrated with the help of work done by a group of 12 patients on an adaptation of Shakespeare's Hamlet. The aim of this form of outpatient treatment is to use the acting technique in order to make it easier for patients to improve their understanding of themselves--their feelings, motivations and behaviors--and also of other people. The participation of a professional director and the general attractiveness of this type of therapy are considered to play an important role in motivating those patients who would not benefit from traditional psychotherapy. In this form of group psychotherapy verbalization of feelings and problems are structured by the role; thus creating a safe atmosphere and greater motivation to participate. The purpose of our work is to make the roles and the play a constructive aspect of the patient's functioning. This is only possible by uniting what for a schizophrenic patient is characteristically separate, namely, internal experience with external expression. Clinical effects are documented by two case vignettes.

The nonlinear, complex sequential organization of behavior in schizophrenic patients: neurocognitive strategies and clinical correlations.

PubMed

Paulus, M P; Perry, W; Braff, D L

1999-09-01

Thought disorder is a hallmark of schizophrenia and can be inferred from disorganized behavior. Measures of the sequential organization of behavior are important because they reflect the cognitive processes of the selection and sequencing of behavioral elements, which generate observable and analyzable behavioral patterns. In this context, sequences of choices generated by schizophrenic patients in a two-choice guessing task fluctuate significantly, which reflects an "oscillating dysregulation" between highly predictable and highly unpredictable subsequences within a single test session. In this study, we aimed to clarify the significance of dysregulation by seeing whether demographic, clinical, neuropsychological, and psychological measures predict the degree of dysregulation observed on this two-choice task. Thirty schizophrenic patients repeatedly performed a LEFT or RIGHT key press that was followed by a stimulus, which occurred randomly on the left or right side of the computer screen. Thus, the stimulus location had nothing to do with the key press behavior. The range of key press sequence predictabilities as measured by the dynamical entropy was used to quantify the dysregulation of response sequences and reflects the range of fixity and randomness of the responses. A factor analysis was performed and step-wise multiple regression analyses were used to relate the factor scores to demographic, clinical, symptomatic, Wisconsin Card Sorting Test (WCST), and Rorschach variables. The LEFT/RIGHT key press sequences were determined by three factors: 1) the degree of win-stay/lose-shift strategy; 2) the degree of contextual influence on the current choice; and 3) the degree of dysregulation on the choice task. Demographic and clinical variables did not predict any of the three response patterns on the choice task. In contrast, the WCST and Rorschach test predicted performance on various factors of choice task response patterns. Schizophrenic patients employ several rules, i.e., "win-stay/lose-shift" and "decide according to the previous choice," that fluctuate significantly when generating sequences on this task, confirming that a basic behavioral dysregulation occurs in a single schizophrenic subject across a single test session. The organization or the "temporal architecture" of the behavioral sequences is not related to symptoms per se, but is related to deficits in executive functioning, problem solving, and perceptual organizational abilities.

[Communicate instead of stigmatizing - does social contact with a depressed person change attitudes of medical students towards psychiatric disorders? A study of attitudes of medical students to psychiatric patients].

PubMed

Schenner, Manuela; Kohlbauer, Daniela; Günther, Verena

2011-01-01

The aim of the present study was to investigate how attitudes to psychiatric patients of medical students change, when given an opportunity to have social contact with a depressed individual, during their usual psychiatric practical. In the course of their compulsory practical at the University Clinic for General and Social Psychiatry, 127 students additionally participated in an information session in which a person suffering from depression reported on his/her life, illness and experiences with the illness. The control group comprised 98 students who did only the psychiatry practical. Both at the beginning and end of the practical, students filled in a questionnaire, among others, on cognitive and affective dimensions and social distance. The questionnaire was preceded by 4 different case vignettes describing a fictional person (a man/woman suffering from paranoid schizophrenia and a man/woman suffering from unipolar depression). The results of our study show that before students took their practical, female students felt more pro-social and socially closer, but at the same time more fearful, in relation to mentally ill persons than male students. Females also considered psychiatric illnesses as better treatable than males. Basically, students felt socially closer towards depressed persons than towards schizophrenic patients who were also perceived to be more severely ill, more dangerous and more unpredictable. Students with personal contact with a female depressed patient during their practical demonstrated significant reduction of social distance and fear in relation to depressed persons, and in the sense of a generalization effect, there was also a significant reduction in their assessment of the danger and unpredictability of schizophrenic patients. As against this, students who did only their compulsory practical developed an even stronger stereotype of schizophrenic patients as being dangerous and unpredictable. Additionally, contact with a depressed person during practical resulted in a better assessment of the treatability of this illness. Students who participated in the compulsory practical alone reduced their fear towards depressed persons and increased prosocial feelings towards schizophrenic patients. Compared to students who did only the psychiatry practical, additional contact with a depressed person resulted in major changes in attitude, in particular, in relation to the stereotype of schizophrenic patients being "dangerous". Thus, enabling direct contact with patients during psychiatry practical represents a meaningful and effective anti-stigma intervention.

Prefrontal cortex, dopamine, and jealousy endophenotype.

PubMed

Marazziti, Donatella; Poletti, Michele; Dell'Osso, Liliana; Baroni, Stefano; Bonuccelli, Ubaldo

2013-02-01

Jealousy is a complex emotion characterized by the perception of a threat of loss of something that the person values,particularly in reference to a relationship with a loved one, which includes affective, cognitive, and behavioral components. Neural systems and cognitive processes underlying jealousy are relatively unclear, and only a few neuroimaging studies have investigated them. The current article discusses recent empirical findings on delusional jealousy, which is the most severe form of this feeling, in neurodegenerative diseases. After reviewing empirical findings on neurological and psychiatric disorders with delusional jealousy, and after considering its high prevalence in patients with Parkinson's disease under dopamine agonist treatment, we propose a core neural network and core cognitive processes at the basis of (delusional) jealousy, characterizing this symptom as possible endophenotype. In any case,empirical investigation of the neural bases of jealousy is just beginning, and further studies are strongly needed to elucidate the biological roots of this complex emotion.

A watershed model of individual differences in fluid intelligence.

PubMed

Kievit, Rogier A; Davis, Simon W; Griffiths, John; Correia, Marta M; Cam-Can; Henson, Richard N

2016-10-01

Fluid intelligence is a crucial cognitive ability that predicts key life outcomes across the lifespan. Strong empirical links exist between fluid intelligence and processing speed on the one hand, and white matter integrity and processing speed on the other. We propose a watershed model that integrates these three explanatory levels in a principled manner in a single statistical model, with processing speed and white matter figuring as intermediate endophenotypes. We fit this model in a large (N=555) adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) using multiple measures of processing speed, white matter health and fluid intelligence. The model fit the data well, outperforming competing models and providing evidence for a many-to-one mapping between white matter integrity, processing speed and fluid intelligence. The model can be naturally extended to integrate other cognitive domains, endophenotypes and genotypes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila

PubMed Central

van der Voet, M; Harich, B; Franke, B; Schenck, A

2016-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant dopamine signaling is thought to be a major theme in ADHD, but how this relates to the vast majority of ADHD candidate genes is illusive. Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. It represents an equally useful outcome measure for testing chemical compounds to define novel treatment options. PMID:25962619

Depression, Stress, and Anhedonia: Toward a Synthesis and Integrated Model

PubMed Central

Pizzagalli, Diego A.

2014-01-01

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (1) anhedonia, (2) dopamine, and (3) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affect mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reinforcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research. PMID:24471371

Family and twin strategies as a head start in defining prodromes and endophenotypes for hypothetical early-interventions in schizophrenia.

PubMed

Gottesman, I I; Erlenmeyer-Kimling, L

2001-08-01

In an effort to share the experiences of 'genotype-hunters'-who have approached the difficult task of forecasting future schizophrenia in the young offspring or other relatives of index cases, in new samples guided by the prior probabilities of 15% in offspring or 50% in identical co-twins-with 'early-interventionists'-who focus on purported prodromal symptoms in children who would be treated pharmacologically to prevent the development of schizophrenia-we provide a focused review that emphasizes the hazards of false positives in both approaches. Despite the advantages prospective high-risk strategies have had from clinical and laboratory findings that implicate some prodromal signs and endophenotypes, e.g. attention, memory, and information processing evaluations, the yields are not sufficient for practical applications involving antipsychotic drugs for undiagnosed children. Even more caution than usual is required, given the suggestions that the developing neocortex is vulnerable to dopaminergic exposure.

Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia?

PubMed

Solowij, Nadia; Michie, Patricia T

2007-01-01

Currently, there is a lot of interest in cannabis use as a risk factor for the development of schizophrenia. Cognitive dysfunction associated with long-term or heavy cannabis use is similar in many respects to the cognitive endophenotypes that have been proposed as vulnerability markers of schizophrenia. In this overview, we examine the similarities between these in the context of the neurobiology underlying cognitive dysfunction, particularly implicating the endogenous cannabinoid system, which plays a significant role in attention, learning and memory, and in general, inhibitory regulatory mechanisms in the brain. Closer examination of the cognitive deficits associated with specific parameters of cannabis use and interactions with neurodevelopmental stages and neural substrates will better inform our understanding of the nature of the association between cannabis use and psychosis. The theoretical and clinical significance of further research in this field is in enhancing our understanding of underlying pathophysiology and improving the provision of treatments for substance use and mental illness.

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

PubMed

Bey, Katharina; Meyhöfer, Inga; Lennertz, Leonhard; Grützmann, Rosa; Heinzel, Stephan; Kaufmann, Christian; Klawohn, Julia; Riesel, Anja; Ettinger, Ulrich; Kathmann, Norbert; Wagner, Michael

2018-05-02

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

EEG correlates of visual short-term memory as neuro-cognitive endophenotypes of ADHD.

PubMed

Wiegand, Iris; Hennig-Fast, Kristina; Kilian, Beate; Müller, Hermann J; Töllner, Thomas; Möller, Hans-Jürgen; Engel, Rolf R; Finke, Kathrin

2016-05-01

Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. A reduction in visual short-term memory (vSTM) storage capacity was recently suggested as a potential neuro-cognitive endophenotype, i.e., a testable marker of an individual's liability for developing ADHD. This study aimed at identifying markers of the brain abnormalities underlying vSTM reductions in adult ADHD. We combined behavioral parameter-based assessment with electrophysiology in groups of adult ADHD patients and healthy age-matched controls. Amplitudes of ERP markers of vSTM storage capacity, the contralateral delay activity (CDA) and the P3b, were analyzed according to (i) differences between individuals with higher vs. lower storage capacity K and (ii) differences between ADHD patients and control participants. We replicated the finding of reduced storage capacity in adult ADHD. Across groups, individuals with higher relative to lower storage capacity showed a larger CDA and P3b. We further found differences between the patient and control groups in the ERPs: The CDA amplitude was attenuated in an early time window for ADHD patients compared to control participants, and was negatively correlated with ADHD patients' symptom severity ratings. Furthermore, the P3b was larger in ADHD patients relative to control participants. These electrophysiological findings indicate altered brain mechanisms underlying visual storage capacity in ADHD, which are characterized by deficient encoding and maintenance, and increased recruitment of control processes. Accordingly, (quantifiable) ERP markers of vSTM in adult ADHD bear candidacy as neuro-cognitive endophenotypes of the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased sensitivity to positive social stimuli in monozygotic twins at risk of bipolar vs. unipolar disorder.

PubMed

Kærsgaard, S; Meluken, I; Kessing, L V; Vinberg, M; Miskowiak, K W

2018-05-01

Abnormalities in affective cognition are putative endophenotypes for bipolar and unipolar disorders but it is unclear whether some abnormalities are disorder-specific. We therefore investigated affective cognition in monozygotic twins at familial risk of bipolar disorder relative to those at risk of unipolar disorder and to low-risk twins. Seventy monozygotic twins with a co-twin history of bipolar disorder (n = 11), of unipolar disorder (n = 38) or without co-twin history of affective disorder (n = 21) were included. Variables of interest were recognition of and vigilance to emotional faces, emotional reactivity and -regulation in social scenarios and non-affective cognition. Twins at familial risk of bipolar disorder showed increased recognition of low to moderate intensity of happy facial expressions relative to both unipolar disorder high-risk twins and low-risk twins. Bipolar disorder high-risk twins also displayed supraliminal attentional avoidance of happy faces compared with unipolar disorder high-risk twins and greater emotional reactivity in positive and neutral social scenarios and less reactivity in negative social scenarios than low-risk twins. In contrast with our hypothesis, there was no negative bias in unipolar disorder high-risk twins. There were no differences between the groups in demographic characteristics or non-affective cognition. The modest sample size limited the statistical power of the study. Increased sensitivity and reactivity to positive social stimuli may be a neurocognitive endophenotype that is specific for bipolar disorder. If replicated in larger samples, this 'positive endophenotype' could potentially aid future diagnostic differentiation between unipolar and bipolar disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

A risk PRODH haplotype affects sensorimotor gating, memory, schizotypy, and anxiety in healthy male subjects.

PubMed

Roussos, Panos; Giakoumaki, Stella G; Bitsios, Panos

2009-06-15

Significant associations have been shown for haplotypes comprising three PRODH single nucleotide polymorphisms (SNPs; 1945T/C, 1766A/G, 1852G/A) located in the 3' region of the gene, suggesting a role of these variants in the etiopathogenesis of schizophrenia. We assessed the relationship between these high-risk PRODH polymorphisms and schizophrenia-related endophenotypes in a large and highly homogeneous cohort of healthy males. Participants (n = 217) were tested in prepulse inhibition (PPI), verbal and working memory, trait anxiety and schizotypy. The QTPHASE from the UNPHASED package was used for the association analysis of each SNP or haplotype data. This procedure revealed significant phenotypic impact of the risk CGA haplotype. Subjects were then divided in two groups; levels of PPI, anxiety, and schizotypy, verbal and working memory were compared with analysis of variance. CGA carriers (n = 32) exhibited attenuated PPI (p < .001) and verbal memory (p < .001) and higher anxiety (p < .004) and schizotypy (p < .008) compared with the noncarriers (n = 185). There were no differences in baseline startle, demographics, and working memory. The main significant correlations were schizotypy x PPI [85-dB, 120-msec trials] in the carriers and schizotypy x anxiety in the entire group and the noncarriers but not the carriers group. Our results strongly support PPI as a valid schizophrenia endophenotype and highlight the importance of examining the role of risk haplotypes on multiple endophenotypes and have implications for understanding the continuum from normality to psychosis, transitional states, and the genetics of schizophrenia-related traits.

Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides.

PubMed

Chen, Pei; Jou, Yuh-Shan; Fann, Cathy S J; Chen, Jaw-Wen; Chung, Chia-Min; Lin, Chin-Yu; Wu, Sheng-Yeu; Kang, Mei-Jyh; Chen, Ying-Chuang; Jong, Yuh-Shiun; Lo, Huey-Ming; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Huang, Nai-Kuei; Wu, Yi-Lin; Pan, Wen-Harn

2009-01-01

Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG. Copyright 2008 Wiley-Liss, Inc.

Cognitive deficits as an endophenotype for anorexia nervosa: an accepted fact or a need for re-examination?

PubMed

Talbot, Amy; Hay, Phillipa; Buckett, Geoffrey; Touyz, Stephen

2015-01-01

To investigate whether impaired set shifting and weak central coherence represent state or trait characteristics and, therefore, candidate endophenotypes of anorexia nervosa (AN). Forty-nine individuals with lifetime AN (24 acutely unwell, 10 weight recovered, and 15 fully recovered) and 43 healthy controls completed the Wisconsin Card Sorting Test (WCST), the Matching Familiar Figures Test, and the Rey Complex Figure Task measuring cognitive flexibility, local processing, and global processing, respectively. Participants also completed questionnaires assessing eating disorder, anxiety and depressive symptoms, obsessional traits, interpersonal functioning, and quality of life. Body mass index was calculated from height and weight measurements. Participants with lifetime AN demonstrated poorer set shifting ability than healthy controls as evidenced by a greater number of perseverative errors on the WCST. When participants were grouped according to illness status, only those in the two recovered groups demonstrated poorer set shifting ability than healthy controls while patients with acute AN performed comparably to all other groups. There were no significant differences between groups on measures of local and global processing. No relationship was found between specific clinical features of AN and cognitive performance. The results of this study are consistent with a global trend toward set shifting difficulties in patients with AN but do not support weak central coherence as a candidate endophenotype for AN. These findings have clinical implications in terms of treatment selection and planning, particularly in relation to the use of cognitive remediation therapy with patients with AN. © 2014 Wiley Periodicals, Inc.

Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB).

PubMed

Gau, Susan Shur-Fen; Shang, Chi-Yung

2010-07-01

Little is known about executive functions among unaffected siblings of children with attention deficit/hyperactivity disorder (ADHD), and there is lack of such information from non-Western countries. We examined verbal and nonverbal executive functions in adolescents with ADHD, unaffected siblings and controls to test whether executive functions could be potential endophenotypes for ADHD. We assessed 279 adolescents (age range: 11-17 years) with a childhood diagnosis of DSM-IV ADHD, 136 biological siblings (108 unaffected, 79.4%), and 173 unaffected controls by using psychiatric interviews, the Wechsler Intelligence Scale for Children - 3rd edition (WISC-III), including digit spans, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC). Compared with the controls, adolescents with ADHD and unaffected siblings had a significantly shorter backward digit span, more extra-dimensional shift errors in the IED, shorter spatial span length in the SSP, more total errors and poorer strategy use in the SWM, and fewer problems solved in the minimum number of moves and shorter initial thinking time in the SOC. The magnitudes of the differences in the SWM and SOC increased with increased task difficulties. In general, neither persistent ADHD nor comorbidity was associated with increased deficits in executive functions among adolescents with ADHD. The lack of much difference in executive dysfunctions between unaffected siblings and ADHD adolescents suggests that executive dysfunctions may be useful cognitive endophenotypes for ADHD genetic studies.

Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.

PubMed

Mosconi, Lisa; Berti, Valentina; Quinn, Crystal; McHugh, Pauline; Petrongolo, Gabriella; Varsavsky, Isabella; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Brinton, Roberta Diaz

2017-09-26

This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men. Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined. All patients had volumetric MRI, 18 F-fluoro-2-deoxyglucose (FDG)-PET (glucose metabolism), and Pittsburgh compound B-PET scans (β-amyloid [Aβ] deposition, a hallmark of AD pathology). As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased Aβ deposition, and reduced gray and white matter volumes in AD-vulnerable regions ( p < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women ( p < 0.001). Aβ deposition was exacerbated in APOE4 -positive MENO women relative to the other groups ( p < 0.001). Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process. © 2017 American Academy of Neurology.

Animal models to improve our understanding and treatment of suicidal behavior

PubMed Central

Gould, T D; Georgiou, P; Brenner, L A; Brundin, L; Can, A; Courtet, P; Donaldson, Z R; Dwivedi, Y; Guillaume, S; Gottesman, I I; Kanekar, S; Lowry, C A; Renshaw, P F; Rujescu, D; Smith, E G; Turecki, G; Zanos, P; Zarate, C A; Zunszain, P A; Postolache, T T

2017-01-01

Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic–pituitary–adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio. PMID:28398339

Risk or resilience? Empathic abilities in patients with bipolar disorders and their first-degree relatives.

PubMed

Seidel, Eva-Maria; Habel, Ute; Finkelmeyer, Andreas; Hasmann, Alexander; Dobmeier, Matthias; Derntl, Birgit

2012-03-01

Endophenotypes are intermediate phenotypes which are considered a more promising marker of genetic risk than illness itself. While previous research mostly used cognitive deficits, emotional functions are of greater relevance for bipolar disorder regarding the characteristic emotional hyper-reactability and deficient social-emotional competence. Hence, the aim of the present study was to clarify whether empathic abilities can serve as a possible endophenotype of bipolar disorder by applying a newly developed task in bipolar patients and their first-degree relatives. Three components of empathy (emotion recognition, perspective taking and affective responsiveness) have been assessed in a sample of 21 bipolar patients, 21 first-degree relatives and 21 healthy controls. Data analysis indicated significant differences between controls and patients for emotion recognition and affective responsiveness but not for perspective taking. This shows that in addition to difficulties in recognizing facial emotional expressions, bipolar patients have difficulties in identifying emotions they would experience in a given situation. However, the ability to take the perspective of another person in an emotional situation was intact but decreased with increasing severity of residual hypomanic and depressive symptoms. Relatives performed comparably bad on emotion recognition but did not differ from controls or patients in affective responsiveness. This study is the first to show that deficient emotion recognition is the only component of empathy which forms a possible endophenotype of bipolar disorder. This has important implications for prevention strategies. Furthermore, changes in affective responsiveness in first-degree relatives show a potential resilience marker. Copyright © 2011 Elsevier Ltd. All rights reserved.

Moderators of neuropsychological mechanism in attention-deficit hyperactivity disorder.

PubMed

Nikolas, Molly A; Nigg, Joel T

2015-02-01

Neuropsychological measures have been proposed as both a way to tap mechanisms and as endophenotypes for child ADHD. However, substantial evidence supporting heterogeneity in neuropsychological performance among youth with ADHD as well as apparent effect differences by sex, age, and comorbidity have slowed progress. To address this, it is important to understand sibling effects in relation to these moderators. 461 youth ages 6-17 years (54.8 % male, including 251 youth with ADHD, 107 of their unaffected biological siblings, and 103 non-ADHD controls) completed diagnostic interviews and a theoretically informed battery of neuropsychological functioning. A structural equation model was used to consolidate neuropsychological domains. Group differences between unaffected siblings of youth with ADHD and controls across each domain were first examined as the primary endophenotype test for ADHD. Moderation of these effects was evaluated via investigation of interactions between diagnostic group and both proband and individual level characteristics, including sex, age, and comorbidity status. Unaffected siblings performed worse than control youth in the domains of inhibition, response time variability, and temporal information processing. Individual age moderated these effects, such that differences between controls and unaffected siblings were pronounced among younger children (ages 6-10 years) but absent among older youth (ages 11-17 years). Evidence for moderation of effects by proband sex and comorbidity status produced more variable and smaller effects. Results support the utility of inhibition, response time variability, and temporal processing as useful endophenotypes for ADHD in future genetic associations studies of the disorder, but suggest this value will vary by age among unaffected family members.

[Attention deficit hyperactivity disorder: its aetiological factors and endophenotypes].

PubMed

Ferrando-Lucas, M T

2006-02-13

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for patients' visits in everyday practice. The academic and social distortion it produces in those affected by this condition have turned it into a subject that is receiving growing attention from researchers and the progress being made in the neurosciences means that it is being investigated from a wide range of approaches. Genetic aspects, as well as anatomical and neurobiological markers, are some of the new lines of research that are being used together with a more precise neuropsychological approach to obtain a more comprehensive understanding of ADHD. Such knowledge now involves genetic factors, centres of cognitive disorder and the search for endophenotypes that account for the complexity of its semiology. The primary cognitive deficits in ADHD appear to be the underlying problem in the disorder, special attention also being given to both the executive functions and the distortion of the capacity to inhibit responses. Furthermore, anatomical factors have been related to the type and severity of the symptomatology of the disorder, although the dispersion of the results and the genetic findings that focus their attention on anomalous alleles for dopamine transporting and receptor genes suggest that the disorder is more complex. The different aetiological factors that have been associated to the disorder and the variability in the semiology of ADHD place us before a situation in disarray; the determination of endophenotypes, however, could enable us carry out a better systematisation of a disorder that is currently still a long way from being fully understood.

Behavioural endophenotypes in mice lacking the auxiliary GABAB receptor subunit KCTD16.

PubMed

Cathomas, Flurin; Sigrist, Hannes; Schmid, Luca; Seifritz, Erich; Gassmann, Martin; Bettler, Bernhard; Pryce, Christopher R

2017-01-15

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABA B receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABA B receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12 -/- ) exhibit increased auditory fear learning and that Kctd12 +/- mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons. KCTD16 has been demonstrated to influence neuronal excitability by regulating GABA B receptor-mediated gating of postsynaptic ion channels. In the present study we investigated for behavioural endophenotypes in Kctd16 -/- and Kctd16 +/- mice. Compared with wild-type (WT) littermates, auditory and contextual fear conditioning were normal in both Kctd16 -/- and Kctd16 +/- mice. When fear memory was tested on the following day, Kctd16 -/- mice exhibited less extinction of auditory fear memory relative to WT and Kctd16 +/- mice, as well as more contextual fear memory relative to WT and, in particular, Kctd16 +/- mice. Relative to WT, both Kctd16 +/- and Kctd16 -/- mice exhibited normal circadian activity. This study adds to the evidence that auxillary KCTD subunits of GABA B receptors contribute to the regulation of behaviours that could constitute endophenotypes for hyper-reactivity to aversive stimuli in neuropsychiatric disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Early identification and high-risk strategies for bipolar disorder.

PubMed

Correll, Christoph U; Penzner, Julie B; Lencz, Todd; Auther, Andrea; Smith, Christopher W; Malhotra, Anil K; Kane, John M; Cornblatt, Barbara A

2007-06-01

To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD). Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high-risk strategies. Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first-degree bipolar relative. On the other hand, emerging work in the clinical-high-risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom 'prodromal' stages of BPD seems to be an under-researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent-onset bipolar, as well as in prospective population-based phenomenology trials and attenuated symptom-based high-risk studies. Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first-degree relative with this disorder, clinical high-risk approaches have great potential to inform early identification and intervention programs.

EEG-LORETA endophenotypes of the common idiopathic generalized epilepsy syndromes.

PubMed

Clemens, B; Puskás, S; Besenyei, M; Emri, M; Opposits, G; Kis, S A; Hollódy, K; Fogarasi, A; Kondákor, I; Füle, K; Bense, K; Fekete, I

2012-05-01

We tested the hypothesis that the cortical areas with abnormal local EEG synchronization are dissimilar in the three common idiopathic generalized epilepsy (IGE) phenotypes: IGE patients with absence seizures (ABS), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures exclusively (EGTCS). Groups of unmedicated ABS, JME and EGTCS patients were investigated. Waking EEG background activity (without any epileptiform potentials) was analyzed by a source localization method, LORETA (Low Resolution Electromagnetic Tomography). Each patient group was compared to a separate, age-matched group of healthy control persons. Voxel-based, normalized broad-band (delta, theta, alpha, and beta) and very narrow band (VNB, 1Hz bandwidth, from 1 to 25Hz) LORETA activity (=current source density, A/m(2)) were computed for each person. Group comparison included subtraction (average patient data minus average control data) and group statistics (multiple t-tests, where Bonferroni-corrected p<0.05 values were accepted as statistically significant). Statistically not significant main findings were: overall increased delta and theta broad band activity in the ABS and JME groups; decrease of alpha and beta activity in the EGTCS group. Statistically significant main findings were as follows. JME group: bilaterally increased theta activity in posterior (temporal, parietal, and occipital) cortical areas; bilaterally increased activity in the medial and basal prefrontal area in the 8Hz VNB; bilaterally decreased activity in the precuneus, posterior cingulate and superior parietal lobule in the 11Hz and 21-22Hz VNBs. ABS group: bilaterally increased theta activity emerged in the basal prefrontal and medial temporal limbic areas. Decreased activity was found at 19-21Hz in the right postcentral gyrus and parts of the right superior and medial temporal gyri. EGTCS group: decreased activity was found in the frontal cortex and the postcentral gyrus at 10-11Hz, increased activity in the right parahippocampal gyrus at 16-18Hz. Increased theta activity in the posterior parts of the cortex is the endophenotype for JME. Increased theta activity in the fronto-temporal limbic areas is the endophenotype for ABS. Statistically not significant findings might indicate diffuse biochemical abnormality of the cortex in JME and ABS. EEG-LORETA endophenotypes may correspond to the selective propensity to generate absence and myoclonic seizures in the ABS and JME syndromes. Copyright © 2011 Elsevier B.V. All rights reserved.

The neurosociology of schizophrenia: vulnerability and functional disability.

PubMed

Carter, M; Flesher, S

1995-08-01

It has been maintained that becoming a schizophrenic is essentially "a social and interpersonal process, not an inevitable consequence of primary symptoms and neurochemical abnormality" (Estroff 1989). It is the intent of this paper to elaborate on this theme by exploring how the neuropsychological deficits of schizophrenia relate to the observed social handicaps of people who carry the diagnosis. We argue that a better understanding of schizophrenia requires inquiry into the handicaps as well as the process whereby schizophrenic and preschizophrenic men and women try and fail to negotiate socially mandated roles. Of necessity, such an inquiry will require mixing levels of explanation (Meehl 1990) and will draw upon insights from the disciplines of psychiatry, neuropsychology, and sociology.

Expected incidence of tardive dyskinesia associated with atypical antipsychotics.

PubMed

Glazer, W M

2000-01-01

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

Self-mutilation of the nose in a schizophrenic patient with Cotard syndrome.

PubMed

Ghaffari-Nejad, Alireza; Kerdegari, Mohammad; Reihani-Kermani, Hamed

2007-10-01

Cotard syndrome is a rare condition, which its main symptom is nihilistic delusion. Self-mutilation of the nose is also a rare condition, which has not been seen in schizophrenic patients with Cotard syndrome. A single case is presented here. A 32-year-old woman who was diagnosed as having schizophrenia and believed that she was dead, cut the tip of her nose. She had no guilt feeling and described her act as a cosmetic surgery. We try to explain how various symptoms that seem to be very far from each other could exist side by side. Misinterpretation of her face is suggested to be the starting point in her complex symptoms.

Interrater reliability levels of multiple clinical examiners in the evaluation of a schizophrenic patient: quality of life, level of functioning, and neuropsychological symptomatology.

PubMed

Cicchetti, D V; Rosenheck, R; Showalter, D; Charney, D; Cramer, J

1999-05-01

Sir Ronald Fisher used a single-subject design to derive the concepts of appropriate research design, randomization, sensitivity, and tests of statistical significance. The seminal work of Broca demonstrated that valid and generalizable findings can and have emerged from studies of a single patient in neuropsychology. In order to assess the reliability and/or validity of any clinical phenomena that derive from single subject research, it becomes necessary to apply appropriate biostatistical methodology. The authors develop just such an approach and apply it successfully to the evaluation of the functioning, quality of life, and neuropsychological symptomatology of a single schizophrenic patient.

[Ambivalence and diachrony].

PubMed

Zoila, A F

1977-04-01

The temporal analysis of ambivalence is based on an account given by two schizophrenic patients and the study of Samuel Becket's "The Nameless One". The narrative process corresponds to a creative expression in which discordance is part of the differences between verbalisation and sensitive phenomenous. Splitting of personality is linked with temporal ambivalence: the immediate past encroaches on the near future, giving an impression of synchronization in the simultaneous interplay of similarity and dissimilarity. The passing of time, disturbed in its accumulative cursus in the schizophrenic patient, results in a conflict between contradictory phenomenous in the same moment. This synchronization of dissimilar perceptions brings together disjunctive and conjunctive categories dominated by such coordinate conjunctions as "and... and", in the living diachronic discordance.

[Evaluation of mimetic expression of schizophrenic and depressed patients by the psychiatrist].

PubMed

Schneider, F; Mattes, R; Adam, B; Heimann, H

1992-01-01

Facial videos of schizophrenic and depressive patients and of healthy controls when watching both funny and horror films and during emotionally positive or negative interviews were rated by psychiatrists (experts) and students (novices). The observers' task was to rate joy, fear, sadness, and expressivity on a 7-point unipolar intensity scale. The soundless facial videos were presented to each observer for exactly 2.5 min. The observer groups did not differ significantly in their ratings except for sadness. Psychiatrists consistently rated expressed sadness as less intense than students. Facial expressivity and joy were rated as less intense in both patient groups in comparison with healthy controls. Depressives expressed significantly more sadness.

The Behavioral Actions of Lithium in Rodent Models

PubMed Central

O’Donnell, Kelley C.; Gould, Todd D.

2007-01-01

For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium. PMID:17532044

Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

PubMed

Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

2016-01-11

Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease mechanisms.

Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study

PubMed Central

Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

2016-01-01

Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural high-resolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00±29.04) showed less scores for sadness compared to healthy controls (128.70±22.26) (p<0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics. PMID:25963262

Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study.

PubMed

Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

2015-06-01

Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural highresolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00+-29.04) showed less scores for sadness compared to healthy controls (128.70+-22.26) (p less than 0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics.

A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

PubMed Central

Logotheti, Marianthi; Papadodima, Olga; Venizelos, Nikolaos; Chatziioannou, Aristotelis; Kolisis, Fragiskos

2013-01-01

Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets. PMID:23554570

[Changes in the EEG spectral power during perception of neutral and emotionally salient words in schizophrenic patients, their relatives and healthy individuals from the general population].

PubMed

Alfimova, M V; Uvarova, L G

2007-01-01

To search for EEG-correlates of emotional processing that might be indicators of genetic predisposition to schizophrenia, changes in EEG spectral power during perception of neutral and emotionally salient words were examined in 36 schizophrenic patients, 50 of their unaffected first-degree relatives, and 47 healthy individuals without any family history of psychoses. In healthy persons, passive listening to neutral words induced minimum changes in cortical rhythmical activity, predominantly in the form of synchronization of slow and fast waves, whereas perception of emotional words was followed by a generalized depression of the alpha and beta1 activity and a locally specific decrease in the power of theta and beta2 frequency bands. The patients and their relatives showed a decrease in the alpha and beta1 activity simultaneously with an increase in the power of delta activity in response to both groups of words. Thus, in the patients and their relatives, reactions to neutral and emotional words were ulterior as a result of augmented reactions to the neutral words. These findings suggest that the EEG changes reflect familial and possibly hereditable abnormal involuntary attention. No prominent decrease in reactivity to emotional stimuli was revealed in schizophrenic families.

Correlation among personal, social performance and cognitive impairment in male schizophrenic patient

NASA Astrophysics Data System (ADS)

Damanik, R.; Effendy, E.; Camellia, V.

2018-03-01

Schizophrenia is a dramatic mental illness with tragic manifestation. The consequences of the illness are for the individual, affected his or her family and society. Schizophrenia is one of the twenty illness that causes Years Lost due to Disability. Treating only the symptom is insufficient. The aim of treatment must include the quality of life of aschizophrenic person. This study aims to examine the relationship between cognitive impairment and performance of the person with schizophrenia. Cognitive test is scaled with Indonesian version of Montreal Cognitive Assessment (MoCA-Ina), while personal and social performance isscaled with Personal and Social Performance scale. There are many studies that search the relationship between cognitive impairment and social functioning of schizophrenic patients, but this is the first study that uses PSP and MoCA-Ina. Both PSP and MoCA-Ina are easy to use but still have high sensitivity and specificity, and perhaps can build people’s interest to use it in clinical practice. Twenty-five male schizophrenic patients were assessed in Prof. M. Ildrem Mental Hospital of North Sumatera Province of Indonesia. Positive correlations between MoCA-Ina and PSP score were identified. Clinicians should pay attention to cognitive and might give some early intervention to it.

Locus of control and self-esteem in depressed, low-income African-American women.

PubMed

Goodman, S H; Cooley, E L; Sewell, D R; Leavitt, N

1994-06-01

Depressed, schizophrenic, and well low-income, African-American women were studied in an effort to extend previous hypotheses of the association between depression and the two personality constructs of low self-esteem and externality to this population. Subjects were 113 low income African-American women including 26 who had been diagnosed as depressed, 54 diagnosed as schizophrenic, and 33 well women. Locus of control was measured with the Adult Nowicki-Strickland Internal-External Control Scale (Nowicki & Duke, 1974). Self-esteem was measured with the Rosenberg Self-Esteem Scale (Rosenberg, 1965). Contrary to predictions, a diagnosis of schizophrenia, but not depression, was associated with more external locus of control. For self-esteem, severity of disturbance, rather than diagnosis, seemed to be of primary importance. Also, lower self-esteem scores were correlated significantly with higher levels of externality for both depressed and schizophrenic women but not for well controls. The present study indicates that self-esteem and locus of control are related to depression differently in low socio-economic status (SES) African-American women than in previously studied middle SES depressed whites. The findings emphasize the need for more normative studies to clarify the complex relations among SES, race, emotional disturbance, self-esteem, and locus of control.

Central- and autonomic nervous system coupling in schizophrenia

PubMed Central

Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

2016-01-01

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

Compliance and schizophrenia: the predictive potential of insight into illness, symptoms, and side effects.

PubMed

Kao, Yu-Cheng; Liu, Yia-Ping

2010-01-01

Personal beliefs about medication compliance have been reliably associated with emotional and behavioral response to mental health problems and health outcomes. This notion has been extensively explored in relation to mental illness. In the current study, a questionnaire designed to assess beliefs about medication compliance (the medication adherence rating scale [MARS]) was translated into Taiwanese to explore beliefs about compliance in schizophrenic patients. In this cross-sectional study, 104 patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenic disorders were recruited and independently interviewed. We first determined the psychometric properties of the translated MARS, including internal consistency, test-retest reliability, and construct validity. In addition, we investigated the relationships between medication compliance and clinical variables through correlation and regression analyses. We found that the translated MARS was a simple and reliable self-reported compliance scale. Furthermore, in this exploratory study, we found that patients with better medication compliance had better insight into mental illness, less severe psychopathologic condition, and less negative subjective response to side effects of antipsychotics. Additional research focusing on these patient outcomes will be of great interest and value in elucidating the role of medication compliance in management of schizophrenic patients. Copyright © 2010 Elsevier Inc. All rights reserved.

Schizophrenic Diblock-Copolymer-Functionalized Nanoparticles as Temperature-Responsive Pickering Emulsifiers.

PubMed

Ranka, Mikhil; Katepalli, Hari; Blankschtein, Daniel; Hatton, T Alan

2017-11-21

Stimuli-responsive pickering emulsions have received considerable attention in recent years, and the utilization of temperature as a stimulus has been of particular interest. Previous efforts have led to responsive systems that enable the formation of stable emulsions at room temperature, which can subsequently be triggered to destabilize with an increase in temperature. The development of a thermoresponsive system that exhibits the opposite response, however, i.e., one that can be triggered to form stable emulsions at elevated temperatures and subsequently be induced to phase separate at lower temperatures, has so far been lacking. Here, we describe a system that accomplishes this goal by leveraging a schizophrenic diblock copolymer that exhibits both an upper and a lower critical solution temperature. The diblock copolymer was conjugated to 20 nm silica nanoparticles, which were subsequently demonstrated to stabilize O/W emulsions at 65 °C and trigger phase separation upon cooling to 25 °C. The effects of particle concentration, electrolyte concentration, and polymer architecture were investigated, and facile control of emulsion stability was demonstrated for multiple oil types. Our approach is likely to be broadly adaptable to other schizophrenic diblock copolymers and find significant utility in applications such as enhanced oil recovery and liquid-phase heterogeneous catalysis, where stable emulsions are desired only at elevated temperatures.

Smooth pursuit eye movement (SPEM) in patients with multiple complex developmental disorder (MCDD), a subtype of the pervasive developmental disorder.

PubMed

Lahuis, Bertine E; Van Engeland, Herman; Cahn, Wiepke; Caspers, Esther; Van der Geest, Jos N; Van der Gaag, Rutger Jan; Kemner, Chantal

2009-01-01

Multiple complex developmental disorder (MCDD) is a well-defined and validated behavioural subtype of pervasive developmental disorder-not otherwise specified (PDD-NOS) and is thought to be associated with a higher risk of developing a schizophrenic spectrum disorder. The question was addressed whether patients with MCDD show the same psychophysiological abnormalities as seen in patients with schizophrenia. Smooth pursuit eye movement (pursuit gain and saccadic parameters) was measured in children with either MCDD (n=18) or autism (n=18), and in age- and IQ-matched controls (n=36), as well as in a group of adult patients with schizophrenia (n=14) and a group of adult controls (n=17). We found the expected effect of lower velocity gain and increased number of saccades in schizophrenic patients. Children with MCDD also showed a lower velocity gain compared to controls children. In contrast, velocity gain was similar in autistic subjects and controls. No differences for velocity gain were found in a direct comparison between MCDD and autism. Saccadic parameters were not significantly different from controls in either MCDD or autistic subjects. Children with MCDD, like schizophrenic adults, show a reduced velocity gain, which could indicate that schizophrenia spectrum disorders and MCDD share (at least to some degree) a common neurobiological background.

Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD).

PubMed

Hallak, Jaime E C; Machado-de-Sousa, João Paulo; Crippa, José Alexandre S; Sanches, Rafael Faria; Trzesniak, Clarissa; Chaves, Cristiano; Bernardo, Sandra Aparecida; Regalo, Simone Cecílio; Zuardi, Antonio Waldo

2010-03-01

The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300 mg or cannabidiol 600 mg or placebo. The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300 mg performing better than those who received cannabidiol 600 mg. The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.

An fMRI study of semantic processing in men with schizophrenia

PubMed Central

Kubicki, M.; McCarley, R.W.; Nestor, P.G.; Huh, T.; Kikinis, R.; Shenton, M.E.; Wible, C.G.

2009-01-01

As a means toward understanding the neural bases of schizophrenic thought disturbance, we examined brain activation patterns in response to semantically and superficially encoded words in patients with schizophrenia. Nine male schizophrenic and 9 male control subjects were tested in a visual levels of processing (LOP) task first outside the magnet and then during the fMRI scanning procedures (using a different set of words). During the experiments visual words were presented under two conditions. Under the deep, semantic encoding condition, subjects made semantic judgments as to whether the words were abstract or concrete. Under the shallow, nonsemantic encoding condition, subjects made perceptual judgments of the font size (uppercase/lowercase) of the presented words. After performance of the behavioral task, a recognition test was used to assess the depth of processing effect, defined as better performance for semantically encoded words than for perceptually encoded words. For the scanned version only, the words for both conditions were repeated in order to assess repetition-priming effects. Reaction times were assessed in both testing scenarios. Both groups showed the expected depth of processing effect for recognition, and control subjects showed the expected increased activation of the left inferior prefrontal cortex (LIPC) under semantic encoding relative to perceptual encoding conditions as well as repetition priming for semantic conditions only. In contrast, schizophrenics showed similar patterns of fMRI activation regardless of condition. Most striking in relation to controls, patients showed decreased LIFC activation concurrent with increased left superior temporal gyrus activation for semantic encoding versus shallow encoding. Furthermore, schizophrenia subjects did not show the repetition priming effect, either behaviorally or as a decrease in LIPC activity. In patients with schizophrenia, LIFC underactivation and left superior temporal gyrus overactivation for semantically encoded words may reflect a disease-related disruption of a distributed frontal temporal network that is engaged in the representation and processing of meaning of words, text, and discourse and which may underlie schizophrenic thought disturbance. PMID:14683698

Psychopharmacological treatment of aggression in schizophrenic patients.

PubMed

Brieden, T; Ujeyl, M; Naber, D

2002-05-01

Aggressive behavior is frequently observed in schizophrenic patients. More than 50 % of all psychiatric patients and 10 % of schizophrenic patients show aggressive symptoms varying from threatening behavior and agitation to assault. The pharmacological treatment of acute, persisting and repetitive aggression is a serious problem for other patients and staff members. Not only is violent behavior from mentally ill patients the most detrimental factor in their stigmatization, aggression is also a considerable direct source of danger for the patients themselves. Based on rather limited evidence, a wide variety of medications for the pharmacological treatment of aggression has been recommended: typical and atypical antipsychotics, benzodiazepines, mood stabilizers, beta-blockers and selective serotonin reuptake inhibitors (SSRIs). Most clinical information on treating aggression has been collected for atypical neuroleptics, particularly for clozapine. Several retrospective and open studies indicate its efficacy. Treatment duration of 6 months is recommended to induce a stable reduction of physical and verbal aggression. Severe side effects have very rarely been seen. At the moment, clozapine seems to be the first choice in aggression treatment. Within the last few years, about 10 articles were published showing that this is the most effective antiaggressive agent in the treatment of aggression and agitation in psychiatric patients, independent of psychiatric diagnosis. However, clozapine, like all the other substances used, does not have an established indication for the treatment of aggressive symptoms. Noncompliance with medication makes it difficult to choose the right preparation for the medication: tablets, liquids, intramuscular injections and readily soluble "FDDFs" are available. Ethical, juridical and methodological problems prevent controlled studies from establishing a reference in the treatment of aggression in mentally ill patients. This review summarizes the current discussion and publications on the pharmacological treatment of aggression in schizophrenic patients of the last 20 years. In addition, we will briefly present studies and case reports concerning the treatment of aggression in other psychiatric patients.

Variants of the D{sub 5} dopamine receptor gene found in patients with schizophrenia: Identification of a nonsense mutation and multiple missense changes

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

Sobell, J.L.; Lind, T.J.; Sommer, S.S.

To determine whether mutations in the D{sub 5} dopamine receptor (D{sub 5}DR) gene are associated with schizophrenia, the gene was examined in 78 unrelated schizophrenic individuals. After amplification by the polymerase chain reaction, products were examined by dideoxy fingerprinting (ddF), a highly sensitive screening method related to single strand conformational polymorphism analysis. All samples with unusual ddF patterns were sequenced to precisely identify the sequence change. In the 156 D{sub 5}DR alleles examined, nine sequence changes were identified. Four of the nine did not affect protein structure; of these, three were silent changes and one was a transition in themore » 3{prime} untranslated region. The remaining five sequence changes result in protein alterations: of these, one is a missense change in a non-conserved amino acid, 3 are missense changes in amino acids that are conserved in some dopamine D{sub 5} receptors and the last is a nonsense mutation. To investigate whether the nonsense mutation was associated with schizophrenia, 400 additional schizophrenic cases of western European descent and 1914 ethnically-similar controls were screened for the change. One additional schizophrenic carrier was identified and verified by direct genomic sequencing (allele frequency: .0013), but eight carriers also were found and confirmed among the non-schizophrenics (allele frequency: .0021)(p>.25). The gene was re-examined in all newly identified carriers of the nonsense mutation by direct sequencing and/or ddF in search of additional mutations. None were identified. Family studies also were conducted to investigate possible cosegregation of the mutation with other neuropsychiatric diseases, but this was not demonstrated. Thus, the mutation does not appear to be associated with an increased risk of schizophrenia nor does an initial analysis suggest cosegregation with other neuropsychiatric disorders or symptom complexes.« less

Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla.

PubMed

Jensen, J Eric; Miller, Jodi; Williamson, Peter C; Neufeld, Richard W J; Menon, Ravi S; Malla, Ashok; Manchanda, Rahul; Schaefer, Betsy; Densmore, Maria; Drost, Dick J

2006-03-31

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder.

PubMed

Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-joon; Han, Mooyoung; Choi, Sang-Sup; Kim, So Won; Lee, Min Goo

2012-02-01

It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. © Copyright 2012 Physicians Postgraduate Press, Inc.

Plasma homovanillic acid differences in clinical subgroups of first episode schizophrenic patients.

PubMed

Baeza, Immaculada; Castro-Fornieles, Josefina; Deulofeu, Ramon; de la Serna, Elena; Goti, Javier; Salvà, Joan; Bernardo, Miquel

2009-07-30

This study evaluates the relationship between plasma homovanillic acid (pHVA) levels, which have been used to study the role of central dopamine in schizophrenia, and the positive/negative syndrome in first episode schizophrenic patients before and after antipsychotic treatment. Forty neuroleptic-naive first episode schizophrenic patients were monitored at baseline and on days 7, 14 and 28. Clinical status was evaluated with the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Brief Psychotic Rating Scale. Plasma HVA levels were also measured. Patients were divided into predominantly positive or negative syndrome groups by subtracting SAPS from SANS scores, at baseline. A healthy control group was also enrolled. Schizophrenic patients as a group had significantly higher pHVA levels than controls at baseline (20.50+/-11.85 vs. 13.04+/-7.22 ng/ml). Moreover, 12 predominantly negative syndrome patients had similar mean baseline pHVA levels (21.30+/-12.36 ng/ml) to those of 28 predominantly positive syndrome patients (19.40+/-11.33 ng/ml). During follow-up, there was a different evolution of pHVA levels in the predominantly positive syndrome group than in the predominantly negative syndrome group, with a significantly greater global reduction of pHVA levels in the former. Although both groups showed clinical improvement following 4 weeks of treatment with risperidone, pHVA levels at endpoint were lower (13.29+/-5.91 ng/ml) than at baseline in patients in the predominantly positive syndrome group, while among those in the predominantly negative syndrome group there was no difference in pHVA levels before and after treatment (21.02+/-13.06 ng/ml). The different pHVA level profiles observed in predominantly positive and negative syndrome first episode patients after 4 weeks of treatment with risperidone suggest that each syndrome may have a different underlying neurobiology.

Development of Antipsychotic Medications with Novel Mechanisms of Action Based on Computational Modeling of Hippocampal Neuropathology

PubMed Central

Siekmeier, Peter J.; vanMaanen, David P.

2013-01-01

A large number of cellular level abnormalities have been identified in the hippocampus of schizophrenic subjects. Nonetheless, it remains uncertain how these pathologies interact at a system level to create clinical symptoms, and this has hindered the development of more effective antipsychotic medications. Using a 72-processor supercomputer, we created a tissue level hippocampal simulation, featuring multicompartmental neuron models with multiple ion channel subtypes and synaptic channels with realistic temporal dynamics. As an index of the schizophrenic phenotype, we used the specific inability of the model to attune to 40 Hz (gamma band) stimulation, a well-characterized abnormality in schizophrenia. We examined several possible combinations of putatively schizophrenogenic cellular lesions by systematically varying model parameters representing NMDA channel function, dendritic spine density, and GABA system integrity, conducting 910 trials in total. Two discrete “clusters” of neuropathological changes were identified. The most robust was characterized by co-occurring modest reductions in NMDA system function (-30%) and dendritic spine density (-30%). Another set of lesions had greater NMDA hypofunction along with low level GABA system dysregulation. To the schizophrenic model, we applied the effects of 1,500 virtual medications, which were implemented by varying five model parameters, independently, in a graded manner; the effects of known drugs were also applied. The simulation accurately distinguished agents that are known to lack clinical efficacy, and identified novel mechanisms (e.g., decrease in AMPA conductance decay time constant, increase in projection strength of calretinin-positive interneurons) and combinations of mechanisms that could re-equilibrate model behavior. These findings shed light on the mechanistic links between schizophrenic neuropathology and the gamma band oscillatory abnormalities observed in the illness. As such, they generate specific falsifiable hypotheses, which can guide postmortem and other laboratory research. Significantly, this work also suggests specific non-obvious targets for potential pharmacologic agents. PMID:23526999

An fMRI study of semantic processing in men with schizophrenia.

PubMed

Kubicki, M; McCarley, R W; Nestor, P G; Huh, T; Kikinis, R; Shenton, M E; Wible, C G

2003-12-01

As a means toward understanding the neural bases of schizophrenic thought disturbance, we examined brain activation patterns in response to semantically and superficially encoded words in patients with schizophrenia. Nine male schizophrenic and 9 male control subjects were tested in a visual levels of processing (LOP) task first outside the magnet and then during the fMRI scanning procedures (using a different set of words). During the experiments visual words were presented under two conditions. Under the deep, semantic encoding condition, subjects made semantic judgments as to whether the words were abstract or concrete. Under the shallow, nonsemantic encoding condition, subjects made perceptual judgments of the font size (uppercase/lowercase) of the presented words. After performance of the behavioral task, a recognition test was used to assess the depth of processing effect, defined as better performance for semantically encoded words than for perceptually encoded words. For the scanned version only, the words for both conditions were repeated in order to assess repetition-priming effects. Reaction times were assessed in both testing scenarios. Both groups showed the expected depth of processing effect for recognition, and control subjects showed the expected increased activation of the left inferior prefrontal cortex (LIPC) under semantic encoding relative to perceptual encoding conditions as well as repetition priming for semantic conditions only. In contrast, schizophrenics showed similar patterns of fMRI activation regardless of condition. Most striking in relation to controls, patients showed decreased LIFC activation concurrent with increased left superior temporal gyrus activation for semantic encoding versus shallow encoding. Furthermore, schizophrenia subjects did not show the repetition priming effect, either behaviorally or as a decrease in LIPC activity. In patients with schizophrenia, LIFC underactivation and left superior temporal gyrus overactivation for semantically encoded words may reflect a disease-related disruption of a distributed frontal temporal network that is engaged in the representation and processing of meaning of words, text, and discourse and which may underlie schizophrenic thought disturbance.