Comorbidity between obsessive-compulsive disorder and body dysmorphic disorder: prevalence, explanatory theories, and clinical characterization

PubMed Central

Frías, Álvaro; Palma, Carol; Farriols, Núria; González, Laura

2015-01-01

Background With the advent of the fifth edition of Diagnostic and Statistical Manual of Mental Disorders, body dysmorphic disorder (BDD) has been subsumed into the obsessive-compulsive disorders and related disorders (OCDRD) category. Objective We aimed to determine the empirical evidence regarding the potential relationship between BDD and obsessive-compulsive disorder (OCD) based on the prevalence data, etiopathogenic pathways, and clinical characterization of patients with both disorders. Method A comprehensive search of databases (PubMed and PsycINFO) was performed. Published manuscripts between 1985 and May 2015 were identified. Overall, 53 studies fulfilled inclusion criteria. Results Lifetime comorbidity rates of BDD–OCD are almost three times higher in samples with a primary diagnosis of BDD than those with primary OCD (27.5% vs 10.4%). However, other mental disorders, such as social phobia or major mood depression, are more likely among both types of psychiatric samples. Empirical evidence regarding the etiopathogenic pathways for BDD–OCD comorbidity is still inconclusive, whether concerning common shared features or one disorder as a risk factor for the other. Specifically, current findings concerning third variables show more divergences than similarities when comparing both disorders. Preliminary data on the clinical characterization of the patients with BDD and OCD indicate that the deleterious clinical impact of BDD in OCD patients is greater than vice versa. Conclusion Despite the recent inclusion of BDD within the OCDRD, data from comparative studies between BDD and OCD need further evidence for supporting this nosological approach. To better define this issue, comparative studies between BDD, OCD, and social phobia should be carried out. PMID:26345330

Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis.

PubMed

Chalmers, John A; Quintana, Daniel S; Abbott, Maree J-Anne; Kemp, Andrew H

2014-01-01

Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis. Studies comparing resting-state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis. Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterized by lower HRV [high frequency (HF): Hedges' g = -0.29. 95% CI: -0.41 to -0.17, p < 0.001; time domain: Hedges' g = -0.45, 95% CI: -0.57 to -0.33, p < 0.001] than controls. Panic disorder (n = 447), post-traumatic stress disorder (n = 192), generalized anxiety disorder (n = 68), and social anxiety disorder (n = 90), but not obsessive-compulsive disorder (n = 40), displayed reductions in HF HRV relative to controls (all ps < 0.001). Anxiety disorders are associated with reduced HRV, findings associated with a small-to-moderate effect size. Findings have important implications for future physical health and well-being of patients, highlighting a need for comprehensive cardiovascular risk reduction.

Meige's Syndrome: Rare Neurological Disorder Presenting as Conversion Disorder.

PubMed

Debadatta, Mohapatra; Mishra, Ajay K

2013-07-01

Meige's syndrome is a rare neurological syndrome characterized by oromandibular dystonia and blepharospasm. Its pathophysiology is not clearly determined. A 35-year-old female presented to psychiatric department with blepharospasm and oromandibular dystonia with clinical provisional diagnosis of psychiatric disorder (Conversion Disorder). After thorough physical examination including detailed neurological exam and psychiatric evaluation no formal medical or psychiatric diagnosis could be made. The other differential diagnoses of extra pyramidal symptom, tardive dyskinesia, conversion disorder, anxiety disorder were ruled out by formal diagnostic criteria. Consequently with suspicion of Meige's syndrome she was referred to the department of Neurology and the diagnosis was confirmed. Hence, Meige's syndrome could be misdiagnosed as a psychiatric disorder such as conversion disorder or anxiety disorder because clinical features of Meige's syndrome are highly variable and affected by psychological factors and also can be inhibited voluntarily to some extent.

Characterization of suicidal behaviour with self-organizing maps.

PubMed

Leiva-Murillo, José M; López-Castromán, Jorge; Baca-García, Enrique

2013-01-01

The study of the variables involved in suicidal behavior is important from a social, medical, and economical point of view. Given the high number of potential variables of interest, a large population of subjects must be analysed in order to get conclusive results. In this paper, we describe a method based on self-organizing maps (SOMs) for finding the most relevant variables even when their relation to suicidal behavior is strongly nonlinear. We have applied the method to a cohort with more than 8,000 subjects and 600 variables and discovered four groups of variables involved in suicidal behavior. According to the results, there are four main groups of risk factors that characterize the population of suicide attempters: mental disorders, alcoholism, impulsivity, and childhood abuse. The identification of specific subpopulations of suicide attempters is consistent with current medical knowledge and may provide a new avenue of research to improve the management of suicidal cases.

Low rates of depressed mood and depression diagnoses in a clinic review of children and adolescents with autistic disorder.

PubMed

Henry, Charles A; Nowinski, Lisa; Koesterer, Karmen; Ferrone, Christine; Spybrook, Jessaca; Bauman, Margaret

2014-09-01

The purpose of this study was to investigate the prevalence of depression diagnoses and related clinical data in an outpatient sample of youth with autistic disorder. Records of 123 psychiatrically referred children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of autistic disorder were examined. Mood disorder diagnoses and chief complaints along with family mood disorder history were the primary variables analyzed. Four subjects (3%) presented with depressed mood. Irritability complaints were frequent (n=78, 63%). Six subjects (5%) received a mood disorder diagnosis; all with mood disorder, not otherwise specified. No subjects received a depressive disorder diagnosis. Family history of mood disorders was common. Findings raise questions about the appropriate characterization and potential misdiagnoses of depression in youth with autistic disorder.

Oral Manifestation of Autosomal Recessive Congenital Ichthyosis in a 2-Year-Old Patient

PubMed Central

Ramar, Kavitha; Annamalai, Sankar; Hariharavel, V. P.; Aravindhan, R.; Ganesh, C.; Ieshwaryah, K.

2014-01-01

Ichthyosis is a heterogeneous family of hereditary keratinisation disorders mostly characterized by variable erythema of the whole body and different scaling patterns. Although these disorders affect tissues of epidermal origin, there is little evidence regarding the oral and dental manifestations of Lamellar Ichthyosis. A case report of early childhood caries in lamellar ichthyosis is presented and the dental consideration and management is discussed in this paper. PMID:24995134

FAMILY ANALYSIS OF IMMUNOGLOBULIN CLASSES AND SUBCLASSES IN CHILDREN WITH AUTISTIC DISORDER

PubMed Central

Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

2009-01-01

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations. PMID:20001993

Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

PubMed

Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

2009-11-01

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

PubMed

Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

2016-08-01

SEE MATTAR ET AL DOI101093/AWW151 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Functional brain networks demonstrate significant temporal variability and dynamic reconfiguration even in the resting state. Currently, most studies investigate temporal variability of brain networks at the scale of single (micro) or whole-brain (macro) connectivity. However, the mechanism underlying time-varying properties remains unclear, as the coupling between brain network variability and neural activity is not readily apparent when analysed at either micro or macroscales. We propose an intermediate (meso) scale analysis and characterize temporal variability of the functional architecture associated with a particular region. This yields a topography of variability that reflects the whole-brain and, most importantly, creates an analytical framework to establish the fundamental relationship between variability of regional functional architecture and its neural activity or structural connectivity. We find that temporal variability reflects the dynamical reconfiguration of a brain region into distinct functional modules at different times and may be indicative of brain flexibility and adaptability. Primary and unimodal sensory-motor cortices demonstrate low temporal variability, while transmodal areas, including heteromodal association areas and limbic system, demonstrate the high variability. In particular, regions with highest variability such as hippocampus/parahippocampus, inferior and middle temporal gyrus, olfactory gyrus and caudate are all related to learning, suggesting that the temporal variability may indicate the level of brain adaptability. With simultaneously recorded electroencephalography/functional magnetic resonance imaging and functional magnetic resonance imaging/diffusion tensor imaging data, we also find that variability of regional functional architecture is modulated by local blood oxygen level-dependent activity and α-band oscillation, and is governed by the ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis

PubMed Central

Chalmers, John A.; Quintana, Daniel S.; Abbott, Maree J.-Anne; Kemp, Andrew H.

2014-01-01

Background: Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis. Method: Studies comparing resting-state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis. Results: Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterized by lower HRV [high frequency (HF): Hedges’ g = −0.29. 95% CI: −0.41 to −0.17, p < 0.001; time domain: Hedges’ g = −0.45, 95% CI: −0.57 to −0.33, p < 0.001] than controls. Panic disorder (n = 447), post-traumatic stress disorder (n = 192), generalized anxiety disorder (n = 68), and social anxiety disorder (n = 90), but not obsessive–compulsive disorder (n = 40), displayed reductions in HF HRV relative to controls (all ps < 0.001). Conclusion: Anxiety disorders are associated with reduced HRV, findings associated with a small-to-moderate effect size. Findings have important implications for future physical health and well-being of patients, highlighting a need for comprehensive cardiovascular risk reduction. PMID:25071612

Motor learning characterization in people with autism spectrum disorder: A systematic review

PubMed Central

de Moraes, Íbis Ariana Peña; Massetti, Thais; Crocetta, Tânia Brusque; da Silva, Talita Dias; de Menezes, Lilian Del Ciello; Monteiro, Carlos Bandeira de Mello; Magalhães, Fernando Henrique

2017-01-01

ABSTRACT Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder primarily characterized by deficits in social interaction, communication and implicit skill learning. OBJECTIVE: To analyse the results of research on "motor learning" and the means used for measuring "autistic disorder". METHODS: A systematic literature search was done using Medline/PubMed, Web of Science, BVS (virtual health library), and PsycINFO. We included articles that contained the keywords "autism" and "motor learning". The variables considered were the methodological aspects; results presented, and the methodological quality of the studies. RESULTS: A total of 42 studies were identified; 33 articles were excluded because they did not meet the inclusion criteria. Data were extracted from nine eligible studies and summarized. CONCLUSION: We concluded that although individuals with ASD showed performance difficulties in different memory and motor learning tasks, acquisition of skills still takes place in this population; however, this skill acquisition is related to heterogeneous events, occurring without the awareness of the individual. PMID:29213525

Behavioral and Neural Sustained Attention Deficits in Disruptive Mood Dysregulation Disorder and Attention-Deficit/Hyperactivity Disorder.

PubMed

Pagliaccio, David; Wiggins, Jillian Lee; Adleman, Nancy E; Curhan, Alexa; Zhang, Susan; Towbin, Kenneth E; Brotman, Melissa A; Pine, Daniel S; Leibenluft, Ellen

2017-05-01

Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients with ADHD (8 to 18 years old) completed a functional magnetic resonance imaging attention task. Group differences in intra-subject variability in reaction time (RT) were examined. The present functional magnetic resonance imaging analytic approach precisely quantified trial-wise associations between RT and brain activity. Group differences manifested in the relation between RT and brain activity (all regions: p < .01, F > 2.54, partial eta-squared [η p 2 ] > 0.06). Patients with DMDD showed specific alterations in the right paracentral lobule, superior parietal lobule, fusiform gyrus, and cerebellar culmen. In contrast, patients with DMDD and those with ADHD exhibited blunted compensatory increases in activity on long RT trials. In addition, youth with DMDD exhibited increased activity in the postcentral gyrus, medial frontal gyrus, and cerebellar tonsil and declive (all regions: p < .05, F > 2.46, η p 2 > 0.06). Groups in the imaging sample did not differ significantly in intra-subject variability in RT (F 2,79  = 2.664, p = .076, η p 2  = 0.063), although intra-subject variability in RT was significantly increased in youth with DMDD and ADHD when including those not meeting strict motion and accuracy criteria for imaging analysis (F 2,96  = 4.283, p = .017, η p 2  = 0.083). Patients with DMDD exhibited specific alterations in the relation between pre-stimulus brain activity and RT. Patients with DMDD and those with ADHD exhibited similar blunting of compensatory neural activity in frontal, parietal, and other regions. In addition, patients with DMDD showed increased RT variability compared with healthy youth. This work is the first to identify common and unique behavioral and neural signatures of DMDD and ADHD. Published by Elsevier Inc.

Multiple endocrine diseases in cats: 15 cases (1997-2008).

PubMed

Blois, Shauna L; Dickie, Erica L; Kruth, Stephen A; Allen, Dana G

2010-08-01

The objective of this retrospective study was to characterize a population of cats from a tertiary care center diagnosed with multiple endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Medical records of 15 cats diagnosed with more than one endocrine disorder were reviewed. The majority of cats were domestic shorthairs, and the mean age at the time of diagnosis of the first disorder was 10.3 years. The most common combination of disorders was diabetes mellitus and hyperthyroidism. Two cats had concurrent diabetes mellitus and hyperadrenocorticism, one cat had concurrent central diabetes insipidus and diabetes mellitus. A mean of 25.7 months elapsed between diagnoses of the first and second endocrine disorder, but this was variable. This study suggests the occurrence of multiple endocrine disorders is uncommon in cats. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Measurement of Psychological Disorders Using Cognitive Diagnosis Models

ERIC Educational Resources Information Center

Templin, Jonathan L.; Henson, Robert A.

2006-01-01

Cognitive diagnosis models are constrained (multiple classification) latent class models that characterize the relationship of questionnaire responses to a set of dichotomous latent variables. Having emanated from educational measurement, several aspects of such models seem well suited to use in psychological assessment and diagnosis. This article…

Dyslexia Laws in the USA

ERIC Educational Resources Information Center

Youman, Martha; Mather, Nancy

2013-01-01

Throughout the various states of the USA, the appropriate identification of dyslexia and the timely provision of interventions are characterized by variability and inconsistency. Several states have recognized the existence of this disorder and the well-established need for services. These states have taken proactive steps to implement laws and…

Molecular characterization of FXI deficiency.

PubMed

Berber, Ergul

2011-02-01

Factor XI (FXI) deficiency is a rare autosomal bleeding disease associated with genetic defects in the FXI gene. It is a heterogeneous disorder with variable tendency in bleeding and variable causative FXI gene mutations. It is characterized as a cross-reacting material-negative (CRM-) FXI deficiency due to decreased FXI levels or cross-reacting material-positive (CRM+) FXI deficiency due to impaired FXI function. Increasing number of mutations has been reported in FXI mutation database, and most of the mutations are affecting serine protease (SP) domain of the protein. Functional characterization for the mutations helps to better understand the molecular basis of FXI deficiency. Prevalence of the disease is higher in certain populations such as Ashkenazi Jews. The purpose of this review is to give an overview of the molecular basis of congenital FXI deficiency.

Characterization of Esophageal Motility Disorders in Children Presenting With Dysphagia Using High-Resolution Manometry.

PubMed

Edeani, Francis; Malik, Adeel; Kaul, Ajay

2017-03-01

The Chicago classification was based on metrics derived from studies in asymptomatic adult subjects. Our objectives were to characterize esophageal motility disorders in children and to determine whether the spectrum of manometric findings is similar between the pediatric and adult populations. Studies have suggested that the metrics utilized in manometric diagnosis depend on age, size, and manometric assembly. This would imply that a different set of metrics should be used for the pediatric population. There are no standardized and generally accepted metrics for use in the pediatric population, though there have been attempts to establish metrics specific to this population. Overall, we found that the distribution of esophageal motility disorders in children was like that described in adults using the Chicago classification. This analysis will serve as a prequel to follow-up studies exploring the individual metrics for variability among patients, with the objective of establishing novel metrics for the pediatric population.

[Family characteristics, organic risk factors, psychopathological picture and premorbid adjustment of hospitalized adolescent patients].

PubMed

Małkiewicz-Borkowska, M; Namysłowska, I; Siewierska, A; Puzyńska, E; Sredniawa, H; Zechowski, C; Iwanek, A; Ruszkowska, E

1996-01-01

The relation of some family characteristics such as cohesion and adaptability with organic risk factors, developmental psychopathology, clinical picture and premorbid adjustment was assessed in the group of 100 hospitalized adolescent patients and families. We found correlation between: some of organic risk factors (pathology of neonatal period, pathology of early childhood), some of indicators of developmental psychopathology (eating disorders, conduct disorders), some of clinical signs (mannerism, grandiosity, hostility, suspciousness, disturbances of content of thinking), premorbid adjustment, and variables related to families, described before. We think that biological variables characterizing child (pathology of neonatal period, pathology of early childhood) have an influence on some family characteristics as independent variable. General system theory and circular thinking support these conclusions. In order to verify them, it is necessary to undertake further investigations, based on other methodology, using this results as preliminary findings.

Psychophysiology of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Schoen, Sarah A.; Miller, Lucy Jane; Brett-Green, Barbara; Hepburn, Susan L.

2008-01-01

This study (1) explored the feasibility of using electrodermal activity (EDA) to characterize the arousal and sensory reactivity of children with high functioning autism (HFA) and Asperger's Syndrome (AS), (2) determined the reliability of electrodermal measures and (3) described the variability of EDA in this sample. Forty children with HFA and…

Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk.

PubMed

Kemp, Andrew H; Quintana, Daniel S; Felmingham, Kim L; Matthews, Slade; Jelinek, Herbert F

2012-01-01

There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction. To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal). A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use. HRV was calculated from electrocardiography under a standardized short-term resting state condition. HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size. Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.

[Mania associated with Usher syndrome type II].

PubMed

Praharaj, Samir Kumar; Acharya, Mahima; Sarvanan, Arul; Kongasseri, Sreejayan; Behere, Rishikesh V; Sharma, P S V N

2012-01-01

Usher syndrome (or Hallgren syndrome) is an autosomal recessive genetic disorder characterized by sensorineural deafness, retinitis pigmentosa, and variable vestibular deficit; Usher syndrome type II is the most common form. Various neuropsychiatric disorders have been reported to occur in those with Usher syndrome, including schizophrenia-like disorder, atypical psychosis, recurrent depressive illness, neurotic disorder, and mental retardation; however, bipolar disorder is not common in those with Usher syndrome. Herein we describe a 30-year-old male with Usher syndrome type II that developed features indicative of a probable manic episode. The patient had complete remission of symptoms in response to treatment with olanzapine 20 mg d-1. In persons with dual sensory impairment there are inherent problems with assessment and diagnosis is difficult due to their limited communication abilities. The diagnosis of Usher syndrome depends heavily on behavioral observation and disturbances in vegetative functions.

Motivation for change as a predictor of treatment response for dysthymia.

PubMed

Frías Ibáñez, Álvaro; González Vallespí, Laura; Palma Sevillano, Carol; Farriols Hernando, Núria

2016-05-01

Dysthymia constitutes a chronic, mild affective disorder characterized by heterogeneous treatment effects. Several predictors of clinical response and attendance have been postulated, although research on the role of the psychological variables involved in this mental disorder is still scarce. Fifty-four adult patients, who met criteria for dysthymia completed an ongoing naturalistic treatment based on the brief interpersonal psychotherapy (IPT-B), which was delivered bimonthly over 16 months. As potential predictor variables, the therapeutic alliance, coping strategies, perceived self-efficacy, and motivation for change were measured at baseline. Outcome variables were response to treatment (Clinical Global Impression and Beck’s Depression Inventory) and treatment attendance. Stepwise multiple linear regression analyses revealed that higher motivation for change predicted better response to treatment. Moreover, higher motivation for change also predicted treatment attendance. Therapeutic alliance was not a predictor variable of neither clinical response nor treatment attendance. These preliminary findings support the adjunctive use of motivational interviewing (MI) techniques in the treatment of dysthymia. Further research with larger sample size and follow-up assessment is warranted.

Elevated left mid-frontal cortical activity prospectively predicts conversion to bipolar I disorder

PubMed Central

Nusslock, Robin; Harmon-Jones, Eddie; Alloy, Lauren B.; Urosevic, Snezana; Goldstein, Kim; Abramson, Lyn Y.

2013-01-01

Bipolar disorder is characterized by a hypersensitivity to reward-relevant cues and a propensity to experience an excessive increase in approach-related affect, which may be reflected in hypo/manic symptoms. The present study examined the relationship between relative left-frontal electroencephalographic (EEG) activity, a proposed neurophysiological index of approach-system sensitivity and approach/reward-related affect, and bipolar course and state-related variables. Fifty-eight individuals with cyclothymia or bipolar II disorder and 59 healthy control participants with no affective psychopathology completed resting EEG recordings. Alpha power was obtained and asymmetry indices computed for homologous electrodes. Bipolar spectrum participants were classified as being in a major/minor depressive episode, a hypomanic episode, or a euthymic/remitted state at EEG recording. Participants were then followed prospectively for an average 4.7 year follow-up period with diagnostic interview assessments every four-months. Sixteen bipolar spectrum participants converted to bipolar I disorder during follow-up. Consistent with hypotheses, elevated relative left-frontal EEG activity at baseline 1) prospectively predicted a greater likelihood of converting from cyclothymia or bipolar II disorder to bipolar I disorder over the 4.7 year follow-up period, 2) was associated with an earlier age-of-onset of first bipolar spectrum episode, and 3) was significantly elevated in bipolar spectrum individuals in a hypomanic episode at EEG recording. This is the first study to identify a neurophysiological marker that prospectively predicts conversion to bipolar I disorder. The fact that unipolar depression is characterized by decreased relative left-frontal EEG activity suggests that unipolar depression and vulnerability to hypo/mania may be characterized by different profiles of frontal EEG asymmetry. PMID:22775582

[Neuropsychology of Tourette's disorder: cognition, neuroimaging and creativity].

PubMed

Espert, R; Gadea, M; Alino, M; Oltra-Cucarella, J

2017-02-24

Tourette's disorder is the result of fronto-striatal brain dysfunction affecting people of all ages, with a debut in early childhood and continuing into adolescence and adulthood. This article reviews the main cognitive, functional neuroimaging and creativity-related studies in a disorder characterized by an excess of dopamine in the brain. Given the special cerebral configuration of these patients, neuropsychological alterations, especially in executive functions, should be expected. However, the findings are inconclusive and are conditioned by factors such as comorbidity with attention deficit hyperactivity disorder and obsessive-compulsive disorder, age or methodological variables. On the other hand, the neuroimaging studies carried out over the last decade have been able to explain the clinical symptoms of Tourette's disorder patients, with special relevance for the supplementary motor area and the anterior cingulate gyrus. Finally, although there is no linear relationship between excess of dopamine and creativity, the scientific literature emphasizes an association between Tourette's disorder and musical creativity, which could be translated into intervention programs based on music.

Sporadic and familial glut1ds Italian patients: A wide clinical variability.

PubMed

De Giorgis, Valentina; Teutonico, Federica; Cereda, Cristina; Balottin, Umberto; Bianchi, Marika; Giordano, Lucio; Olivotto, Sara; Ragona, Francesca; Tagliabue, Anna; Zorzi, Giovanna; Nardocci, Nardo; Veggiotti, Pierangelo

2015-01-01

GLUT1 deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission. We present clinical and genetic features in a series of 22 GLUT1DS Italian patients. Our patients were classified in two different groups: familial cases including GLUT1DS patients with genetically confirmed affected relatives and sporadic cases with detection of SLC2A1 de novo mutation. We found remarkable differences in the severity of the clinical picture regarding the type of genetic inheritance (sporadic versus familial): sporadic patients were characterized by an earlier epilepsy-onset and higher degree of intellectual disability. No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS. In familial cases the clinical manifestation of the disease was particularly variable and heterogeneous, also including asymptomatic patients or those with minimal-symptoms. The finding of a "mild" phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

SIL1-related Marinesco-Sjoegren syndrome (MSS) with associated motor neuronopathy and bradykinetic movement disorder.

PubMed

Byrne, Susan; Dlamini, Nomazulu; Lumsden, Daniel; Pitt, Matthew; Zaharieva, Irina; Muntoni, Francesco; King, Andrew; Robert, Leema; Jungbluth, Heinz

2015-07-01

Marinesco-Sjoegren syndrome (MSS) is a recessively inherited multisystem disorder caused by mutations in SIL1 and characterized by cerebellar atrophy with ataxia, cataracts, a skeletal muscle myopathy, and variable degrees of developmental delay. Pathogenic mechanisms implicated to date include mitochondrial, nuclear envelope and lysosomal-autophagic pathway abnormalities. Here we present a 5-year-old girl with SIL1-related MSS and additional unusual features of an associated motor neuronopathy and a bradykinetic movement disorder preceding the onset of ataxia. These findings suggest that an associated motor neuronopathy may be part of the phenotypical spectrum of SIL1-related MSS and should be actively investigated in genetically confirmed cases. The additional observation of a bradykinetic movement disorder suggests an intriguing continuum between neurodevelopmental and neurodegenerative multisystem disorders intricately linked in the same cellular pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Early Brain Damage and the Development of Motor Behavior in Children: Clues for Therapeutic Intervention?

PubMed Central

Hadders-Algra, Mijna

2001-01-01

The Neuronal Group Selection Theory (NGST) could offer new insights into the mechanisms directing motor disorders, such as cerebral palsy and developmental coordination disorder. According to NGST, normal motor development is characterized by two phases of variability. Variation is not at random but determined by criteria set by genetic information. Development starts with the phase of primary variability,during which variation in motor behavior is not geared to external conditions. At function-specific ages secondary variability starts, during which motor performance can be adapted to specific situations. In both forms, of variability, selection on the basis of afferent information plays a significant role. From the NGST point of view, children with pre- or perinatally acquired brain damage, such as children with cerebral palsy and part of the children with developmental coordination disorder, suffer from stereotyped motor behavior, produced by a limited repertoire or primary (sub)cortical neuronal networks. These children also have roblems in selecting the most efficient neuronal activity, due to deficits in the processing of sensory information. Therefore, NGST suggests that intervention in these children at early age should aim at an enlargement of the primary neuronal networks. With increasing age, the emphasis of intervention could shift to the provision of ample opportunities for active practice, which might form a compensation for the impaired selection. PMID:11530887

Multi-centre diagnostic classification of individual structural neuroimaging scans from patients with major depressive disorder.

PubMed

Mwangi, Benson; Ebmeier, Klaus P; Matthews, Keith; Steele, J Douglas

2012-05-01

Quantitative abnormalities of brain structure in patients with major depressive disorder have been reported at a group level for decades. However, these structural differences appear subtle in comparison with conventional radiologically defined abnormalities, with considerable inter-subject variability. Consequently, it has not been possible to readily identify scans from patients with major depressive disorder at an individual level. Recently, machine learning techniques such as relevance vector machines and support vector machines have been applied to predictive classification of individual scans with variable success. Here we describe a novel hybrid method, which combines machine learning with feature selection and characterization, with the latter aimed at maximizing the accuracy of machine learning prediction. The method was tested using a multi-centre dataset of T(1)-weighted 'structural' scans. A total of 62 patients with major depressive disorder and matched controls were recruited from referred secondary care clinical populations in Aberdeen and Edinburgh, UK. The generalization ability and predictive accuracy of the classifiers was tested using data left out of the training process. High prediction accuracy was achieved (~90%). While feature selection was important for maximizing high predictive accuracy with machine learning, feature characterization contributed only a modest improvement to relevance vector machine-based prediction (~5%). Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity. These results indicate that machine learning techniques have the potential to inform clinical practice and research, as they can make accurate predictions about brain scan data from individual subjects. Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure.

Variability and predictors of negative mood intensity in patients with borderline personality disorder and recurrent suicidal behavior: multilevel analyses applied to experience sampling methodology.

PubMed

Nisenbaum, Rosane; Links, Paul S; Eynan, Rahel; Heisel, Marnin J

2010-05-01

Variability in mood swings is a characteristic of borderline personality disorder (BPD) and is associated with suicidal behavior. This study investigated patterns of mood variability and whether such patterns could be predicted from demographic and suicide-related psychological risk factors. Eighty-two adults with BPD and histories of recurrent suicidal behavior were recruited from 3 outpatient psychiatric programs in Canada. Experience sampling methodology (ESM) was used to assess negative mood intensity ratings on a visual analogue scale, 6 random times daily, for 21 days. Three-level models estimated variability between times (52.8%), days (22.2%), and patients (25.1%) and supported a quadratic pattern of daily mood variability. Depression scores predicted variability between patients' initial rating of the day. Average daily mood patterns depended on levels of hopelessness, suicide ideation, and sexual abuse history. Patients reporting moderate to severe sexual abuse and elevated suicide ideation were characterized by worsening moods from early morning up through evening, with little or no relief; patients reporting mild sexual abuse and low suicide ideation reported improved mood throughout the day. These patterns, if replicated in larger ESM studies, may potentially assist the clinician in determining which patients require close monitoring.

Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation.

PubMed

Minoia, Francesca; Bertamino, Marta; Picco, Paolo; Severino, Mariasavina; Rossi, Andrea; Fiorillo, Chiara; Minetti, Carlo; Nesti, Claudia; Santorelli, Filippo Maria; Di Rocco, Maja

2017-01-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder, characterized by a wide clinical and genetic heterogeneity, and is the most frequent disorder of mitochondrial energy production in children. Beside its great variability in clinical, biochemical, and genetic features, LS is pathologically uniformly characterized by multifocal bilateral and symmetric spongiform degeneration of the basal ganglia, brainstem, thalamus, cerebellum, spinal cord, and optic nerves. Isolated complex I deficiency is the most common defect identified in Leigh syndrome. In 2011, the first child with a mutation of NDUFA10 gene, coding for an accessory subunits of complex I, was described. Here, we present an additional description of a child with Leigh syndrome harboring a homozygous mutation in NDUFA10, providing insights in clinical, biochemical, and neuroradiologic features for future earlier recognition.

Familial pseudoxanthoma elasticum associated with multiple comedones.

PubMed

Maarouf, Melody; Sharon, Victoria R; Sivamani, Raja K; Prakash, Neha; Bipin, T H; Davis, Tracy; Shi, Vivian Y

2017-09-15

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by atypical elastic fibers that causes connective tissue abnormalities of the skin, eyes, and heart, among other organs. The disorder is rare, with a classic presentation of yellow-orange cobblestone-like papules on flexural areas, lax skin, ocular degeneration, and moribund vasculature in multiple organs. There is wide variability in the presentation of the affected organs [1]. We present two sisters with classic cutaneous findings of PXE with the additional unusual findings of numerous open comedones on the neck. To our knowledge, this is the first report of numerous open comedones in familial PXE.

Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.

PubMed

Reid, Emma S; Papandreou, Apostolos; Drury, Suzanne; Boustred, Christopher; Yue, Wyatt W; Wedatilake, Yehani; Beesley, Clare; Jacques, Thomas S; Anderson, Glenn; Abulhoul, Lara; Broomfield, Alex; Cleary, Maureen; Grunewald, Stephanie; Varadkar, Sophia M; Lench, Nick; Rahman, Shamima; Gissen, Paul; Clayton, Peter T; Mills, Philippa B

2016-11-01

Neurometabolic disorders are markedly heterogeneous, both clinically and genetically, and are characterized by variable neurological dysfunction accompanied by suggestive neuroimaging or biochemical abnormalities. Despite early specialist input, delays in diagnosis and appropriate treatment initiation are common. Next-generation sequencing approaches still have limitations but are already enabling earlier and more efficient diagnoses in these patients. We designed a gene panel targeting 614 genes causing inborn errors of metabolism and tested its diagnostic efficacy in a paediatric cohort of 30 undiagnosed patients presenting with variable neurometabolic phenotypes. Genetic defects that could, at least partially, explain observed phenotypes were identified in 53% of cases. Where biochemical abnormalities pointing towards a particular gene defect were present, our panel identified diagnoses in 89% of patients. Phenotypes attributable to defects in more than one gene were seen in 13% of cases. The ability of in silico tools, including structure-guided prediction programmes to characterize novel missense variants were also interrogated. Our study expands the genetic, clinical and biochemical phenotypes of well-characterized (POMGNT1, TPP1) and recently identified disorders (PGAP2, ACSF3, SERAC1, AFG3L2, DPYS). Overall, our panel was accurate and efficient, demonstrating good potential for applying similar approaches to clinically and biochemically diverse neurometabolic disease cohorts. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Cognitive Profiles in Youth with Autism Spectrum Disorder: An Investigation of Base Rate Discrepancies Using the Differential Ability Scales-Second Edition

ERIC Educational Resources Information Center

Nowell, Kerri P.; Schanding, G. Thomas, Jr.; Kanne, Stephen M.; Goin-Kochel, Robin P.

2015-01-01

Extant data suggest that the cognitive profiles of individuals with ASD may be characterized by variability, particularly in terms of verbal intellectual functioning (VIQ) and non-verbal intellectual functioning (NVIQ) discrepancies. The "Differential Ability Scales, Second Edition" (DAS-II) has limited data available on its use with…

[Basics of early intervention in children with autism spectrum disorders].

PubMed

Zalaquett, Daniela F; Schönstedt, Marianne G; Angeli, Milagros; Herrrera, Claudia C; Moyano, Andrea C

2015-01-01

Autism Spectrum Disorders (ASD) are characterized by impairments in communication and social interaction, as well as restricted and repetitive patterns of behavior. They have a prevalence of 0.6% in the general population, although there are no national statistics. Even though their evolution is variable, it has been observed that early intervention is an important factor determining prognosis. The aim of this study is to update concepts regarding the current available evidence on the importance of early intervention. After analyzing the collected information, the importance of early intervention programs for children with ASD is confirmed, as well as the role of pediatricians and other health professionals in the early detection of these disorders. Copyright © 2015. Publicado por Elsevier España, S.L.U.

Gerodermia osteodysplastica and wrinkly skin syndrome: are they the same?

PubMed

Al-Gazali, L I; Sztriha, L; Skaff, F; Haas, D

2001-07-01

Gerodermia osteodysplastica (GO) is a connective tissue disorder characterized by premature aging, wrinkled, and lax skin with reduced elasticity which is more marked on the dorsum of the hands and feet associated with hyperextensible joints and osteoporosis. The wrinkly skin syndrome (WSS) is characterized by wrinkled skin over the dorsum of the hands, feet, and abdomen; hyperextensible joints, particularly of the hands; intrauterine growth retardation; postnatal failure to thrive; and mental and developmental delay. We report on five children from two consanguineous Arab families with features overlapping both GO and WSS. All five children had similar dysmorphic facial features consisting of broad and prominent forehead, hypotelorism with epicanthal folds, prominent bulbous nose, flat malar region, and large protruding ears. All had wrinkling of the skin more marked on the dorsum of the hands, feet, and abdomen; hyperextensibility of the joints, particularly of the hands; and aged appearance. Intrauterine growth retardation, subsequent failure to thrive, developmental delay, and variable degree of osteoporosis was also present in all of them. The older three children developed progressive prognathism. We suggest that GO and WSS could represent variable manifestation of the same disorder. Copyright 2001 Wiley-Liss, Inc.

Expressed emotion is not associated with disorder severity in first-episode mental disorder.

PubMed

Heikkilä, Jyrki; Karlsson, Hasse; Taiminen, Tero; Lauerma, Hannu; Ilonen, Tuula; Leinonen, Kirsi-Marja; Wallenius, Elina; Virtanen, Hilkka; Heinimaa, Markus; Koponen, Salla; Jalo, Päivi; Kaljonen, Anne; Salakangas, Raimo K R

2002-08-30

A family atmosphere characterized by expressed emotion (EE) is a robust predictor of clinical outcome of patients with schizophrenia and mood disorders. However, there is ongoing discussion as to whether EE is more a cause of clinical outcome or a parental reaction to disorder severity. This cross-sectional study examines a sample of 42 consecutive first-episode patients from a defined geographical area with severe mental disorders (schizophrenia-related disorders, psychotic mood disorders, and non-psychotic mood disorders). Their 42 relatives were interviewed, and the relationships between EE variables derived with the five-minute speech sample method (FMSS) and the patients' demographic, premorbid and clinical measures were analyzed. A high EE score was found in 40% of the relatives. High EE was associated with the interviewed relative's not being a spouse and the patient's being young and unmarried. It was not associated with premorbid characteristics, symptom dimensions or the diagnostic group of the patient. These results do not support the hypothesis that EE is a reaction to the clinical features of the patient. Instead, demographic factors may partly mediate the effect of EE on prognosis.

A Novel Truncating LMNA Mutation in Patients with Cardiac Conduction Disorders and Dilated Cardiomyopathy.

PubMed

Kawakami, Hiroshi; Ogimoto, Akiyoshi; Tokunaga, Naohito; Nishimura, Kazuhisa; Kawakami, Hideo; Higashi, Haruhiko; Iio, Chiharuko; Kono, Tamami; Aono, Jun; Uetani, Teruyoshi; Nagai, Takayuki; Inoue, Katsuji; Suzuki, Jun; Ikeda, Shuntaro; Okura, Takafumi; Ohyagi, Yasumasa; Tabara, Yasuharu; Higaki, Jitsuo

2018-05-30

The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM.Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells.

PubMed

Li, Jin; Jørgensen, Silje F; Maggadottir, S Melkorka; Bakay, Marina; Warnatz, Klaus; Glessner, Joseph; Pandey, Rahul; Salzer, Ulrich; Schmidt, Reinhold E; Perez, Elena; Resnick, Elena; Goldacker, Sigune; Buchta, Mary; Witte, Torsten; Padyukov, Leonid; Videm, Vibeke; Folseraas, Trine; Atschekzei, Faranaz; Elder, James T; Nair, Rajan P; Winkelmann, Juliane; Gieger, Christian; Nöthen, Markus M; Büning, Carsten; Brand, Stephan; Sullivan, Kathleen E; Orange, Jordan S; Fevang, Børre; Schreiber, Stefan; Lieb, Wolfgang; Aukrust, Pål; Chapel, Helen; Cunningham-Rundles, Charlotte; Franke, Andre; Karlsen, Tom H; Grimbacher, Bodo; Hakonarson, Hakon; Hammarström, Lennart; Ellinghaus, Eva

2015-04-20

Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10(-9)) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10(-16)). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features

PubMed Central

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-01-01

Ehlers–Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

The impact of genital self-image on sexual function in women with pelvic floor disorders.

PubMed

Handelzalts, Jonathan E; Yaakobi, Tal; Levy, Sigal; Peled, Yoav; Wiznitzer, Arnon; Krissi, Haim

2017-04-01

There is conflicting evidence regarding the impact of urinary incontinence and pelvic organ prolapse on overall sexual function. However, psychological variables thought to be associated with sexual function, have not been fully explored. We assessed the sexual functioning of women with pelvic floor disorders while measuring for psychological factors such as distress and genital self-image. In a cross-sectional study, 155 women in an urogynecology outpatient clinic of a tertiary health center completed a demographic questionnaire, the Brief Symptom Index-18 (BSI-18), Pelvic Floor Distress Inventory-20 (PFDI-20), Genital Self-Image Scale-20 (GSIS-20) and the Female Sexual Function Index (FSFI). Linear regression showed that when controlling for age and depression, GSIS significantly predicted FSFI total score (Beta=0.38, p<0.001) and the Desire subscale (Beta=0.55, p<0.001). Due to the low response rate in the GSIS and FSFI questionnaires, a preliminary analysis was conducted to characterize the responders. On univariate logistic regression, response to the GSIS was negatively correlated with age (OR=0.94, p=0.02) and being in a relationship (OR=2.3, p=0.016), yet the effect of being in a relationship was diminished in a multivariate model that included age. The main variable associated with overall sexual function in women with pelvic floor disorders was low genital self-image. This variable is more important than self-reported symptoms, type of specific disorder or other demographic variables. Older women tended not to complete the scales concerning more intimate matters. We suggest that urogynecologists should inquire about genital self-image as well as sexual function in this population. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent developments in the genetics of schizophrenia.

PubMed

Shastry, B S

1999-09-01

Schizophrenia, which is also called "split personality," is a complex and multifactorial mental disorder with variable clinical manifestations. It perhaps represents several diseases and occurs throughout the world. It is a more-prevalent disorder among homeless people and is clinically characterized by hallucinations and delusions. The pathophysiology of schizophrenia is not localized to a single region of the brain and the etiology of this illness is not understood. Because of its complex pattern of inheritance, genetic techniques are not readily applicable in identifying the genes responsible for this disorder. Family, twin, and adoption studies, however, provide strong but indirect support for genetic components in the etiology of schizophrenia. Extensive linkage analyses now suggest that susceptibility genes may be present on chromosomes 5q, 6p, 8p, 13q, 18p, and 22q. Identification and characterization of these and other genes, as well as non-genetic factors, is one of the greatest challenges in biomedicine. This may ultimately lead to the development of a new line of effective and safe drugs or treatments for its prevention or cure.

Shah-Waardenburg Syndrome

PubMed Central

Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

2013-01-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities. PMID:23565307

Shah-Waardenburg syndrome.

PubMed

Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

2013-01-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities.

Phenotypic variability in patients with Fanconi anemia and biallelic FANCF mutations.

PubMed

Tryon, Rebecca; Zierhut, Heather; MacMillan, Margaret L; Wagner, John E

2017-01-01

Fanconi anemia is a heterogeneous genetic disorder that is characterized by progressive bone marrow failure, congenital anomalies, and markedly increased risk for malignancies. Mutations in the FANCF (FA-F) gene represent approximately 2% of affected patients. Currently, information on the phenotypic findings of patients with Fanconi anemia from biallelic mutations in FANCF is limited. Here, we report three patients who illustrate the clinical variability within the FA-F group. This analysis suggests a more severe phenotype for those with the common c.484_485delCT mutation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Behavioral and Neural Sustained Attention Deficits in Disruptive Mood Dysregulation Disorder and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Pagliaccio, David; Wiggins, Jillian Lee; Adleman, Nancy E.; Curhan, Alexa; Zhang, Susan; Towbin, Kenneth E.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

2017-01-01

Objective Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. Method Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients with ADHD (8–18-year-olds) completed a functional magnetic resonance imaging (fMRI) attention task. Group differences in intra-subject variability in reaction time (ISVRT) were examined. The current fMRI analytic approach precisely quantified trial-wise associations between reaction time and brain activity. Results Group differences manifested in the relationship between reaction time and brain activity (all regions: p<.01, F>2.54, ηp2>0.06). Patients with DMDD showed specific alterations in the right paracentral lobule, superior parietal lobule, fusiform gyrus, and cerebellar culmen. In contrast, both patients with DMDD and ADHD exhibited blunted compensatory increases in activity on long reaction time trials. Additionally, youth with DMDD exhibited increased activity in the postcentral gyrus, medial frontal gyrus, and cerebellar tonsil and declive (all regions: p<.05, F>2.46, ηp2>0.06). The groups in the imaging sample did not differ significantly in ISVRT (F[2,79]=2.664, p=.076, ηp2=0.063), though ISVRT was significantly elevated among youth with DMDD and ADHD when including those not meeting strict motion and accuracy criteria for the imaging analysis (F[2,96]=4.283, p=.017, ηp2=0.083). Conclusion Patients with DMDD exhibited specific alterations in the relationship between pre-stimulus brain activity and reaction time. Both patients with DMDD and ADHD exhibited similar blunting of compensatory neural activity in frontal, parietal, and other regions. Additionally, patients with DMDD demonstrated elevated reaction time variability relative to healthy youth. This work is the first to identify common and unique behavioral and neural signatures of DMDD and ADHD. PMID:28433092

Factors affecting reproductive performance of dairy cows.

PubMed

Coleman, D A; Thayne, W V; Dailey, R A

1985-07-01

We conducted two studies to determine how herd management practices and traits of individual cows affect performance of the herd and of the cow within a herd. Management practices, reproductive performance of the herd, and relationships between management and reproductive performance were characterized on 83 dairy farms with 7596 cows. Data included 21 management variables (e.g., facilities, herd health program, estrous detection program) and 8 performance variables obtained from Dairy Herd Improvement or unofficial records (e.g., size of herd, production, days open). Although varying among herds, annual average herd incidences of reproductive disorders and reproductive performance were similar to those reported. Managerial practices influenced incidences of retained placenta and uterine infection, days open of cows not bred and of all cows, services per conception, and percentages of herd open more than 100 days and culled for low production. Veterinarian was the most consistent variable influencing herd reproductive performance. Data also were collected from production and lifetime records of 2532 cows in 19 herds. Reproductive performance was affected by season of calving, production, maturity, and reproductive disorders. Several cows with extremely poor reproductive records were maintained.

The neurobiology of psychopathic traits in youths

PubMed Central

Blair, R. James J.

2015-01-01

Conduct disorder is a childhood behaviour disorder that is characterized by persistent aggressive or antisocial behaviour that disrupts the child’s environment and impairs his or her functioning. A proportion of children with conduct disorder have psychopathic traits. Psychopathic traits consist of a callous–unemotional component and an impulsive–antisocial component, which are associated with two core impairments. The first is a reduced empathic response to the distress of other individuals, which primarily reflects reduced amygdala responsiveness to distress cues; the second is deficits in decision making and in reinforcement learning, which reflects dysfunction in the ventromedial prefrontal cortex and striatum. Genetic and prenatal factors contribute to the abnormal development of these neural systems, and social–environmental variables that affect motivation influence the probability that antisocial behaviour will be subsequently displayed. PMID:24105343

Compulsive Buying Behavior: Clinical Comparison with Other Behavioral Addictions

PubMed Central

Granero, Roser; Fernández-Aranda, Fernando; Mestre-Bach, Gemma; Steward, Trevor; Baño, Marta; del Pino-Gutiérrez, Amparo; Moragas, Laura; Mallorquí-Bagué, Núria; Aymamí, Neus; Gómez-Peña, Mónica; Tárrega, Salomé; Menchón, José M.; Jiménez-Murcia, Susana

2016-01-01

Compulsive buying behavior (CBB) has been recognized as a prevalent mental health disorder, yet its categorization into classification systems remains unsettled. The objective of this study was to assess the sociodemographic and clinic variables related to the CBB phenotype compared to other behavioral addictions. Three thousand three hundred and twenty four treatment-seeking patients were classified in five groups: CBB, sexual addiction, Internet gaming disorder, Internet addiction, and gambling disorder. CBB was characterized by a higher proportion of women, higher levels of psychopathology, and higher levels in the personality traits of novelty seeking, harm avoidance, reward dependence, persistence, and cooperativeness compared to other behavioral addictions. Results outline the heterogeneity in the clinical profiles of patients diagnosed with different behavioral addiction subtypes and shed new light on the primary mechanisms of CBB. PMID:27378999

Compulsive Buying Behavior: Clinical Comparison with Other Behavioral Addictions.

PubMed

Granero, Roser; Fernández-Aranda, Fernando; Mestre-Bach, Gemma; Steward, Trevor; Baño, Marta; Del Pino-Gutiérrez, Amparo; Moragas, Laura; Mallorquí-Bagué, Núria; Aymamí, Neus; Gómez-Peña, Mónica; Tárrega, Salomé; Menchón, José M; Jiménez-Murcia, Susana

2016-01-01

Compulsive buying behavior (CBB) has been recognized as a prevalent mental health disorder, yet its categorization into classification systems remains unsettled. The objective of this study was to assess the sociodemographic and clinic variables related to the CBB phenotype compared to other behavioral addictions. Three thousand three hundred and twenty four treatment-seeking patients were classified in five groups: CBB, sexual addiction, Internet gaming disorder, Internet addiction, and gambling disorder. CBB was characterized by a higher proportion of women, higher levels of psychopathology, and higher levels in the personality traits of novelty seeking, harm avoidance, reward dependence, persistence, and cooperativeness compared to other behavioral addictions. Results outline the heterogeneity in the clinical profiles of patients diagnosed with different behavioral addiction subtypes and shed new light on the primary mechanisms of CBB.

The neurobiology of psychopathic traits in youths.

PubMed

Blair, R James R

2013-11-01

Conduct disorder is a childhood behaviour disorder that is characterized by persistent aggressive or antisocial behaviour that disrupts the child's environment and impairs his or her functioning. A proportion of children with conduct disorder have psychopathic traits. Psychopathic traits consist of a callous-unemotional component and an impulsive-antisocial component, which are associated with two core impairments. The first is a reduced empathic response to the distress of other individuals, which primarily reflects reduced amygdala responsiveness to distress cues; the second is deficits in decision making and in reinforcement learning, which reflects dysfunction in the ventromedial prefrontal cortex and striatum. Genetic and prenatal factors contribute to the abnormal development of these neural systems, and social-environmental variables that affect motivation influence the probability that antisocial behaviour will be subsequently displayed.

Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

PubMed Central

Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

2015-01-01

Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be—in part—due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID:26191015

Neuropsychological and FDG-PET profiles in VGKC autoimmune limbic encephalitis.

PubMed

Dodich, Alessandra; Cerami, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Alongi, Pierpaolo; Crespi, Chiara; Canessa, Nicola; Andreetta, Francesca; Falini, Andrea; Cappa, Stefano F; Perani, Daniela

2016-10-01

Limbic encephalitis (LE) is characterized by an acute or subacute onset with memory impairments, confusional state, behavioral disorders, variably associated with seizures and dystonic movements. It is due to inflammatory processes that selectively affect the medial temporal lobe structures. Voltage-gate potassium channel (VGKC) autoantibodies are frequently observed. In this study, we assessed at the individual level FDG-PET brain metabolic dysfunctions and neuropsychological profiles in three autoimmune LE cases seropositive for neuronal VGKC-complex autoantibodies. LGI1 and CASPR2 potassium channel complex autoantibody subtyping was performed. Cognitive abilities were evaluated with an in-depth neuropsychological battery focused on episodic memory and affective recognition/processing skills. FDG-PET data were analyzed at single-subject level according to a standardized and validated voxel-based Statistical Parametric Mapping (SPM) method. Patients showed severe episodic memory and fear recognition deficits at the neuropsychological assessment. No disorder of mentalizing processing was present. Variable patterns of increases and decreases of brain glucose metabolism emerged in the limbic structures, highlighting the pathology-driven selective vulnerability of this system. Additional involvement of cortical and subcortical regions, particularly in the sensorimotor system and basal ganglia, was found. Episodic memory and fear recognition deficits characterize the cognitive profile of LE. Commonalities and differences may occur in the brain metabolic patterns. Single-subject voxel-based analysis of FDG-PET imaging could be useful in the early detection of the metabolic correlates of cognitive and non-cognitive deficits characterizing LE condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Reliable individual-level neural markers of high-level language processing: A necessary precursor for relating neural variability to behavioral and genetic variability.

PubMed

Mahowald, Kyle; Fedorenko, Evelina

2016-10-01

The majority of functional neuroimaging investigations aim to characterize an average human brain. However, another important goal of cognitive neuroscience is to understand the ways in which individuals differ from one another and the significance of these differences. This latter goal is given special weight by the recent reconceptualization of neurological disorders where sharp boundaries are no longer drawn either between health and neuropsychiatric and neurodevelopmental disorders, or among different disorders (e.g., Insel et al., 2010). Consequently, even the variability in the healthy population can inform our understanding of brain disorders. However, because the use of functional neural markers is still in its infancy, no consensus presently exists about which measures (e.g., effect size?, extent of activation?, degree of lateralization?) are the best ones to use. We here attempt to address this question with respect to one large-scale neural system: the set of brain regions in the frontal and temporal cortices that jointly support high-level linguistic processing (e.g., Binder et al., 1997; Fedorenko, Hsieh, Nieto-Castanon, Whitfield-Gabrieli, & Kanwisher, 2010). In particular, using data from 150 individuals all of whom had performed a language "localizer" task contrasting sentences and nonword sequences (Fedorenko et al., 2010), we: a) characterize the distributions of the values for four key neural measures of language activity (region effect sizes, region volumes, lateralization based on effect sizes, and lateralization based on volumes); b) test the reliability of these measures in a subset of 32 individuals who were scanned across two sessions; c) evaluate the relationship among the different regions of the language system; and d) evaluate the relationship among the different neural measures. Based on our results, we provide some recommendations for future studies of brain-behavior and brain-genes relationships. Although some of our conclusions are specific to the language system, others (e.g., the fact that effect-size-based measures tend to be more reliable than volume-based measures) are likely to generalize to the rest of the brain. Copyright © 2016 Elsevier Inc. All rights reserved.

A rare case of bleeding disorder: Glanzmann's thrombasthenia.

PubMed

Swathi, Jami; Gowrishankar, A; Jayakumar, S A; Jain, Karun

2017-01-01

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. To highlight this rare but potentially life-threating disorder, GT. We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.

A Rare Case of Bleeding Disorder: Glanzmann's Thrombasthenia

PubMed Central

Swathi, Jami; Gowrishankar, A.; Jayakumar, S. A.; Jain, Karun

2017-01-01

Background: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. Objective: To highlight this rare but potentially life-threating disorder, GT. Case Report: We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. Conclusion: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder. PMID:29063905

Multivariate prediction of motor diagnosis in Huntington's disease: 12 years of PREDICT‐HD

PubMed Central

Long, Jeffrey D.

2015-01-01

Abstract Background It is well known in Huntington's disease that cytosine‐adenine‐guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years. Methods One thousand seventy‐eight Huntington's disease gene–expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean = 5, standard deviation = 3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right‐censored data. Results Adding 34 variables along with cytosine‐adenine‐guanine and age substantially increased predictive accuracy relative to cytosine‐adenine‐guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5‐y predictive accuracy than when using cytosine‐adenine‐guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model. Conclusions Measurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine‐adenine‐guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:26340420

Multivariate prediction of motor diagnosis in Huntington's disease: 12 years of PREDICT-HD.

PubMed

Long, Jeffrey D; Paulsen, Jane S

2015-10-01

It is well known in Huntington's disease that cytosine-adenine-guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years. One thousand seventy-eight Huntington's disease gene-expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean = 5, standard deviation = 3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right-censored data. Adding 34 variables along with cytosine-adenine-guanine and age substantially increased predictive accuracy relative to cytosine-adenine-guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5-y predictive accuracy than when using cytosine-adenine-guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model. Measurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine-adenine-guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

What characterizes substance abusers who commit suicide attempts? Factors related to Axis I disorders and patterns of substance use disorders. A study of treatment-seeking substance abusers in Norway.

PubMed

Landheim, A S; Bakken, K; Vaglum, P

2006-01-01

The frequency of suicide attempts and clinical characteristics of attempters among poly-substance abusers and alcoholics were examined. A consecutive sample (n = 260) of in- and outpatients from two Norwegian counties were assessed by Composite International Diagnostic Interview (Axis I disorders), Millon's Clinical Multiaxial Inventory (Axis II disorders) and the Norwegian National Client Assessment Form. When analysing the association between suicide attempters and the range of predictor variables, logistic regression analysis was conducted. Almost half (47%) of the sample reported lifetime suicide attempts; significantly more frequently in poly-substance abusers (58%) than alcoholics (38%). A substance use disorder with duration of >or=15 years and an early onset (<18 years of age) were independently associated with being a suicide attempter after controlling for Axis I disorders. In addition, eating disorders, agoraphobia and major depression were strongly and independently associated with being a suicide attempter. Attempts at preventing suicidal behaviour should not ignore the suicide risk among poly-substance abusers. In addition, prevention of suicidal behaviour demands a treatment programme focusing concomitantly on both addictive behaviour and comorbid psychiatric disorders. Copyright 2006 S. Karger AG, Basel.

Membranous lipodystrophy: case report and review of the literature.

PubMed

Akpinar, Fatma; Demir, Ektan; Apa, Duygu Dusmez

2015-01-01

Membranous lipodystrophy is a distinct type of membranocystic fat necrosis. It is associated with many local and systemic diseases, including vascular disorders. The histopathological changes which characterize this phenomenon are variably sized cysts in the fat lobules of the subcutaneous tissue, which are surrounded by eosinophilic membranes projecting into the cystic space. We report a case of secondary membranous lipodystrophy associated with both hypertension and venous insufficiency.

Higher Impulsivity As a Distinctive Trait of Severe Cocaine Addiction among Individuals Treated for Cocaine or Alcohol Use Disorders.

PubMed

García-Marchena, Nuria; Ladrón de Guevara-Miranda, David; Pedraz, María; Araos, Pedro Fernando; Rubio, Gabriel; Ruiz, Juan Jesús; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Santín, Luis J; Rodríguez de Fonseca, Fernando

2018-01-01

Despite alcohol being the most often used addictive substance among addicted patients, use of other substances such as cocaine has increased over recent years, and the combination of both drugs aggravates health impairment and complicates clinical assessment. The aim of this study is to identify and characterize heterogeneous subgroups of cocaine- and alcohol-addicted patients with common characteristics based on substance use disorders, psychiatric comorbidity and impulsivity. A total of 214 subjects with cocaine and/or alcohol use disorders were recruited from outpatient treatment programs and clinically assessed. A latent class analysis was used to establish phenotypic categories according to diagnosis of cocaine and alcohol use disorders, mental disorders, and impulsivity scores. Relevant variables were examined in the latent classes (LCs) using correlation and analyses of variance and covariance. Four LCs of addicted patients were identified: Class 1 (45.3%) formed by alcohol-dependent patients exhibiting lifetime mood disorder diagnosis and mild impulsivity; Class 2 (14%) formed mainly by lifetime cocaine use disorder patients with low probability of comorbid mental disorders and mild impulsivity; Class 3 (10.7%) formed by cocaine use disorder patients with elevated probability to course with lifetime anxiety, early and personality disorders, and greater impulsivity scores; and Class 4 (29.9%) formed mainly by patients with alcohol and cocaine use disorders, with elevated probability in early and personality disorders and elevated impulsivity. Furthermore, there were significant differences among classes in terms of Diagnostic and Statistical Manual of Mental Disorders-4th Edition-Text Revision criteria for abuse and dependence: Class 3 showed more criteria for cocaine use disorders than other classes, while Class 1 and Class 4 showed more criteria for alcohol use disorders. Cocaine- and alcohol-addicted patients who were grouped according to diagnosis of substance use disorders, psychiatric comorbidity, and impulsivity show different clinical and sociodemographic variables. Whereas mood and anxiety disorders are more prevalent in alcohol-addicted patients, personality disorders are associated with cocaine use disorders and diagnosis of comorbid substance use disorders. Notably, increased impulsivity is a distinctive characteristic of patients with severe cocaine use disorder and comorbid personality disorders. Psychiatric disorders and impulsivity should be considered for improving the stratification of addicted patients with shared clinical and sociodemographic characteristics to select more appropriate treatments.

Cloning and molecular characterization of the cDNAs encoding the variable regions of an anti-CD20 monoclonal antibody.

PubMed

Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili

2017-01-01

CD20-based targeting of B-cells in hematologic malignancies and autoimmune disorders is associated with outstanding clinical outcomes. Isolation and characterization of VH and VL cDNAs encoding the variable regions of the heavy and light chains of monoclonal antibodies (MAb) is necessary to produce next generation MAbs and their derivatives such as bispecific antibodies (bsAb) and single-chain variable fragments (scFv). This study was aimed at cloning and characterization of the VH and VL cDNAs from a hybridoma cell line producing an anti-CD20 MAb. VH and VL fragments were amplified, cloned and characterized. Furthermore, amino acid sequences of VH, VL and corresponding complementarity-determining regions (CDR) were determined and compared with those of four approved MAbs including Rituximab (RTX), Ibritumomab tiuxetan, Ofatumumab and GA101. The cloned VH and VL cDNAs were found to be functional and follow a consensus pattern. Amino acid sequences corresponding to the VH and VL fragments also indicated noticeable homologies to those of RTX and Ibritumomab. Furthermore, amino acid sequences of the relating CDRs had remarkable similarities to their counterparts in RTX and Ibritumomab. Successful recovery of VH and VL fragments encourages the development of novel CD20 targeting bsAbs, scFvs, antibody conjugates and T-cells armed with chimeric antigen receptors.

Cluster analysis of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder: clinical and genetic correlates.

PubMed

Lochner, Christine; Hemmings, Sian M J; Kinnear, Craig J; Niehaus, Dana J H; Nel, Daniel G; Corfield, Valerie A; Moolman-Smook, Johanna C; Seedat, Soraya; Stein, Dan J

2005-01-01

Comorbidity of certain obsessive-compulsive spectrum disorders (OCSDs; such as Tourette's disorder) in obsessive-compulsive disorder (OCD) may serve to define important OCD subtypes characterized by differing phenomenology and neurobiological mechanisms. Comorbidity of the putative OCSDs in OCD has, however, not often been systematically investigated. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , Axis I Disorders-Patient Version as well as a Structured Clinical Interview for Putative OCSDs (SCID-OCSD) were administered to 210 adult patients with OCD (N = 210, 102 men and 108 women; mean age, 35.7 +/- 13.3). A subset of Caucasian subjects (with OCD, n = 171; control subjects, n = 168), including subjects from the genetically homogeneous Afrikaner population (with OCD, n = 77; control subjects, n = 144), was genotyped for polymorphisms in genes involved in monoamine function. Because the items of the SCID-OCSD are binary (present/absent), a cluster analysis (Ward's method) using the items of SCID-OCSD was conducted. The association of identified clusters with demographic variables (age, gender), clinical variables (age of onset, obsessive-compulsive symptom severity and dimensions, level of insight, temperament/character, treatment response), and monoaminergic genotypes was examined. Cluster analysis of the OCSDs in our sample of patients with OCD identified 3 separate clusters at a 1.1 linkage distance level. The 3 clusters were named as follows: (1) "reward deficiency" (including trichotillomania, Tourette's disorder, pathological gambling, and hypersexual disorder), (2) "impulsivity" (including compulsive shopping, kleptomania, eating disorders, self-injury, and intermittent explosive disorder), and (3) "somatic" (including body dysmorphic disorder and hypochondriasis). Several significant associations were found between cluster scores and other variables; for example, cluster I scores were associated with earlier age of onset of OCD and the presence of tics, cluster II scores were associated with female gender and childhood emotional abuse, and cluster III scores were associated with less insight and with somatic obsessions and compulsions. However, none of these clusters were associated with any particular genetic variant. Analysis of comorbid OCSDs in OCD suggested that these lie on a number of different dimensions. These dimensions are partially consistent with previous theoretical approaches taken toward classifying OCD spectrum disorders. The lack of genetic validation of these clusters in the present study may indicate the involvement of other, as yet untested, genes. Further genetic and cluster analyses of comorbid OCSDs in OCD may ultimately contribute to a better delineation of OCD endophenotypes.

Hereditary motor and sensory neuropathy with agenesis of the corpus callosum.

PubMed

Dupré, Nicolas; Howard, Heidi C; Mathieu, Jean; Karpati, George; Vanasse, Michel; Bouchard, Jean-Pierre; Carpenter, Stirling; Rouleau, Guy A

2003-07-01

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.

Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication.

PubMed

Green Snyder, LeeAnne; D'Angelo, Debra; Chen, Qixuan; Bernier, Raphael; Goin-Kochel, Robin P; Wallace, Arianne Stevens; Gerdts, Jennifer; Kanne, Stephen; Berry, Leandra; Blaskey, Lisa; Kuschner, Emily; Roberts, Timothy; Sherr, Elliot; Martin, Christa L; Ledbetter, David H; Spiro, John E; Chung, Wendy K; Hanson, Ellen

2016-08-01

The 16p11.2 duplication (BP4-BP5) is associated with Autism Spectrum Disorder (ASD), although significant heterogeneity exists. Quantitative ASD, behavioral and neuropsychological measures and DSM-IV diagnoses in child and adult carriers were compared with familial non-carrier controls, and to published results from deletion carriers. The 16p11.2 duplication phenotype ranges widely from asymptomatic presentation to significant disability. The most common diagnoses were intellectual disability, motor delays and Attention Deficit Hyperactivity Disorder in children, and anxiety in adults. ASD occurred in nearly 20 % of child cases, but a majority of carriers did not show the unique social features of ASD. The 16p11.2 duplication phenotype is characterized by wider variability than the reciprocal deletion, likely reflecting contributions from additional risk factors.

Can biological components predict short-term evolution in Autism Spectrum Disorders? A proof-of-concept study.

PubMed

Emberti Gialloreti, Leonardo; Benvenuto, Arianna; Battan, Barbara; Benassi, Francesca; Curatolo, Paolo

2016-07-22

The clinical and pathogenetic heterogeneity of Autism Spectrum Disorders (ASD) limits our ability to predict its short- and long-term evolution. Aim of this naturalistic study was to observe the clinical evolution of very young children with ASD for 12 months after first diagnosis, in order to identify those children who might develop a more positive trajectory and understand how a wide range of biological, clinical and familial factors can influence prognosis. Ninety-two children were characterized in terms of family history, prenatal and perinatal variables, and clinical conditions. The sample was divided into four subgroups based on the association of 22 biological, clinical and family history variables. Developmental Quotient (DQ), determined using the Psychoeducational Profile Revised (PEP-R), and symptoms severity, measured by means of the Autism Diagnostic Observation Schedule (ADOS), were evaluated at baseline (T0) and after one year (T1), while receiving treatment as usual. Changes in DQ and ADOS between baseline and follow-up and differences in the short-term evolution of the four subgroups were analyzed. At T1, 55.4 % of the children demonstrated some gains either of autistic symptomatology or of developmental skills. Mean ADOS score was 13.63 ± 3.67 at T0 and 10.85 ± 4.10 at T1 and mean DQ was 0.64 ± 0.14 at T0 and 0.66 ± 0.15 at T1. At follow-up, 33.7 % of the children showed an improvement in DQ and 37 % presented a less severe symptomatology, measured by means of ADOS. Overall, 15.2 % of the sample displayed major improvements both on developmental quotient and ADOS severity score; these children presented less EEG abnormalities and familial psychiatric disorders. The four subgroups, based on biological, clinical and familial variables, showed differing trends in terms of evolution. Categorizing very young children with ASD in terms of biological, clinical and familial variables can be instrumental in predicting short-term evolution. This exploratory study highlights the importance of a precise characterization and thorough analysis of interactions among biological and clinical variables, in order to predict the developmental evolution in children with ASD.

Utility of Time and Frequency Domain Parameters of Heart Rate Variability in the Context of Autonomic Disorders Characterized by Orthostatic Dysfunction.

PubMed

Baker, Jacquie; Racosta, Juan M; Balint, Brittany; Kimpinski, Kurt

2018-03-01

The clinical significance of heart rate variability in the context of autonomic dysfunction continues to be a matter of debate. A consensus is lacking on the best heart rate variability measures for clinical purposes. Therefore, the purpose of this study was to investigate the utility of heart rate variability parameters in healthy versus autonomic dysfunction. Healthy young (n = 134), healthy older (n = 32), and patients with mild (postural tachycardia syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34) autonomic dysfunction were included. Time and frequency parameters during baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB) were compared. Cardiovagal time parameters were significantly reduced during HUT in healthy young and postural tachycardia syndrome (P < 0.001). Healthy young had significantly higher time parameters during baseline, HUT, and HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate (HR) (61.4 ± 9.0 bpm vs. 76.8 ± 13.6 bpm; P < 0.001) and a smaller [INCREMENT]HR during HUT (32.8 ± 10.5 bpm vs. 44.4 ± 13.3 bpm; P < 0.001). Time parameters increased in young and postural tachycardia syndrome during HRDB, which was characterized by a nonsignificant difference in [INCREMENT]HR between both groups. Time parameters were significantly higher in healthy old versus neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During HUT, only the SD of all normal RR intervals remained significantly higher. Heart rate changes corroborated these findings. Resting HR was significantly lower in healthy older (62.6 ± 11.0 bpm vs. 70.7 ± 12.4 bpm), and [INCREMENT]HR during HRDB was significantly higher (15.9 ± 9.2 bpm vs. 3.9 ± 4.2 bpm; P < 0.001). During HUT, [INCREMENT]HR showed no significant differences. Time domain parameters of heart rate variability have a greater utility than frequency parameters in clinical autonomic disorders.

POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome

PubMed Central

Lessel, Davor; Hisama, Fuki M.; Szakszon, Katalin; Saha, Bidisha; Sanjuanelo, Alexander Barrios; Salbert, Bonnie A.; Steele, Pamela D.; Baldwin, Jennifer; Brown, W. Ted; Piussan, Charles; Plauchu, Henri; Szilvássy, Judit; Horkay, Edit; Hoögel, Josef; Martin, George M.; Herr, Alan J.; Oshima, Junko; Kubisch, Christian

2015-01-01

Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%–15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome. PMID:26172944

From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics.

PubMed

Trigueros Genao, M; Torres, R J

2014-11-01

Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The genetics of aniridia - simple things become complicated.

PubMed

Wawrocka, Anna; Krawczynski, Maciej R

2018-05-01

Aniridia is a rare, panocular disorder characterized by a variable degree of hypoplasia or the absence of iris tissue associated with additional ocular abnormalities. It is inherited in an autosomal dominant manner, with high penetrance and variable expression even within the same family. In most cases the disease is caused by haploinsufficiency truncating mutations in the PAX6 gene; however, in up to 30% of aniridia patients, disease results from chromosomal rearrangements at the 11p13 region. The aim of this review is to present the clinical and genetic aspects of the disease. Furthermore, we present a molecular diagnostic strategy in the aniridia patients. Recent improvement in the genetic diagnostic approach will precisely diagnosis aniridia patients, which is essential especially for children with aniridia in order to determine the risk of developing a Wilms tumor or neurodevelopmental disorder. Finally, based on the previous studies we describe the current knowledge and latest research findings in the topic of pathogenesis of aniridia and possible future treatment.

Integrating genetic and toxicogenomic information for determining underlying susceptibility to developmental disorders.

PubMed

Robinson, Joshua F; Port, Jesse A; Yu, Xiaozhong; Faustman, Elaine M

2010-10-01

To understand the complex etiology of developmental disorders, an understanding of both genetic and environmental risk factors is needed. Human and rodent genetic studies have identified a multitude of gene candidates for specific developmental disorders such as neural tube defects (NTDs). With the emergence of toxicogenomic-based assessments, scientists now also have the ability to compare and understand the expression of thousands of genes simultaneously across strain, time, and exposure in developmental models. Using a systems-based approach in which we are able to evaluate information from various parts and levels of the developing organism, we propose a framework for integrating genetic information with toxicogenomic-based studies to better understand gene-environmental interactions critical for developmental disorders. This approach has allowed us to characterize candidate genes in the context of variables critical for determining susceptibility such as strain, time, and exposure. Using a combination of toxicogenomic studies and complementary bioinformatic tools, we characterize NTD candidate genes during normal development by function (gene ontology), linked phenotype (disease outcome), location, and expression (temporally and strain-dependent). In addition, we show how environmental exposures (cadmium, methylmercury) can influence expression of these genes in a strain-dependent manner. Using NTDs as an example of developmental disorder, we show how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains. © Wiley-Liss, Inc.

Early-adult correlates of maltreatment in girls with attention-deficit/hyperactivity disorder: Increased risk for internalizing symptoms and suicidality

PubMed Central

GUENDELMAN, MAYA D.; OWENS, ELIZABETH B.; GALÁN, CHARDEE; GARD, ARIANNA; HINSHAW, STEPHEN P.

2016-01-01

We examined whether maltreatment experienced in childhood and/or adolescence prospectively predicts young adult functioning in a diverse and well-characterized sample of females with childhood-diagnosed attention-deficit/hyperactivity disorder (N = 140). Participants were part of a longitudinal study and carefully evaluated in childhood, adolescence, and young adulthood (Mage = 9.6, 14.3, and 19.7 years, respectively), with high retention rates across time. A thorough review of multisource data reliably established maltreatment status for each participant (Mκ = 0.78). Thirty-two (22.9%) participants experienced at least one maltreatment type (physical abuse, sexual abuse, or neglect). Criterion variables included a broad array of young adult measures of functioning gleaned from multiple-source, multiple-informant instruments. With stringent statistical control of demographic, prenatal, and family status characteristics as well as baseline levels of the criterion variable in question, maltreated participants were significantly more impaired than nonmaltreated participants with respect to self-harm (suicide attempts), internalizing symptomatology (anxiety and depression), eating disorder symptomatology, and well-being (lower overall self-worth). Effect sizes were medium. Comprising the first longitudinal evidence linking maltreatment with key young adult life impairments among a carefully diagnosed and followed sample of females with attention-deficit/hyperactivity disorder, these findings underscore the clinical importance of trauma experiences within this population. PMID:25723055

Fibromyalgia and psychiatric disorders.

PubMed

Fietta, Pierluigi; Fietta, Pieranna; Manganelli, Paolo

2007-08-01

Fibromyalgia (FM) is a common and polymorphic syndrome, characterized by long-lasting, widespread musculoskeletal pain, in the presence of 11 or more tender points located at specific anatomical sites. A heterogeneous series of disturbances, mainly involving autonomic, neuroendocrine and neuropsychic systems, is usually present. Even if subjective, the chronic psychophysical suffering state of FM adversely affects the patient's quality of life, performance and mood. Cognitive behavioural therapy and antidepressant drugs are useful in FM treatment, suggesting a close link between the syndrome and psychiatric, psychological and behavioural factors. Our aim was to evaluate the personality profiles of FM patients, as well as the aggregation and relationships between FM and psychiatric disorders (PD), reviewing the available evidences in current literature on this comorbidity. Personality variables associated with psychological vulnerability are frequent in FM patients. Personality disorders are rarely reported. Compared with controls, FM patients show a significantly higher prevalence of depressive and anxiety disorders, reported in 20-80% and 13-63.8% of cases, respectively. This high variability may depend on the psychosocial characteristics of patients, since most of the studies were performed on tertiary care consulting patients, however, even referring to the lower percentages, the occurrence of PD is significantly higher in FM subjects compared to the general population (7%). Moreover, elevated frequencies of PD have been detected in relatives of FM patients. The FM/PD aggregation suggests a common physiopathology, and alterations of neurotransmitter systems may constitute the shared underlying factor.

Early-adult correlates of maltreatment in girls with attention-deficit/hyperactivity disorder: Increased risk for internalizing symptoms and suicidality.

PubMed

Guendelman, Maya D; Owens, Elizabeth B; Galán, Chardee; Gard, Arianna; Hinshaw, Stephen P

2016-02-01

We examined whether maltreatment experienced in childhood and/or adolescence prospectively predicts young adult functioning in a diverse and well-characterized sample of females with childhood-diagnosed attention-deficit/hyperactivity disorder (N = 140). Participants were part of a longitudinal study and carefully evaluated in childhood, adolescence, and young adulthood (M age = 9.6, 14.3, and 19.7 years, respectively), with high retention rates across time. A thorough review of multisource data reliably established maltreatment status for each participant (M κ = 0.78). Thirty-two (22.9%) participants experienced at least one maltreatment type (physical abuse, sexual abuse, or neglect). Criterion variables included a broad array of young adult measures of functioning gleaned from multiple-source, multiple-informant instruments. With stringent statistical control of demographic, prenatal, and family status characteristics as well as baseline levels of the criterion variable in question, maltreated participants were significantly more impaired than nonmaltreated participants with respect to self-harm (suicide attempts), internalizing symptomatology (anxiety and depression), eating disorder symptomatology, and well-being (lower overall self-worth). Effect sizes were medium. Comprising the first longitudinal evidence linking maltreatment with key young adult life impairments among a carefully diagnosed and followed sample of females with attention-deficit/hyperactivity disorder, these findings underscore the clinical importance of trauma experiences within this population.

Heritability of the melatonin synthesis variability in autism spectrum disorders.

PubMed

Benabou, Marion; Rolland, Thomas; Leblond, Claire S; Millot, Gaël A; Huguet, Guillaume; Delorme, Richard; Leboyer, Marion; Pagan, Cécile; Callebert, Jacques; Maronde, Erik; Bourgeron, Thomas

2017-12-18

Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with a complex genetic architecture. They are characterized by impaired social communication, stereotyped behaviors and restricted interests and are frequently associated with comorbidities such as intellectual disability, epilepsy and severe sleep disorders. Hyperserotonemia and low melatonin levels are among the most replicated endophenotypes reported in ASD, but their genetic causes remain largely unknown. Based on the biochemical profile of 717 individuals including 213 children with ASD, 128 unaffected siblings and 376 parents and other relatives, we estimated the heritability of whole-blood serotonin, platelet N-acetylserotonin (NAS) and plasma melatonin levels, as well as the two enzymes arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT) activities measured in platelets. Overall, heritability was higher for NAS (0.72 ± 0.091) and ASMT (0.59 ± 0.097) compared with serotonin (0.31 ± 0.078), AANAT (0.34 ± 0.077) and melatonin (0.22 ± 0.071). Bivariate analyses showed high phenotypic and genetic correlations between traits of the second step of the metabolic pathway (NAS, ASMT and melatonin) indicating the contribution of shared genetic factors. A better knowledge of the heritability of the melatonin synthesis variability constitutes an important step to identify the factors that perturb this pathway in individuals with ASD.

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

PubMed

Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

2018-01-17

Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Substance use disorders in adolescent and young adult relatives of probands with bipolar disorder: What drives the increased risk?

PubMed

Hulvershorn, Leslie A; King, Jennifer; Monahan, Patrick O; Wilcox, Holly C; Mitchell, Philip B; Fullerton, Janice M; Edenberg, Howard J; Roberts, Gloria M P; Kamali, Masoud; Glowinski, Anne L; Ghaziuddin, Neera; McInnis, Melvin; Iyer-Eimerbrink, Priya A; Nurnberger, John I

2017-10-01

Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006-2011. Youth offspring/relatives ("Relatives of BD probands;" n=267; mean age=16.8years; ±2.9S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands ("relatives of control probands;" n=149; mean age=17.4years; ±2.9S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p=0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR=2.80-3.17; p<0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population. Copyright © 2017 Elsevier Inc. All rights reserved.

Emotional Functioning in Obsessive-Compulsive Personality Disorder: Comparison to Borderline Personality Disorder and Healthy Controls.

PubMed

Steenkamp, Maria M; Suvak, Michael K; Dickstein, Benjamin D; Shea, M Tracie; Litz, Brett T

2015-12-01

Few studies have investigated emotional functioning in obsessive-compulsive personality disorder (OCPD). To explore the nature and extent of emotion difficulties in OCPD, the authors examined four domains of self-reported emotional functioning--negative affectivity, anger, emotion regulation, and emotion expressivity--in women with OCPD and compared them to a borderline personality disorder (BPD) group and a healthy control group. Data were collected as part of a larger psychophysiological experimental study on emotion regulation and personality. Compared to healthy controls, participants with OCPD reported significantly higher levels of negative affectivity, trait anger, emotional intensity, and emotion regulation difficulties. Emotion regulation difficulties included lack of emotional clarity, nonacceptance of emotional responses, and limited access to effective emotion regulation strategies. Participants with OCPD scored similarly to participants with BPD on only one variable, namely, problems engaging in goal-directed behavior when upset. Results suggest that OCPD may be characterized by notable difficulties in several emotional domains.

Personality disorders and associated features in cocaine-dependent inpatients.

PubMed

Kranzler, H R; Satel, S; Apter, A

1994-01-01

Previous research has shown a high prevalence of comorbid personality disorders among individuals seeking treatment for cocaine dependence. We studied axis II disorders (using the Structured Clinical Interview for DSM-III-R Personality Disorders [SCID-II]) in 50 patients admitted for inpatient rehabilitation. All patients met lifetime criteria for cocaine dependence and reported cocaine use during the month before admission. Seventy percent of patients met criteria for at least one axis II diagnosis; the mean number of axis II diagnoses among these patients was 2.54 (range, one to six). The most common axis II diagnosis was borderline (34% of all patients), followed by antisocial and narcissistic (each 28%), avoidant and paranoid (each 22%), obsessive-compulsive (16%), and dependent (10%). To evaluate the relationship between comorbid personality pathology, substance abuse, and other psychiatric symptomatology, patients were divided into two groups based on whether they received an axis II disorder diagnosis. The groups did not differ on substance abuse variables. However, there were significant group differences on a measure of psychosis proneness and in the number of comorbid depressive and anxiety disorder diagnoses. These results are consistent with other studies of personality disorders in substance abuse patients, and suggest that it may be clinically useful to characterize cocaine-dependent patients with respect to comorbid axis II disorders.

DRINKING PATTERNS AND DSM-IV ALCOHOL USE DISORDERS’ CRITERIA IN ARGENTINEAN EMERGENCY DEPARTMENT PATIENTS

PubMed Central

Cremonte, Mariana; Cherpitel, Cheryl J.; Borges, Guilherme; Peltzer, Raquel I.; Santángelo, Pablo R.

2011-01-01

Background Previous studies have shown cultural variations in normative drinking and furthermore, in the quantity and frequency of drinking related to alcohol use disorders. Aim The main goal of this study is to characterize alcohol drinking patterns in Argentinean Emergency Department patients, and secondly, to explore the association between those drinking patterns and DSM-IV alcohol use disorders. Method Data were collected from a probability sample of patients admitted to the Emergency Department of a large public hospital in Mar del Plata, Argentina. Data analyzed here pertain to those who reported consuming at least one drink during the last twelve months (n=529). A factor analysis of multiple correspondences and a hierarchic classification were performed. For the factor analysis, usual quantity and frequency of drinking (for the last 12 months) were considered active variables; number of DSM-IV dependence criteria met, positive or negative diagnostic status for abuse, positive or negative diagnostic status for dependence (both for the last 12 months), and socio-demographic characteristics (age, gender and economic level) were considered illustrative variables. Results The first five factorial axes were retained, accounting for 88% of the total variance. Hierarchic classification resulted in six distinctive classes of drinking patterns. Two patterns were associated with a positive diagnosis of abuse and dependence, respectively. One, drinking between 4 and 6 drinks per occasion mostly on a weekly basis, was associated with a diagnosis of abuse; this pattern was also associated with meeting one or two dependence criteria (dependence orphans). The other, drinking 7 or more drinks per occasion, was associated with a diagnosis of dependence, and also with a diagnostic orphan condition. This class, composed primarily of males, was not characterized by any particular frequency of drinking. The other four drinking patterns were not associated with a positive diagnosis of an alcohol use disorder. Two of them were characterized by drinking low quantities with a low frequency (either monthly or yearly). Participants in both of these classes tended to be female. The other two patterns were characterized by drinking less than 3 drinks per occasion, either daily or weekly: the former associated with being older than 35 years, and the later with no distinctive socio-demographic characteristics. Conclusions Results demonstrated six distinct drinking patterns, two of them related to a positive diagnosis of an alcohol use disorder. Our findings support previous research indicating that dependence orphans share some characteristics with abuse and dependence cases. Given the lack of similar studies in the region, these findings, although descriptive, enrich the knowledge of alcohol use disorders in the regional context. Furthermore, they may contribute to the development of local drinking guidelines and prevention strategies. PMID:22984352

Temperament and character profiles in bipolar I, bipolar II and major depressive disorder: Impact over illness course, comorbidity pattern and psychopathological features of depression.

PubMed

Zaninotto, Leonardo; Souery, Daniel; Calati, Raffaella; Di Nicola, Marco; Montgomery, Stuart; Kasper, Siegfried; Zohar, Joseph; Mendlewicz, Julien; Robert Cloninger, C; Serretti, Alessandro; Janiri, Luigi

2015-09-15

Studies comparing temperament and character traits between patients with mood disorders and healthy individuals have yielded variable results. The Temperament and Character Inventory (TCI) was administered to 101 bipolar I (BP-I), 96 bipolar II (BP-II), 123 major depressive disorder (MDD) patients, and 125 HS. A series of generalized linear models were performed in order to: (a) compare the TCI dimensions across groups; (b) test any effect of the TCI dimensions on clinical features of mood disorders; and (c) detect any association between TCI dimensions and the psychopathological features of a major depressive episode. Demographic and clinical variables were also included in the models as independent variables. Higher Harm Avoidance was found in BP-II and MDD, but not in BP-I. Higher Self-Transcendence was found in BP-I. Our models also showed higher Self-Directedness in HS, either vs MDD or BP-II. No association was found between any TCI dimension and the severity of symptoms. Conversely, a positive association was found between Harm Avoidance and the overall burden of depressive episodes during lifetime. The cross-sectional design and the heterogeneity of the sample may be the main limitations of our study. In general, our sample seems to support the view of a similar profile of temperament and character between MDD and BP-II, characterized by high Harm Avoidance and low Self-Directedness. In contrast, patients with BP-I only exhibit high Self-Transcendence, having a near-normal profile in terms of Harm Avoidance or Self-Directedness. Copyright © 2015 Elsevier B.V. All rights reserved.

Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.

PubMed

Cheng, Hanyin; Dharmadhikari, Avinash V; Varland, Sylvia; Ma, Ning; Domingo, Deepti; Kleyner, Robert; Rope, Alan F; Yoon, Margaret; Stray-Pedersen, Asbjørg; Posey, Jennifer E; Crews, Sarah R; Eldomery, Mohammad K; Akdemir, Zeynep Coban; Lewis, Andrea M; Sutton, Vernon R; Rosenfeld, Jill A; Conboy, Erin; Agre, Katherine; Xia, Fan; Walkiewicz, Magdalena; Longoni, Mauro; High, Frances A; van Slegtenhorst, Marjon A; Mancini, Grazia M S; Finnila, Candice R; van Haeringen, Arie; den Hollander, Nicolette; Ruivenkamp, Claudia; Naidu, Sakkubai; Mahida, Sonal; Palmer, Elizabeth E; Murray, Lucinda; Lim, Derek; Jayakar, Parul; Parker, Michael J; Giusto, Stefania; Stracuzzi, Emanuela; Romano, Corrado; Beighley, Jennifer S; Bernier, Raphael A; Küry, Sébastien; Nizon, Mathilde; Corbett, Mark A; Shaw, Marie; Gardner, Alison; Barnett, Christopher; Armstrong, Ruth; Kassahn, Karin S; Van Dijck, Anke; Vandeweyer, Geert; Kleefstra, Tjitske; Schieving, Jolanda; Jongmans, Marjolijn J; de Vries, Bert B A; Pfundt, Rolph; Kerr, Bronwyn; Rojas, Samantha K; Boycott, Kym M; Person, Richard; Willaert, Rebecca; Eichler, Evan E; Kooy, R Frank; Yang, Yaping; Wu, Joseph C; Lupski, James R; Arnesen, Thomas; Cooper, Gregory M; Chung, Wendy K; Gecz, Jozef; Stessman, Holly A F; Meng, Linyan; Lyon, Gholson J

2018-05-03

N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical features of affected individuals with LGD variants in NAA15 include variable levels of intellectual disability, delayed speech and motor milestones, and autism spectrum disorder. Additionally, mild craniofacial dysmorphology, congenital cardiac anomalies, and seizures are present in some subjects. RNA analysis in cell lines from two individuals showed degradation of the transcripts with LGD variants, probably as a result of nonsense-mediated decay. Functional assays in yeast confirmed a deleterious effect for two of the LGD variants in NAA15. Further supporting a mechanism of haploinsufficiency, individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. We propose that defects in NatA-mediated N-terminal acetylation (NTA) lead to variable levels of neurodevelopmental disorders in humans, supporting the importance of the NatA complex in normal human development. Copyright © 2018 American Society of Human Genetics. All rights reserved.

Clinical and molecular features of Joubert syndrome and related disorders

PubMed Central

Parisi, Melissa A.

2009-01-01

Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions.

PubMed

Scala, Marcello; Accogli, Andrea; De Grandis, Elisa; Allegri, Anna; Bagowski, Christoph P; Shoukier, Moneef; Maghnie, Mohamad; Capra, Valeria

2018-03-01

Sheldon-Hall syndrome (SHS) is the most common of the distal arthrogryposes (DAs), a group of disorders characterized by congenital non-progressive contractures. Patients with SHS present with contractures of the limbs and a distinctive triangular facies with prominent nasolabial folds. Calcaneovalgus deformity is frequent, as well as camptodactyly and ulnar deviation. Causative mutations in at least four different genes have been reported (MYH3, TNNI2, TPM2, and TNNT3). MYH3 plays a pivotal role in fetal muscle development and mutations in this gene are associated with Freeman-Sheldon syndrome, distal arthrogryposis 8 (DA8), and autosomal dominant spondylocarpotarsal synostosis. The last two disorders are characterized by skeletal abnormalities, in particular bony fusions. The observation that MYH3 may be mutated in these syndromes has suggested the involvement of this gene in bone development. We report the case of a boy with a novel pathogenic MYH3 mutation, presenting with the classical clinical features of SHS in association with unilateral carpal bone fusion and multiple vertebral fusions. This distinctive phenotype has never been reported in the literature so far and expands the phenotypic spectrum of SHS, endorsing the clinical variability of patients with MYH3-related disorders. Our findings also support a role for MYH3 in both muscle and bone development, suggesting a phenotypic continuum in MYH3-related disorders. © 2018 Wiley Periodicals, Inc.

[How to characterize and treat sleep complaints in bipolar disorders?

PubMed

Geoffroy, P A; Micoulaud Franchi, J-A; Lopez, R; Poirot, I; Brion, A; Royant-Parola, S; Etain, B

2017-08-01

Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs"). Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders. BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Phosphatase and tensin homolog (PTEN) gene mutations and autism: literature review and a case report of a patient with Cowden syndrome, autistic disorder, and epilepsy.

PubMed

Conti, Sara; Condò, Maria; Posar, Annio; Mari, Francesca; Resta, Nicoletta; Renieri, Alessandra; Neri, Iria; Patrizi, Annalisa; Parmeggiani, Antonia

2012-03-01

Phosphatase and tensin homolog (PTEN) gene mutations are associated with a spectrum of clinical disorders characterized by skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Autism has rarely been described in association with these variable clinical features. At present, 24 patients with phosphatase and tensin homolog gene mutation, autism, macrocephaly, and some clinical findings described in phosphatase and tensin homolog syndromes have been reported in the literature. We describe a 14-year-old boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly, and multiple papular skin lesions and palmoplantar punctate keratoses, characteristic of Cowden syndrome. The boy has a de novo phosphatase and tensin homolog gene mutation. Our patient is the first case described to present a typical Cowden syndrome and autism associated with epilepsy.

Novel ETFDH mutation and imaging findings in an adult with glutaric aciduria type II.

PubMed

Rosenbohm, Angela; Süssmuth, Sigurd D; Kassubek, Jan; Müller, Hans-Peter; Pontes, Christina; Abicht, Angela; Bulst, Stefanie; Ludolph, Albert C; Pinkhardt, Elmar

2014-03-01

Glutaric aciduria type II (GAII) is a rare autosomal recessive disorder with variable clinical course. The disorder is caused by a defect in the mitochondrial electron transfer flavoprotein or the electron transfer flavoprotein dehydrogenase (ETFDH). We performed clinical characterization, brain and whole body MRI, muscle histopathology, and genetic analysis of the ETFDH gene in a young woman. She presented with rhabdomyolysis and severe quadriparesis. We identified a novel homozygous missense mutation in ETFDH (c.1544G>T, p.Ser515Ile). Body fat MRI revealed a large amount of subcutaneous fat but no increase in visceral fat despite steatosis of liver and muscle. Diffusion tensor imaging (DTI) of cerebral MRI revealed reduced directionality of the white matter tracts. Histopathological findings showed lipid storage myopathy. In this study, we highlight diagnostic clues and body fat MRI in this rare metabolic disorder. Copyright © 2013 Wiley Periodicals, Inc.

[Mathematic concept model of accumulation of functional disorders associated with environmental factors].

PubMed

Zaĭtseva, N V; Trusov, P V; Kir'ianov, D A

2012-01-01

The mathematic concept model presented describes accumulation of functional disorders associated with environmental factors, plays predictive role and is designed for assessments of possible effects caused by heterogenous factors with variable exposures. Considering exposure changes with self-restoration process opens prospects of using the model to evaluate, analyse and manage occupational risks. To develop current theoretic approaches, the authors suggested a model considering age-related body peculiarities, systemic interactions of organs, including neuro-humoral regulation, accumulation of functional disorders due to external factors, rehabilitation of functions during treatment. General objective setting covers defining over a hundred unknow coefficients that characterize speed of various processes within the body. To solve this problem, the authors used iteration approach, successive identification, that starts from the certain primary approximation of the model parameters and processes subsequent updating on the basis of new theoretic and empirical knowledge.

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

Animal Models of Post-Traumatic Stress Disorder and Recent Neurobiological Insights

PubMed Central

Whitaker, Annie M.; Gilpin, Nicholas W.; Edwards, Scott

2014-01-01

Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder characterized by the intrusive re-experiencing of past trauma, avoidant behavior, enhanced fear, and hyperarousal following a traumatic event in vulnerable populations. Preclinical animal models do not replicate the human condition in its entirety, but seek to mimic symptoms or endophenotypes associated with PTSD. Although many models of traumatic stress exist, few adequately capture the complex nature of the disorder and the observed individual variability in susceptibility of humans to develop PTSD. In addition, various types of stressors may produce different molecular neuroadaptations that likely contribute to the various behavioral disruptions produced by each model, although certain consistent neurobiological themes related to PTSD have emerged. For example, animal models report traumatic stress- and trauma reminder-induced alterations in neuronal activity in the amygdala and prefrontal cortex, in agreement with the human PTSD literature. Models have also provided a conceptual framework for the often observed combination of PTSD and co-morbid conditions such as alcohol use disorder (AUD). Future studies will continue to refine preclinical PTSD models in hopes of capitalizing on their potential to deliver new and more efficacious treatments for PTSD and associated psychiatric disorders. PMID:25083568

Waardenburg syndrome--a case report.

PubMed

Bansal, Yuvika; Jain, Parul; Goyal, Gaurav; Singh, Malvika; Mishra, Chittranjan

2013-02-01

Waardenburg syndrome is a rare genetic disorder characterized by varying degree of deafness associated with pigmentary anomaly and defects of neural crest cell derived structures. Four subtypes (I-IV) with variable penetrance and gene expression of different clinical features have been described. We report a patient showing constellation of complete heterochromia, dystopia canthorum, white forelock, and synophrys. Other affected family relatives with heterochromia have been depicted in pedigree. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Acculturative heterogeneity among Asian/Pacific Islanders in the United States: Associations with DSM mental and substance use disorders.

PubMed

Salas-Wright, Christopher P; Lee, Sharon; Vaughn, Michael G; Jang, Yuri; Sanglang, Cindy C

2015-07-01

Extant studies on the links between acculturation and mental and substance use disorders among Asian/Pacific Islanders have been based on the assumption that acculturation is a homogeneous construct. However, emerging evidence suggests that the various components of acculturation do not manifest independently, but rather cluster in ways that reflect distinct profiles. We employ data on Asian/Pacific Islanders from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 968). Latent profile analysis is used to identify acculturation subgroups on the basis of indicator variables related to cultural identification, language ability and preference, and social engagement. Subsequently, the distribution of outcome variables in the domains of DSM disorders (lifetime history of clinical, personality, and substance use disorders) is examined across latent subgroups. We identified a 5-class solution: Class 1: Separated (12.91%), Class 2: Partial Bilingual/Bicultural (30.06%), Class 3: English Dominant/Asian Oriented (12.29%), Class 4: Full Bilingual/Bicultural (19.42%) and Class 5: Assimilated (25.31%). The highest rates of clinical disorders were observed among members of the 2 classes characterized by a strong preference for the use of the English language (Classes 3 and 5). The highest prevalence of nicotine (12%) and illicit drug use (15%) disorders was observed among members of the Assimilated class. Consistent with prior research, findings suggest that risk of morbidity is greater among more acculturated individuals; however, findings also suggest that an important level of nuance can be observed with respect to acculturative subtypes identified on the basis of cultural identification, language ability and preference, and social engagement. (c) 2015 APA, all rights reserved).

Acculturative Heterogeneity among Asian/Pacific Islanders in the United States: Associations with DSM Mental and Substance Use Disorders

PubMed Central

Salas-Wright, Christopher P.; Lee, Sharon; Vaughn, Michael G.; Jang, Yuri; Sanglang, Cindy C.

2014-01-01

Extant studies on the links between acculturation and mental and substance use disorders among Asian/Pacific Islanders have been based on the assumption that acculturation is a homogeneous construct. However, emerging evidence suggests that the various components of acculturation do not manifest independently, but rather cluster in ways that reflect distinct profiles. We employ data on Asian/Pacific Islanders from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 968). Latent profile analysis is used to identify acculturation subgroups on the basis of indicator variables related to cultural identification, language ability and preference, and social engagement. Subsequently, the distribution of outcome variables in the domains of DSM disorders (lifetime history of clinical, personality, and substance use disorders) is examined across latent subgroups. We identified a five class solution: Class 1: “Separated” (12.91%), Class 2: “Partial Bilingual/Bicultural” (30.06%), Class 3: “English Dominant/Asian Oriented” (12.29%), Class 4:”Full Bilingual/Bicultural” (19.42%) and Class 5: “Assimilated” (25.31%). The highest rates of clinical disorders were observed among members of the two classes characterized by a strong preference for the use of the English language (Classes 3 and 5). The highest prevalence of nicotine (12%) and illicit drug use (15%) disorders was observed among members of the “Assimilated” class. Consistent with prior research, findings suggest that risk of morbidity is greater among more acculturated individuals; however, findings also suggest that an important level of nuance can be observed with respect to acculturative subtypes identified on the basis of cultural identification, language ability and preference, and social engagement. PMID:26167805

Evaluation of the DSM-5 severity indicator for binge eating disorder in a clinical sample

PubMed Central

Grilo, Carlos M.; Ivezaj, Valentina; White, Marney A.

2015-01-01

Objective This study tested the new DSM-5 severity criterion for binge eating disorder (BED) based on frequency of binge-eating in a clinical sample. This study also tested overvaluation of shape/weight as an alternative severity specifier. Method Participants were 834 treatment-seeking adults diagnosed with DSM-5 BED using semistructured diagnostic and eating-disorder interviews. Participants sub-grouped based on DSM-5 severity levels and on overvaluation of shape/weight were compared on demographic and clinical variables. Results Based on DSM-5 severity definitions, 331 (39.7%) participants were categorized as mild, 395 (47.5%) as moderate, 83 (10.0%) as severe, and 25 (3.0%) as extreme. Analyses comparing three (mild, moderate, and severe/extreme) severity groups revealed no significant differences in demographic variables or body mass index (BMI). Analyses revealed significantly higher eating-disorder psychopathology in the severe/extreme than moderate and mild groups and higher depression in moderate and severe/extreme groups than the mild group; effect sizes were small. Participants characterized with overvaluation (N = 449; 54%) versus without overvaluation (N = 384; 46%) did not differ significantly in age, sex, BMI, or binge-eating frequency, but had significantly greater eating-disorder psychopathology and depression. The robustly greater eating-disorder psychopathology and depression levels (medium-to-large effect sizes) in the overvaluation group was observed without attenuation of effect sizes after adjusting for ethnicity/race and binge-eating severity/frequency. Conclusions Our findings provide support for overvaluation of shape/weight as a severity specifier for BED as it provides stronger information about the severity of homogeneous groupings of patients than the DSM-5 rating based on binge-eating. PMID:26114779

GWAS-based machine learning approach to predict duloxetine response in major depressive disorder.

PubMed

Maciukiewicz, Malgorzata; Marshe, Victoria S; Hauschild, Anne-Christin; Foster, Jane A; Rotzinger, Susan; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J; Geraci, Joseph

2018-04-01

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders and is commonly treated with antidepressant drugs. However, large variability is observed in terms of response to antidepressants. Machine learning (ML) models may be useful to predict treatment outcomes. A sample of 186 MDD patients received treatment with duloxetine for up to 8 weeks were categorized as "responders" based on a MADRS change >50% from baseline; or "remitters" based on a MADRS score ≤10 at end point. The initial dataset (N = 186) was randomly divided into training and test sets in a nested 5-fold cross-validation, where 80% was used as a training set and 20% made up five independent test sets. We performed genome-wide logistic regression to identify potentially significant variants related to duloxetine response/remission and extracted the most promising predictors using LASSO regression. Subsequently, classification-regression trees (CRT) and support vector machines (SVM) were applied to construct models, using ten-fold cross-validation. With regards to response, none of the pairs performed significantly better than chance (accuracy p > .1). For remission, SVM achieved moderate performance with an accuracy = 0.52, a sensitivity = 0.58, and a specificity = 0.46, and 0.51 for all coefficients for CRT. The best performing SVM fold was characterized by an accuracy = 0.66 (p = .071), sensitivity = 0.70 and a sensitivity = 0.61. In this study, the potential of using GWAS data to predict duloxetine outcomes was examined using ML models. The models were characterized by a promising sensitivity, but specificity remained moderate at best. The inclusion of additional non-genetic variables to create integrated models may improve prediction. Copyright © 2017. Published by Elsevier Ltd.

Variability in Institutional Screening Practices Related to Collegiate Student-Athlete Mental Health.

PubMed

Kroshus, Emily

2016-05-01

Universal screening for mental health concerns, as part of the preparticipation examination in collegiate sports medicine settings, can be an important and feasible strategy for facilitating early detection of mental health disorders. To assess whether sports medicine departments at National Collegiate Athletic Association (NCAA) member colleges have policies related to identifying student-athlete mental health problems, the nature of preparticipation examination screening related to mental health, and whether other departmental or institutional screening initiatives are in place. I also aimed to characterize the variability in screening by institutional characteristics. Cross-sectional study. College sports medicine departments. Team physicians and head athletic trainers at NCAA member colleges (n = 365, 30.3% response rate). Electronic survey of departmental mental health screening activities. A total of 39% of respondents indicated that their institution had a written plan related to identifying student-athletes with mental health concerns. Fewer than half reported that their sports medicine department administers a written or verbal screening instrument for symptoms of disordered eating (44.5%), depression (32.3%), or anxiety (30.7%). The strongest predictors of mental health screening were the presence of a written plan related to identifying student-athlete mental health concerns and the employment of a clinical psychologist. Additionally, Division I institutions and institutions with a greater ratio of athletic trainers to student-athletes tended to engage in more screening. The substantial among-institutions variability in mental health screening suggests that opportunities exist to make these practices more widespread. To address this variability, recent NCAA mental health best-practice guidelines suggested that institutions should screen for a range of mental health disorders and risk behaviors. However, at some institutions, staffing deficits may need to be addressed to allow for implementation of screening-related activities.

Sex Differences in Cannabis Use Disorder Diagnosis Involved Hospitalizations in the United States

PubMed Central

Zhu, He; Wu, Li-Tzy

2017-01-01

Objectives: The study examined sex differences in trend and clinical characteristics of cannabis use disorder (CUD) diagnosis involved hospitalizations among adult patients. Methods: We analyzed hospitalization data from the 2007–2011 Nationwide Inpatient Samples for patients aged 18–64 years (N = 15,114,930). Descriptive statistics were used to characterize demographic variables and to compare the proportions of CUD diagnosis and comorbid patterns between male and female hospitalizations. Logistic regressions were performed to examine the association of sex and other demographic variables with CUD diagnosis. Results: During the study period, 3.3% of male and 1.5% of female hospitalizations had any-listed CUD diagnoses, and both sexes presented an upward trend in the number, rate, and proportion of CUD diagnosis. Among hospitalizations for patients aged 18–25 years, about 1 in 10 males and 1 in 20 females included a CUD diagnosis, and this proportion decreased with age strata. Mental disorders accounted for the highest proportion of CUD involved inpatient hospitalizations, and female CUD involved hospitalizations included a higher proportion of mental disorders that required hospitalized care compared with male hospitalizations (41% vs 36%). In each sex group, younger age, black race, lower household income, large metropolitan residence, non-private insurance, substance use diagnosis, and mental disorders were associated with elevated odds of having CUD diagnosis. Conclusion: The large sample of clinical hospitalization data suggest an increased trend in CUD diagnosis and sex differences in several comorbidities with CUD-involved hospital admissions. Prevention and treatment for CUD should consider sex differences in clinical comorbidities. PMID:28700366

Gorlin-Goltz Syndrome: An Uncommon Cause of Facial Pain and Asymmetry.

PubMed

Pickrell, Brent B; Nguyen, Harrison P; Buchanan, Edward P

2015-10-01

Gorlin-Goltz syndrome is an underdiagnosed autosomal dominant disorder with variable expressivity that is characterized by an increased predisposition to tumorigenesis of multiple types. The major clinical features include multiple basal cell carcinomas (BCCs) appearing in early childhood, palmar and plantar pits, odontogenic keratocysts of the oral cavity, skeletal defects, craniofacial dysmorphism, and ectopic intracranial calcification. The authors present the clinical course of a 12-year-old girl presenting with facial asymmetry and pain because of previously undiagnosed Gorlin-Goltz syndrome. Early diagnosis and attentive management by a multidisciplinary team are paramount to improving outcomes in patients with this disorder, and this report serves as a paradigm for maintaining a high clinical suspicion, which must be accompanied by an appropriate radiologic workup.

Influence of Family Structure and School Variables on Behavior Disorders of Children

ERIC Educational Resources Information Center

Lindholm, Byron W.; And Others

1977-01-01

This study examined the influence of family structure and school variables on behavior disorders of children (N=1,162). Results indicated grade in school, sex, social class, ordinal position in the family, and teacher were important variables in the determination of behavior disorders. (Author)

Insular and hippocampal gray matter volume reductions in patients with major depressive disorder.

PubMed

Stratmann, Mirjam; Konrad, Carsten; Kugel, Harald; Krug, Axel; Schöning, Sonja; Ohrmann, Patricia; Uhlmann, Christina; Postert, Christian; Suslow, Thomas; Heindel, Walter; Arolt, Volker; Kircher, Tilo; Dannlowski, Udo

2014-01-01

Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder. For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes. Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala. The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.

Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder

PubMed Central

Kugel, Harald; Krug, Axel; Schöning, Sonja; Ohrmann, Patricia; Uhlmann, Christina; Postert, Christian; Suslow, Thomas; Heindel, Walter; Arolt, Volker; Kircher, Tilo; Dannlowski, Udo

2014-01-01

Background Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder. Methods For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes. Results Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala. Conclusions The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy. PMID:25051163

Differences in clinical presentation and pregnancy outcomes in antepartum preeclampsia and new-onset postpartum preeclampsia: Are these the same disorder?

PubMed

Vilchez, Gustavo; Hoyos, Luis R; Leon-Peters, Jocelyn; Lagos, Moraima; Argoti, Pedro

2016-11-01

New-onset postpartum preeclampsia is a poorly defined condition that accounts for a significant percentage of eclampsia cases. It is unclear whether new-onset postpartum preeclampsia is a different disorder from or belongs to the same spectrum of classic antepartum preeclampsia. The objective of this study was to compare the clinical presentation and pregnancy outcomes of antepartum preeclampsia and new-onset postpartum preeclampsia. A retrospective study including 92 patients with antepartum preeclampsia and 92 patients with new-onset postpartum preeclampsia was performed. Clinical presentation and pregnancy outcomes were compared. Chi-square test was used to analyze categorical variables, and independent t -test and Mann-Whitney U -test for numerical variables. P -values of <0.05 were used to indicate statistical signifi cance. Patients with antepartum preeclampsia and new-onset postpartum preeclampsia differ significantly in profile, symptoms at presentation, laboratory markers and pregnancy outcomes. New-onset postpartum preeclampsia has a distinct patient profile and clinical presentation than antepartum preeclampsia, suggesting they may represent different disorders. Characterization of a patient profile with increased risk of developing this condition will help clinicians to identify patients at risk and provide early and targeted interventions to decrease the morbidity associated with this condition.

Development of lifetime comorbidity in the WHO World Mental Health (WMH) Surveys

PubMed Central

Kessler, Ronald C.; Ormel, Johan; Petukhova, Maria; McLaughlin, Katie A.; Green, Jennifer Greif; Russo, Leo J.; Stein, Dan J.; Zaslavsky, Alan M; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Andrade, Laura; Benjet, Corina; de Girolamo, Giovanni; de Graaf, Ron; Demyttenaere, Koen; Fayyad, John; Haro, Josep Maria; Hu, Chi yi; Karam, Aimee; Lee, Sing; Lepine, Jean-Pierre; Matchsinger, Herbert; Mihaescu-Pintia, Constanta; Posada-Villa, Jose; Sagar, Rajesh; Üstün, T. Bedirhan

2010-01-01

CONTEXT Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the WHO World Mental Health (WMH) surveys. SETTING/PARTICIPANTS Nationally or regionally representative community surveys in 14 countries with a total of 21,229 respondents. MAIN OUTCOME MEASURES First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the WHO Composite International Diagnostic Interview (CIDI). RESULTS Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (i.e., internalizing or externalizing) associations were generally stronger than between-domain associations. The vast majority of time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity disorder and oppositional-defiant disorder (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered here. These common pathways should be the focus of future research on the development of comorbidity, although several important pair-wise associations that cannot be accounted for by latent variables also exist that warrant further focused study. PMID:21199968

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

PubMed Central

2011-01-01

Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

Characterizing cognitive control abilities in children with 16p11.2 deletion using adaptive 'video game' technology: a pilot study.

PubMed

Anguera, J A; Brandes-Aitken, A N; Rolle, C E; Skinner, S N; Desai, S S; Bower, J D; Martucci, W E; Chung, W K; Sherr, E H; Marco, E J

2016-09-20

Assessing cognitive abilities in children is challenging for two primary reasons: lack of testing engagement can lead to low testing sensitivity and inherent performance variability. Here we sought to explore whether an engaging, adaptive digital cognitive platform built to look and feel like a video game would reliably measure attention-based abilities in children with and without neurodevelopmental disabilities related to a known genetic condition, 16p11.2 deletion. We assessed 20 children with 16p11.2 deletion, a genetic variation implicated in attention deficit/hyperactivity disorder and autism, as well as 16 siblings without the deletion and 75 neurotypical age-matched children. Deletion carriers showed significantly slower response times and greater response variability when compared with all non-carriers; by comparison, traditional non-adaptive selective attention assessments were unable to discriminate group differences. This phenotypic characterization highlights the potential power of administering tools that integrate adaptive psychophysical mechanics into video-game-style mechanics to achieve robust, reliable measurements.

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1.

PubMed

Alfadhel, Majid; Alhasan, Khalid A; Alotaibi, Mohammed; Al Fakeeh, Khalid

2012-01-01

Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene. Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function. Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder.

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.

PubMed

Clementz, Brett A; Sweeney, John A; Hamm, Jordan P; Ivleva, Elena I; Ethridge, Lauren E; Pearlson, Godfrey D; Keshavan, Matcheri S; Tamminga, Carol A

2016-04-01

Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.

Rheumatologic complications in a cohort of 227 patients with common variable immunodeficiency.

PubMed

Azizi, G; Kiaee, F; Hedayat, E; Yazdani, R; Dolatshahi, E; Alinia, T; Sharifi, L; Mohammadi, H; Kavosi, H; Jadidi-Niaragh, F; Ziaee, V; Abolhassani, H; Aghamohammadi, A

2018-05-01

Common variable immunodeficiency (CVID) is the most prevalent symptomatic type of human primary immunodeficiency diseases (PID). Clinically, CVID is characterized by increased susceptibility to infections and a wide variety of autoimmune and rheumatologic disorders. All patients with CVID registered in Iranian PID Registry (IPIDR) were enrolled in this retrospective cohort study. We investigated the frequency of rheumatologic diseases and its association with immunological and clinical phenotypes in patients with CVID. A total of 227 patients with CVID were enrolled in this study. The prevalence of rheumatologic disorders was 10.1% with a higher frequency in women than men. Most common rheumatologic manifestations were juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) followed by juvenile spondyloarthritis (JSpA) and undifferentiated inflammatory arthritis (UIA). Septic arthritis in patients with CVID with a history of RA and JIA was higher than patients without rheumatologic complication. Patients with CVID with a history of autoimmunity (both rheumatologic and non-rheumatologic autoimmunity) had lower regulatory T cells counts in comparison with patients without autoimmune disorders. There was an association between defect in specific antibody responses and negative serologic test results in patients with rheumatologic manifestations. JIA, RA, JSpA and UIA are the most frequent rheumatologic disorders in patients with CVID. Due to antibody deficiency, serologic tests may be negative in these patients. Therefore, these conditions pose significant diagnostic and therapeutic challenges for immunologists and rheumatologists in charge of the care for these patients. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Examining Affect and Perfectionism in Relation to Eating Disorder Symptoms among Women with Anorexia Nervosa

PubMed Central

Lavender, Jason M.; Mason, Tyler B.; Utzinger, Linsey M.; Wonderlich, Stephen A.; Crosby, Ross D.; Engel, Scott G.; Mitchell, James E.; Le Grange, Daniel; Crow, Scott J.; Peterson, Carol B.

2016-01-01

This study examined personality and affective variables in relation to eating disorder symptoms in anorexia nervosa (AN). Women (N=118) with DSM-IV AN completed baseline questionnaires (Beck Depression Inventory, Frost Multidimensional Perfectionism Scale) and interviews (Eating Disorder Examination, Yale-Brown-Cornell Eating Disorder Scale), followed by two weeks of ecological momentary assessment (EMA) involving multiple daily reports of affective states and eating disorder behaviors. Hierarchical regression analyses were conducted using eating disorder symptoms as dependent variables (i.e., EMA binge eating, EMA self-induced vomiting, eating disorder rituals, eating disorder preoccupations, dietary restraint). Predictor variables were maladaptive perfectionism (baseline), depressive symptoms (baseline), and affect lability (EMA). Results revealed that affect lability was independently associated with binge eating, whereas depressive symptoms were independently associated with self-induced vomiting. Depressive symptoms were independently associated with eating disorder rituals, whereas both depressive symptoms and maladaptive perfectionism were independently associated with eating disorder preoccupations. Finally, maladaptive perfectionism and affect lability were both independently associated with dietary restraint. This pattern of findings suggests the importance of affective and personality constructs in relation to eating disorder symptoms in AN and may highlight the importance of targeting these variables in the context of treatment. PMID:27208513

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

PubMed Central

Viñas-Jornet, Marina; Esteba-Castillo, Susanna; Gabau, Elisabeth; Ribas-Vidal, Núria; Baena, Neus; San, Joan; Ruiz, Anna; Coll, Maria Dolors; Novell, Ramon; Guitart, Miriam

2014-01-01

Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance. PMID:25614873

Rationale, design and objectives of ARegPKD, a European ARPKD registry study.

PubMed

Ebner, Kathrin; Feldkoetter, Markus; Ariceta, Gema; Bergmann, Carsten; Buettner, Reinhard; Doyon, Anke; Duzova, Ali; Goebel, Heike; Haffner, Dieter; Hero, Barbara; Hoppe, Bernd; Illig, Thomas; Jankauskiene, Augustina; Klopp, Norman; König, Jens; Litwin, Mieczyslaw; Mekahli, Djalila; Ranchin, Bruno; Sander, Anja; Testa, Sara; Weber, Lutz Thorsten; Wicher, Dorota; Yuzbasioglu, Ayse; Zerres, Klaus; Dötsch, Jörg; Schaefer, Franz; Liebau, Max Christoph

2015-02-18

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish. ARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research. The novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.

Sex differences in prevalence and comorbidity of alcohol and drug use disorders: results from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.

PubMed

Goldstein, Risë B; Dawson, Deborah A; Chou, S Patricia; Grant, Bridget F

2012-11-01

The present study examined sex differences in lifetime Axis I and II psychiatric comorbidity of DSM-IV alcohol use disorders (AUDs) and drug use disorders (DUDs) among general population U.S. adults. Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, Wave 2 lifetime prevalences of each disorder comorbid with alcohol abuse, alcohol dependence, drug abuse, and drug dependence were compared between men and women. Sex-specific associations of alcohol, any drug, and cannabis- and cocaine-specific abuse and dependence with each comorbid disorder were examined using logistic regression, first with adjustment for sociodemographic variables and then with additional adjustment for all other psychiatric disorders. Prevalences of most comorbid disorders differed significantly by sex among respondents with each AUD and DUD. However, after adjustment for sociodemographic characteristics and additional co-occurring psychiatric diagnoses, there were few sex differences in unique comorbid associations of specific AUDs and DUDs with specific psychiatric disorders. Rates of psychiatric disorders comorbid with AUDs and DUDs indicate large burdens of morbidity in both sexes, highlighting the need for careful assessment and appropriate treatment of both substance use and mental health disorders. The unique comorbid associations with AUDs and DUDs identified in this study further indicate the need for prospective etiological research to characterize these associations, their underlying mechanisms, and the possible sex specificity of those mechanisms.

Sex Differences in Prevalence and Comorbidity of Alcohol and Drug Use Disorders: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

PubMed Central

Goldstein, Risë B.; Dawson, Deborah A.; Chou, S. Patricia; Grant, Bridget F.

2012-01-01

Objective: The present study examined sex differences in lifetime Axis I and II psychiatric comorbidity of DSM-IV alcohol use disorders (AUDs) and drug use disorders (DUDs) among general population U.S. adults. Method: Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, Wave 2 lifetime prevalences of each disorder comorbid with alcohol abuse, alcohol dependence, drug abuse, and drug dependence were compared between men and women. Sex-specific associations of alcohol, any drug, and cannabis- and cocaine-specific abuse and dependence with each comorbid disorder were examined using logistic regression, first with adjustment for sociodemographic variables and then with additional adjustment for all other psychiatric disorders. Results: Prevalences of most comorbid disorders differed significantly by sex among respondents with each AUD and DUD. However, after adjustment for sociodemographic characteristics and additional co-occurring psychiatric diagnoses, there were few sex differences in unique comorbid associations of specific AUDs and DUDs with specific psychiatric disorders. Conclusions: Rates of psychiatric disorders comorbid with AUDs and DUDs indicate large burdens of morbidity in both sexes, highlighting the need for careful assessment and appropriate treatment of both substance use and mental health disorders. The unique comorbid associations with AUDs and DUDs identified in this study further indicate the need for prospective etiological research to characterize these associations, their underlying mechanisms, and the possible sex specificity of those mechanisms. PMID:23036212

Predictors of course and outcome in hypochondriasis after cognitive-behavioral treatment.

PubMed

Hiller, Wolfgang; Leibbrand, Rolf; Rief, Winfried; Fichter, Manfred M

2002-01-01

Predictors of treatment outcome were evaluated in a clinical sample suffering from hypochondriasis. The sample consisted of 96 patients with hypochondriacal disorder according to DSM-IV or high syndrome scores on the Illness Attitude Scales (IAS) or Whiteley Index (WI). After intense inpatient cognitive-behavioral treatment (CBT), 60% of the patients were classified as responders because of substantial improvements or recovery from hypochondriacal symptomatology. Non-responders were characterized by a higher degree of pre-treatment hypochondriasis, more somatization symptoms and general psychopathology (SCL-90R), more dysfunctional cognitions related to bodily functioning, higher levels of psychosocial impairments, and more utilization of the health care system as indicated by the number of hospital days and costs for inpatient treatments and medication. No predictive value was found for sociodemographic variables, comorbidity with other mental disorders and chronicity. Multiple linear regression showed that pre-treatment variables significantly predicted IAS scores at post-treatment (R(2) = 0.59), changes during treatment (0.10), IAS scores at follow-up two years later (0.41) and changes between baseline and follow-up (0.25). The results demonstrate the relevance of various psychopathological variables and health care utilization as important indicators for outcome and further course of clinical hypochondriasis. Copyright 2002 S. Karger AG, Basel

Gait disorders in patients with fibromyalgia.

PubMed

Auvinet, Bernard; Bileckot, Richard; Alix, Anne-Sophie; Chaleil, Denis; Barrey, Eric

2006-10-01

The objective of this study was to compare gait in patients with fibromyalgia and in matched controls. Measurements must be obtained in patients with fibromyalgia, as the evaluation scales for this disorder are semi-quantitative. We used a patented gait analysis system (Locometrix Centaure Metrix, France) developed by the French National Institute for Agricultural Research. Relaxed walking was evaluated in 14 women (mean age 50+/-5 years; mean height 162+/-5 cm; and mean body weight 68+/-13 kg) meeting American College of Rheumatology criteria for fibromyalgia and in 14 controls matched on sex, age, height, and body weight. Gait during stable walking was severely altered in the patients. Walking speed was significantly diminished (P<0.001) as a result of reductions in stride length (P<0.001) and cycle frequency (P<0.001). The resulting bradykinesia (P<0.001) was the best factor for separating the two groups. Regularity was affected in the patients (P<0.01); this variable is interesting because it is independent of age and sex in healthy, active adults. Measuring the variables that characterize relaxed walking provides useful quantitative data in patients with fibromyalgia.

Matching the bipolar patient and the mood stabilizer.

PubMed

Gelenberg, Alan J; Pies, Ronald

2003-01-01

Bipolar disorder poses many treatment challenges, including "matching" a particular patient with the optimal treatment regimen. Although there are a number of extant guidelines to assist the clinician in selecting treatment, these recommendations are largely based on general variables and fail to take into account the subtleties and complications that confront a clinician in practice. An analysis of predictors of medication response in bipolar disorder provides a basis for matching patients with optimal medication regimens. Response to treatment may depend on the polarity of an episode or on clinical features such as mixed or psychotic symptomatology and rate of cycling. Comorbid psychiatric disorders such as substance abuse, anxiety disorders, or attention-deficit/hyperactivity disorder should also be considered in designing a treatment regimen. Similarly, medical conditions, especially metabolic abnormalities or kidney insufficiency, must be taken into account. Selection of medication may also involve an analysis of demographic factors, including family and personal history of response to a particular agent. When selecting the most appropriate mood stabilizer for a patient--particularly when polypharmacy is required--the clinician should keep potential side effects and drug interactions in mind. Randomized, controlled studies in bipolar populations are needed to further characterize optimal matching of patient and medication.

SLEEP AND MENTAL DISORDERS: A META-ANALYSIS OF POLYSOMNOGRAPHIC RESEARCH

PubMed Central

Baglioni, Chiara; Nanovska, Svetoslava; Regen, Wolfram; Spiegelhalder, Kai; Feige, Bernd; Nissen, Christoph; Reynolds, Charles F.; Riemann, Dieter

2016-01-01

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, ADHD, and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the “Comprehensive Meta-Analysis” and “R” softwares. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges’g). Sources of variability, i.e., sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in one condition; however, no two conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in one single variable. PMID:27416139

Anomalous negative magnetoresistance of two-dimensional electrons

NASA Astrophysics Data System (ADS)

Kanter, Jesse; Vitkalov, Sergey; Bykov, A. A.

2018-05-01

Effects of temperature T (6-18 K) and variable in situ static disorder on dissipative resistance of two-dimensional electrons are investigated in GaAs quantum wells placed in a perpendicular magnetic-field B⊥. Quantum contributions to the magnetoresistance, leading to quantum positive magnetoresistance (QPMR), are separated by application of an in-plane magnetic field. QPMR decreases considerably with both the temperature and the static disorder and is in good quantitative agreement with theory. The remaining resistance R decreases with the magnetic field exhibiting an anomalous polynomial dependence on B⊥:[R (B⊥) -R (0 ) ] =A (T ,τq) B⊥η where the power is η ≈1.5 ±0.1 in a broad range of temperatures and disorder. The disorder is characterized by electron quantum lifetime τq. The scaling factor A (T ,τq) ˜[κ(τq) +β (τq) T2] -1 depends significantly on both τq and T where the first term κ ˜τq-1/2 decreases with τq. The second term is proportional to the square of the temperature and diverges with increasing static disorder. Above a critical disorder the anomalous magnetoresistance is absent, and only a positive magnetoresistance, exhibiting no distinct polynomial behavior with the magnetic field, is observed. The presented model accounts memory effects and yields η = 3/2.

Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison

PubMed Central

Lochner, Christine; Seedat, Soraya; du Toit, Pieter L; Nel, Daniel G; Niehaus, Dana JH; Sandler, Robin; Stein, Dan J

2005-01-01

Background Similarities between obsessive-compulsive disorder (OCD) and trichotillomania (TTM) have been widely recognized. Nevertheless, there is evidence of important differences between these two disorders. Some authors have conceptualized the disorders as lying on an OCD spectrum of conditions. Methods Two hundred and seventy eight OCD patients (n = 278: 148 male; 130 female) and 54 TTM patients (n = 54; 5 male; 49 female) of all ages were interviewed. Female patients were compared on select demographic and clinical variables, including comorbid axis I and II disorders, and temperament/character profiles. Results OCD patients reported significantly more lifetime disability, but fewer TTM patients reported response to treatment. OCD patients reported higher comorbidity, more harm avoidance and less novelty seeking, more maladaptive beliefs, and more sexual abuse. OCD and TTM symptoms were equally likely to worsen during menstruation, but OCD onset or worsening was more likely associated with pregnancy/puerperium. Conclusions These findings support previous work demonstrating significant differences between OCD and TTM. The classification of TTM as an impulse control disorder is also problematic, and TTM may have more in common with conditions characterized by stereotypical self-injurious symptoms, such as skin-picking. Differences between OCD and TTM may reflect differences in underlying psychobiology, and may necessitate contrasting treatment approaches. PMID:15649315

Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

PubMed

Coccaro, Emil F

2011-01-01

This study was designed to develop a revised diagnostic criteria set for intermittent explosive disorder (IED) for consideration for inclusion in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). This revised criteria set was developed by integrating previous research criteria with elements from the current DSM-IV set of diagnostic criteria. Evidence supporting the reliability and validity of IED-IR ("IED Integrated Criteria") in a new and well-characterized group of subjects with personality disorder is presented. Clinical, phenomenologic, and diagnostic data from 201 individuals with personality disorder were reviewed. All IED diagnoses were assigned using a best-estimate process (eg, kappa for IED-IR >0.85). In addition, subjects meeting IED-IR criteria had higher scores on dimensional measures of aggression and had lower global functioning scores than non-IED-IR subjects, even when related variables were controlled. The IED-IR criteria were more sensitive than the DSM-IV criteria only in identifying subjects with significant impulsive-aggressive behavior by a factor of 16. We conclude that the IED-IR criteria can be reliably applied and have sufficient validity to warrant consideration as DSM-V criteria for IED. Copyright © 2011 Elsevier Inc. All rights reserved.

Examining affect and perfectionism in relation to eating disorder symptoms among women with anorexia nervosa.

PubMed

Lavender, Jason M; Mason, Tyler B; Utzinger, Linsey M; Wonderlich, Stephen A; Crosby, Ross D; Engel, Scott G; Mitchell, James E; Le Grange, Daniel; Crow, Scott J; Peterson, Carol B

2016-07-30

This study examined personality and affective variables in relation to eating disorder symptoms in anorexia nervosa (AN). Women (N=118) with DSM-IV AN completed baseline questionnaires (Beck Depression Inventory, Frost Multidimensional Perfectionism Scale) and interviews (Eating Disorder Examination, Yale-Brown-Cornell Eating Disorder Scale), followed by two weeks of ecological momentary assessment (EMA) involving multiple daily reports of affective states and eating disorder behaviors. Hierarchical regression analyses were conducted using eating disorder symptoms as dependent variables (i.e., EMA binge eating, EMA self-induced vomiting, eating disorder rituals, eating disorder preoccupations, dietary restraint). Predictor variables were maladaptive perfectionism (baseline), depressive symptoms (baseline), and affect lability (EMA). Results revealed that affect lability was independently associated with binge eating, whereas depressive symptoms were independently associated with self-induced vomiting. Depressive symptoms were independently associated with eating disorder rituals, whereas both depressive symptoms and maladaptive perfectionism were independently associated with eating disorder preoccupations. Finally, maladaptive perfectionism and affect lability were both independently associated with dietary restraint. This pattern of findings suggests the importance of affective and personality constructs in relation to eating disorder symptoms in AN and may highlight the importance of targeting these variables in the context of treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Linear and non-linear analyses of Conner's Continuous Performance Test-II discriminate adult patients with attention deficit hyperactivity disorder from patients with mood and anxiety disorders.

PubMed

Fasmer, Ole Bernt; Mjeldheim, Kristin; Førland, Wenche; Hansen, Anita L; Syrstad, Vigdis Elin Giæver; Oedegaard, Ketil J; Berle, Jan Øystein

2016-08-11

Attention Deficit Hyperactivity Disorder (ADHD) is a heterogeneous disorder. Therefore it is important to look for factors that can contribute to better diagnosis and classification of these patients. The aims of the study were to characterize adult psychiatric out-patients with a mixture of mood, anxiety and attentional problems using an objective neuropsychological test of attention combined with an assessment of mood instability. Newly referred patients (n = 99; aged 18-65 years) requiring diagnostic evaluation of ADHD, mood or anxiety disorders were recruited, and were given a comprehensive diagnostic evaluation including the self-report form of the cyclothymic temperament scale and Conner's Continuous Performance Test II (CPT-II). In addition to the traditional measures from this test we have extracted raw data and analysed time series using linear and non-linear mathematical methods. Fifty patients fulfilled criteria for ADHD, while 49 did not, and were given other psychiatric diagnoses (clinical controls). When compared to the clinical controls the ADHD patients had more omission and commission errors, and higher reaction time variability. Analyses of response times showed higher values for skewness in the ADHD patients, and lower values for sample entropy and symbolic dynamics. Among the ADHD patients 59 % fulfilled criteria for a cyclothymic temperament, and this group had higher reaction time variability and lower scores on complexity than the group without this temperament. The CPT-II is a useful instrument in the assessment of ADHD in adult patients. Additional information from this test was obtained by analyzing response times using linear and non-linear methods, and this showed that ADHD patients with a cyclothymic temperament were different from those without this temperament.

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

PubMed

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

2014-09-15

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

Sleep and mental disorders: A meta-analysis of polysomnographic research.

PubMed

Baglioni, Chiara; Nanovska, Svetoslava; Regen, Wolfram; Spiegelhalder, Kai; Feige, Bernd; Nissen, Christoph; Reynolds, Charles F; Riemann, Dieter

2016-09-01

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, attention-deficit-hyperactivity disorder (ADHD), and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the "Comprehensive Meta-Analysis" and "R" software. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges' g). Sources of variability, that is, sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in 1 condition; however, no 2 conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in 1 single variable. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Characterizing Brain Cortical Plasticity and Network Dynamics Across the Age-Span in Health and Disease with TMS-EEG and TMS-fMRI

PubMed Central

Pascual-Leone, Alvaro; Freitas, Catarina; Oberman, Lindsay; Horvath, Jared C.; Halko, Mark; Eldaief, Mark; Bashir, Shahid; Vernet, Marine; Shafi, Mouhshin; Westover, Brandon; Vahabzadeh-Hagh, Andrew M.; Rotenberg, Alexander

2012-01-01

Brain plasticity can be conceptualized as nature’s invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the life-span. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable ‘starting-points’ and different ‘slopes of change’ defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer’s disease. PMID:21842407

Increased Anterior Pelvic Angle Characterizes the Gait of Children with Attention Deficit/Hyperactivity Disorder (ADHD).

PubMed

Naruse, Hiroaki; Fujisawa, Takashi X; Yatsuga, Chiho; Kubota, Masafumi; Matsuo, Hideaki; Takiguchi, Shinichiro; Shimada, Seiichiro; Imai, Yuto; Hiratani, Michio; Kosaka, Hirotaka; Tomoda, Akemi

2017-01-01

Children with attention deficit/hyperactivity disorder (ADHD) frequently have motor problems. Previous studies have reported that the characteristic gait in children with ADHD is immature and that subjects demonstrate higher levels of variability in gait characteristics for the lower extremities than healthy controls. However, little is known about body movement during gait in children with ADHD. The purpose of this study was to identify the characteristic body movements associated with ADHD symptoms in children with ADHD. Using a three-dimensional motion analysis system, we compared gait variables in boys with ADHD (n = 19; mean age, 9.58 years) and boys with typical development (TD) (n = 21; mean age, 10.71 years) to determine the specific gait characteristics related to ADHD symptoms. We assessed spatiotemporal gait variables (i.e. speed, stride length, and cadence), and kinematic gait variables (i.e. angle of pelvis, hip, knee, and ankle) to measure body movement when walking at a self-selected pace. In comparison with the TD group, the ADHD group demonstrated significantly higher values in cadence (t = 3.33, p = 0.002) and anterior pelvic angle (t = 3.08, p = 0.004). In multiple regression analysis, anterior pelvic angle was associated with the ADHD rating scale hyperactive/impulsive scores (β = 0.62, t = 2.58, p = 0.025), but not other psychiatric symptoms in the ADHD group. Our results suggest that anterior pelvic angle represents a specific gait variable related to ADHD symptoms. Our kinematic findings could have potential implications for evaluating the body movement in boys with ADHD.

Is increased sexual behavior a symptom of bipolar disorder in children and adolescents?

PubMed

Adelson, Stewart; Bell, Robinette; Graff, Adam; Goldenberg, David; Haase, Elizabeth; Downey, Jennifer I; Friedman, Richard C

2013-01-01

While there is consensus that bipolar disorder exists in children and adolescents, its diagnostic criteria are debated. Excessive sexual behavior has been reported in youth who may have juvenile bipolar disorder (JBD), and has been termed "hypersexuality." Although there is no universal definition of this term, this observation has led to a hypothesis that increased sexual behavior characterizes the bipolar syndrome in children and adolescents, and differentiates it from attention deficit hyperactivity disorder. Although this hypothesis is plausible, evidence for it is incomplete, because testing it definitively would require both establishing a standard definition of hypersexuality in children and adolescents, and also reaching consensus about the other nonsexual criteria for pediatric bipolar disorder. In addition, studies to test it would need to control factors other than JBD that are known to increase sexual behavior in children and adolescents. These include sexual abuse and related posttraumatic stress disorder, excessive exposure to sexual stimuli, psychiatric illness in general, and social variables such as family chaos and social stress. Some of these factors might increase sexual behavior in youth with bipolar disorder through psychodynamic mechanisms rather than as a result of the illness itself. Therefore, further research is needed to determine whether increased sexual behavior can serve as a diagnostically valuable criterion for bipolar disorder in children and adolescents, and whether it differentiates the disorder from other conditions known to be associated with increased sexual behavior in youth.

Intrapersonal, interpersonal, and physical space in anorexia nervosa: a virtual reality and repertory grid investigation.

PubMed

Cipolletta, Sabrina; Malighetti, Clelia; Serino, Silvia; Riva, Giuseppe; Winter, David

2017-06-01

Anorexia nervosa (AN) is an eating disorder characterized by severe body image disturbances. Recent studies from spatial cognition showed a connection between the experience of body and of space. The objectives of this study were to explore the meanings that characterize AN experience and to deepen the examination of spatiality in relational terms, through the study of how the patient construes herself and her interpersonal world. More specifically this study aimed (1) to verify whether spatial variables and aspects of construing differentiate patients with AN and healthy controls (HCs) and are related to severity of anorexic symptomatology; (2) to explore correlations between impairments in spatial abilities and interpersonal construing. A sample of 12 AN patients and 12 HCs participated in the study. The Eating Disorder Inventory, a virtual reality-based procedure, traditional measures of spatial abilities, and repertory grids were administered. The AN group compared to HCs showed significant impairments in spatial abilities, more unidimensional construing, and more extreme construing of the present self and of the self as seen by others. All these dimensions correlated with the severity of symptomatology. Extreme ways of construing characterized individuals with AN and might represent the interpersonal aspect of impairment in spatial reference frames. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Psychopathological features in Noonan syndrome.

PubMed

Perrino, Francesca; Licchelli, Serena; Serra, Giulia; Piccini, Giorgia; Caciolo, Cristina; Pasqualetti, Patrizio; Cirillo, Flavia; Leoni, Chiara; Digilio, Maria Cristina; Zampino, Giuseppe; Tartaglia, Marco; Alfieri, Paolo; Vicari, Stefano

2018-01-01

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, skeletal and haematological/lymphatic defects, distinctive facies, cryptorchidism, and a wide spectrum of congenital heart defects. Recurrent features also include variable cognitive deficits and behavioural problems. Recent research has been focused on the assessment of prevalence, age of onset and characterization of psychiatric features in this disorder. Herein, we evaluated the prevalence of attention deficit and hyperactivity disorder (ADHD), anxiety and depressive symptoms and syndromes in a cohort of individuals with clinical and molecular diagnosis of NS. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version (K-SADS PL) has been used for the assessment of psychiatric disorders according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Multidimensional Anxiety Scale for Children (MASC) and the Children's Depression Inventory (CDI) have been assessed for the evaluation of anxiety and depressive symptoms and syndromes, whereas Conners Teacher and Parent Rating Scales-long version (CRS-R) have been used to evaluate ADHD. The study included 27 individuals (67% males) with an average age of 10.4 years (range 6-18 years) receiving molecular diagnosis of NS or a clinically related condition, evaluated and treated at the Neuropsychiatric Unit of Children's Hospital Bambino Gesù and at the Center for Rare Diseases of Fondazione Policlinico Universitario Agostino Gemelli, in Rome. Twenty individuals showed mutations in PTPN11, five in SOS1 and two in SHOC2. The mean IQ was 94 (Standard Deviation = 17, min = 56, max = 130). Seventy percent of the individuals (n = 19; 95% Confidence Interval = 52-85%) showed ADHD features, with six individuals reaching DSM-IV-TR criteria for ADHD disorder, and thirteen showing subsyndromal traits. Symptoms or syndrome of anxiety were present in 37% of the cohort (n = 10; 95% Confidence Interval = 19-56%), with two individuals showing anxiety disorder and eight cases exhibiting subsyndromal traits. Our results show individuals with NS do present a very high risk to develop psychiatric disorders or symptoms during paediatric age. Based on these findings, preschool assessment of inattentive, hyperactivity/impulsivity and anxiety/depressive symptoms is recommended in order to plan a personalized treatment for psychological/psychiatric issues in affected individuals. Dedicated prospective studies are required to confirm the present data and better characterize the psychopathological profile in NS. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity

PubMed Central

2014-01-01

Background A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder. Methods Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer. Results DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*). Conclusions Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals. PMID:24571530

Nonuniversality of density and disorder in jammed sphere packings

NASA Astrophysics Data System (ADS)

Jiao, Yang; Stillinger, Frank H.; Torquato, Salvatore

2011-01-01

We show for the first time that collectively jammed disordered packings of three-dimensional monodisperse frictionless hard spheres can be produced and tuned using a novel numerical protocol with packing density ϕ as low as 0.6. This is well below the value of 0.64 associated with the maximally random jammed state and entirely unrelated to the ill-defined "random loose packing" state density. Specifically, collectively jammed packings are generated with a very narrow distribution centered at any density ϕ over a wide density range ϕ ɛ(0.6,0.740 48…) with variable disorder. Our results support the view that there is no universal jamming point that is distinguishable based on the packing density and frequency of occurrence. Our jammed packings are mapped onto a density-order-metric plane, which provides a broader characterization of packings than density alone. Other packing characteristics, such as the pair correlation function, average contact number, and fraction of rattlers are quantified and discussed.

Advances in understanding the pathogenesis of the red cell volume disorders.

PubMed

Badens, Catherine; Guizouarn, Hélène

2016-09-01

Genetic defects of erythrocyte transport proteins cause disorders of red blood cell volume that are characterized by abnormal permeability to the cations Na(+) and K(+) and, consequently, by changes in red cell hydration. Clinically, these disorders are associated with chronic haemolytic anaemia of variable severity and significant co-morbidities, such as iron overload. This review provides an overview of recent insights into the molecular basis of this group of rare anaemias involving cation channels and transporters dysfunction. To date, a total of 5 different membrane proteins have been reported to be responsible for volume homeostasis alteration when mutated, 3 of them leading to overhydrated cells (AE1 [also termed SLC4A1], RHAG and GLUT1 [also termed SCL2A1) and 2 others to dehydrated cells (PIEZO1 and the Gardos Channel). These findings are not only of basic scientific interest, but also of direct clinical significance for improving diagnostic procedures and identify potential approaches for novel therapeutic strategies. © 2016 John Wiley & Sons Ltd.

Differentiation of women with premenstrual dysphoric disorder, recurrent brief depression, and healthy controls by daily mood rating dynamics.

PubMed

Pincus, Steven M; Schmidt, Peter J; Palladino-Negro, Paula; Rubinow, David R

2008-04-01

Enhanced statistical characterization of mood-rating data holds the potential to more precisely classify and sub-classify recurrent mood disorders like premenstrual dysphoric disorder (PMDD) and recurrent brief depressive disorder (RBD). We applied several complementary statistical methods to differentiate mood rating dynamics among women with PMDD, RBD, and normal controls (NC). We compared three subgroups of women: NC (n=8); PMDD (n=15); and RBD (n=9) on the basis of daily self-ratings of sadness, study lengths between 50 and 120 days. We analyzed mean levels; overall variability, SD; sequential irregularity, approximate entropy (ApEn); and a quantification of the extent of brief and staccato dynamics, denoted 'Spikiness'. For each of SD, irregularity (ApEn), and Spikiness, we showed highly significant subgroup differences, ANOVA0.001 for each statistic; additionally, many paired subgroup comparisons showed highly significant differences. In contrast, mean levels were indistinct among the subgroups. For SD, normal controls had much smaller levels than the other subgroups, with RBD intermediate. ApEn showed PMDD to be significantly more regular than the other subgroups. Spikiness showed NC and RBD data sets to be much more staccato than their PMDD counterparts, and appears to suitably characterize the defining feature of RBD dynamics. Compound criteria based on these statistical measures discriminated diagnostic subgroups with high sensitivity and specificity. Taken together, the statistical suite provides well-defined specifications of each subgroup. This can facilitate accurate diagnosis, and augment the prediction and evaluation of response to treatment. The statistical methodologies have broad and direct applicability to behavioral studies for many psychiatric disorders, and indeed to similar analyses of associated biological signals across multiple axes.

Parent, Sibling and Peer Associations with Subtypes of Psychiatric and Substance Use Disorder Comorbidity in Offspring

PubMed Central

McCutcheon, Vivia V.; Scherrer, Jeffrey F.; Grant, Julia D.; Xian, Hong; Haber, Jon Randolph; Jacob, Theodore; Bucholz, Kathleen K

2012-01-01

BACKGROUND Parental substance use disorder (SUD) is associated with a range of negative offspring outcomes and psychopathology, but the clustering of these outcomes into subtypes has seldom been examined, nor have the familial and environmental contexts of these subtypes been reported. The present study examines the clustering of offspring lifetime substance use and psychiatric disorders into subtypes and characterizes them in terms of familial and non-familial influences using an offspring-of-twins design. METHOD Telephone-administered diagnostic interviews were used to collect data on psychiatric disorders and SUD from 488 twin fathers, 420 biological mothers and 831 offspring. Latent class analysis (LCA) was used to derive subtypes of lifetime comorbidity in offspring. Familial risk and environmental variables associated with each subtype (i.e. parenting, childhood physical or sexual abuse, perceived sibling and peer substance use) were identified using multinomial logistic regression. RESULTS Four classes identified by LCA were characterized as 1) unaffected, 2) alcohol abuse/dependence, 3) alcohol abuse/dependence comorbid with anxiety and depression, and 4) alcohol, cannabis abuse/dependence and nicotine dependence comorbid with conduct disorder. Inconsistent parenting, childhood physical/sexual abuse, and perceived sibling and peer substance use were significantly associated with profiles of offspring comorbidity after adjusting for familial vulnerability. Some associations were specific (i.e. perceived peer alcohol use to the AUD class), while others were general (peer smoking to all 3 comorbidity classes). CONCLUSIONS We observed distinct subtypes of psychiatric and SUD comorbidity in adolescents and young adults. Subtypes of offspring psychopathology have varied associations with parental psychopathology, family environment, and sibling and peer behaviors. PMID:22921146

Personal stigma in schizophrenia spectrum disorders: a systematic review of prevalence rates, correlates, impact and interventions

PubMed Central

Gerlinger, Gabriel; Hauser, Marta; De Hert, Marc; Lacluyse, Kathleen; Wampers, Martien; Correll, Christoph U

2013-01-01

A systematic electronic PubMed, Medline and Web of Science database search was conducted regarding the prevalence, correlates, and effects of personal stigma (i.e., perceived and experienced stigmatization and self-stigma) in patients with schizophrenia spectrum disorders. Of 54 studies (n=5,871), published from 1994 to 2011, 23 (42.6%) reported on prevalence rates, and 44 (81.5%) reported on correlates and/or consequences of perceived or experienced stigmatization or self-stigma. Only two specific personal stigma intervention studies were found. On average, 64.5% (range: 45.0–80.0%) of patients perceived stigma, 55.9% (range: 22.5–96.0%) actually experienced stigma, and 49.2% (range: 27.9–77.0%) reported alienation (shame) as the most common aspect of self-stigma. While socio-demographic variables were only marginally associated with stigma, psychosocial variables, especially lower quality of life, showed overall significant correlations, and illness-related factors showed heterogeneous associations, except for social anxiety that was unequivocally associated with personal stigma. The prevalence and impact of personal stigma on individual outcomes among schizophrenia spectrum disorder patients are well characterized, yet measures and methods differ significantly. By contrast, research regarding the evolution of personal stigma through the illness course and, particularly, specific intervention studies, which should be conducted utilizing standardized methods and outcomes, are sorely lacking. PMID:23737425

Social Difficulties As Risk and Maintaining Factors in Anorexia Nervosa: A Mixed-Method Investigation.

PubMed

Cardi, Valentina; Mallorqui-Bague, Núria; Albano, Gaia; Monteleone, Alessio Maria; Fernandez-Aranda, Fernando; Treasure, Janet

2018-01-01

Anorexia nervosa (AN) is a serious psychiatric disorder characterized by severe restriction of energy intake and dangerously low body weight. Other domains of functioning are affected, including social functioning. Although difficulties within this domain have started to be acknowledged by the literature, some important gaps remain to be filled. Do social difficulties predate the onset of the illness? What difficulties in particular are relevant for the development and maintenance of the illness? The aim of this study is to combine the use of quantitative and qualitative methods to answer these questions. Ninety participants with lifetime AN (88 women and 2 men) completed an online survey assessing memories of involuntary submissiveness within the family, fear of negative evaluation from others, perceived lack of social competence, feelings of social belonging, eating disorder symptoms, and work and social adjustment. Participants also answered three open questions regarding their experience of social relationships before and after the illness onset. The findings provided support for the hypothesized relationships between the study variables. Involuntary submissiveness and fear of negative evaluation predicted eating disorder symptoms and these associations were partially mediated by perceived lack of social competence. Two-thirds of the sample recalled early social difficulties before illness onset and recognized that these had played a role in the development of the illness. A larger proportion of participants stated that the eating disorder had affected their social relationships in a negative way. This study sheds some light on patients' perspective on the predisposing and maintaining role that social difficulties play in AN and identifies key psychological variables that could be targeted in treatment.

Perceptual and response-dependent profiles of attention in children with ADHD.

PubMed

Caspersen, Ida Dyhr; Petersen, Anders; Vangkilde, Signe; Plessen, Kerstin Jessica; Habekost, Thomas

2017-05-01

Attention-deficit hyperactivity disorder (ADHD) is a complex developmental neuropsychiatric disorder, characterized by inattentiveness, impulsivity, and hyperactivity. Recent literature suggests a potential core deficit underlying these behaviors may involve inefficient processing when contextual stimulation is low. In order to specify this inefficiency, the aim of the present study was to disentangle perceptual and response-based deficits of attention by supplementing classic reaction time (RT) measures with an accuracy-only test. Moreover, it was explored whether ADHD symptom severity was systematically related to perceptual and response-based processes. We applied an RT-independent paradigm (Bundesen, 1990) and a sustained attention task (Dockree et al., 2006) to test visual attention in 24 recently diagnosed, medication-naïve children with ADHD, 14 clinical controls with pervasive developmental disorder, and 57 healthy controls. Outcome measures included perceptual processing speed, capacity of visual short-term memory, and errors of commission and omission. Children with ADHD processed information abnormally slow (d = 0.92), and performed poorly on RT variability and response stability (d's ranging from 0.60 to 1.08). In the ADHD group only, slowed visual processing speed was significantly related to response lapses (omission errors). This correlation was not explained by behavioral ratings of ADHD severity. Based on combined assessment of perceptual and response-dependent variables of attention, the present study demonstrates a specific cognitive profile in children with ADHD. This profile distinguishes the disorder at a basic level of attentional functioning, and may define subgroups of children with ADHD in a way that is more sensitive than clinical rating scales. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers

PubMed Central

Clementz, Brett A.; Sweeney, John A.; Hamm, Jordan P.; Ivleva, Elena I.; Ethridge, Lauren E.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Tamminga, Carol A.

2017-01-01

Objective Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. Method A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Results Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. Conclusions These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard. PMID:26651391

Personality, emotion-related variables, and media pressure predict eating disorders via disordered eating in Lebanese university students.

PubMed

Sanchez-Ruiz, Maria Jose; El-Jor, Claire; Abi Kharma, Joelle; Bassil, Maya; Zeeni, Nadine

2017-04-18

Disordered eating behaviors are on the rise among youth. The present study investigates psychosocial and weight-related variables as predictors of eating disorders (ED) through disordered eating (DE) dimensions (namely restrained, external, and emotional eating) in Lebanese university students. The sample consisted of 244 undergraduates (143 female) aged from 18 to 31 years (M = 20.06; SD = 1.67). Using path analysis, two statistical models were built separately with restrained and emotional eating as dependent variables, and all possible direct and indirect pathways were tested for mediating effects. The variables tested for were media influence, perfectionism, trait emotional intelligence, and the Big Five dimensions. In the first model, media pressure, self-control, and extraversion predicted eating disorders via emotional eating. In the second model, media pressure and perfectionism predicted eating disorders via restrained eating. Findings from this study provide an understanding of the dynamics between DE, ED, and key personality, emotion-related, and social factors in youth. Lastly, implications and recommendations for future studies are advanced.

Cognitive functioning and insight in schizophrenia and in schizoaffective disorder.

PubMed

Birindelli, Nadia; Montemagni, Cristiana; Crivelli, Barbara; Bava, Irene; Mancini, Irene; Rocca, Paola

2014-01-01

The aim of this study was to investigate cognitive functioning and insight of illness in two groups of patients during their stable phases, one with schizophrenia and one with schizoaffective disorder. We recruited 104 consecutive outpatients, 64 with schizophrenia, 40 with schizoaffective disorder, in the period between July 2010 and July 2011. They all fulfilled formal Diagnostic and Statistical Manual of Mental disorders (DSM-IV-TR) diagnostic criteria for schizophrenia and schizoaffective disorder. Psychiatric assessment included the Clinical Global Impression Scale-Severity (CGI-S), the Positive and Negative Sindrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Global Assessment of Functioning (GAF). Insight of illness was evaluated using SUMD. Neuropsychological assessment included Winsconsin Card Sorting Test (WCST), California Verbal Learning Test (CVLT), Stroop Test and Trail Making Test (TMT). Differences between the groups were tested using Chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. All variables significantly different between the two groups of subjects were subsequently analysed using a logistic regression with a backward stepwise procedure using diagnosis (schizophrenia/schizoaffective disorder) as dependent variable. After backward selection of variables, four variables predicted a schizoaffective disorder diagnosis: marital status, a higher number of admission, better attentive functions and awareness of specific signs or symptoms of disease. The prediction model accounted for 55% of the variance of schizoaffective disorder diagnosis. With replication, our findings would allow higher diagnostic accuracy and have an impact on clinical decision making, in light of an amelioration of vocational functioning.

Profiles of drug addicts in relation to personality variables and disorders.

PubMed

Carou, María; Romero, Estrella; Luengo, Mª Ángeles

2016-10-07

In recent decades, research has identified a set of impulsive/disinhibited personality variables closely associated with drug addiction. As well as this, disorders linked with these variables, such as ADHD and personality disorders, are being closely studied in the field of drug addiction. Although much knowledge has been accumulated about the relation of these variables and disorders taken separately, less is known about how these constructs allow identify-specific profiles within the drug dependent population to be identified. This work, on the basis of data collected on a sample of drug addicts in treatment, analyzes how impulsiveness, sensation seeking, self-control, ADHD and personality disorders contribute to identifying specific profiles of addicts. Cluster analysis allowed two profiles to be outlined according to these personality and psychopathology characteristics. Self-control, impulsiveness, impulsive and antisocial personality disorders, as well as scores in ADHD, emerge as the variables that contribute more to profile differentiation. One of these profiles (56.1% of participants) with a high disinhibition pattern, is associated with severe indicators of consumption and criminal career patterns. These results allow us to emphasize the role of personality and impulsiveness-related disorders in the identification of distinctive profiles within the addict population, and suggest the need to generate treatment strategies adapted to personal/psychopathology configurations of drug addicts.

Birt-Hogg-Dubé Syndrome.

PubMed

Gupta, Nishant; Sunwoo, Bernie Y; Kotloff, Robert M

2016-09-01

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the Folliculin gene and is characterized by the formation of fibrofolliculomas, early onset renal cancers, pulmonary cysts, and spontaneous pneumothoraces. The exact pathogenesis of tumor and lung cyst formation in BHD remains unclear. There is great phenotypic variability in the clinical features of BHD, and patients can present with any combination of skin, pulmonary, or renal findings. More than 80% of adult patients with BHD have pulmonary cysts on high-resolution computed tomography scan of the chest. Published by Elsevier Inc.

Primary microcephaly caused by novel compound heterozygous mutations in ASPM

PubMed Central

Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

2018-01-01

Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated (ASPM) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified. PMID:29644084

Primary microcephaly caused by novel compound heterozygous mutations in ASPM.

PubMed

Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

2018-01-01

Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated ( ASPM ) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified.

A novel COL1A1 mutation in a family with osteogenesis imperfecta associated with phenotypic variabilities

PubMed Central

Seto, Toshiyuki; Yamamoto, Toshiyuki; Shimojima, Keiko; Shintaku, Haruo

2017-01-01

Osteogenesis imperfecta (OI) is a heterogeneous disorder that is characterized by bone fragility and systemic complications, and is mainly caused by gene mutations in COL1A1 or COL1A2. A novel COL1A1 splicing mutation, c.750+2T>A, was identified in a Japanese OI family. Only the proband in this family showed various complications, such as heart valve diseases and severe scoliosis. The clinical heterogeneity in the family is discussed in this study. PMID:28326186

[Bilateral macular retinoschisis associated with unilateral peripheral retinoschisis].

PubMed

Oummad, Hanane; Elkaddoumi, Maryama; Maré, Josiane; Lezrek, Mounir; Cherkaoui, Ouafae

2017-01-01

X-linked juvenile retinoschisis is a hereditary disorder which usually occurs in boys rather than in girls, who are rarely affected. First clinical manifestations usually appear during the first decade. It is responsible for variable severity and slowly progressive vision loss. This progression can be characterized by vitreous hemorrhages and recurrent retinal detachments. We report the case of a 17-year old patient with stellar bilateral microcistic macular rearrangement of the eye-ground, centered on the foveola, associated with peripheral schisis with retinal detachment and unilateral tearing of internal and external layers.

An Investigation into the Roles of Theory of Mind, Emotion Regulation, and Attachment Styles in Predicting the Traits of Borderline Personality Disorder

PubMed Central

Ghiasi, Hamed; Mohammadi, Abolalfazl; Zarrinfar, Pouria

2016-01-01

Objective: Borderline personality disorder is one of the most complex and prevalent personality disorders. Many variables have so far been studied in relation to this disorder. This study aimed to investigate the role of emotion regulation, attachment styles, and theory of mind in predicting the traits of borderline personality disorder. Method: In this study, 85 patients with borderline personality disorder were selected using convenience sampling method. To measure the desired variables, the questionnaires of Gross emotion regulation, Collins and Read attachment styles, and Baron Cohen's Reading Mind from Eyes Test were applied. The data were analyzed using multivariate stepwise regression technique. Results: Emotion regulation, attachment styles, and theory of mind predicted 41.2% of the variance criterion altogether; among which, the shares of emotion regulation, attachment styles and theory of mind to the distribution of the traits of borderline personality disorder were 27.5%, 9.8%, and 3.9%, respectively.‎‎ Conclusion: The results of the study revealed that emotion regulation, attachment styles, and theory of mind are important variables in predicting the traits of borderline personality disorder and that these variables can be well applied for both the treatment and identification of this disorder. PMID:28050180

An Investigation into the Roles of Theory of Mind, Emotion Regulation, and Attachment Styles in Predicting the Traits of Borderline Personality Disorder.

PubMed

Ghiasi, Hamed; Mohammadi, Abolalfazl; Zarrinfar, Pouria

2016-10-01

Objective: Borderline personality disorder is one of the most complex and prevalent personality disorders. Many variables have so far been studied in relation to this disorder. This study aimed to investigate the role of emotion regulation, attachment styles, and theory of mind in predicting the traits of borderline personality disorder. Method: In this study, 85 patients with borderline personality disorder were selected using convenience sampling method. To measure the desired variables, the questionnaires of Gross emotion regulation, Collins and Read attachment styles, and Baron Cohen's Reading Mind from Eyes Test were applied. The data were analyzed using multivariate stepwise regression technique. Results: Emotion regulation, attachment styles, and theory of mind predicted 41.2% of the variance criterion altogether; among which, the shares of emotion regulation, attachment styles and theory of mind to the distribution of the traits of borderline personality disorder were 27.5%, 9.8%, and 3.9%, respectively.‎‎ Conclusion : The results of the study revealed that emotion regulation, attachment styles, and theory of mind are important variables in predicting the traits of borderline personality disorder and that these variables can be well applied for both the treatment and identification of this disorder.

A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.

PubMed

Marcadier, Julien L; Mears, Alan J; Woods, Elizabeth A; Fisher, Jamie; Airheart, Cory; Qin, Wen; Beaulieu, Chandree L; Dyment, David A; Innes, A Micheil; Curry, Cynthia J

2016-01-01

PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder. © 2015 Wiley Periodicals, Inc.

Variability in Institutional Screening Practices Related to Collegiate Student-Athlete Mental Health

PubMed Central

Kroshus, Emily

2016-01-01

Context:  Universal screening for mental health concerns, as part of the preparticipation examination in collegiate sports medicine settings, can be an important and feasible strategy for facilitating early detection of mental health disorders. Objective:  To assess whether sports medicine departments at National Collegiate Athletic Association (NCAA) member colleges have policies related to identifying student-athlete mental health problems, the nature of preparticipation examination screening related to mental health, and whether other departmental or institutional screening initiatives are in place. I also aimed to characterize the variability in screening by institutional characteristics. Design:  Cross-sectional study. Setting:  College sports medicine departments. Patients or Other Participants:  Team physicians and head athletic trainers at NCAA member colleges (n = 365, 30.3% response rate). Main Outcome Measure(s):  Electronic survey of departmental mental health screening activities. Results:  A total of 39% of respondents indicated that their institution had a written plan related to identifying student-athletes with mental health concerns. Fewer than half reported that their sports medicine department administers a written or verbal screening instrument for symptoms of disordered eating (44.5%), depression (32.3%), or anxiety (30.7%). The strongest predictors of mental health screening were the presence of a written plan related to identifying student-athlete mental health concerns and the employment of a clinical psychologist. Additionally, Division I institutions and institutions with a greater ratio of athletic trainers to student-athletes tended to engage in more screening. Conclusions:  The substantial among-institutions variability in mental health screening suggests that opportunities exist to make these practices more widespread. To address this variability, recent NCAA mental health best-practice guidelines suggested that institutions should screen for a range of mental health disorders and risk behaviors. However, at some institutions, staffing deficits may need to be addressed to allow for implementation of screening-related activities. PMID:27111587

Longitudinal variations of laryngeal overpressure and voice-related quality of life in spasmodic dysphonia.

PubMed

Yeung, Jeffrey C; Fung, Kevin; Davis, Eric; Rai, Sunita K; Day, Adam M B; Dzioba, Agnieszka; Bornbaum, Catherine; Doyle, Philip C

2015-03-01

Adductor spasmodic dysphonia (AdSD) is a voice disorder characterized by variable symptom severity and voice disability. Those with the disorder experience a wide spectrum of symptom severity over time, resulting in varied degrees of perceived voice disability. This study investigated the longitudinal variability of AdSD, with a focus on auditory-perceptual judgments of a dimension termed laryngeal overpressure (LO) and patient self-assessments of voice-related quality of life (V-RQOL). Longitudinal, correlational study. Ten adults with AdSD were followed over three time periods. At each, both voice samples and self-ratings of V-RQOL were gathered prior to their scheduled Botox injection. Voice recordings subsequently were perceptually evaluated by eight listeners for LO using a visual analog scale. LO ratings for all-voiced and Rainbow Passage sentence stimuli were found to be highly correlated. However, only the LO ratings obtained from judgments of AV stimuli were found to correlate moderately with self-ratings of voice disability for both the physical functioning and social-emotional subscores, as well as the total V-RQOL score. Based on perceptual judgments, LO appears to provide a reliable means of quantifying the severity of voice abnormalities in AdSD. Variability in self-ratings of the V-RQOL suggest that perceived disability related to AdSD should be actively monitored. Further, auditory-perceptual judgments may provide an accurate index of the potential impact of the disorder on the speaker. Similarly, LO was supported as a simple clinical measure that serves as a reliable index of voice change over time. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Genetic modifiers of Velo- cardio- facial syndrome/DiGeorge syndrome

PubMed Central

Aggarwal, Vimla S.; Morrow, Bernice E.

2009-01-01

Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that Tbx1, a T- box containing transcription factor present on the deleted region, is likely responsible for the etiology of the syndrome. Furthermore, mutations in TBX1 have been found in rare non-deleted patients. Despite having the same sized deletion, most VCFS/DGS patients exhibit significant clinical variability. Stochastic, environmental and genetic factors likely modify the phenotype of patients with the disorder. Here, we review mouse genetics studies which may help identify genetic modifiers for VCFS/DGS. PMID:18636633

Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier.

PubMed

Vinod, K V; Hitha, B; Kaaviya, R; Dutta, T K

2015-03-01

Congenital factor X (FX) deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis

PubMed Central

Flex, Elisabetta; Jaiswal, Mamta; Pantaleoni, Francesca; Martinelli, Simone; Strullu, Marion; Fansa, Eyad K.; Caye, Aurélie; De Luca, Alessandro; Lepri, Francesca; Dvorsky, Radovan; Pannone, Luca; Paolacci, Stefano; Zhang, Si-Cai; Fodale, Valentina; Bocchinfuso, Gianfranco; Rossi, Cesare; Burkitt-Wright, Emma M.M.; Farrotti, Andrea; Stellacci, Emilia; Cecchetti, Serena; Ferese, Rosangela; Bottero, Lisabianca; Castro, Silvana; Fenneteau, Odile; Brethon, Benoît; Sanchez, Massimo; Roberts, Amy E.; Yntema, Helger G.; Van Der Burgt, Ineke; Cianci, Paola; Bondeson, Marie-Louise; Cristina Digilio, Maria; Zampino, Giuseppe; Kerr, Bronwyn; Aoki, Yoko; Loh, Mignon L.; Palleschi, Antonio; Di Schiavi, Elia; Carè, Alessandra; Selicorni, Angelo; Dallapiccola, Bruno; Cirstea, Ion C.; Stella, Lorenzo; Zenker, Martin; Gelb, Bruce D.; Cavé, Hélène; Ahmadian, Mohammad R.; Tartaglia, Marco

2014-01-01

RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2S2G mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease. PMID:24705357

[Characterization of patients with skeletal genetic diseases in a Colombian referral center].

PubMed

Velasco, Harvy Mauricio; Buelvas, Lina Patricia

2017-06-01

Short height in Colombia has an estimated prevalence of 10%. The 2009 Nosology and Classification of Skeletal Genetic Diseases described 456 clinical conditions using biochemical, molecular and radiological criteria for diagnosis. To analyze demographic, epidemiological and clinical variables in a group of patients with skeletal genetic diseases referred to the Instituto de Ortopedia Infantil Roosevelt. Patients referred between 2008 and 2014 were analyzed filtering 167 diagnoses of the International Classification of Diseases, 10th revision (ICD 10), related to skeletal genetic diseases. Demographic, epidemiological and clinical variables were explored using descriptive statistics. An intervention score was generated contemplating different combinations of treatments. An inferential statistical analysis using Student's t test was performed on such variables. The most frequent reason for consultation was suspicion of a genetic skeletal disorder. The types of treatments considered included support, surgical, pharmacological and orthotics, and it was established that genetic skeletal disorders were associated with higher intervention scores while tall and short height showed a lower score. Most referred patients were classified with genetic bone diseases, short stature and other monogenic genetic diseases. Significant differences were found between the age at symptoms onset and the age of diagnosis. Diversity was found in the therapeutic approach among different groups of pathologies. Patients with tall and short height showed lower intervention scores, which may warn on the need to reassess the therapeutic requirements of these groups.

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.

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1

PubMed Central

Alfadhel, Majid; Alhasan, Khalid A; Alotaibi, Mohammed; Al Fakeeh, Khalid

2012-01-01

Background Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene. Case report Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function. Conclusion Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder. PMID:22956877

Characterizing cognitive control abilities in children with 16p11.2 deletion using adaptive ‘video game' technology: a pilot study

PubMed Central

Anguera, J A; Brandes-Aitken, A N; Rolle, C E; Skinner, S N; Desai, S S; Bower, J D; Martucci, W E; Chung, W K; Sherr, E H; Marco, E J

2016-01-01

Assessing cognitive abilities in children is challenging for two primary reasons: lack of testing engagement can lead to low testing sensitivity and inherent performance variability. Here we sought to explore whether an engaging, adaptive digital cognitive platform built to look and feel like a video game would reliably measure attention-based abilities in children with and without neurodevelopmental disabilities related to a known genetic condition, 16p11.2 deletion. We assessed 20 children with 16p11.2 deletion, a genetic variation implicated in attention deficit/hyperactivity disorder and autism, as well as 16 siblings without the deletion and 75 neurotypical age-matched children. Deletion carriers showed significantly slower response times and greater response variability when compared with all non-carriers; by comparison, traditional non-adaptive selective attention assessments were unable to discriminate group differences. This phenotypic characterization highlights the potential power of administering tools that integrate adaptive psychophysical mechanics into video-game-style mechanics to achieve robust, reliable measurements. PMID:27648915

The anterior segment disorder autosomal dominant keratitis is linked to the Aniridia/PAX-6 gene

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

Mirzayans, F.; Pearce, W.G.; Mah, T.S.

1994-09-01

Autosomal dominant keratitis (ADK) is an eye disease characterized by anterior stromal corneal opacification and vascularization in the peripheral cornea. Progression into the central cornea may compromise visual acuity. Other anterior segment features include minimal radial defects of the iris stroma. Posterior segment involvement is characterized by foveal hypoplasia with minimal effect on visual acuity. Aniridia is a second autosomal dominantly inherited ocular disorder defined by structural defects of the iris, frequently severe enough to cause an almost complete absence of iris. This may be accompanied by other anterior segment manifestations, including cataract and keratitis. Posterior segment involvement in aniridiamore » is characterized by foveal hypoplasia resulting in a highly variable impairment of visual acuity, often with nystagmus. Aniridia is usually inherited as an autosomal dominant disease and occurs in 1 in 50,000 to 100,000 people. Aniridia has been shown to result from mutations in PAX-6, a gene thought to regulate fetal eye development. The similar clinical findings in ADK and aniridia, with the similar patterns of inheritance, compelled us to investigate if these two ocular disorders are variants of the same genetic disorder. We have tested for linkage between PAX-6 and ADK within an ADK family with 33 members over four generations, including 11 affected individuals. Linkage studies reveal that D11S914 (located within 3 cM of PAX-6) does not recombine with ADK (LOD score 3.61; {theta} = 0.00), consistent with PAX-6 mutations being responsible for ADK. Direct sequencing of PAX-6 RT-PCR products from ADK patients is underway to identify the mutation within the PAX-6 gene that results in ADK. The linkage of PAX-6 with ADK, along with a recent report that mutations in PAX-6 also underlie Peter`s anomaly, implicates PAX-6 widely in anterior segment malformations.« less

The Dynamics of Self-Esteem in Cognitive Therapy for Avoidant and Obsessive-Compulsive Personality Disorders: An Adaptive Role of Self-Esteem Variability?

PubMed Central

Cummings, Jorden A.; Hayes, Adele M.; Cardaciotto, LeeAnn; Newman, Cory F.

2011-01-01

Self-esteem variability is often associated with poor functioning. However, in disorders with entrenched negative views of self and in a context designed to challenge those views, variable self-esteem might represent a marker of change. We examined self-esteem variability in a sample of 27 patients with Avoidant and Obsessive-Compulsive Personality Disorders who received Cognitive Therapy (CT). A therapy coding system was used to rate patients’ positive and negative views of self expressed in the first ten sessions of a 52-week treatment. Ratings of negative (reverse scored) and positive view of self were summed to create a composite score for each session. Self-esteem variability was calculated as the standard deviation of self-esteem scores across sessions. More self-esteem variability predicted more improvement in personality disorder and depression symptoms at the end of treatment, beyond baseline and average self-esteem. Early variability in self-esteem, in this population and context, appeared to be a marker of therapeutic change. PMID:22923855

Personality Disorders in Hypochondriasis: Prevalence and comparison with two anxiety disorders

PubMed Central

Fallon, Brian A.; Harper, Katy M.; Landa, Alla; Pavlicova, Martina; Schneier, Franklin R.; Carson, Amanda; Harding, Kelli; Keegan, Kathryn; Schwartz, Theresa; Liebowitz, Michael R.

2012-01-01

Objective Symptoms of hypochondriasis are sometimes attributed to personality psychopathology by health care providers. The goals of this study were to assess the prevalence of personality disorder comorbidity (PD) in hypochondriasis (HYP) and to compare the PD comorbidity profile of patients with HYP to that found among patients with other disorders characterized by intrusive thoughts and fears. Methods SCID-I and SCID-II were administered to 179 individuals: 62 with HYP, 46 with Obsessive Compulsive Disorder (OCD), and 71 with Social Anxiety Disorder (SAD). For group contrasts, the samples were “purified” of the comparison comorbid disorders. General linear models were used to test the combined effect of group (HYP, OCD, SAD), age, and gender on the PD outcome variables. Results 59.7% of HYP subjects had no Axis II comorbidity. The most common PDs in HYP were paranoid (19.4%), avoidant (17.7%), and obsessive compulsive (14.5%). HYP significantly differed from SAD in the likelihood of a cluster C disorder, whereas no significant difference was noted for HYP vs OCD. The proportion of subjects having at least two PDs was not significantly different for HYP vs OCD or for HYP vs SAD. Conclusion Although 40% of patients with hypochondriasis have PD comorbidity as assessed by the SCID-II, the amount of PD comorbidity is not significantly different than found among individuals with two comparison anxiety disorders. Therefore, health providers should be aware that PD may complicate the clinical profile of HYP but they should avoid assuming that PD psychopathology is the primary source of hypochondriacal distress. PMID:22658329

Differences in clinical intrusive thoughts between obsessive-compulsive disorder, generalized anxiety disorder, and hypochondria.

PubMed

Romero-Sanchiz, Pablo; Nogueira-Arjona, Raquel; Godoy-Ávila, Antonio; Gavino-Lázaro, Aurora; Freeston, Mark H

2017-11-01

Differences and similarities between intrusive thoughts typical of obsessive-compulsive disorder, generalized anxiety disorder, and hypochondriasis are relevant for their differential diagnosis, formulation, and psychological treatment. Previous research in non-clinical samples pointed out the relevance of some process variables, such as responsibility, guilt, or neutralization strategies. This research is aimed to investigate the differences and similarities between clinical obsessions, worries, and illness intrusions in some of these process variables. A second aim is to identify models based on these variables that could reliably differentiate between them. Three groups of patients with obsessive-compulsive disorder (n = 35; 60% women, mean age 38.57), generalized anxiety disorder (n = 36; 61.1% women, mean age 41.50), and hypochondriasis (n = 34; 70.6% women, mean age 31.59) were evaluated using the Cognitive Intrusions Questionnaire-Transdiagnostic Version (Romero-Sanchiz, Nogueira-Arjona, Godoy-Ávila, Gavino-Lázaro, & Freeston, ). The results showed that some appraisals (e.g., responsibility or egodystonicity), emotions (e.g., guilt or insecurity), neutralization strategies, and other variables (e.g., verbal content or trigger from body sensation) are relevant for the discrimination between obsessions, worries, and illness intrusions. The results also showed 3 stable models based on these variables for the discrimination between these thoughts. The implication of these results in the diagnosis, formulation, and psychological treatment of obsessive-compulsive disorder, generalized anxiety disorder, and hypochondriasis is discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders

PubMed Central

Levman, Jacob; Takahashi, Emi

2015-01-01

Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us. PMID:26640765

Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders.

PubMed

Levman, Jacob; Takahashi, Emi

2015-01-01

Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us.

Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia.

PubMed

Ward, C; Lucas, M; Piris, J; Collier, J; Chapel, H

2008-09-01

Patients with common variable immunodeficiency disorders are monitored for liver function test abnormalities. A proportion of patients develop deranged liver function and some also develop hepatomegaly. We investigated the prevalence of abnormalities and types of liver disease, aiming to identify those at risk and determine outcomes. The local primary immunodeficiency database was searched for patients with a common variable immunodeficiency disorder and abnormal liver function and/or a liver biopsy. Patterns of liver dysfunction were determined and biopsies reviewed. A total of 47 of 108 patients had deranged liver function, most commonly raised alkaline phosphatase levels. Twenty-three patients had liver biopsies. Nodular regenerative hyperplasia was found in 13 of 16 with unexplained pathology. These patients were more likely to have other disease-related complications of common variable immunodeficiency disorders, in particular non-coeliac (gluten insensitive) lymphocytic enteropathy. However, five had no symptoms of liver disease and only one died of liver complications. Nodular regenerative hyperplasia is a common complication of common variable immunodeficiency disorders but was rarely complicated by portal hypertension.

Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids

NASA Astrophysics Data System (ADS)

Ruggiero, Michael T.; Zhang, Wei; Bond, Andrew D.; Mittleman, Daniel M.; Zeitler, J. Axel

2018-05-01

The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems.

Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids.

PubMed

Ruggiero, Michael T; Zhang, Wei; Bond, Andrew D; Mittleman, Daniel M; Zeitler, J Axel

2018-05-11

The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems.

[Cognitive and emotional impairments in patients with protracted anxiety-phobic disorders].

PubMed

Chutko, L S; Surushkina, S Iu; Iakovenko, E A; Nikishena, I S; Anisimova, T I; Bondarchuk, Iu L

2014-01-01

To study cognitive and emotional impairments in patients with anxiety-phobic disorders (APDs), to comparatively analyze the clinical manifestations of acute (less than one-year) and protracted (1-to-5-year) forms of this disease, and to evaluate the efficacy of noofen used to treat this pathology. Sixty-two patients aged 18 to 50 years with APDs were examined. The investigators collected clinical history data, performed neurological examination, and assessed autonomic disorders in accordance with the questionnaire to reveal their signs, anxiety using the Hamilton anxiety rating scale, memory impairment employing the methods developed by A.R. Luria, attention disorders applying the test of variables of attention, and diagnosed emotional intelligence using the Mayer-Salovey-Caruso emotional intelligence test. Noofen 1000 mg/day was used to treat the patients. Protracted APDs were shown to be characterized by the higher degree of psychosomatic symptoms and by more pronounced impairments in attention, memory, and emotional intelligence. The data of posttreatment clinical and psychological studiesare indicative of improvements in 73.3% of cases. The findings may lead to the conclusion that noofen is highly effective in the treatment of patients with protracted APDs.

High internal noise and poor external noise filtering characterize perception in autism spectrum disorder.

PubMed

Park, Woon Ju; Schauder, Kimberly B; Zhang, Ruyuan; Bennetto, Loisa; Tadin, Duje

2017-12-14

An emerging hypothesis postulates that internal noise is a key factor influencing perceptual abilities in autism spectrum disorder (ASD). Given fundamental and inescapable effects of noise on nearly all aspects of neural processing, this could be a critical abnormality with broad implications for perception, behavior, and cognition. However, this proposal has been challenged by both theoretical and empirical studies. A crucial question is whether and how internal noise limits perception in ASD, independently from other sources of perceptual inefficiency, such as the ability to filter out external noise. Here, we separately estimated internal noise and external noise filtering in ASD. In children and adolescents with and without ASD, we computationally modeled individuals' visual orientation discrimination in the presence of varying levels of external noise. The results revealed increased internal noise and worse external noise filtering in individuals with ASD. For both factors, we also observed high inter-individual variability in ASD, with only the internal noise estimates significantly correlating with severity of ASD symptoms. We provide evidence for reduced perceptual efficiency in ASD that is due to both increased internal noise and worse external noise filtering, while highlighting internal noise as a possible contributing factor to variability in ASD symptoms.

Measurement of psychological disorders using cognitive diagnosis models.

PubMed

Templin, Jonathan L; Henson, Robert A

2006-09-01

Cognitive diagnosis models are constrained (multiple classification) latent class models that characterize the relationship of questionnaire responses to a set of dichotomous latent variables. Having emanated from educational measurement, several aspects of such models seem well suited to use in psychological assessment and diagnosis. This article presents the development of a new cognitive diagnosis model for use in psychological assessment--the DINO (deterministic input; noisy "or" gate) model--which, as an illustrative example, is applied to evaluate and diagnose pathological gamblers. As part of this example, a demonstration of the estimates obtained by cognitive diagnosis models is provided. Such estimates include the probability an individual meets each of a set of dichotomous Diagnostic and Statistical Manual of Mental Disorders (text revision [DSM-IV-TR]; American Psychiatric Association, 2000) criteria, resulting in an estimate of the probability an individual meets the DSM-IV-TR definition for being a pathological gambler. Furthermore, a demonstration of how the hypothesized underlying factors contributing to pathological gambling can be measured with the DINO model is presented, through use of a covariance structure model for the tetrachoric correlation matrix of the dichotomous latent variables representing DSM-IV-TR criteria. Copyright 2006 APA

Characteristics, correlates, and outcomes of childhood and adolescent depressive disorders

PubMed Central

Rao, Uma; Chen, Li-Ann

2009-01-01

Depressive illness beginning early in life can have serious developmental and functional consequences. Therefore, understanding the disorder during this developmental stage is critical for determining its etiology and course, as well as for deveiopinq effective intervention straieqies. This paper summarizes current knoviedqe reqardinq the etiology, phenomenoiogy, correlates, natural course, and consequences of unipolar depression in children and adolescents. Using adult depression as a framevork, the unique aspects of childhood and adolescence are considered in order to better understand depression within a developmental context. The data suggest that the clinical presentation, correlates, and natural course of depression are remarkably similar across the lifespan. There are, however, important developmental differences. Specifically, the familial and psychological context in which depression develops in youngsters is associated with variability in the frequency and nature of depressive symptoms and comorbid conditions among children and adolescents. Maturational differences have also been identified in the neurobiological correlates of depression. These developmental differences may be associated with the observed variability in clinical response to treatment and longitudinal course. Characterization of the developmental differences will be helpful in developing more specific and effective interventions for youngsters, thereby allowing them to reach their full potential as adults. PMID:19432387

Corpus Callosum Size, Reaction Time Speed and Variability in Mild Cognitive Disorders and in a Normative Sample

ERIC Educational Resources Information Center

Anstey, Kaarin J.; Mack, Holly A.; Christensen, Helen; Li, Shu-Chen; Reglade-Meslin, Chantal; Maller, Jerome; Kumar, Rajeev; Dear, Keith; Easteal, Simon; Sachdev, Perminder

2007-01-01

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and…

Correlates Associated with Unipolar Depressive Disorders in a Latino Population

PubMed Central

Correa-Fernandez, Virmarie; Carrión-Baralt, José R.; Alegría, Margarita; Albizu-García, Carmen E.

2014-01-01

Background This study reports the comparison and associations of demographic, clinical, and psychosocial correlates with three unipolar depressive disorders: dysthymia (DYS), major depression (MD), and double depression (DD), and examines to which extent these variables predict the disorders. Sampling and Method Previously collected data from 563 adults from a community in Puerto Rico were analyzed. One hundred and thirty individuals with DYS, 260 with MD, and 173 with DD were compared by demographic variables, psychiatric and physical comorbidity, familial psychopathology, psychosocial stressors, functional impairment, self-reliance, problem recognition and formal use of mental health services. Multinomial regression was used to assess the association of the predictor variables with each of the three disorders. Results Similarities outweighed the discrepancies between disorders. The main differences observed were between MD and DD, while DYS shared common characteristics with both MD and DD. After other variables were controlled, anxiety, functional impairment, and problem recognition most strongly predicted a DD diagnosis while age predicted a DYS diagnosis. Conclusion MD, DYS, and DD are not completely different disorders but they do differ in key aspects that might be relevant for nosology, research, and practice. A dimensional system that incorporates specific categories of disorders would better reflect the different manifestations of unipolar depressive disorders. PMID:23006435

Condensation with two constraints and disorder

NASA Astrophysics Data System (ADS)

Barré, J.; Mangeolle, L.

2018-04-01

We consider a set of positive random variables obeying two additive constraints, a linear and a quadratic one; these constraints mimic the conservation laws of a dynamical system. In the simplest setting, without disorder, it is known that such a system may undergo a ‘condensation’ transition, whereby one random variable becomes much larger than the others; this transition has been related to the spontaneous appearance of non linear localized excitations in certain nonlinear chains, called breathers. Motivated by the study of breathers in a disordered discrete nonlinear Schrödinger equation, we study different instances of this problem in presence of a quenched disorder. Unless the disorder is too strong, the phase diagram looks like the one without disorder, with a transition separating a fluid phase, where all variables have the same order of magnitude, and a condensed phase, where one variable is much larger than the others. We then show that the condensed phase exhibits various degrees of ‘intermediate symmetry breaking’: the site hosting the condensate is chosen neither uniformly at random, nor is it fixed by the disorder realization. Throughout the article, our heuristic arguments are complemented with direct Monte Carlo simulations.

Heart rate variability in normal and pathological sleep.

PubMed

Tobaldini, Eleonora; Nobili, Lino; Strada, Silvia; Casali, Karina R; Braghiroli, Alberto; Montano, Nicola

2013-10-16

Sleep is a physiological process involving different biological systems, from molecular to organ level; its integrity is essential for maintaining health and homeostasis in human beings. Although in the past sleep has been considered a state of quiet, experimental and clinical evidences suggest a noteworthy activation of different biological systems during sleep. A key role is played by the autonomic nervous system (ANS), whose modulation regulates cardiovascular functions during sleep onset and different sleep stages. Therefore, an interest on the evaluation of autonomic cardiovascular control in health and disease is growing by means of linear and non-linear heart rate variability (HRV) analyses. The application of classical tools for ANS analysis, such as HRV during physiological sleep, showed that the rapid eye movement (REM) stage is characterized by a likely sympathetic predominance associated with a vagal withdrawal, while the opposite trend is observed during non-REM sleep. More recently, the use of non-linear tools, such as entropy-derived indices, have provided new insight on the cardiac autonomic regulation, revealing for instance changes in the cardiovascular complexity during REM sleep, supporting the hypothesis of a reduced capability of the cardiovascular system to deal with stress challenges. Interestingly, different HRV tools have been applied to characterize autonomic cardiac control in different pathological conditions, from neurological sleep disorders to sleep disordered breathing (SDB). In summary, linear and non-linear analysis of HRV are reliable approaches to assess changes of autonomic cardiac modulation during sleep both in health and diseases. The use of these tools could provide important information of clinical and prognostic relevance.

Mental capacity, diagnosis and insight in psychiatric in-patients: a cross-sectional study.

PubMed

Owen, G S; David, A S; Richardson, G; Szmukler, G; Hayward, P; Hotopf, M

2009-08-01

Mental capacity is now a core part of UK mental health law and clinicians will increasingly be expected to assess it. Because it is a legal concept there is a need to clarify associations with variables that clinicians are more familiar with, especially insight. In this cross-sectional study we recruited consecutive psychiatric admissions to the Maudsley Hospital, London. We carried out structured assessments of decision making using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), resulting in a clinical judgement about capacity status. We analysed associations with a range of sociodemographic and clinical variables, including insight score on the Expanded Schedule for the Assessment of Insight (SAI-E). The same variables were compared in an analysis stratified according to diagnostic group: psychotic disorders/bipolar affective disorder (BPAD)/non-psychotic disorders. Psychotic disorders and manic episodes of BPAD are most strongly associated with incapacity. In such patients, insight is the best discriminator of capacity status. In patients with non-psychotic disorders, insight is less strongly associated with capacity; in this group depressed mood discriminates capacity status whereas it does not in psychotic disorders. Cognitive performance does not discriminate capacity status in patients with psychotic disorders. Mental capacity has complex relationships with psychopathological variables, and these relationships are different according to diagnostic group. Insight is the best discriminator of capacity status in psychotic disorders and BPAD but not in non-psychotic disorders.

A personality-based latent class typology of outpatients with major depressive disorder: association with symptomatology, prescription pattern and social function.

PubMed

Hori, Hiroaki; Teraishi, Toshiya; Nagashima, Anna; Koga, Norie; Ota, Miho; Hattori, Kotaro; Kim, Yoshiharu; Higuchi, Teruhiko; Kunugi, Hiroshi

2017-08-01

While major depressive disorder (MDD) is considered to be a heterogeneous disorder, the nature of the heterogeneity remains unclear. Studies have attempted to classify patients with MDD using latent variable techniques, yet the empirical approaches to symptom-based subtyping of MDD have not provided conclusive evidence. Here we aimed to identify homogeneous classes of MDD based on personality traits, using a latent profile analysis. We studied 238 outpatients with DSM-IV MDD recruited from our specialized depression outpatient clinic and assessed their dimensional personality traits with the Temperament and Character Inventory. Latent profile analysis was conducted with 7 dimensions of the Temperament and Character Inventory as indicators. Relationships of the identified classes with symptomatology, prescription pattern, and social function were then examined. The latent profile analysis indicated that a 3-class solution best fit the data. Of the sample, 46.2% was classified into a "neurotic" group characterized by high harm avoidance and low self-directedness; 30.3% into an "adaptive" group characterized by high self-directedness and cooperativeness; and 23.5% into a "socially-detached" group characterized by low reward dependence and cooperativeness and high self-transcendence. The 2 maladaptive groups, namely neurotic and socially-detached groups, demonstrated unique patterns of symptom expression, different classes of psychotropic medication use, and lower social functioning. Generalizability of the findings was limited since our patients were recruited from the specialized depression outpatient clinic. Our personality-based latent profile analysis identified clinically meaningful 3 MDD groups that were markedly different in their personality profiles associated with distinct symptomatology and functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Motivation to change and perceptions of the admission process with respect to outcome in adolescent anorexia nervosa.

PubMed

Hillen, Simona; Dempfle, Astrid; Seitz, Jochen; Herpertz-Dahlmann, Beate; Bühren, Katharina

2015-07-02

In patients with anorexia nervosa (AN), there is evidence that readiness to change is an important predictor of outcome with respect to weight gain and improvement in eating disorder psychopathology. In particular, young patients are characterized by a low level of motivation for recovery and perceive more coercion at hospitalization. Thus, a better understanding of the variables that influence readiness to change and perception of the admission process in adolescent AN may help to support patients in initiating change and staying motivated for treatment. In 40 adolescent patients diagnosed with AN according to DSM-IV criteria, we assessed in a prospective clinical cohort study the motivation to change using the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) at admission to inpatient treatment, in week 9 after admission and at discharge. Additional variables were assessed, including depressive symptoms (Beck Depression Inventory, BDI), eating disorder-specific psychopathology (Eating Disorder Inventory, EDI-2), body mass index (BMI) and the percentage of expected body weight (%EBW). The patients' perceptions of the admission process and their perceived need for hospitalization were assessed using a self-report scale developed by Guarda et al. (2007). Younger patients perceived more coercion than older patients did. Low %EBW and more severe eating disorder-specific psychopathology were associated with a greater perceived need for hospitalization. Moreover, low %EBW at admission and a longer duration of illness were accompanied by a greater motivation to change at admission, whereas more severe eating disorder psychopathology was associated with a low motivation to change. The motivation to change increased significantly between admission and discharge. Patients with a greater motivation to change at admission exhibited a higher weekly weight gain during treatment but did not show better outcome in eating disorder-specific psychopathology and depression. Motivation to change is an important predictor of short-term outcome with respect to weight gain trajectory during treatment of adolescent AN. As patients with a higher BMI at admission and those with more severe eating disorder-specific symptoms seem to be less motivated to change, the crucial issue of motivation to change should be addressed with these patients during the therapeutic process.

Temporary stages and motivational variables: Two complementary perspectives in the help-seeking process for mental disorders.

PubMed

Del Valle Del Valle, Gema; Carrió, Carmen; Belloch, Amparo

2017-10-09

Help-seeking for mental disorders is a complex process, which includes different temporary stages, and in which the motivational variables play an especially relevant role. However, there is a lack of instruments to evaluate in depth both the temporary and motivational variables involved in the help-seeking process. This study aims to analyse in detail these two sets of variables, using a specific instrument designed for the purpose, to gain a better understanding of the process of treatment seeking. A total of 152 patients seeking treatment in mental health outpatient clinics of the NHS were individually interviewed: 71 had Obsessive-Compulsive Disorder, 21 had Agoraphobia, 18 had Major Depressive Disorder), 20 had Anorexia Nervosa, and 22 had Cocaine Dependence. The patients completed a structured interview assessing the help-seeking process. Disorder severity and quality of life was also assessed. The patients with agoraphobia and with major depression took significantly less time in recognising their mental health symptoms. Similarly, patients with major depression were faster in seeking professional help. Motivational variables were grouped in 3 sets: motivators for seeking treatment, related to the negative impact of symptoms on mood and to loss of control over symptoms; motivators for delaying treatment, related to minimisation of the disorder; and stigma-associated variables. The results support the importance of considering the different motivational variables involved in the several stages of the help-seeking process. The interview designed to that end has shown its usefulness in this endeavour. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Comorbidity of Autism Spectrum Disorders and Emotional/behavioral Disorders: Towards Improved Diagnostic Procedures, Instructional Programming, and Personnel Preparation

ERIC Educational Resources Information Center

Clinton, Elias

2016-01-01

An emotional/behavioral disorder is a mental health disability characterized by intensive internalized behaviors (e.g., anxiety, depression) and/or externalized behaviors (e.g., physical aggression, verbal aggression). Autism is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors (i.e., stereo…

KBG syndrome involving a single-nucleotide duplication in ANKRD11

PubMed Central

Kleyner, Robert; Malcolmson, Janet; Tegay, David; Ward, Kenneth; Maughan, Annette; Maughan, Glenn; Nelson, Lesa; Wang, Kai; Robison, Reid; Lyon, Gholson J.

2016-01-01

KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain. PMID:27900361

Indirect associations of combat exposure with post-deployment physical symptoms in U.S. soldiers: roles of post-traumatic stress disorder, depression and insomnia.

PubMed

Quartana, Phillip J; Wilk, Joshua E; Balkin, Thomas J; Hoge, Charles W

2015-05-01

To characterize the indirect associations of combat exposure with post-deployment physical symptoms through shared associations with post-traumatic stress disorder (PTSD), depression and insomnia symptoms. Surveys were administered to a sample of U.S. soldiers (N = 587) three months after a 15-month deployment to Iraq. A multiple indirect effects model was used to characterize direct and indirect associations between combat exposure and physical symptoms. Despite a zero-order correlation between combat exposure and physical symptoms, the multiple indirect effects analysis did not provide evidence of a direct association between these variables. Evidence for a significant indirect association of combat exposure and physical symptoms was observed through PTSD, depression, and insomnia symptoms. In fact, 92% of the total effect of combat exposure on physical symptoms scores was indirect. These findings were evident even after adjusting for the physical injury and relevant demographics. This is the first empirical study to suggest that PTSD, depression and insomnia collectively and independently contribute to the association between combat exposure and post-deployment physical symptoms. Limitations, future research directions, and potential policy implications are discussed. Published by Elsevier Inc.

Preschool Predictors of School-Age Academic Achievement in Autism Spectrum Disorder

PubMed Central

Miller, Lauren E.; Burke, Jeffrey D.; Troyb, Eva; Knoch, Kelley; Herlihy, Lauren E.; Fein, Deborah A.

2017-01-01

Objective Characterization of academic functioning in children with autism spectrum disorder (ASD), particularly predictors of achievement, may have important implications for intervention. The current study aimed to characterize achievement profiles, confirm associations between academic ability and concurrent intellectual and social skills, and explore preschool predictors of school-age academic achievement in a sample of children with ASD. Method Children with ASD (N = 26) were evaluated at the approximate ages of two, four, and ten years. Multiple regression was used to predict school-age academic achievement in reading and mathematics from both concurrent (i.e., school-age) and preschool variables. Results Children with ASD demonstrated a weakness in reading comprehension relative to word reading. There was a smaller difference between mathematics skills; math reasoning was lower than numerical operations, but this did not quite reach trend level significance. Concurrent IQ and social skills were associated with school-age academic achievement across domains. Preschool verbal abilities significantly predicted school-age reading comprehension, above and beyond concurrent IQ, and early motor functioning predicted later math skills. Conclusions Specific developmental features of early ASD predict specific aspects of school-age achievement. Early intervention targeting language and motor skills may improve later achievement in this population. PMID:27705180

Preschool predictors of school-age academic achievement in autism spectrum disorder.

PubMed

Miller, Lauren E; Burke, Jeffrey D; Troyb, Eva; Knoch, Kelley; Herlihy, Lauren E; Fein, Deborah A

2017-02-01

Characterization of academic functioning in children with autism spectrum disorder (ASD), particularly predictors of achievement, may have important implications for intervention. The current study aimed to characterize achievement profiles, confirm associations between academic ability and concurrent intellectual and social skills, and explore preschool predictors of school-age academic achievement in a sample of children with ASD. Children with ASD (n = 26) were evaluated at the approximate ages of two, four, and ten. Multiple regression was used to predict school-age academic achievement in reading and mathematics from both concurrent (i.e. school-age) and preschool variables. Children with ASD demonstrated a weakness in reading comprehension relative to word reading. There was a smaller difference between mathematics skills; math reasoning was lower than numerical operations, but this did not quite reach trend level significance. Concurrent IQ and social skills were associated with school-age academic achievement across domains. Preschool verbal abilities significantly predicted school-age reading comprehension, above and beyond concurrent IQ, and early motor functioning predicted later math skills. Specific developmental features of early ASD predict specific aspects of school-age achievement. Early intervention targeting language and motor skills may improve later achievement in this population.

Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

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

Prager, D.; Braunstein, G.D.

Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linkedmore » form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.« less

Personality disorders in hypochondriasis: prevalence and comparison with two anxiety disorders.

PubMed

Fallon, Brian A; Harper, Katy M; Landa, Alla; Pavlicova, Martina; Schneier, Franklin R; Carson, Amanda; Harding, Kelli; Keegan, Kathryn; Schwartz, Theresa; Liebowitz, Michael R

2012-01-01

Symptoms of hypochondriasis are sometimes attributed to personality psychopathology by health care providers. The goals of this study were to assess the prevalence of personality disorder (PD) comorbidity in hypochondriasis (HYP) and to compare the PD comorbidity profile of patients with HYP with that found among patients with other disorders characterized by intrusive thoughts and fears. Structured Clinical Interview for DSM-IV Axis I and Axis II Disorders (SCID-I and SCID-II) were administered to 179 individuals: 62 with HYP, 46 with obsessive-compulsive disorder (OCD), and 71 with social anxiety disorder (SAD). For group contrasts, the samples were "purified" of the comparison comorbid disorders. General linear models were used to test the combined effect of group (HYP, OCD, SAD), age, and gender on the PD outcome variables. 59.7% of HYP subjects had no Axis II comorbidity. The most common PDs in HYP were paranoid (19.4%), avoidant (17.7%), and obsessive-compulsive (14.5%). HYP significantly differed from SAD in the likelihood of a cluster C disorder, whereas no significant difference was noted for HYP vs. OCD. The proportion of subjects having at least two PDs was not significantly different for HYP vs. OCD or for HYP vs. SAD. Although 40% of patients with hypochondriasis have PD comorbidity as assessed by the SCID-II, the amount of PD comorbidity is not significantly different than found among individuals with two comparison anxiety disorders. Therefore, health providers should be aware that PD may complicate the clinical profile of HYP, but they should avoid assuming that PD psychopathology is the primary source of hypochondriacal distress. Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Comorbid symptomatology moderates response to risperidone, stimulant, and parent training in children with severe aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder.

PubMed

Farmer, Cristan A; Brown, Nicole V; Gadow, Kenneth D; Arnold, L Eugene; Kolko, David G; Findling, Robert L; Molina, Brooke S G; Buchan-Page, Kristin A; Rice, Robert R; Bangalore, Srihari S; Bukstein, Oscar; Rundberg-Rivera, E Victoria; McNamara, Nora; Aman, Michael G

2015-04-01

In this study, we evaluated parent and child characteristics as predictors and moderators of response in the four-site Treatment of Severe Childhood Aggression (TOSCA) study. A total of 168 children with severe aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder (ADHD) were enrolled in a 9-week trial of basic treatment (n=84, stimulant+parent training+placebo) versus augmented treatment (n=84, stimulant+parent training+risperidone). In the initial report, augmented treatment surpassed basic treatment in reducing the primary outcome of disruptive behavior (D-Total) scores. In the current study, we evaluated parent (income, education, family functioning, employment) and child variables (intelligence quotient [IQ], aggression type, comorbid symptomatology) as predictors or moderators, using linear mixed models and the MacArthur guidelines. Higher scores on ADHD symptom severity and callous/unemotional traits predicted better outcome on D-Total regardless of treatment assignment. Two moderators of D-Total were found: Higher anger/irritability symptoms and lower mania scores were associated with faster response, although not better overall effect at endpoint, in the augmented but not the basic group. Several variables moderated response on secondary outcomes (ADHD severity and prosocial behavior), and were characterized by faster response, although not better outcome, in the augmented but not in the basic group. Maternal education moderated outcome on the measure of positive social behavior; children of mothers with less education benefited more from augmented treatment relative to basic than those with more education. Although these findings require validation, they tentatively suggest that augmented treatment works equally well across the entire sample. Nevertheless, certain child characteristics may be useful indicators for the speed of response to augmented treatment.

Behavioural and emotional disorders in childhood: A brief overview for paediatricians

PubMed Central

Ogundele, Michael O

2018-01-01

Mental health problems in children and adolescents include several types of emotional and behavioural disorders, including disruptive, depression, anxiety and pervasive developmental (autism) disorders, characterized as either internalizing or externalizing problems. Disruptive behavioural problems such as temper tantrums, attention deficit hyperactivity disorder, oppositional, defiant or conduct disorders are the commonest behavioural problems in preschool and school age children. The routine Paediatric clinic or Family Medicine/General Practitioner surgery presents with several desirable characteristics that make them ideal for providing effective mental health services to children and adolescents. DSM-5 and ICD-10 are the universally accepted standard criteria for the classification of mental and behaviour disorders in childhood and adults. The age and gender prevalence estimation of various childhood behavioural disorders are variable and difficult to compare worldwide. A review of relevant published literature was conducted, including published meta-analyses and national guidelines. We searched for articles indexed by Ovid, PubMed, PubMed Medical Central, CINAHL, EMBASE, Database of Abstracts and Reviews, and the Cochrane Database of Systematic reviews and other online sources. The searches were conducted using a combination of search expressions including “childhood”, “behaviour”, “disorders” or “problems”. Childhood behaviour and emotional problems with their related disorders have significant negative impacts on the individual, the family and the society. They are commonly associated with poor academic, occupational, and psychosocial functioning. It is important for all healthcare professionals, especially the Paediatricians to be aware of the range of presentation, prevention and management of the common mental health problems in children and adolescents. PMID:29456928

[Program of sanitary education for people with autistic spectrum disorder].

PubMed

Nieto Vizcaíno, C; Ventoso Roncero, R; Covaleda Rodrigo, A; Andériz Cebrián, D; de Oro Villora, E

2008-02-01

Autism is a developmental disorder that it is characterized by a qualitative alteration of social interaction, communication and repetitive and stereotyped behaviours, interests and activities. Recent studies about health are showing that people with autism have lower hope of life. Among other causes, difficulty to identify and to communicate uneasiness and resistance to allow medical explorations are important factors to consider. To design and to implant a specific program for people with Autistic Spectrum Disorder (ASD) with the objective of habituating them to the medical explorations so that they admit it and collaborate, facilitating the sanitary personnel's work. Our aim was to evaluate the effectiveness of the program and the maintenance of the potentials improvements. Our sample was formed by twenty-two children with ASD (mean chronological age, 9;10 years). A quasi-experimental design of interrupted temporary series was carried out. two grouping variables (clinical characteristics of the groups about QI and about linguistic abilities) as dependent variable a measure of percentage of success has been used through an observation protocol designed for this program. Improvements in all the groups. Results are not conditioned neither for the level of intellectual abilities (IQ) neither for the existence or not of linguistic abilities. Likewise, it is found that carrying out maintenance sessions in period of seven weeks allows to maintain long term achievements reached by the program. However, we found that those children which were severely impaired could obtain more benefit from more frequent maintenance sessions.

Recurrent 15q11.2 BP1-BP2 microdeletions and microduplications in the etiology of neurodevelopmental disorders.

PubMed

Picinelli, Chiara; Lintas, Carla; Piras, Ignazio Stefano; Gabriele, Stefano; Sacco, Roberto; Brogna, Claudia; Persico, Antonio Maria

2016-12-01

Rare and common CNVs can contribute to the etiology of neurodevelopmental disorders. One of the recurrent genomic aberrations associated with these phenotypes and proposed as a susceptibility locus is the 15q11.2 BP1-BP2 CNV encompassing TUBGCP5, CYFIP1, NIPA2, and NIPA1. Characterizing by array-CGH a cohort of 243 families with various neurodevelopmental disorders, we identified five patients carrying the 15q11.2 duplication and one carrying the deletion. All CNVs were confirmed by qPCR and were inherited, except for one duplication where parents were not available. The phenotypic spectrum of CNV carriers was broad but mainly neurodevelopmental, in line with all four genes being implicated in axonal growth and neural connectivity. Phenotypically normal and mildly affected carriers complicate the interpretation of this aberration. This variability may be due to reduced penetrance or altered gene dosage on a particular genetic background. We evaluated the expression levels of the four genes in peripheral blood RNA and found the expected reduction in the deleted case, while duplicated carriers displayed high interindividual variability. These data suggest that differential expression of these genes could partially account for differences in clinical phenotypes, especially among duplication carriers. Furthermore, urinary Mg 2+ levels appear negatively correlated with NIPA2 gene copy number, suggesting they could potentially represent a useful biomarker, whose reliability will need replication in larger samples. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ambivalence About Interpersonal Problems and Traits Predicts Cross-Situational Variability of Social Behavior.

PubMed

Erickson, Thane M; Newman, Michelle G; Peterson, Jessica; Scarsella, Gina

2015-08-01

Multiple theoretical perspectives suggest that maladjusted personality is characterized by not only distress, but also opposing or "ambivalent" self-perceptions and behavioral lability across social interactions. However, the degree to which ambivalence about oneself predicts cross-situational variability in social behavior has not been examined empirically. Using the interpersonal circumplex (IPC) as a nomological framework, the present study investigated the extent to which endorsing opposing or "ambivalent" tendencies on IPC measures predicted variability in social behavior across a range of hypothetical interpersonal scenarios (Part 1; N = 288) and naturalistic social interactions (Part 2; N = 192). Ambivalent responding for interpersonal problems and traits was associated with measures of distress, maladaptive interpersonal tendencies, and greater variability of social behavior across both hypothetical and daily social interactions, though more consistently for interpersonal problems. More conservative tests suggested that ambivalence predicted some indexes of behavioral variability even when accounting for mean levels and squared means of social behaviors, vector length, gender, and depressive symptoms. Results suggest that processes theorized as typifying personality disorder may apply more broadly to personality maladjustment occurring outside of clinical samples. © 2014 Wiley Periodicals, Inc.

Pathophysiology of Hereditary Hemochromatosis

PubMed Central

Fleming, Robert E.; Britton, Robert S.; Waheed, Abdul; Sly, William S.; Bacon, Bruce R.

2008-01-01

Hereditary hemochromatosis (HH) encompasses several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue iron deposition. The most common form of this disorder is HFE-related HH, nearly always caused by homozygosity for the C282Y mutation. A substantial proportion of C282Y homozygotes do not develop clinically significant iron overload, suggesting roles for environmental factors and modifier genes in determining the phenotype. Recent studies have demonstrated that the pathogenesis of nearly all forms of HH involves inappropriately decreased expression of the iron-regulatory hormone hepcidin. Hepcidin serves to decrease the export of iron from reticuloendothelial cells and absorptive enterocytes. Thus, HH patients demonstrate increased iron release from these cell types, elevated circulating iron, and iron deposition in vulnerable tissues. The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE. PMID:16315135

Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome.

PubMed

Rohena, Luis; Kuehn, Devon; Marchegiani, Shannon; Higginson, Jason D

2011-04-01

Ablepharon-macrostomia syndrome (AMS) is characterized by absent or short eyelids, macrostomia, ear anomalies, absent lanugo and hair, redundant skin, abnormal genitalia, and developmental delay in two-thirds of the reported patients. Additional anomalies include dry skin, growth retardation, hearing loss, camptodactyly, hypertelorism, absent zygomatic arches, and umbilical abnormalities. We present the second familial case of ablepharon-macrostomia syndrome in a newborn female and her 22-year-old father making autosomal dominant inheritance more likely than the previously proposed autosomal recessive transmission for this disorder. These cases likely represent the 16th and 17th reported cases of AMS and the first case suspected on prenatal ultrasound. Additionally, the child shows more prominent features of the disorder when compared to her father documenting variable expression and possible anticipation. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2011 Wiley-Liss, Inc.

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

PubMed

Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

2017-04-01

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

[Diabetes insipidus].

PubMed

Krysiak, Robert; Handzlik-Orlik, Gabriela; Okopień, Bogusław

2014-01-01

Diabetes insipidus is an uncommon disorder of water-electrolyte balance characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The disease may result from the insufficient production of vasopressin, its increased degradation, an impaired response of kidneys to vasopressin, or may be secondary to excessive water intake. Patients with severe and uncompensated symptoms may develop marked dehydration, neurologic symptoms and encephalopathy, and therefore diabetes insipidus can be a life-threatening condition if not properly diagnosed and managed. Patients with diabetes insipidus require treatment with desmopressin or drugs increasing sensitivity of the distal nephron to vasopressin, but this treatment may be confusing because of the disorder's variable pathophysiology and side-effects of pharmacotherapy. This review summarizes the current knowledge on different aspects of the pathophysiology, classification, clinical presentation, diagnosis, and management of diabetes insipidus. The reader is also provided with some practical recommendations on dealing with patients suffering from this disease.

Sudden death in Leigh syndrome: an autopsy case.

PubMed

Ventura, Francesco; Rocca, Gabriele; Gentile, Raffaella; De Stefano, Francesco

2012-09-01

The present report describes the sudden death of a 3-year-old female child who had been clinically diagnosed with Leigh syndrome.Leigh syndrome is a heterogeneous progressive neurodegenerative disorder, which is characterized by focal or bilateral lesions in the thalamus, basal ganglia, brainstem, cerebellum, and spinal cord. Affected patients exhibit a variable clinical picture that frequently includes psychomotor retardation or regression, recurrent episodes of vomiting, failure to thrive, and signs of brainstem and basal ganglia dysfunction.The child was found dead in bed. Autopsy described the presence of symmetrical, necrotizing lesions scattered within the basal ganglia, thalamus, diencephalon, brainstem, and spinal-cord gray matter and revealed the presence of gastric contents in the upper and lower airways. We report the results of genetic investigations and describe the histological and immunohistochemical features that confirmed the diagnosis. These findings suggest that Leigh syndrome should be regarded as predisposing children to sudden death, especially by asphyxia secondary to the neurological disorder.

Early orthodontic management of Crouzon Syndrome: a case report.

PubMed

Hlongwa, P

2009-03-01

Crouzon Syndrome is an autosomal dominant disorder with complete penetrance and variable expressivity. Described by a French neurosurgeon in 1912, it is a rare genetic disorder. Crouzon syndrome is caused by mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The disease is characterized by premature synostosis of coronal and sagittal sutures which begins in the first year of life. Once the sutures become closed, growth potential to those sutures is restricted. However, multiple sutural synostoses frequently extend to premature fusion of skull base causing midfacial hypoplasia, shallow orbit, maxillary hypoplasia and occasional upper airway obstruction.The case of a 7-year-old South African black boy with Crouzon Syndrome is presented. He presented with characteristic triad of cranial deformity, maxillary hypoplasia and exophthalmos. The clinical, cephalometric features and initial orthodontic management of this patient are discussed as part of multidisciplinary management.

Social Networks and Participation with Others for Youth with Learning, Attention and Autism Spectrum Disorders

PubMed Central

Kreider, Consuelo M.; Bendixen, Roxanna M.; Young, Mary Ellen; Prudencio, Stephanie M.; McCarty, Christopher; Mann, William C.

2015-01-01

Background Social participation involves activities and roles providing interactions with others, including those within their social networks. Purpose Characterize social networks and participation with others for 36 adolescents, ages 11-16 years, with (n = 19) and without (n = 17) learning disability, attention disorder or high-functioning autism. Methods Social networks were measured using methods of personal network analysis. The Children's Assessment of Participation and Enjoyment With Whom dimension scores was used to measure participation with others. Youth from the clinical group were interviewed regarding their experiences within their social networks. Findings Group differences were observed for six social network variables and in the proportion of overall, physical, recreational, social and informal activities engaged with family and/or friends. Qualitative findings explicated strategies used in building, shaping and maintaining their social networks. Implications Social network factors should be considered when seeking to understand social participation. PMID:26755040

Characterizing sleep disorders of adults with tuberous sclerosis complex: a questionnaire-based study and review.

PubMed

van Eeghen, Agnies M; Numis, Adam I; Staley, Brigid A; Therrien, Samuel E; Thibert, Ronald L; Thiele, Elizabeth A

2011-01-01

An adult cohort with tuberous sclerosis complex was investigated for the prevalence of sleep disturbances and the relationship with seizure variables, medication, and psychological functioning. Information on 35 adults was gathered using four questionnaires: Epworth Sleepiness Scale (ESS), Sleep and Epilepsy Questionnaire (SEQ), Sleep Diagnosis List (SDL), and Adult Self-Report Scale (ASR). In addition, clinical, genetic and electrophysiological data were collected. Of 35 respondents, 25 had a history of epilepsy. A subjective sleep disorder was found in 31% of the cohort. Insomnia scores showed a significant positive correlation with obstructive sleep apnea syndrome and restless legs syndrome scores. Significant correlations were found between daytime sleepiness and scores on depression, antisocial behavior, and use of mental health medication. A subgroup using antiepileptic medication showed high correlations between daytime sleepiness, attention deficits, and anxiety scores. Copyright © 2010 Elsevier Inc. All rights reserved.

Nummular headache update.

PubMed

Pareja, Juan A; Montojo, Teresa; Alvarez, Mónica

2012-04-01

Nummular headache is characterized by head pain exclusively felt in a rounded or elliptical area, typically 1 to 6 cm in diameter. The pain remains confined to the same symptomatic area, which does not change in shape or size with time. The symptomatic area may be localized in any part of the head but mostly in the parietal region. Rarely, the disorder may be multifocal, each symptomatic area keeping all the characteristics of nummular headache. The pain is generally mild or moderate, commonly described as oppressive or stabbing, and lasting minutes, hours, or days, with a remitting or unremitting pattern. Superimposed on the baseline pain, there may be spontaneous or triggered exacerbations. During and between symptomatic periods, the affected area may show variable combinations of hypoesthesia, dysesthesia, paresthesia, tenderness, and trophic changes. Nummular headache emerges as a primary disorder with a clear-cut clinical picture developed in a unique topography.

Psychophysiological investigations in depersonalization disorder and effects of electrodermal biofeedback.

PubMed

Schoenberg, Poppy L A; Sierra, Mauricio; David, Anthony S

2012-01-01

Previous studies investigating depersonalization disorder (DPD) report a lower baseline skin conductance level (SCL) and attenuated skin conductance response (SCR) to emotive stimuli. We hypothesized that increasing physiological arousal levels via electrodermal biofeedback may ameliorate disembodiment and emotional numbing symptomatology. Real-time versus sham biofeedback yielded a significant SCL increase after just 3 real-time biofeedback sessions in healthy volunteers. Subsequently, a randomized controlled biofeedback trial was administered with DPD patients. Findings were not replicated as SCL tended to fall, curiously more substantially in the real-time condition, concomitant with increased low- and high-frequency heart rate variability. To further investigate abnormal autonomic regulation in DPD, we compared basal autonomic activity between patients and healthy volunteers and found the former to be significantly more labile, indexed by greater nonspecific SCRs and higher resting SCLs. Rather than low sympathetic arousal, DPD might be better characterized by abnormal autonomic regulation affecting emotional and physiological responsivity.

Video game therapy for emotional regulation and impulsivity control in a series of treated cases with bulimia nervosa.

PubMed

Fagundo, Ana B; Santamaría, Juan J; Forcano, Laura; Giner-Bartolomé, Cristina; Jiménez-Murcia, Susana; Sánchez, Isabel; Granero, Roser; Ben-Moussa, Maher; Magnenat-Thalmann, Nadia; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Bults, Richard G A; Tarrega, Salomé; Menchón, José M; de la Torre, Rafael; Cardi, Valentina; Treasure, Janet; Fernández-Aranda, Fernando

2013-11-01

Although standard psychological treatments have been successful in treating several core features in eating disorders (ED), other characteristics such as emotional regulation or impulsivity appear to be more resistant to change. There is a growing body of evidence to support the efficacy of cognitive remediation for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video game (VG) designed to specifically treat mental disorders, characterized by problems in impulse control. The objective of the game is to increase self-control over emotions, decision making and behaviours. The aim of this study is to describe the results from a consecutive series of nine bulimia nervosa patients who were treated with the VG in addition to cognitive behaviour therapy (CBT). The outcomes included clinical and psychopathological questionnaires, and physiological measures were obtained during the VG. Emotional regulation improved, heart rate variability increased, and respiratory rate and impulsivity measures reduced after the treatment. These findings suggest that VG training may enhance treatment for ED. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Multiple Symmetrical Lipomatosis--a mitochondrial disorder of brown fat.

PubMed

Plummer, C; Spring, P J; Marotta, R; Chin, J; Taylor, G; Sharpe, D; Athanasou, N A; Thyagarajan, D; Berkovic, S F

2013-07-01

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Transducer-based evaluation of tremor.

PubMed

Haubenberger, Dietrich; Abbruzzese, Giovanni; Bain, Peter G; Bajaj, Nin; Benito-León, Julián; Bhatia, Kailash P; Deuschl, Günther; Forjaz, Maria João; Hallett, Mark; Louis, Elan D; Lyons, Kelly E; Mestre, Tiago A; Raethjen, Jan; Stamelou, Maria; Tan, Eng-King; Testa, Claudia M; Elble, Rodger J

2016-09-01

The International Parkinson and Movement Disorder Society established a task force on tremor that reviewed the use of transducer-based measures in the quantification and characterization of tremor. Studies of accelerometry, electromyography, activity monitoring, gyroscopy, digitizing tablet-based measures, vocal acoustic analysis, and several other transducer-based methods were identified by searching PubMed.gov. The availability, use, acceptability, reliability, validity, and responsiveness were reviewed for each measure using the following criteria: (1) used in the assessment of tremor; (2) used in published studies by people other than the developers; and (3) adequate clinimetric testing. Accelerometry, gyroscopy, electromyography, and digitizing tablet-based measures fulfilled all three criteria. Compared to rating scales, transducers are far more sensitive to changes in tremor amplitude and frequency, but they do not appear to be more capable of detecting a change that exceeds random variability in tremor amplitude (minimum detectable change). The use of transducer-based measures requires careful attention to their limitations and validity in a particular clinical or research setting. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Usher syndrome with psychotic symptoms: two cases in the same family.

PubMed

Wu, Chen-Ying; Chiu, Chih-Chiang

2006-10-01

Usher syndrome is a heterogeneous autosomal recessive disorder characterized by hearing and visual sensory impairment. Retinitis pigmentosa is essential for its diagnosis. There are only a few reports describing patients with Usher syndrome presenting with psychotic features and the etiology of its psychiatric manifestation is still unknown. Herein, the authors report variable congenital hearing impairment and progressive visual loss occurring in five of seven family members and two of them meeting the diagnostic criteria of Usher syndrome with psychotic features. Furthermore, the authors compare their psychiatric symptoms with other reports and the possible etiologies of psychotic symptoms are discussed.

Relationship between neural rhythm generation disorders and physical disabilities in Parkinson's disease patients' walking.

PubMed

Ota, Leo; Uchitomi, Hirotaka; Ogawa, Ken-ichiro; Orimo, Satoshi; Miyake, Yoshihiro

2014-01-01

Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson's disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients' walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent α. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and α. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and α to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn-Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, α differentiated obvious-PRD from mild-PRD. Considering α reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have potential to evaluate the symptoms of PD.

Phenotypic variability in gap junction syndromic skin disorders: experience from KID and Clouston syndromes' clinical diagnostics.

PubMed

Kutkowska-Kaźmierczak, Anna; Niepokój, Katarzyna; Wertheim-Tysarowska, Katarzyna; Giza, Aleksandra; Mordasewicz-Goliszewska, Maria; Bal, Jerzy; Obersztyn, Ewa

2015-08-01

Connexins belong to the family of gap junction proteins which enable direct cell-to-cell communication by forming channels in adjacent cells. Mutations in connexin genes cause a variety of human diseases and, in a few cases, result in skin disorders. There are significant differences in the clinical picture of two rare autosomal dominant syndromes: keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (Clouston syndrome), which are caused by GJB2 and GJB6 mutations, respectively. This is despite the fact that, in both cases, malfunctioning of the same family proteins and some overlapping clinical features (nail dystrophy, hair loss, and palmoplantar keratoderma) is observed. KID syndrome is characterized by progressive vascularizing keratitis, ichthyosiform erythrokeratoderma, and neurosensory hearing loss, whereas Clouston syndrome is characterized by nail dystrophy, hypotrichosis, and palmoplantar keratoderma. The present paper presents a Polish patient with sporadic KID syndrome caused by the mutation of p.Asp50Asn in GJB2. The patient encountered difficulties in obtaining a correct diagnosis. The other case presented is that of a family with Clouston syndrome (caused by p.Gly11Arg mutation in GJB6), who are the first reported patients of Polish origin suffering from this disorder. Phenotype diversity among patients with the same genotypes reported to date is also summarized. The conclusion is that proper diagnosis of these syndromes is still challenging and should always be followed by molecular verification.

Clinical status of comorbid bipolar disorder and borderline personality disorder.

PubMed

Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

2016-09-01

The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

An introduction to the clinical phenomenology of Tourette syndrome.

PubMed

Martino, Davide; Madhusudan, Namrata; Zis, Panagiotis; Cavanna, Andrea E

2013-01-01

Tourette syndrome (TS) is the primary tic disorder that reaches most commonly medical attention and monitoring, with an estimated prevalence close to 1% between 5 and 18 years of age. Motor and phonic tics are the core features of TS. In addition to their well-characterized phenomenology, tics display a peculiar variability over time, which is strongly influenced by a variety of contextual factors. The sensory phenomena of TS are increasingly recognized as another crucial symptom of TS and consist of premonitory urges and somatic hypersensitivity. A relevant proportion of patients with TS display complex, tic-like, repetitive behaviors that include echophenomena, coprophenomena, and nonobscene socially inappropriate behaviors (NOSIBs). The burden of behavioral comorbidities is very important in determining the degree of disability of TS patients. Only a small minority of TS patients presents exclusively with a tic disorder. Obsessive-compulsive symptoms and related disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. Probably, the presence of comorbid attention deficit hyperactivity disorder (ADHD) is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Affective disorders, impulse control disorders, autism spectrum disorders, and personality disorders complete the wide psychopathological spectrum of this condition, but have been less investigated than OCD and ADHD. The complexity of the Tourette spectrum has been confirmed by cluster and factor analytical approaches, and is likely to inform the study of the genetic basis of this disorder, as well as future reappraisal of its nosography, with the development of novel clinical subtypes. © 2013 Elsevier Inc. All rights reserved.

Biochemical Characterization of Prions.

PubMed

Fiorini, Michele; Bongianni, Matilde; Monaco, Salvatore; Zanusso, Gianluigi

2017-01-01

Prion disease or transmissible spongiform encephalopathies are characterized by the presence of the abnormal form of the prion protein (PrP Sc ). The pathological and transmissible properties of PrP Sc are enciphered in its secondary and tertiary structures. Since it's well established that different strains of prions are linked to different conformations of PrP Sc , biochemical characterization of prions seems a preliminary but reliable approach to detect, analyze, and compare prion strains. Experimental biochemical procedures might be helpful in distinguishing PrP Sc physicochemical properties and include resistance to proteinase K (PK) digestion, insolubility in nonionic detergents, PK-resistance under denaturing conditions and sedimentation properties in sucrose gradients. This biochemical approach has been extensively applied in human prion disorders and subsequently expanded for PrP Sc characterization in animals. In particular, in sporadic Creutzfedlt-Jakob disease (sCJD) PrP Sc is characterized by two main glycotypes conventionally named Type 1 and Type 2, based on the apparent gel migration at 21 and 19kDa of the PrP Sc PK-resistant fragment. An additional PrP Sc type was identified in sCJD characterized by an unglycosylated dominant glycoform pattern and in 2010 a variably protease-sensitive prionopathy (VPSPr) was reported showing a PrP Sc with an electrophoretic ladder like pattern. Additionally, the presence of PrP Sc truncated fragments completes the electrophoretic characterization of different prion strains. By two-dimensional (2D) electrophoretic analysis additional PrP Sc pattern was identified, since this procedure provides information about the isoelectric point and the different peptides length related to PK cleavage, as well as to glycosylation extent or GPI anchor presence. We here provide and extensive review on PrP Sc biochemical analysis in human and animal prion disorders. Further, we show that PrP Sc glycotypes observed in CJD share similarities with PrP Sc in bovine spongiform encephalopathy forms (BSE). © 2017 Elsevier Inc. All rights reserved.

Depression, Impulse Control Disorder, and Life Style According to Smartphone Addiction.

PubMed

Kim, E Y; Joo, S W; Han, S J; Kim, M J; Choi, S Y

2017-01-01

We examined depression, impulse control disorder, and life style by degree of smartphone addiction. Chi-square tests and ANOVA were used to identify significant variables. CART was used to generate a decision making diagram of variables affecting smartphone addiction. The severe smartphone addiction group had rates of depression and impulse control disorder than the initial smartphone group.

Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

PubMed

Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

2016-02-28

The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

PubMed

Galimberti, Daniela; Prunas, Cecilia; Paoli, Riccardo A; Dell'Osso, Bernardo; Fenoglio, Chiara; Villa, Chiara; Palazzo, Carlotta; Cigliobianco, Michela; Camuri, Giulia; Serpente, Maria; Scarpini, Elio; Altamura, A Carlo

2014-11-01

Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examining Differences between Students with Specific Learning Disabilities and Those with Specific Language Disorders on Cognition, Emotions and Psychopathology

ERIC Educational Resources Information Center

Filippatou, Diamanto; Dimitropoulou, Panagiota; Sideridis, Georgios

2009-01-01

The purpose of the present study was to investigate the differences between students with LD and SLI on emotional psychopathology and cognitive variables. In particular, the study examined whether cognitive, emotional, and psychopathology variables are significant discriminatory variables of speech and language disordered groups versus those…

Family Histories of Anxiety in Overweight Men and Women with Binge Eating Disorder: A Preliminary Investigation

PubMed Central

Blomquist, Kerstin K.; Grilo, Carlos M.

2015-01-01

Objective A preliminary examination of the significance of family histories of anxiety in the expression of binge eating disorder (BED) and associated functioning. Methods Participants were 166 overweight patients with BED assessed using diagnostic interviews. Participants were administered a structured psychiatric history interview about their first-degree relatives (parents, siblings, children) (N=897) to determine lifetime diagnoses of DSM-IV anxiety disorders and completed a battery of questionnaires assessing current and historical eating and weight variables and associated psychological functioning (depression). Results BED patients with a family history of anxiety disorder were significantly more likely than BED patients without a family history of anxiety disorder to have lifetime diagnoses of anxiety disorders and mood disorders but not substance use disorders. A family history of anxiety was not significantly associated with timing or sequencing of age at onset of anxiety disorder, binge eating, dieting, or obesity, or with variability in current levels of binge eating, eating disorder psychopathology, or psychological functioning. Conclusions Although replication with direct interview method is needed, our preliminary findings suggest that a family history of anxiety confers greater risk for comorbid anxiety and mood disorders but is largely unrelated to the development of binge eating, dieting, or obesity and unrelated to variability in eating disorder psychopathology or psychological functioning in overweight patients with BED. PMID:26343481

Decomposing ADHD-Related Effects in Response Speed and Variability

PubMed Central

Karalunas, Sarah L.; Huang-Pollock, Cynthia L.; Nigg, Joel T.

2012-01-01

Objective Slow and variable reaction times (RTs) on fast tasks are such a prominent feature of Attention Deficit Hyperactivity Disorder (ADHD) that any theory must account for them. However, this has proven difficult because the cognitive mechanisms responsible for this effect remain unexplained. Although speed and variability are typically correlated, it is unclear whether single or multiple mechanisms are responsible for group differences in each. RTs are a result of several semi-independent processes, including stimulus encoding, rate of information processing, speed-accuracy trade-offs, and motor response, which have not been previously well characterized. Method A diffusion model was applied to RTs from a forced-choice RT paradigm in two large, independent case-control samples (NCohort 1= 214 and N Cohort 2=172). The decomposition measured three validated parameters that account for the full RT distribution, and assessed reproducibility of ADHD effects. Results In both samples, group differences in traditional RT variables were explained by slow information processing speed, and unrelated to speed-accuracy trade-offs or non-decisional processes (e.g. encoding, motor response). Conclusions RT speed and variability in ADHD may be explained by a single information processing parameter, potentially simplifying explanations that assume different mechanisms are required to account for group differences in the mean and variability of RTs. PMID:23106115

Risk factors for eating disorders in Greek- and Anglo-Australian adolescent girls.

PubMed

Mildred, H; Paxton, S J; Wertheim, E H

1995-01-01

Past research indicates ethnicity may be related to eating disorder and related risk factors. The present study examines risk factors for eating disorders in 50 Anglo- and 50 Greek-Australian girls (mean age = 13.5 years). The variables assessed included bulimic tendencies, body dissatisfaction, use of extreme weight loss behaviors (EWLBs), self-esteem, depression and family cohesion and adaptability. Cultural eating patterns were also explored. A stepwise discriminant function analysis to examine whether the two groups could be discriminated on these variables was significant and correctly classified 73.9% of the sample, the chief discriminating variables being Pressure to Eat, EWLBs, and Family Adaptability. Univariate analyses indicated differences between the groups on Pressure to Eat, Family Adaptability, and Mother's Shape. Although the groups were discriminable, a number of variables generally associated with eating disorder did not contribute to the function. These data are discussed in terms of cultural assimilation.

Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder: A Danish National Register-Based Study.

PubMed

Musliner, Katherine L; Munk-Olsen, Trine; Laursen, Thomas M; Eaton, William W; Zandi, Peter P; Mortensen, Preben B

2016-04-01

Evidence suggests that long-term trajectories of major depressive disorder (MDD) are heterogeneous. The Danish Psychiatric Central Research Register (DPCRR) provides a rare opportunity to examine patterns and correlates of long-term trajectories in a large sample of patients with moderate to severe MDD. To characterize patterns and correlates of 10-year course trajectories of MDD in the DPCRR. A cohort containing 11 640 individuals born in Denmark in 1955 or later with their first recorded MDD diagnosis in the DPCRR between 1995 and 2002 was established. Patients were followed for 10 years from the date of their initial MDD diagnosis. Data were obtained from Danish civil and psychiatric national registers in June 2013 and were analyzed from April 4, 2014, to December 17, 2015. Correlates of trajectory class membership were sex, characteristics of the first recorded MDD episode (ie, age, severity, inpatient treatment, and record of suicide attempt or self-harm), and psychiatric diagnoses in parents (ie, depression, bipolar disorder, schizophrenia-spectrum disorders, substance abuse, and anxiety or somatoform disorders). The outcome variable was past-year contact at a psychiatric hospital with a main diagnosis of MDD during each of the 10 years following the initial MDD diagnosis. Trajectories were modeled using latent class growth analysis. The sample included 11 640 individuals (7493 [64.4%] women) aged 18 to 48 years (mean [SD], 31.4 [7.3]) at their first recorded MDD diagnosis. Four trajectory classes were identified: brief contact (77.0%) (characterized by low probability of contact after 2 years); prolonged initial contact (12.8%) (characterized by high decreasing probability of contact during the first 5 years); later reentry (7.1%) (characterized by moderate probability of contact during the second 5 years); and persistent contact (3.1%) (characterized by high or moderate probability of contact throughout). Female sex (odds ratio [OR] range, 1.82-2.22), inpatient treatment (OR range, 1.40-1.50), and severity at first recorded MDD episode (OR range: moderate, 1.61-1.84; severe, 1.93-2.23; and psychotic, 2.73-3.07) were associated with more severe trajectories. Parental anxiety (OR, 1.34 [95% CI, 1.10-1.63]) and depression (OR, 1.63 [95% CI, 1.28-2.09]) were associated with the prolonged initial contact and later reentry classes, respectively. Parental schizophrenia was associated with the persistent contact class (OR range, 2.55-3.04). Most people treated for moderate to severe MDD in Danish psychiatric hospitals do not receive additional MDD treatment after 2 years; however, a minority receive specialty treatment for up to a decade. Observable heterogeneity in the course may be indicative of underlying etiologic differences.

[Minimal emotional dysfunction and first impression formation in personality disorders].

PubMed

Linden, M; Vilain, M

2011-01-01

"Minimal cerebral dysfunctions" are isolated impairments of basic mental functions, which are elements of complex functions like speech. The best described are cognitive dysfunctions such as reading and writing problems, dyscalculia, attention deficits, but also motor dysfunctions such as problems with articulation, hyperactivity or impulsivity. Personality disorders can be characterized by isolated emotional dysfunctions in relation to emotional adequacy, intensity and responsivity. For example, paranoid personality disorders can be characterized by continuous and inadequate distrust, as a disorder of emotional adequacy. Schizoid personality disorders can be characterized by low expressive emotionality, as a disorder of effect intensity, or dissocial personality disorders can be characterized by emotional non-responsivity. Minimal emotional dysfunctions cause interactional misunderstandings because of the psychology of "first impression formation". Studies have shown that in 100 ms persons build up complex and lasting emotional judgements about other persons. Therefore, minimal emotional dysfunctions result in interactional problems and adjustment disorders and in corresponding cognitive schemata.From the concept of minimal emotional dysfunctions specific psychotherapeutic interventions in respect to the patient-therapist relationship, the diagnostic process, the clarification of emotions and reality testing, and especially an understanding of personality disorders as impairment and "selection, optimization, and compensation" as a way of coping can be derived.

Altered Heart Rate Variability During Gaming in Internet Gaming Disorder.

PubMed

Lee, Deokjong; Hong, Sung Jun; Jung, Young-Chul; Park, Jinsick; Kim, In Young; Namkoong, Kee

2018-04-01

Internet gaming disorder (IGD) is characterized by addiction to online gaming and reduced executive control, particularly when individuals are exposed to gaming-related cues. Executive control can be measured as vagally mediated heart rate variability (HRV), which corresponds to variability in the time interval between heart beats. In this study, we investigated whether individuals with IGD have altered HRV while playing online games. We hypothesized that while gaming, individuals with IGD would exhibit phasic suppression of vagally mediated HRV, which would reflect executive control dysfunction during game play. To test this, we measured the changes of HRV when young males with IGD were engaged in real-time online gaming. The changes of HRV were associated with the severity of IGD assessed by self-reports and prefrontal gray matter volume (GMV) calculated by voxel-based morphometry. We included 23 IGD subjects and 18 controls in our analyses. Changes in HRV were not statistically different between IGD subjects and controls. Within the IGD group, however, subjects showed significant decreases in high-frequency (HF) HRV during gaming. Furthermore, the degree of decrease correlated with IGD severity and prefrontal GMV. Importantly, this phasic suppression of HF-HRV in response to gaming did not occur in control subjects. In conclusion, young males with IGD showed an altered HRV response while playing an online game, reflecting their difficulties in executive control over gaming. The dynamics between executive control and reward seeking may be out of balance during game play in IGD.

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

PubMed Central

Willemsen, Marjolein H; Fernandez, Bridget A; Bacino, Carlos A; Gerkes, Erica; de Brouwer, Arjan PM; Pfundt, Rolph; Sikkema-Raddatz, Birgit; Scherer, Stephen W; Marshall, Christian R; Potocki, Lorraine; van Bokhoven, Hans; Kleefstra, Tjitske

2010-01-01

The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes. PMID:19920853

Sleep Disturbances in Child and Adolescent Mental Health Disorders: A Review of the Variability of Objective Sleep Markers.

PubMed

Baddam, Suman K R; Canapari, Craig A; van Noordt, Stefon J R; Crowley, Michael J

2018-06-04

Sleep disturbances are often observed in child and adolescent mental health disorders. Although previous research has identified consistent subjective reports of sleep disturbances, specific objective sleep markers have not yet been identified. We evaluated the current research on subjective and objective sleep markers in relation to attention deficit hyperactivity disorders, autism spectrum disorders, anxiety and depressive disorders. Subjective sleep markers are more consistent than objective markers of actigraphy, polysomnography, and circadian measures. We discuss the causes of variability in objective sleep findings and suggest future directions for research.

Chrna7 deficient mice manifest no consistent neuropsychiatric and behavioral phenotypes.

PubMed

Yin, Jiani; Chen, Wu; Yang, Hongxing; Xue, Mingshan; Schaaf, Christian P

2017-01-03

The alpha7 nicotinic acetylcholine receptor, encoded by the CHRNA7 gene, has been implicated in various psychiatric and behavioral disorders, including schizophrenia, bipolar disorder, epilepsy, autism, Alzheimer's disease, and Parkinson's disease, and is considered a potential target for therapeutic intervention. 15q13.3 microdeletion syndrome is a rare genetic disorder, caused by submicroscopic deletions on chromosome 15q. CHRNA7 is the only gene in this locus that has been deleted entirely in cases involving the smallest microdeletions. Affected individuals manifest variable neurological and behavioral phenotypes, which commonly include developmental delay/intellectual disability, epilepsy, and autism spectrum disorder. Subsets of patients have short attention spans, aggressive behaviors, mood disorders, or schizophrenia. Previous behavioral studies suggested that Chrna7 deficient mice had attention deficits, but were normal in baseline behavioral responses, learning, memory, and sensorimotor gating. Given a growing interest in CHRNA7-related diseases and a better appreciation of its associated human phenotypes, an in-depth behavioral characterization of the Chrna7 deficient mouse model appeared prudent. This study was designed to investigate whether Chrna7 deficient mice manifest phenotypes related to those seen in human individuals, using an array of 12 behavioral assessments and electroencephalogram (EEG) recordings on freely-moving mice. Examined phenotypes included social interaction, compulsive behaviors, aggression, hyperactivity, anxiety, depression, and somatosensory gating. Our data suggests that mouse behavior and EEG recordings are not sensitive to decreased Chrna7 copy number.

Use of the TAT in the assessment of DSM-IV cluster B personality disorders.

PubMed

Ackerman, S J; Clemence, A J; Weatherill, R; Hilsenroth, M J

1999-12-01

The Social Cognition and Object Relations Scale (SCORS), developed by Western, Lohr, Silk, Kerber, and Goodrich (1985), is a diagnostic instrument used to assess an array of psychological functioning by using clinical narratives such as the Thematic Apperception Test (TAT; Murray, 1943) stories. This study investigated the utility of the SCORS to differentiate between Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) antisocial personality disorder (ANPD), borderline personality disorder (BPD), narcissistic personality disorder (NPD), and Cluster C personality disorder (CPD). A sample of 58 patients was separated into four groups: ANPD (n = 9), BPD (n = 21; 18 with a primary BPD diagnosis and 3 with prominent borderline traits who met 4 of the 5 DSM-IV criteria necessary for a BPD diagnosis), NPD (n = 16; 8 with a primary NPD diagnosis and 8 with prominent narcissistic traits who met 4 of the 5 DSM-IV criteria necessary for a NPD diagnosis), and CPD (n = 12). These groups were then compared on the 8 SCORS variables by using 5 TAT cards (1, 2, 3BM, 4, and 13MF). Spearman-Brown correction for 2-way mixed effects model of reliability for the 8 SCORS variables ranged from .70 to .95. The results of categorical and dimensional analyses indicate that (a) SCORS variables can be used to differentiate ANPD, BPD, and NPD; (b) the BPD group scored significantly lower (greater maladjustment) than did the CPD group on certain variables; (c) the BPD group scored significantly lower (greater maladjustment) than did the NPD group on all 8 SCORS variables; (d) the ANPD group scored significantly lower than did the NPD group on certain variables; (e) certain variables were found to be empirically related to the total number of DSM-IV ANPD, BPD, and NPD criteria; and (f) certain variables were found to be empirically related to Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Personality disorder scales. The results of this study are discussed in terms of clinical utility, conceptual, and theoretical implications.

Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Richey, J. Anthony; Damiano, Cara R.; Sabatino, Antoinette; Rittenberg, Alison; Petty, Chris; Bizzell, Josh; Voyvodic, James; Heller, Aaron S.; Coffman, Marika C.; Smoski, Moria; Davidson, Richard J.; Dichter, Gabriel S.

2015-01-01

Autism spectrum disorder (ASD) is characterized by high rates of comorbid internalizing and externalizing disorders. One mechanistic account of these comorbidities is that ASD is characterized by impaired emotion regulation (ER) that results in deficits modulating emotional responses. We assessed neural activation during cognitive reappraisal of…

Family accommodation in obsessive-compulsive disorder: Relation to symptom dimensions, clinical and family characteristics.

PubMed

Albert, Umberto; Bogetto, Filippo; Maina, Giuseppe; Saracco, Paola; Brunatto, Cinthia; Mataix-Cols, David

2010-09-30

Family accommodation is the term used to indicate the process whereby family members of patients with obsessive-compulsive disorder (OCD) assist or participate in the patients' rituals. Family accommodation is a relatively under-researched phenomenon in OCD but an important one because it may be predictive of poor treatment outcome. This study systematically examined several socio-demographic and clinical variables that are associated with family accommodation in a well-characterized sample of adult patients and their healthy family members. Experienced clinicians administered the Family Accommodation Scale (FAS) to 141 psychopathology-free family members cohabiting with 97 patients with OCD. The items of the FAS were first subjected to principal component analysis (PCA) and the resulting domains of family accommodation (Participation, Modification, and Distress and Consequences) introduced as dependent variables in a series of multiple regression models assessing the relationship between family accommodation domains and a wide range of clinical variables, including Axis I and II psychopathology and symptom dimensions derived from the Yale-Brown Obsessive-Compulsive Scale (YBOCS) Symptom Checklist. The results showed that family accommodation was common, with the provision of reassurance, participation in rituals and assisting the patient in avoidance being the most frequent practices (occurring on a daily basis in 47%, 35%, and 43% of family members, respectively). The PCA of the YBOCS Symptom Checklist yielded four symptom dimensions, which were identical to those previously identified in the international literature. Multiple linear regression analyses showed that a higher score on the contamination/washing symptom dimension and a positive family history for an anxiety disorder other than OCD (referring to a family member other than the participant in this study) predicted greater scores on several domains of family accommodation. Our study confirms that family accommodation is frequent and distressing in psychopathology-free family members cohabiting with adult OCD patients. Family accommodation is particularly frequent and distressing when the patient has prominent contamination/washing symptoms and/or when another family member has a history of an anxiety disorder. Such families may be more likely to benefit from family-based interventions but this remains to be tested in controlled trials. Copyright © 2009 Elsevier Ltd. All rights reserved.

Alexithymia and illness behaviour among female Indian outpatients with multiple somatic symptoms

PubMed Central

Sarkar, Jaydip; Chandra, Prabha

2003-01-01

Sixty Indian muslim women outpatients with multiple somatic complaints of nonorganic origin were assessed for alexithymia and abnormal illness behavior using the Toronto Alexithymia Scale (TAS) and the Illness Behaviour Assessment Schedule (IBAS). Alexithymia represented by TAS scores correlated best with the IBAS variables of communication of affect, somatic illness causal beliefs and denial. Correlation with other IBAS variables was modest to poor.There was no correlation of IBAS variables with age of patient, duration of illness or nature of diagnosis: somatoform disorder or anxiety and depressive disorders, The study showed that alexithymia and illness behaviour are overlapping constructs and confirmed the usefulness of TAS as an instrument to discriminate between patients with anxiety/ depressive disorders and somatoform disorders PMID:21206863

Attention bias in adults with anorexia nervosa, obsessive-compulsive disorder, and social anxiety disorder

PubMed Central

Schneier, Franklin R.; Kimeldorf, Marcia B.; Choo, Tse; Steinglass, Joanna E.; Wall, Melanie; Fyer, Abby J.; Simpson, H. Blair

2016-01-01

Background Attention bias to threat (selective attention toward threatening stimuli) has been frequently found in anxiety disorder samples, but its distribution both within and beyond this category is unclear. Attention bias has been studied extensively in social anxiety disorder (SAD) but relatively little in obsessive compulsive disorder (OCD), historically considered an anxiety disorder, or anorexia nervosa (AN), which is often characterized by interpersonal as well as body image/eating fears. Methods Medication-free adults with SAD (n=43), OCD (n=50), or AN (n=30), and healthy control volunteers (HC, n=74) were evaluated for attention bias with an established dot probe task presenting images of angry and neutral faces. Additional outcomes included attention bias variability (ABV), which summarizes fluctuation in attention between vigilance and avoidance, and has been reported to have superior reliability. We hypothesized that attention bias would be elevated in SAD and associated with SAD severity. Results Attention bias in each disorder did not differ from HC, but within the SAD group attention bias correlated significantly with severity of social avoidance. ABV was significantly lower in OCD versus HC, and it correlated positively with severity of OCD symptoms within the OCD group. Conclusions Findings do not support differences from HC in attention bias to threat faces for SAD, OCD, or AN. Within the SAD sample, the association of attention bias with severity of social avoidance is consistent with evidence that attention bias moderates development of social withdrawal. The association of ABV with OCD diagnosis and severity is novel and deserves further study. PMID:27174402

The 1% of the population accountable for 63% of all violent crime convictions.

PubMed

Falk, Orjan; Wallinius, Märta; Lundström, Sebastian; Frisell, Thomas; Anckarsäter, Henrik; Kerekes, Nóra

2014-04-01

Population-based studies on violent crime and background factors may provide an understanding of the relationships between susceptibility factors and crime. We aimed to determine the distribution of violent crime convictions in the Swedish population 1973-2004 and to identify criminal, academic, parental, and psychiatric risk factors for persistence in violent crime. The nationwide multi-generation register was used with many other linked nationwide registers to select participants. All individuals born in 1958-1980 (2,393,765 individuals) were included. Persistent violent offenders (those with a lifetime history of three or more violent crime convictions) were compared with individuals having one or two such convictions, and to matched non-offenders. Independent variables were gender, age of first conviction for a violent crime, nonviolent crime convictions, and diagnoses for major mental disorders, personality disorders, and substance use disorders. A total of 93,642 individuals (3.9%) had at least one violent conviction. The distribution of convictions was highly skewed; 24,342 persistent violent offenders (1.0% of the total population) accounted for 63.2% of all convictions. Persistence in violence was associated with male sex (OR 2.5), personality disorder (OR 2.3), violent crime conviction before age 19 (OR 2.0), drug-related offenses (OR 1.9), nonviolent criminality (OR 1.9), substance use disorder (OR 1.9), and major mental disorder (OR 1.3). The majority of violent crimes are perpetrated by a small number of persistent violent offenders, typically males, characterized by early onset of violent criminality, substance abuse, personality disorders, and nonviolent criminality.

Neuroanatomical phenotypes in mental illness: identifying convergent and divergent cortical phenotypes across autism, ADHD and schizophrenia.

PubMed

Park, Min Tae M; Raznahan, Armin; Shaw, Philip; Gogtay, Nitin; Lerch, Jason P; Chakravarty, M Mallar

2018-05-01

There is evidence suggesting neuropsychiatric disorders share genomic, cognitive and clinical features. Here, we ask if autism-spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and schizophrenia share neuroanatomical variations. First, we used measures of cortical anatomy to estimate spatial overlap of neuroanatomical variation using univariate methods. Next, we developed a novel methodology to determine whether cortical deficits specifically target or are "enriched" within functional resting-state networks. We found cortical anomalies were preferentially enriched across functional networks rather than clustering spatially. Specifically, cortical thickness showed significant enrichment between patients with ASD and those with ADHD in the default mode network, between patients with ASD and those with schizophrenia in the frontoparietal and limbic networks, and between patients with ADHD and those with schizophrenia in the ventral attention network. Networks enriched in cortical thickness anomalies were also strongly represented in functional MRI results (Neurosynth; r = 0.64, p = 0.032). We did not account for variable symptom dimensions and severity in patient populations, and our cross-sectional design prevented longitudinal analyses of developmental trajectories. These findings suggest that common deficits across neuropsychiatric disorders cannot simply be characterized as arising out of local changes in cortical grey matter, but rather as entities of both local and systemic alterations targeting brain networks.

Sociodemographic and clinical differences between suicide ideators and attempters: a study of mood disordered patients 50 years and older.

PubMed

Pompili, Maurizio; Innamorati, Marco; Di Vittorio, Cristina; Sher, Leo; Girardi, Paolo; Amore, Mario

2014-02-01

Our study sought to characterize mood disordered suicide ideators and attempters 50 years and older admitted to a psychiatric ward either for a recent suicide attempt or for ongoing suicidal ideation. We enrolled 50 patients with suicide ideation consecutively admitted to an inpatient department and 50 patients admitted for a suicide attempt made in the last 48 hours. Suicide attempters more frequently had low social support and an age of onset of mood disorder of 46 years and older, and less frequently had a history of suicidal behaviors in the family members and pharmacological treatment, despite the fact that the groups did not differ with regard to antidepressants prescribed. The groups were not distinguishable based on several variables assumed to be risk factors for suicide behavior, such as proximal life events and stressors or alcohol use disorders. In both samples, comorbidity with organic diseases, the presence of stressful life events in the past 12 months, and a diagnosis of major depression were frequently reported. In conclusion, the presence of low social support and the absence of a pharmacotherapy may increase suicidal behaviors in patients at risk. © 2013 The American Association of Suicidology.

Neuroanatomical phenotypes in mental illness: identifying convergent and divergent cortical phenotypes across autism, ADHD and schizophrenia.

PubMed

Park, Min Tae M; Raznahan, Armin; Shaw, Philip; Gogtay, Nitin; Lerch, Jason P; Chakravarty, M Mallar

2018-02-05

There is evidence suggesting neuropsychiatric disorders share genomic, cognitive and clinical features. Here, we ask if autism-spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and schizophrenia share neuroanatomical variations. First, we used measures of cortical anatomy to estimate spatial overlap of neuroanatomical variation using univariate methods. Next, we developed a novel methodology to determine whether cortical deficits specifically target or are "enriched" within functional resting-state networks. We found cortical anomalies were preferentially enriched across functional networks rather than clustering spatially. Specifically, cortical thickness showed significant enrichment between patients with ASD and those with ADHD in the default mode network, between patients with ASD and those with schizophrenia in the frontoparietal and limbic networks, and between patients with ADHD and those with schizophrenia in the ventral attention network. Networks enriched in cortical thickness anomalies were also strongly represented in functional MRI results (Neurosynth; r = 0.64, p = 0.032). We did not account for variable symptom dimensions and severity in patient populations, and our cross-sectional design prevented longitudinal analyses of developmental trajectories. These findings suggest that common deficits across neuropsychiatric disorders cannot simply be characterized as arising out of local changes in cortical grey matter, but rather as entities of both local and systemic alterations targeting brain networks.

Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

PubMed

Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

2014-04-10

In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

A Cognitive Dimensional Approach to Understanding Shared and Unique Contributions to Reading, Math, and Attention Skills.

PubMed

Child, Amanda E; Cirino, Paul T; Fletcher, Jack M; Willcutt, Erik G; Fuchs, Lynn S

2018-05-01

Disorders of reading, math, and attention frequently co-occur in children. However, it is not yet clear which cognitive factors contribute to comorbidities among multiple disorders and which uniquely relate to one, especially because they have rarely been studied as a triad. Thus, the present study considers how reading, math, and attention relate to phonological awareness, numerosity, working memory, and processing speed, all implicated as either unique or shared correlates of these disorders. In response to findings that the attributes of all three disorders exist on a continuum rather than representing qualitatively different groups, this study employed a dimensional approach. Furthermore, we used both timed and untimed academic variables in addition to attention and activity level variables. The results supported the role of working memory and phonological awareness in the overlap among reading, math, and attention, with a limited role of processing speed. Numerosity was related to the comorbidity between math and attention. The results from timed variables and activity level were similar to those from untimed and attention variables, although activity level was less strongly related to cognitive and academic/attention variables. These findings have implications for understanding cognitive deficits that contribute to comorbid reading disability, math disability, and/or attention-deficit/hyperactivity disorder.

Mental health trajectories from adolescence to adulthood: Language disorder and other childhood and adolescent risk factors.

PubMed

Bao, Lin; Brownlie, E B; Beitchman, Joseph H

2016-05-01

Longitudinal research on mental health development beyond adolescence among nonclinical populations is lacking. This study reports on psychiatric disorder trajectories from late adolescence to young adulthood in relation to childhood and adolescent risk factors. Participants were recruited for a prospective longitudinal study tracing a community sample of 5-year-old children with communication disorders and a matched control cohort to age 31. Psychiatric disorders were measured at ages 19, 25, and 31. Known predictors of psychopathology and two school-related factors specifically associated with language disorder (LD) were measured by self-reports and semistructured interviews. The LD cohort was uniquely characterized by a significantly decreasing disorder trajectory in early adulthood. Special education was associated with differential disorder trajectories between LD and control cohorts, whereas maltreatment history, specific learning disorder, family structure, and maternal psychological distress were associated with consistent trajectories between cohorts. From late adolescence to young adulthood, childhood LD was characterized by a developmentally limited course of psychiatric disorder; maltreatment was consistently characterized by an elevated risk of psychiatric disorder regardless of LD history, whereas special education was associated with significantly decreasing risk of psychiatric disorder only in the presence of LD.

Responsibility for managing musculoskeletal disorders--a cross-sectional postal survey of attitudes.

PubMed

Larsson, Maria E H; Nordholm, Lena A

2008-08-05

Musculoskeletal disorders are a major burden on individuals, health systems and social care systems and rehabilitation efforts in these disorders are considerable. Self-care is often considered a cost effective treatment alternative owing to limited health care resources. But what are the expectations and attitudes in this question in the general population? The purpose of this study was to describe general attitudes to responsibility for the management of musculoskeletal disorders and to explore associations between attitudes and background variables. A cross-sectional, postal questionnaire survey was carried out with a random sample of a general adult Swedish population of 1770 persons. Sixty-one percent (n = 1082) responded to the questionnaire and was included for the description of general attitudes towards responsibility for the management of musculoskeletal disorders. For the further analyses of associations to background variables 683-693 individuals could be included. Attitudes were measured by the "Attitudes regarding Responsibility for Musculoskeletal disorders" (ARM) instrument, where responsibility is attributed on four dimensions; to myself, as being out of my hands, to employers or to (medical) professionals. Multiple logistic regression was used to explore associations between attitudes to musculoskeletal disorders and the background variables age, sex, education, physical activity, presence of musculoskeletal disorders, sick leave and whether the person had visited a care provider. A majority of participants had internal views, i.e. showed an attitude of taking personal responsibility for musculoskeletal disorders, and did not place responsibility for the management out of their own hands or to employers. However, attributing shared responsibility between self and medical professionals was also found. The main associations found between attitude towards responsibility for musculoskeletal disorders and investigated background variables were that physical inactivity (OR 2.92-9.20), musculoskeletal disorder related sick leave (OR 2.31-3.07) and no education beyond the compulsory level (OR 3.12-4.76) increased the odds of attributing responsibility externally, i.e placing responsibility on someone or something else. Respondents in this study mainly saw themselves as responsible for managing musculoskeletal disorders. The associated background variables refined this finding and one conclusion is that, to optimise outcome when planning the prevention, treatment and management of these disorders, people's attitudes should be taken into account.

Responsibility for managing musculoskeletal disorders – A cross-sectional postal survey of attitudes

PubMed Central

Larsson, Maria EH; Nordholm, Lena A

2008-01-01

Background Musculoskeletal disorders are a major burden on individuals, health systems and social care systems and rehabilitation efforts in these disorders are considerable. Self-care is often considered a cost effective treatment alternative owing to limited health care resources. But what are the expectations and attitudes in this question in the general population? The purpose of this study was to describe general attitudes to responsibility for the management of musculoskeletal disorders and to explore associations between attitudes and background variables. Methods A cross-sectional, postal questionnaire survey was carried out with a random sample of a general adult Swedish population of 1770 persons. Sixty-one percent (n = 1082) responded to the questionnaire and was included for the description of general attitudes towards responsibility for the management of musculoskeletal disorders. For the further analyses of associations to background variables 683–693 individuals could be included. Attitudes were measured by the "Attitudes regarding Responsibility for Musculoskeletal disorders" (ARM) instrument, where responsibility is attributed on four dimensions; to myself, as being out of my hands, to employers or to (medical) professionals. Multiple logistic regression was used to explore associations between attitudes to musculoskeletal disorders and the background variables age, sex, education, physical activity, presence of musculoskeletal disorders, sick leave and whether the person had visited a care provider. Results A majority of participants had internal views, i.e. showed an attitude of taking personal responsibility for musculoskeletal disorders, and did not place responsibility for the management out of their own hands or to employers. However, attributing shared responsibility between self and medical professionals was also found. The main associations found between attitude towards responsibility for musculoskeletal disorders and investigated background variables were that physical inactivity (OR 2.92–9.20), musculoskeletal disorder related sick leave (OR 2.31–3.07) and no education beyond the compulsory level (OR 3.12–4.76) increased the odds of attributing responsibility externally, i.e placing responsibility on someone or something else. Conclusion Respondents in this study mainly saw themselves as responsible for managing musculoskeletal disorders. The associated background variables refined this finding and one conclusion is that, to optimise outcome when planning the prevention, treatment and management of these disorders, people's attitudes should be taken into account. PMID:18681967

Reasoning in people with obsessive-compulsive disorder.

PubMed

Simpson, Jane; Cove, Jennifer; Fineberg, Naomi; Msetfi, Rachel M; J Ball, Linden

2007-11-01

The aim of this study was to investigate the inductive and deductive reasoning abilities of people with obsessive-compulsive disorder (OCD). Following previous research, it was predicted that people with OCD would show different abilities on inductive reasoning tasks but similar abilities to controls on deductive reasoning tasks. A two-group comparison was used with both groups matched on a range of demographic variables. Where appropriate, unmatched variables were entered into the analyses as covariates. Twenty-three people with OCD and 25 control participants were assessed on two tasks: an inductive reasoning task (the 20-questions task) and a deductive reasoning task (a syllogistic reasoning task with a content-neutral and content-emotional manipulation). While no group differences emerged on several of the parameters of the inductive reasoning task, the OCD group did differ on one, and arguably the most important, parameter by asking fewer correct direct-hypothesis questions. The syllogistic reasoning task results were analysed using both correct response and conclusion acceptance data. While no main effects of group were evident, significant interactions indicated important differences in the way the OCD group reasoned with content neutral and emotional syllogisms. It was argued that the OCD group's patterns of response on both tasks were characterized by the need for more information, states of uncertainty, and doubt and postponement of a final decision.

Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders.

PubMed

Capello, Daniela; Cerri, Michaela; Muti, Giuliana; Lucioni, Marco; Oreste, Pierluigi; Gloghini, Annunziata; Berra, Eva; Deambrogi, Clara; Franceschetti, Silvia; Rossi, Davide; Alabiso, Oscar; Morra, Enrica; Rambaldi, Alessandro; Carbone, Antonino; Paulli, Marco; Gaidano, Gianluca

2006-12-01

Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n=10; diffuse large B-cell lymphoma, n=35; and Burkitt/Burkitt-like lymphoma, n=5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations.

Epidermal multinucleated keratinocytes: a histopathologic clue to dermatitis artefacta.

PubMed

Gutierrez, Daniel; Schowalter, Michael K; Piliang, Melissa P; Fernandez, Anthony P

2016-10-01

Dermatitis artefacta is a psycho-cutaneous disorder characterized by self-inflicted cutaneous injuries, often in association with an underlying psychiatric disorder or as a response to external stressors. Cutaneous lesions suggestive of dermatitis artefacta are dependent on the means of injury and thus may be morphologically variable, but typically have geometric shapes, spare hard-to-reach anatomic areas, and are present in variable stages of evolution at any specific time. Although a dermatologist may be suspicious of dermatitis artefacta in a given patient, making a definitive diagnosis is extremely challenging. Patients often clinically evade questioning and deny creating skin lesions, and histopathologic evaluation of lesional biopsies usually reveals non-specific epidermal and dermal changes and inflammation. Thus, identification of clues that lend support to a diagnosis of dermatitis artefacta would be welcomed by both clinicians and pathologists. Here we present a case of dermatitis artefacta with a unique, yet previously reported, histopathological finding of multinucleated keratinocytes within the epidermis. Although probably uncommon and dependent on the etiology of cutaneous injury, we believe this finding is important for dermatopathologists to be aware of as a potential diagnostic clue when evaluating biopsies in patients suspected to have dermatitis artefacta. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke.

PubMed

Gore, Aniket V; Lampugnani, Maria Grazia; Dye, Louis; Dejana, Elisabetta; Weinstein, Brant M

2008-01-01

Intracranial hemorrhage (ICH) is a particularly severe form of stroke whose etiology remains poorly understood, with a highly variable appearance and onset of the disease (Felbor et al., 2006; Frizzell, 2005; Lucas et al., 2003). In humans, mutations in any one of three CCM genes causes an autosomal dominant genetic ICH disorder characterized by cerebral cavernous malformations (CCM). Recent evidence highlighting multiple interactions between the three CCM gene products and other proteins regulating endothelial junctional integrity suggests that minor deficits in these other proteins could potentially predispose to, or help to initiate, CCM, and that combinations of otherwise silent genetic deficits in both the CCM and interacting proteins might explain some of the variability in penetrance and expressivity of human ICH disorders. Here, we test this idea by combined knockdown of CCM pathway genes in zebrafish. Reducing the function of rap1b, which encodes a Ras GTPase effector protein for CCM1/Krit1, disrupts endothelial junctions in vivo and in vitro, showing it is a crucial player in the CCM pathway. Importantly, a minor reduction of Rap1b in combination with similar reductions in the products of other CCM pathway genes results in a high incidence of ICH. These findings support the idea that minor polygenic deficits in the CCM pathway can strongly synergize to initiate ICH.

The interaction between awareness of one's own speech disorder with linguistics variables: distinctive features and severity of phonological disorder.

PubMed

Dias, Roberta Freitas; Melo, Roberta Michelon; Mezzomo, Carolina Lisbôa; Mota, Helena Bolli

2013-01-01

To analyze the possible relationship among the awareness of one's own speech disorder and some aspects of the phonological system, as the number and the type of changed distinctive features, as well as the interaction among the severity of the disorder and the non-specification of distinctive features. The analyzed group has 23 children with diagnosis of speech disorder, aged 5:0 to 7:7. The speech data were analyzed through the Distinctive Features Analysis and classified by the Percentage of Correct Consonants. One also applied the Awareness of one's own speech disorder test. The children were separated in two groups: with awareness of their own speech disorder established (more than 50% of correct identification) and without awareness of their own speech disorder established (less than 50% of correct identification). Finally, the variables of this research were submitted to analysis using descriptive and inferential statistics. The type of changed distinctive features weren't different between the groups, as well as the total of changed features and the severity disorder. However, a correlation between the severity disorder and the non-specification of distinctive features was verified, because the more severe disorders have more changes in these linguistic variables. The awareness of one's own speech disorder doesn't seem to be directly influenced by the type and by the number of changed distinctive features, neither by the speech disorder severity. Moreover, one verifies that the greater phonological disorder severity, the greater the number of changed distinctive features.

Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype

PubMed Central

Karalunas, Sarah L.; Geurts, Hilde M.; Konrad, Kerstin; Bender, Stephan; Nigg, Joel T.

2014-01-01

Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and Methodology Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. Findings Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders. PMID:24628425

Analysis of occlusal variables, dental attrition, and age for distinguishing healthy controls from female patients with intracapsular temporomandibular disorders.

PubMed

Seligman, D A; Pullinger, A G

2000-01-01

Confusion about the relationship of occlusion to temporomandibular disorders (TMD) persists. This study attempted to identify occlusal and attrition factors plus age that would characterize asymptomatic normal female subjects. A total of 124 female patients with intracapsular TMD were compared with 47 asymptomatic female controls for associations to 9 occlusal factors, 3 attrition severity measures, and age using classification tree, multiple stepwise logistic regression, and univariate analyses. Models were tested for accuracy (sensitivity and specificity) and total contribution to the variance. The classification tree model had 4 terminal nodes that used only anterior attrition and age. "Normals" were mainly characterized by low attrition levels, whereas patients had higher attrition and tended to be younger. The tree model was only moderately useful (sensitivity 63%, specificity 94%) in predicting normals. The logistic regression model incorporated unilateral posterior crossbite and mediotrusive attrition severity in addition to the 2 factors in the tree, but was slightly less accurate than the tree (sensitivity 51%, specificity 90%). When only occlusal factors were considered in the analysis, normals were additionally characterized by a lack of anterior open bite, smaller overjet, and smaller RCP-ICP slides. The log likelihood accounted for was similar for both the tree (pseudo R(2) = 29.38%; mean deviance = 0.95) and the multiple logistic regression (Cox Snell R(2) = 30.3%, mean deviance = 0.84) models. The occlusal and attrition factors studied were only moderately useful in differentiating normals from TMD patients.

Relationship of Social Network to Protective Factors in Suicide and Alcohol Use Disorder Intervention for Rural Yup’ik Alaska Native Youth

PubMed Central

Philip, Jacques; Ford, Tara; Henry, David; Rasmus, Stacy; Allen, James

2015-01-01

Suicide and alcohol use disorders are significant Alaska Native health disparities, yet there is limited understanding of protection and no studies of social network factors in protection in this or other populations. The Qungasvik intervention enhances protective factors from suicide and alcohol use disorders through activities grounded in Yup’ik cultural practices and values. Identification of social network factors associated with protection within the cultural context of these tight, close knit, and high density rural Yup’ik Alaska Native communities in southwest Alaska can help identify effective prevention strategies for suicide and alcohol use disorder risk. Using data from ego-centered social network and protective factors from suicide and alcohol use disorders surveys with 50 Yup’ik adolescents, we provide descriptive data on structural and network composition variables, identify key network variables that explain major proportions of the variance in a four principal component structure of these network variables, and demonstrate the utility of these key network variables as predictors of family and community protective factors from suicide and alcohol use disorder risk. Connections to adults and connections to elders, but not peer connections, emerged as predictors of family and community level protection, suggesting these network factors as important intervention targets for intervention. PMID:27110094

Osteogenesis imperfecta in childhood: treatment strategies.

PubMed

Engelbert, R H; Pruijs, H E; Beemer, F A; Helders, P J

1998-12-01

Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.

EXTRACTING PRINCIPLE COMPONENTS FOR DISCRIMINANT ANALYSIS OF FMRI IMAGES

PubMed Central

Liu, Jingyu; Xu, Lai; Caprihan, Arvind; Calhoun, Vince D.

2009-01-01

This paper presents an approach for selecting optimal components for discriminant analysis. Such an approach is useful when further detailed analyses for discrimination or characterization requires dimensionality reduction. Our approach can accommodate a categorical variable such as diagnosis (e.g. schizophrenic patient or healthy control), or a continuous variable like severity of the disorder. This information is utilized as a reference for measuring a component’s discriminant power after principle component decomposition. After sorting each component according to its discriminant power, we extract the best components for discriminant analysis. An application of our reference selection approach is shown using a functional magnetic resonance imaging data set in which the sample size is much less than the dimensionality. The results show that the reference selection approach provides an improved discriminant component set as compared to other approaches. Our approach is general and provides a solid foundation for further discrimination and classification studies. PMID:20582334

EXTRACTING PRINCIPLE COMPONENTS FOR DISCRIMINANT ANALYSIS OF FMRI IMAGES.

PubMed

Liu, Jingyu; Xu, Lai; Caprihan, Arvind; Calhoun, Vince D

2008-05-12

This paper presents an approach for selecting optimal components for discriminant analysis. Such an approach is useful when further detailed analyses for discrimination or characterization requires dimensionality reduction. Our approach can accommodate a categorical variable such as diagnosis (e.g. schizophrenic patient or healthy control), or a continuous variable like severity of the disorder. This information is utilized as a reference for measuring a component's discriminant power after principle component decomposition. After sorting each component according to its discriminant power, we extract the best components for discriminant analysis. An application of our reference selection approach is shown using a functional magnetic resonance imaging data set in which the sample size is much less than the dimensionality. The results show that the reference selection approach provides an improved discriminant component set as compared to other approaches. Our approach is general and provides a solid foundation for further discrimination and classification studies.

Variety Is Not the Spice of Life for People with Autism Spectrum Disorders: Frequency Ratings of Central, Variable and Inappropriate Aspects of Common Real-Life Events

ERIC Educational Resources Information Center

Loth, Eva; Happe, Francesca; Gomez, Juan Carlos

2010-01-01

This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in…

Correlates of Irritability in College Students With Depressive Symptoms

PubMed Central

Pedrelli, Paola; Nyer, Maren; Holt, Daphne; Bakow, Brianna R.; Fava, Maurizio; Baer, Lee; Cassiello, Clair; Mulligan, Maura; Cusin, Cristina; Farabaugh, Amy

2015-01-01

Depression is a prevalent psychiatric disorder associated with significant personal and societal burden. There is accumulating evidence for the presence of a subtype of depression characterized by the presence of irritability that is associated with increased morbidity, risk for suicidal ideation, and functional impairments in adults. Little is known about the features of depressive symptoms with and without irritability among young adults in college. The primary aim of this study was to characterize the presentation of college students with depressive symptoms and irritability. Two-hundred eighty-seven undergraduate college students with depressive symptoms with and without irritability were compared across several psychiatric and functional outcome variables. Independent samples t-tests or logistic regressions were conducted for each outcome variable using the irritability item of the Beck Depression Inventory as a dichotomous grouping variable. Analyses were conducted separately for the men and the women. Both male and female students with depressive symptoms and severe irritability reported a greater severity of depressive symptoms compared with their peers with no or mild irritability. In the women, the presence of irritability was associated with greater symptoms of anxiety, whereas in the men, it was associated with increased likelihood of engaging in risky behaviors, including compulsive use of alcohol, illicit drugs, and prescription drugs. The male and female college students with depressive symptoms with and without irritability did not differ on severity of suicidal ideation, hopelessness, or cognitive functioning. The findings from this study suggest that depressive symptoms and irritability may characterize a subtype of college students who have a greater symptom burden and with the potential need for more aggressive and prompt treatment. PMID:24177482

Increased task-uncorrelated muscle activity in childhood dystonia.

PubMed

Lunardini, Francesca; Maggioni, Serena; Casellato, Claudia; Bertucco, Matteo; Pedrocchi, Alessandra L G; Sanger, Terence D

2015-06-12

Even if movement abnormalities in dystonia are obvious on observation-based examinations, objective measures to characterize dystonia and to gain insights into its pathophysiology are still strongly needed. We hypothesize that motor abnormalities in childhood dystonia are partially due to the inability to suppress involuntary variable muscle activity irrelevant to the achievement of the desired motor task, resulting in the superposition of unwanted motion components on the desired movement. However, it is difficult to separate and quantify appropriate and inappropriate motor signals combined in the same muscle, especially during movement. We devise an innovative and practical method to objectively measure movement abnormalities during the performance of a continuous figure-eight writing task in 7 children with dystonia and 9 age-matched healthy controls. During the execution of a continuous writing task, muscle contractions should occur at frequencies that match the frequencies of the writing outcome. We compare the power spectra of kinematic trajectories and electromyographic signals of 8 upper limb muscles to separate muscle activity with the same frequency content of the figure-eight movement (task-correlated) from activity occurring at frequencies extraneous to the task (task-uncorrelated). Children with dystonia present a greater magnitude of task-uncorrelated muscle components. The motor performance achieved by children with dystonia is characterized by an overall lower quality, with high spatial and temporal variability and an altered trade-off between speed and accuracy. Findings are consistent with the hypothesis that, in childhood dystonia, the ability to appropriately suppress variable and uncorrelated elements of movement is impaired. Here we present a proof-of-concept of a promising tool to characterize the phenomenology of movement disorders and to inform the design of neurorehabilitation therapies.

[A case of an anti-Ma2 antibody-positive patient presenting with variable CNS symptoms mimicking multiple system atrophy with a partial response to immunotherapy].

PubMed

Shiraishi, Wataru; Iwanaga, Yasutaka; Yamamoto, Akifumi

2015-01-01

A 70-year-old man with a 5-month history of progressive bradykinesia of the bilateral lower extremities was admitted to our hospital. At the age of 64, he underwent proximal gastrectomy for gastric cancer. He also had a history of subacute combined degeneration of the spinal cord since the age of 67, which was successfully treated with vitamin B12 therapy. Four weeks before admission to our hospital, he admitted himself to his former hospital complaining of walking difficulty. Two weeks later, however, his symptoms progressed rapidly; he was immobilized for two weeks and did not respond to the vitamin therapy. On admission to our hospital, he showed moderate paralysis of the lower extremities, cog-wheel rigidity of the four extremities, and dystonic posture of his left hand. He also showed orthostatic hypotension and vesicorectal disorders. Blood examination and cerebrospinal fluid analysis revealed no remarkable abnormalities. Electroencephalography showed frontal dominant, high voltage, sharp waves. His brain and spinal MRI revealed no notable abnormalities. We suspected autoimmune disease and commenced one course of intravenous methylprednisolone therapy, resulting in improvement of the parkinsonism and orthostatic hypotension. Based on these results, we investigated possible neural antigens and detected anti-Ma2 antibody. In addition to limbic encephalitis, anti-Ma2 antibody-positive neural disorders are characterized by rapid eye movement sleep behavior disorders or parkinsonism. Here, we report an anti-Ma2 antibody positive patient presenting variable CNS symptoms mimicking multiple system atrophy, who responded to immunotherapy.

Increased Intrasubject Variability in Response Time in Youths with Bipolar Disorder and At-Risk Family Members

ERIC Educational Resources Information Center

Brotman, Melissa A.; Rooney, Melissa H.; Skup, Martha; Pine, Daniel S.; Leibenluft, Ellen

2009-01-01

Intrasubject variability in response time (ISV-RT) was higher in youths with bipolar disorder (BD) and those with first-degree relatives with BD compared to youths without BD. ISV-RT may be a risk marker for BD.

Analysis of Relationship between the Body Mass Composition and Physical Activity with Body Posture in Children

PubMed Central

Baran, Joanna; Czenczek-Lewandowska, Ewelina; Leszczak, Justyna; Mazur, Artur

2016-01-01

Introduction. Excessive body mass in turn may contribute to the development of many health disorders including disorders of musculoskeletal system, which still develops intensively at that time. Aim. The aim of this study was to assess the relationship between children's body mass composition and body posture. The relationship between physical activity level of children and the parameters characterizing their posture was also evaluated. Material and Methods. 120 school age children between 11 and 13 years were enrolled in the study, including 61 girls and 59 boys. Each study participant had the posture evaluated with the photogrammetric method using the projection moiré phenomenon. Moreover, body mass composition and the level of physical activity were evaluated. Results. Children with the lowest content of muscle tissue showed the highest difference in the height of the inferior angles of the scapulas in the coronal plane. Children with excessive body fat had less slope of the thoracic-lumbar spine, greater difference in the depth of the inferior angles of the scapula, and greater angle of the shoulder line. The individuals with higher level of physical activity have a smaller angle of body inclination. Conclusion. The content of muscle tissue, adipose tissue, and physical activity level determines the variability of the parameter characterizing the body posture. PMID:27761467

Seronegative celiac disease: Shedding light on an obscure clinical entity.

PubMed

Volta, Umberto; Caio, Giacomo; Boschetti, Elisa; Giancola, Fiorella; Rhoden, Kerry J; Ruggeri, Eugenio; Paterini, Paola; De Giorgio, Roberto

2016-09-01

Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Analysis of cardiovascular regulation.

PubMed

Wilhelm, F H; Grossman, P; Roth, W T

1999-01-01

Adequate characterization of hemodynamic and autonomic responses to physical and mental stress can elucidate underlying mechanisms of cardiovascular disease or anxiety disorders. We developed a physiological signal processing system for analysis of continuously recorded ECG, arterial blood pressure (BP), and respiratory signals using the programming language Matlab. Data collection devices are a 16-channel digital, physiological recorder (Vitaport), a finger arterial pressure transducer (Finapres), and a respiratory inductance plethysmograph (Respitrace). Besides the conventional analysis of the physiological channels, power spectral density and transfer functions of respiration, heart rate, and blood pressure variability are used to characterize respiratory sinus arrhythmia (RSA), 0.10-Hz BP oscillatory activity (Mayer-waves), and baroreflex sensitivity. The arterial pressure transducer waveforms permit noninvasive estimation of stroke volume, cardiac output, and systemic vascular resistance. Time trends in spectral composition of indices are assessed using complex demodulation. Transient dynamic changes of cardiovascular parameters at the onset of stress and recovery periods are quantified using a regression breakpoint model that optimizes piecewise linear curve fitting. Approximate entropy (ApEn) is computed to quantify the degree of chaos in heartbeat dynamics. Using our signal processing system we found distinct response patterns in subgroups of patients with coronary artery disease or anxiety disorders, which were related to specific pharmacological and behavioral factors.

Predictors of premature discontinuation of outpatient treatment after discharge of patients with posttraumatic stress disorder.

PubMed

Wang, Hee Ryung; Woo, Young Sup; Jun, Tae-Youn; Bahk, Won-Myong

2015-01-01

This study aimed to examine the sociodemographic and disease-related variables associated with the premature discontinuation of psychiatric outpatient treatment after discharge among patients with noncombat-related posttraumatic stress disorder. We retrospectively reviewed the medical records of patients who were discharged with a diagnosis of posttraumatic stress disorder. Fifty-five percent of subjects (57/104) prematurely discontinued outpatient treatment within 6 months of discharge. Comparing sociodemographic variables between the 6-month non-follow-up group and 6-month follow-up group, there were no variables that differed between the two groups. However, comparing disease-related variables, the 6-month follow-up group showed a longer hospitalization duration and higher Global Assessment of Function score at discharge. The logistic regression analysis showed that a shorter duration of hospitalization predicted premature discontinuation of outpatient treatment within 6 months of discharge. The duration of psychiatric hospitalization for posttraumatic stress disorder appeared to influence the premature discontinuation of outpatient treatment after discharge.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

PubMed Central

Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

2016-01-01

ABSTRACT The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and ATP7B contributes to the biological understanding of protein function, with relevance for future development of therapy. PMID:26747866

The course of major depressive disorder from childhood to young adulthood: Recovery and recurrence in a longitudinal observational study.

PubMed

Kovacs, Maria; Obrosky, Scott; George, Charles

2016-10-01

The episodic nature of major depressive disorder (MDD) in clinically referred adults has been well-characterized, particularly by the NIMH Collaborative Depression Study. Previous work has established that MDD also is episodic prior to adulthood, but no study has yet provided comprehensive information on the actual course of MDD in clinically referred juveniles. Thus, the present investigation sought to characterize recovery, recurrence, and their predictors across multiple episodes of MDD in initially 8- to 13-year-old outpatients (N=102), and to estimate freedom from morbidity ("well-time") across the years. Clinically referred youngsters with MDD were repeatedly assessed in an observational study across two decades (median follow up length: 15 years). Survival analytic techniques served to model recovery from the 1st, 2nd and 3rd lifetime episodes of MDD, the risk of developing the 2nd, 3rd, and 4th episodes, and the effects of traditional psychosocial and clinical predictors of outcomes. "Well-time" across the follow-up and its predictors also were examined. Recovery rates ranged from 96% to 100% across MDD episodes; episode lengths ranged from 6 to 7 months. Up to 72% of those recovered from the first episode of MDD had a further episode; median inter-episode intervals were about 3-5 years. No single demographic, social, or clinical variable, nor treatment, consistently predicted recovery/recurrence. Psychiatric morbidity over time derived mostly from non-affective disorders, which, however, did not alter the course of MDD. The sample was relatively small and power to detect small effects further declined with each MDD episode recurrence. Echoing findings on adults, the course of pediatric-onset MDD in this clinical sample was unequivocally episodic. Traditional course predictors had limited temporal stability, highlighting the need to examine novel predictor variables. The ongoing risk of depression episodes into the second and third decades of life suggests that prevention efforts should start in late childhood. Copyright © 2016 Elsevier B.V. All rights reserved.

Recombinant Intrinsically Disordered Proteins for NMR: Tips and Tricks.

PubMed

Calçada, Eduardo O; Korsak, Magdalena; Kozyreva, Tatiana

2015-01-01

The growing recognition of the several roles that intrinsically disordered proteins play in biology places an increasing importance on protein sample availability to allow the characterization of their structural and dynamic properties. The sample preparation is therefore the limiting step to allow any biophysical method being able to characterize the properties of an intrinsically disordered protein and to clarify the links between these properties and the associated biological functions. An increasing array of tools has been recruited to help prepare and characterize the structural and dynamic properties of disordered proteins. This chapter describes their sample preparation, covering the most common drawbacks/barriers usually found working in the laboratory bench. We want this chapter to be the bedside book of any scientist interested in preparing intrinsically disordered protein samples for further biophysical analysis.

Mechanical properties of 3D printed warped membranes

NASA Astrophysics Data System (ADS)

Kosmrlj, Andrej; Xiao, Kechao; Weaver, James C.; Vlassak, Joost J.; Nelson, David R.

2015-03-01

We explore how a frozen background metric affects the mechanical properties of solid planar membranes. Our focus is a special class of ``warped membranes'' with a preferred random height profile characterized by random Gaussian variables h (q) in Fourier space with zero mean and variance < | h (q) | 2 > q-m . It has been shown theoretically that in the linear response regime, this quenched random disorder increases the effective bending rigidity, while the Young's and shear moduli are reduced. Compared to flat plates of the same thickness t, the bending rigidity of warped membranes is increased by a factor hv / t while the in-plane elastic moduli are reduced by t /hv , where hv =√{< | h (x) | 2 > } describes the frozen height fluctuations. Interestingly, hv is system size dependent for warped membranes characterized with m > 2 . We present experimental tests of these predictions, using warped membranes prepared via high resolution 3D printing.

Is 'subthreshold' bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

PubMed

Bayes, Adam; Graham, Rebecca K; Parker, Gordon B; McCraw, Stacey

2018-06-01

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional Impairments in Attention Deficit Hyperactivity Disorder: The Mediating Role of Neuropsychological Functioning

PubMed Central

Sjöwall, Douglas; Thorell, Lisa B.

2014-01-01

Attention deficit hyperactivity disorder (ADHD) is associated with multiple neuropsychological deficits and the present study aimed to investigate to what extent these deficits are related to the functional impairments associated with the disorder. The results showed that all executive functioning deficits and reaction time variability acted as mediators in the relation between ADHD and academic achievement. However, only the effect of working memory for language skills, and the effects of reaction time variability and working memory for mathematics, remained significant when studying independent effects. Regulation of anger was a significant mediator for peer problems. Gender or symptoms of oppositional defiant disorder (ODD) or conduct disorder (CD) did not moderate these findings. PMID:24742310

Hydrogen-Exchange Mass Spectrometry for the Study of Intrinsic Disorder in Proteins

PubMed Central

Balasubramaniam, Deepa; Komives, Elizabeth A.

2012-01-01

Amide hydrogen/deuterium exchange detected by mass spectrometry (HXMS) is seeing wider use for the identification of intrinsically disordered parts of proteins. In this review, we discuss examples of how discovery of intrinsically disordered regions and their removal can aid in structure determination, biopharmaceutical quality control, the characterization of how posttranslational modifications affect weak structuring of disordered regions, the study of coupled folding and binding, and the characterization of amyloid formation. PMID:23099262

Identifying a clinical signature of suicidality among patients with mood disorders: A pilot study using a machine learning approach.

PubMed

Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C

2016-03-15

A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to 'train' a machine learning algorithm. The resulting algorithm was utilized in identifying novel or 'unseen' individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65% and 72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity. Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying a clinical signature of suicidality among patients with mood disorders: a pilot study using a machine learning approach

PubMed Central

Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B.; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C.

2016-01-01

Objective A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. Method A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to ‘train’ a machine learning algorithm. The resulting algorithm was utilized in identifying novel or ‘unseen’ individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. Results All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65%-72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity. Conclusion Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. PMID:26773901

Female patient with autistic disorder, intellectual disability, and co-morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2-q13.31 microdeletion.

PubMed

Quintela, Ines; Gomez-Guerrero, Lorena; Fernandez-Prieto, Montse; Resches, Mariela; Barros, Francisco; Carracedo, Angel

2015-12-01

In recent years, the advent of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and its use as a first genetic test for the diagnosis of patients with neurodevelopmental phenotypes has allowed the identification of novel submicroscopic chromosomal abnormalities (namely, copy number variants or CNVs), imperceptible by conventional cytogenetic techniques. The 3q13.31 microdeletion syndrome (OMIM #615433) has been defined as a genomic disorder mainly characterized by developmental delay, postnatal overgrowth, hypotonia, genital abnormalities in males, and characteristic craniofacial features. Although the 3q13.31 CNVs are variable in size, a 3.4 Mb recurrently altered region at 3q13.2-q13.31 has been recently described and non-allelic homologous recombination (NAHR) mediated by flanking human endogenous retrovirus (HERV-H) elements has been suggested as the mechanism of deletion formation. We expand the phenotypic spectrum associated with this recurrent deletion performing the clinical description of a 9-year-old female patient with autistic disorder, total absence of language, intellectual disability, anxiety disorder and disruptive, and compulsive eating behaviors. The array-based molecular karyotyping allowed the identification of a de novo recurrent 3q13.2-q13.31 deletion encompassing 25 genes. In addition, we compare her clinical phenotype with previous reports of patients with neurodevelopmental and behavioral disorders and proximal 3q microdeletions. Finally, we also review the candidate genes proposed so far for these phenotypes. © 2015 Wiley Periodicals, Inc.

Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

PubMed

Castro, V M; Kong, S W; Clements, C C; Brady, R; Kaimal, A J; Doyle, A E; Robinson, E B; Churchill, S E; Kohane, I S; Perlis, R H

2016-01-05

Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.

A case of choking phobia: towards a conceptual approach.

PubMed

Lopes, Rui; Melo, Raquel; Curral, Rosário; Coelho, Rui; Roma-Torres, António

2014-03-01

Choking phobia, also known as phagophobia or swallowing phobia is an uncommon clinical entity that has been underappreciated and is included in the new DSM-5 and upcoming ICD-11 diagnostic category of avoidant/restrictive food intake disorder. Phenomenologically distinct from other eating disorders, it is characterized by the phobic stimulus of swallowing that results in the avoidance of food or drinks, and ultimately to low weight, social withdrawal, anxiety and depression states. Its prevalence and long-term course on the general population still needs to be determined, probably reflecting years of indefiniteness regarding its nosology and by the absence of a clear set of diagnostic criteria. We present a clinical case of choking phobia in a 32-year-old male patient after an episode of choke when eating chicken. An early diagnosis and distinction from other eating disorders is important for proper treatment and fundamental for prognosis. We also make a thorough revision on literature in clinical features, differential diagnosis and treatment approaches, suggesting a conceptual approach for choking phobia as a clinical spectrum settled by different degrees of phobic subtypes, which may depend on a varied number of clinical variables.

Stress-induced laboratory eating behavior in obese women with binge eating disorder.

PubMed

Schulz, S; Laessle, R G

2012-04-01

Aim of the study was to compare the microstructural eating behavior of obese patients with and without binge eating disorder (BED) after stress induction in laboratory. Seventy-one female subjects were investigated (mean BMI 36.9). Thirty-five fulfilled criteria for BED. A 2×2 factorial design with repeated measurement (stress vs. no stress) on the second factor was applied. Stress was induced by the Trier Social Stress Test (TSST) and chocolate pudding served as laboratory food. Variables of eating behavior were measured by a universal eating monitor (UEM). Only in participants with BED stress was associated with an increase in the initial eating rate and a diminished deceleration of eating at the end of the meal. Generally, BED subjects ate with larger size of spoonfuls during the laboratory meal than non BED controls. The eating behavior of obese patients with binge eating disorder seems to be significantly affected by stress. The stress-induced eating behavior of BED patients is characterized by a stronger motivation to eat (indicated by a fast initial eating rate) as well as by a lack of satiety perception (indicated by less deceleration of eating rate). Copyright © 2011 Elsevier Ltd. All rights reserved.

Predictors of back disorder among Almeda textile factory workers, North Ethiopia.

PubMed

Abraha, Teklehaymanot Huluf; Demoz, Asmelash Tekie; Moges, Haimanot Gebrehiwot; Ahmmed, Ansha Nega

2018-05-16

To guide the development of targeted interventions for the prevention of work-related back pain, this manuscript estimates the prevalence of back pain and its association with a variety of risk factors among Almeda textile factory production works from March to April 2015. An institutional-based cross-sectional study was carried out in Almeda textile factory, North Ethiopia. Randomly selected workers were administered a structured questionnaire about their socio-economic status, lifestyle, working conditions, back pain and selected risk factors. The data was entered to Epi Info 3.5.4 version and analyzed using SPSS version 16. Descriptive statistics were done to characterize the study participants. Bivariate and multiple logistic regressions were fitted to control confounding variables. Adjusted odds ratio with 95% confidence intervals was computed. The prevalence of work-related musculoskeletal disorders was 53.1%. Gender, age, years of service, lack of physical activity, unavailability of adjustable chair, work-load and poor light were significantly associated with increased risk of back pain. The high prevalence of work-related back pain disorder implies that; habit of doing physical exercise, availing adjustable chair and light at the working place, are key issues which require specific interventions.

Mental illness and homicide--prevention of recidivism.

PubMed

Talevska, Valentina; Stefanovski, Branko

2011-12-01

We hypothesized that the integration of forensic psychiatrists and the forensic system into the general stream of mental health should lead to better reintegration of forensic patients into the society. The aims of the study were to explore the link between violence, murder, psychiatric disorders and other variables, and to suggest a mode of prevention of criminal recidivism. This investigation provided a more reflective profile of mentally ill persons convicted of murder, hospitalized in Psychiatric Hospital in Demir Hisar in Macedonia between 2007 and 2009. Study results indicated the offender with severe mental illness incarcerated for murder in Demir Hisar Psychiatric Hospital to be predominantly suffering from a mood disorder, to be a male with secondary school education, and to have significant intimate and family relationships characterized by rage as a frequently mentioned motive for murder. On committing homicide, they frequently used firearm or sharp objects. The offenders lived in dysfunctional families, had extensive histories of substance abuse and criminal activity before their murder conviction, and received inadequate treatment for their mental disorder and substance abuse. We suggest that the offenders (murderers) continue their treatment in mental health forensic services upon completing their obligatory treatment at a psychiatric hospital.

Non-Systemic Drugs: A Critical Review

PubMed Central

Charmot, Dominique

2012-01-01

Non-systemic drugs act within the intestinal lumen without reaching the systemic circulation. The first generation included polymeric resins that sequester phosphate ions, potassium ions, or bile acids for the treatment of electrolyte imbalances or hypercholesteremia. The field has evolved towards non-absorbable small molecules or peptides targeting luminal enzymes or transporters for the treatment of mineral metabolism disorders, diabetes, gastrointestinal (GI) disorders, and enteric infections. From a drug design and development perspective, non-systemic agents offer novel opportunities to address unmet medical needs while minimizing toxicity risks, but also present new challenges, including developing a better understanding and control of non-transcellular leakage pathways into the systemic circulation. The pharmacokinetic-pharmacodynamic relationship of drugs acting in the GI tract can be complex due to the variability of intestinal transit, interaction with chyme, and the complex environment of the surface epithelia. We review the main classes of non-absorbable agents at various stages of development, and their therapeutic potential and limitations. The rapid progress in the identification of intestinal receptors and transporters, their functional characterization and role in metabolic and inflammatory disorders, will undoubtedly renew interest in the development of novel, safe, non-systemic therapeutics. PMID:22300258

The Limited Effects of Obstetrical and Neonatal Complications on Conduct and ADHD Symptoms in Middle Childhood

PubMed Central

Wagner, Anna I.; Schmidt, Nicole L.; Lemery-Chalfant, Kathryn; Leavitt, Lewis A.; Goldsmith, H. Hill

2016-01-01

Objective The purpose of this study was to examine the effects of a wide range of obstetrical and neonatal complications as well as socioeconomic variables on the behaviors characterized by attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Method Data were collected on 7–8 year old twins, using multiple instruments assessing many areas of individual and family functioning. The influence of several aspects of prenatal care, labor and delivery, and early life were considered as well as indicators of socioeconomic status such as family income and maternal education. Results The observed associations were stronger for ADHD than CD symptoms and stronger for females than males. Family income and gender significantly predicted both behavioral outcomes, while birthweight predicted ADHD symptoms only. However, the presence of ADHD and conduct symptom behaviors were not associated with an occurrence of more obstetrical or neonatal complications as indicated by hierarchical linear modeling (HLM) analyses. Conclusions By school age, behavioral problems related to inattention, impulsivity, hyperactivity, defiance, and conduct are relatively unaffected by general adversity in the neonatal and perinatal periods. PMID:19433988

Adipsic diabetes insipidus in adult patients.

PubMed

Cuesta, Martín; Hannon, Mark J; Thompson, Christopher J

2017-06-01

Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI. A literature search was performed to review the background, etiology, management and associated complications of this rare condition. ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI. The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.

[Relationships between alexithymia, depression and interpersonal dependency in addictive subjects].

PubMed

Speranza, Mario; Stéphan, Philippe; Corcos, Maurice; Loas, Gwenolé; Taieb, Olivier; Guilbaud, Olivier; Perez-Diaz, Fernando; Venisse, Jean-Luc; Bizouard, Paul; Halfon, Olivier; Jeammet, Philippe

2003-06-01

In the scientific literature, the term of addiction is currently used to describe a whole range of phenomena characterized by an irresistible urge to engage in a series of behaviors carried out in a repetitive and persistent manner despite accruing adverse somatic, psychological and social consequences for the individual. It has been suggested that subjects presenting such behaviors would share specific features of personality which support the appearance or are associated with these addictive behaviors. Dimensions such as alexithymia and depression have been particularly well investigated. The aim of this study was to explore the hypothesis of a specific psychopathological model relating alexithymia and depression in different addictive disorders such as alcoholism, drug addiction or eating disorders. Alexithymic and depressive dimensions were explored and analyzed through the statistical tool of path analysis in a large clinical sample of addicted patients and controls. The results of this statistical method, which tests unidirectional causal relationships between a certain number of observed variables, showed a good adjustment between the observed data and the ideal model, and support the hypothesis that a depressive dimension can facilitate the development of dependence in vulnerable alexithymic subjects. These results can have clinical implications in the treatment of addictive disorders.

Cardiovascular disease and risk of acute pancreatitis in a population-based study.

PubMed

Bexelius, Tomas Sjöberg; Ljung, Rickard; Mattsson, Fredrik; Lagergren, Jesper

2013-08-01

The low-grade inflammation that characterizes cardiovascular disorders may facilitate the development of pancreatitis; therefore, we investigated the connection between cardiovascular disorders and acute pancreatitis. A nested population-based case-control study was conducted in Sweden in 2006-2008. Cases had a first episode of acute pancreatitis diagnosed in the nationwide Patient Register. Controls were matched on age, sex, and calendar year and randomly selected from all Swedish residents (40-84 years old). Exposure to cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure, and stroke) was identified in the Patient Register. Relative risk of acute pancreatitis was estimated by odds ratios with 95% confidence intervals using logistic regression adjusting for confounders (matching variables, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases). The study included 6161 cases and 61,637 control subjects. Cardiovascular disorders were positively associated with acute pancreatitis (adjusted odds ratio, 1.35; 95% confidence interval, 1.25-1.45). This population-based study indicates an association between cardiovascular disease and acute pancreatitis. Specifically, ischemic heart disease and hypertension seem to increase the risk of acute pancreatitis. Further research is needed to determine causality.

Diagnostic criteria for psychosomatic research and somatic symptom disorders.

PubMed

Sirri, Laura; Fava, Giovanni A

2013-02-01

The Diagnostic Criteria for Psychosomatic Research (DCPR) were introduced in 1995 by an international group of investigators to expand the traditional domains of the disease model. The DCPR are a set of 12 'psychosomatic syndromes' which provide operational tools for psychosocial variables with prognostic and therapeutic implications in clinical settings. Eight syndromes concern the main manifestations of abnormal illness behaviour: somatization, hypochondriacal fears and beliefs, and illness denial. The other four syndromes (alexithymia, type A behaviour, demoralization and irritable mood) refer to the domain of psychological factors affecting medical conditions. This review describes the conceptual bases of the DCPR and the main findings concerning their application, with particular reference to the incremental information they added to the customary psychiatric classification. The DCPR were also compared with the provisional DSM-5 somatic symptom disorders. The DCPR were found to be more sensitive than DSM-IV in identifying subthreshold psychological distress and characterizing patients' psychological response to medical illness. DSM-5 somatic symptom disorders seem to neglect important clinical phenomena, such as illness denial, resulting in a narrow view of patients' functioning. The additional information provided by the DCPR may enhance the decision-making process.

[Violence and post-traumatic stress disorder in childhood].

PubMed

Ximenes, Liana Furtado; de Oliveira, Raquel de Vasconcelos Carvalhães; de Assis, Simone Gonçalves

2009-01-01

This study presents the prevalence of symptoms of Posttraumatic Stress Disorder (PTSD) in 500 schoolchildren (6-13 years old) in São Gonçalo, Rio de Janeiro. It also investigates the association between PTSD, violence and other adverse events in the lives of these children. The multi-stage cluster sampling strategy involved three selection stages. Parents were interviewed about their children's behavior. The instrument used to screen symptoms of PTSD was the Child Behavior Checklist-Posttraumatic Stress Disorder Scale (CBCL-PTSD). Conflict Tactics Scales (CTS) were applied to evaluate family violence and other scales to investigate the socioeconomic profile, familiar relationship, characteristics and adverse events in the lives of the children. Multivariate analysis was performed using a hierarchical model with a significance level of 5%. The prevalence of clinical symptoms of PTSD was of 6.5%. The multivariate analysis suggested an explanation model of PTSD characterized by 18 variables, such as the child's characteristics; specific life events; family violence; and other family factors. The results reveal that it is necessary to work with the child in particularly difficult moments of his/her life in order to prevent or minimize the impact of adverse events on their mental and social functioning.

An exploratory study of clinical measures associated with subsyndromal pathological gambling in patients with binge eating disorder.

PubMed

Yip, Sarah W; White, Marney A; Grilo, Carlos M; Potenza, Marc N

2011-06-01

Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems.

Innovative biomarkers in psychiatric disorders: a major clinical challenge in psychiatry.

PubMed

Lozupone, Madia; Seripa, Davide; Stella, Eleonora; La Montagna, Maddalena; Solfrizzi, Vincenzo; Quaranta, Nicola; Veneziani, Federica; Cester, Alberto; Sardone, Rodolfo; Bonfiglio, Caterina; Giannelli, Gianluigi; Bisceglia, Paola; Bringiotti, Roberto; Daniele, Antonio; Greco, Antonio; Bellomo, Antonello; Logroscino, Giancarlo; Panza, Francesco

2017-09-01

Currently, the diagnosis of psychiatric illnesses is based upon DSM-5 criteria. Although endophenotype-specificity for a particular disorder is discussed, the identification of objective biomarkers is ongoing for aiding diagnosis, prognosis, or clinical response to treatment. We need to improve the understanding of the biological abnormalities in psychiatric illnesses across conventional diagnostic boundaries. The present review investigates the innovative post-genomic knowledge used for psychiatric illness diagnostics and treatment response, with a particular focus on proteomics. Areas covered: This review underlines the contribution that psychiatric innovative biomarkers have reached in relation to diagnosis and theragnosis of psychiatric illnesses. Furthermore, it encompasses a reliable representation of their involvement in disease through proteomics, metabolomics/pharmacometabolomics and lipidomics techniques, including the possible role that gut microbiota and CYP2D6 polimorphisms may play in psychiatric illnesses. Expert opinion: Etiologic heterogeneity, variable expressivity, and epigenetics may impact clinical manifestations, making it difficult for a single measurement to be pathognomonic for multifaceted psychiatric disorders. Academic, industry, or government's partnerships may successfully identify and validate new biomarkers so that unfailing clinical tests can be developed. Proteomics, metabolomics, and lipidomics techniques are considered to be helpful tools beyond neuroimaging and neuropsychology for the phenotypic characterization of brain diseases.

Norrie disease: extraocular clinical manifestations in 56 patients.

PubMed

Smith, Sharon E; Mullen, Thomas E; Graham, Dionne; Sims, Katherine B; Rehm, Heidi L

2012-08-01

Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients. Copyright © 2012 Wiley Periodicals, Inc.

Clustering of adversity in young adults on disability pension due to mental disorders: a latent class analysis.

PubMed

Joensuu, Matti; Mattila-Holappa, Pauliina; Ahola, Kirsi; Ervasti, Jenni; Kivimäki, Mika; Kivekäs, Teija; Koskinen, Aki; Vahtera, Jussi; Virtanen, Marianna

2016-02-01

Mental disorders are the leading cause of work disability among young adults. This study examined whether distinct classes could be identified among young adults on the basis of medical history before receiving a disability pension due to a mental disorder. Medical history was obtained from pension applications and attached medical certificates for 1163 individuals aged 18-34 years who, in 2008, received a disability pension due to a mental disorder. Using latent class analysis, 10 clinical and individual adversities and their associations with sex, age and diagnostic category were examined. Three classes were identified: childhood adversity (prevalence, 33%), comorbidity (23%), and undefined (44%). The childhood adversity class was characterized by adverse events and symptoms reported during childhood and it associated with depressive disorders. The comorbidity class was characterized by comorbid mental disorders, suicide attempts and substance abuse and associated with younger age and bipolar disorder. The undefined class formed no distinct profile; individuals in this class had the lowest number of adversities and it associated with psychotic disorders. The identification of subgroups characterized by childhood circumstances and comorbidity may help planning of prevention and support practices for young adults with mental disorders and risk of work disability.

Victimization and perpetration of intimate partner violence and substance use disorders in a nationally representative sample.

PubMed

Afifi, Tracie O; Henriksen, Christine A; Asmundson, Gordon J G; Sareen, Jitender

2012-08-01

The aim of this study was to examine the relationship between perpetration and victimization of physical and sexual intimate partner violence (IPV) in the past year and substance use disorders (SUDs) in the past year, including alcohol, sedatives/tranquilizers, cocaine, cannabis, and nicotine stratified according to sex. Data were from the National Epidemiologic Survey on Alcohol and Related Conditions. A series of adjusted logistic regression models were conducted. Among men and women, all types of SUDs were associated with increased odds of IPV perpetration (odds ranging from 1.4 to 8.5 adjusting for sociodemographic variables). IPV victimization increased the odds of having all types of SUDs for male and female victims, with the exception of sedatives/tranquilizer abuse/dependence among women (odds ranging from 1.5 to 6.0 adjusting for sociodemographic variables). Substances that had the most robust relationship with perpetration and victimization of IPV included alcohol and cannabis, after adjusting for sociodemographic variables, mood disorders, anxiety disorders, personality disorders, and mutual violence.

Electrodermal Variability and Symptom Severity in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Fenning, Rachel M.; Baker, Jason K.; Baucom, Brian R.; Erath, Stephen A.; Howland, Mariann A.; Moffitt, Jacquelyn

2017-01-01

Associations between variability in sympathetic nervous system arousal and individual differences in symptom severity were examined for children with autism spectrum disorder (ASD). Thirty-four families participated in a laboratory visit that included continuous measurement of electrodermal activity (EDA) during a battery of naturalistic and…

Neuroepileptic Correlates of Autistic Symptomatology in Tuberous Sclerosis

ERIC Educational Resources Information Center

Bolton, Patrick F.

2004-01-01

Tuberous sclerosis is a genetic condition that is strongly associated with the development of an autism spectrum disorder. However, there is marked variability in expression, and only a subset of children with tuberous sclerosis develop autism spectrum disorder. Clarification of the mechanisms that underlie the association and variability in…

Dysthymic disorder: clinical characteristics in relation to age at onset.

PubMed

Barzega, G; Maina, G; Venturello, S; Bogetto, F

2001-09-01

The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. The study is retrospective and enrolls a limited number of cases. The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.

Sickness absence due to mental disorders and psychosocial stressors at work.

PubMed

Silva-Junior, João Silvestre; Fischer, Frida Marina

2015-01-01

Mental disorders are the third leading cause of social security benefit due to sickness in Brazil. Occupational exposure to psychosocial stressors can affect the workers' mental health. The social security medical experts are responsible for characterizing if those sicknesses are work-related. To evaluate the factors associated with sick leave due to mental disorders, in particular, the perception of workers on psychosocial factors at work. This is an analytical study carried out in São Paulo, Brazil, with 131 applicants for sickness benefit due to mental disorders. Questionnaires were applied to assess the sociodemographic data, habits/lifestyle information, and perceived psychosocial factors at work. The most common diagnosis was depressive disorders (40.4%). The medical experts considered 23.7% of all applications as work-related. Most of the participants were female (68.7%), up to 40 years of age (73.3%), married/common-law marriage (51.1%), with educational level greater than or equal to 11 years (80.2%), nonsmokers (80.9%), not alcohol consumers (84%), and practice of physical activities (77.9%). Regarding psychosocial factors, most of the participants informed a high job strain (56.5%), low social support (52.7%), effort-reward imbalance (55.7%), and high overcommitment (87.0%). There was no statistical association between the work-related mental disorders sickness benefits and independent variables. The concession of social security sickness benefits is not associated with sociodemographic data, habits/lifestyle, or psychosocial factors at work. Occupational exposure to unfavorable psychosocial factors was reported by most workers on sick leave due to mental disorders. However, several cases were not recognized by the social security medical experts as work-related, which may have influenced the results of the associations.

The differences between patients with panic disorder and healthy controls in psychophysiological stress profile.

PubMed

Kotianova, Antonia; Kotian, Michal; Slepecky, Milos; Chupacova, Michaela; Prasko, Jan; Tonhajzerova, Ingrid

2018-01-01

Alarming somatic symptoms, in particular, cardiovascular symptoms, are the characteristic feature of panic attacks. Increased cardiac mortality and morbidity have been found in these patients. Power spectral analysis of electrocardiogram R-R intervals is known to be a particularly successful tool in the detection of autonomic instabilities in various clinical disorders. Our study aimed to compare patients with panic disorder and healthy controls in heart rate variation (HRV) parameters (very-low-frequency [VLF], low-frequency [LF], and high-frequency [HF] band components of R-R interval) in baseline and during the response to the mental task. We assessed psychophysiological variables in 33 patients with panic disorder (10 men, 23 women; mean age 35.9±10.7 years) and 33 age- and gender-matched healthy controls (10 men, 23 women; mean age 35.8±12.1 years). Patients were treatment naïve. Heart rate, blood pressure, muscle tension, and HRV in basal conditions and after the psychological task were assessed. Power spectrum was computed for VLF (0.003-0.04 Hz), LF (0.04-0.15 Hz), and HF (0.15-0.40 Hz) bands using fast Fourier transformation. In the baseline period, the VLF band was significantly lower in panic disorder group compared to controls ( p <0.005). In the period of mental task, the LF/HF ratio was significantly higher in panic disorder patients compared to controls ( p <0.05). No significant differences were found in the remaining parameters. There was a significant difference in ΔHF and ΔLF/HF ratio between patients and controls, with Δ increasing in patients and decreasing in controls. These findings revealed that patients suffering from panic disorder were characterized by relative sympathetic dominance (reactivity) in response to mental stress compared with healthy controls.

Syndromology: an updated conceptual overview. VI. Molecular and biochemical aspects of dysmorphology.

PubMed

Cohen, M M

1989-12-01

The role of chance using a stochastic single gene model has been shown to generate a continuous liability curve resembling that obtained from a multifactorial threshold model. Segregation of some malformations may be explained by a single defective gene that predisposes to, but does not necessarily result in, the malformation. Low penetrance and remarkably variable expressivity that characterize a number of presumed autosomal dominant malformation syndromes are possibly reflections of specific stochastic influences that are intrinsic to the embryonic process itself. Gene analysis is discussed and illustrated. Using polymorphic DNA probes to study cleft palate and ankyloglossia in males and ankyloglossia only in females in a large Icelandic family, the responsible gene was found to be located on the long arm of the X chromosome in the Xq21.1 region. In addition to gene analysis, some of the implications of transgenic analysis using mice are discussed. Among disorders of collagen metabolism, both the osteogenesis imperfectas and the Ehlers-Danlos syndromes are shown to represent genetically heterogeneous groups of connective tissue disorders. The days of thinking about osteogenesis imperfecta as one disorder and the Ehlers-Danlos syndrome as another are a thing of the past; persistence of such thinking is erroneous and misleading. Of the many disorders affecting bone mineral, the complexities of hypophosphatasia and pseudohypoparathyroidism are singled out for discussion. For lysosomal storage disorders, an overview of the mucopolysaccharidoses is provided. Finally, the recently delineated peroxisomal disorders--hyperpipecolic acidemia, rhizomelic chondrodysplasia, neonatal adrenoleukodystrophy, Zellweger syndrome, and infantile Refsum disease--are known to share a distinctive biochemical phenotype, although fibroblast complementation analysis suggests that some of these disorders are etiologically distinct.

The impact of comorbid impulsive/compulsive disorders in problematic Internet use.

PubMed

Chamberlain, Samuel R; Ioannidis, Konstantinos; Grant, Jon E

2018-05-23

Background and aims Problematic Internet use (PIU) is commonplace but is not yet recognized as a formal mental disorder. Excessive Internet use could result from other conditions such as gambling disorder. The aim of the study was to assess the impact of impulsive-compulsive comorbidities on the presentation of PIU, defined using Young's Diagnostic Questionnaire. Methods A total of 123 adults aged 18-29 years were recruited using media advertisements, and attended the research center for a detailed psychiatric assessment, including interviews, completion of questionnaires, and neuropsychological testing. Participants were classified into three groups: PIU with no comorbid impulsive/compulsive disorders (n = 18), PIU with one or more comorbid impulsive/compulsive disorders (n = 37), and healthy controls who did not have any mental health diagnoses (n = 67). Differences between the three groups were characterized in terms of demographic, clinical, and cognitive variables. Effect sizes for overall effects of group were also reported. Results The three groups did not significantly differ on age, gender, levels of education, nicotine consumption, or alcohol use (small effect sizes). Quality of life was significantly impaired in PIU irrespective of whether or not individuals had comorbid impulsive/compulsive disorders (large effect size). However, impaired response inhibition and decision-making were only identified in PIU with impulsive/compulsive comorbidities (medium effect sizes). Discussion and conclusions Most people with PIU will have one or more other impulsive/compulsive disorders, but PIU can occur without such comorbidities and still present with impaired quality of life. Response inhibition and decision-making appear to be disproportionately impacted in the case of PIU comorbid with other impulsive/compulsive conditions, which may account for some of the inconsistencies in the existing literature. Large scale international collaborations are required to validate PIU and further assess its clinical, cognitive, and biological sequelae.

Clinical variables and implications of the personality on the outcome of bipolar illness: a pilot study

PubMed Central

Casas-Barquero, Nieves; García-López, Olga; Fernández-Argüelles, Pedro; Camacho-Laraña, Manuel

2007-01-01

Outcome in bipolar patients is affected by comorbidity. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. This pilot study examined a series of 40 euthymic bipolar patients (DSM-IV criteria) (bipolar I disorder 31, bipolar II disorder 9) to assess the effect of clinical variables and the influence of comorbid personality on the clinical course of bipolar illness. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with “pure” bipolar patients (n = 10) with regard to demographic, clinical, and course of illness variables. Comorbid personality disorder was diagnosed in 75% of patients according to ICD-10 criteria, with obsessive-compulsive personality disorder being the most frequent type. Sixty-three per cent of subjects had more than one comorbid personality disorder. Bipolar patients with and without comorbid personality disorder showed no significant differences regarding features of the bipolar illness, although the group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness. In subjects with comorbid personality disorders, the number of hospitalizations correlated significantly with depressive episodes and there was an inverse correlation between age at the first episode and duration of bipolar illness. These findings, however, should be interpreted taking into account the preliminary nature of a pilot study and the contamination of the sample with too many bipolar II patients. PMID:19300559

The therapeutic potential of cannabinoids for movement disorders.

PubMed

Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

2015-03-01

There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders. © 2015 International Parkinson and Movement Disorder Society.

Disentangling the relative contribution of parental antisociality and family discord to child disruptive disorders.

PubMed

Bornovalova, Marina A; Blazei, Ryan; Malone, Stephen H; McGue, Matt; Iacono, William G

2013-07-01

A number of familial risk factors for childhood disruptive disorders have been identified. However, many of these risk factors often co-occur with parental antisociality, which by itself may account for both the familial risk factors and the increased likelihood of offspring disruptive behavior disorders (DBDs). The current study aimed to examine the association of parenting behaviors, marital conflict, and divorce with child DBDs while accounting for (a) coparent parenting behaviors, and (b) parental adult antisocial behavior (AAB). A series of regressions tested the association between family-level variables (namely, parent-child relationship quality, parental willingness to use physical punishment, marital adjustment, and history of divorce) and DBDs (attention deficit hyperactivity disorder, conduct disorder, and oppositional defiant disorder) alone and after statistically adjusting for coparent variables and parental AAB. Results indicated that parents with AAB were more likely to engage in various forms of maladaptive parenting, to divorce, and to have conflictual marriages. Maladaptive parenting, marital conflict, and divorce were associated with heightened rates of child DBDs, and these associations persisted after adjusting for coparent parenting and parental AAB. Finally, the mother's parenting behaviors had a higher impact on child DBDs than the father's parenting behaviors. Thus, familial variables continue to have an effect on childhood DBDs even after accounting for confounding influences. These variables should be a focus of research on etiology and intervention.

Disentangling the Relative Contribution of Parental Antisociality and Family Discord to Child Disruptive Disorders

PubMed Central

Bornovalova, Marina A.; Blazei, Ryan; Malone, Steve; McGue, Matt; Iacono, William G.

2012-01-01

A number of familial risk factors for childhood disruptive disorders have been identified. However, many of these risk factors often co-occur with parental antisociality, which by itself may account for both the familial risk factors and the increased likelihood of offspring disruptive behavior disorders (DBDs). The current study aimed to examine the association of parenting behaviors, marital conflict, and divorce with child DBDs while accounting for a) co-parent parenting behaviors, and b) parental adult antisocial behavior (AAB). A series of regressions tested the association between family-level variables (namely, parent-child relationship quality, parental willingness to use physical punishment, marital adjustment, and history of divorce) and DBDs (attention-deficit hyperactivity disorder, conduct disorder, and oppositional defiant disorder) alone and after statistically adjusting for co-parent variables and parental AAB. Results indicated that parents with AAB were more likely to engage in various forms of maladaptive parenting, to divorce, and to have conflictual marriages. Maladaptive parenting, marital conflict, and divorce were associated with heightened rates of child DBDs, and these associations persisted after adjusting for co-parent parenting and parental AAB. Finally, the mother’s parenting behaviors had a higher impact on child DBDs than the father’s parenting behaviors. Thus, familial variables continue to have an effect on childhood DBDs even after accounting for confounding influences. These variables should be a focus of research on etiology and intervention. PMID:22888991

Social cognition in bipolar disorder: Focus on emotional intelligence.

PubMed

Varo, C; Jimenez, E; Solé, B; Bonnín, C M; Torrent, C; Valls, E; Morilla, I; Lahera, G; Martínez-Arán, A; Vieta, E; Reinares, M

2017-08-01

The present study aims to characterize emotional intelligence (EI) variability in a sample of euthymic bipolar disorder (BD) patients through the Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT). A total of 134 euthymic BD outpatients were recruited and divided into three groups according to the total Emotional Intelligence Quotient (EIQ) score of the MSCEIT, following a statistical criterion of scores 1.5SDs above/below the normative group mean, as follows: a low performance (LP) group (EIQ <85), a normal performance (NP) group (85≤EIQ≤115), and a high performance (HP) group (EIQ >115). Afterwards, main sociodemographic, clinical, functional and neurocognitive variables were compared between the groups. Three groups were identified: 1) LP group (n=16, 12%), 2) NP group (n=93, 69%) and 3) HP group (n=25, 19%). There were significant differences between the groups in premorbid intelligence quotient (IQ) (p=0.010), axis II comorbidity (p=0.008), subthreshold depressive symptoms (p=0.027), general functioning (p=0.013) and in four specific functional domains: autonomy, occupation, interpersonal relations and leisure time. Significant differences in neurocognitive performance were found between groups with the LP group showing the lowest attainments. The cross-sectional design of the study. Our results suggest that EI variability among BD patients, assessed through MSCEIT, is lower than expected. EI could be associated with premorbid IQ, subthreshold depressive symptoms, neurocognitive performance and general functioning. The identification of different profiles of SC may help guide specific interventions for distinct patient subgroups aimed at improving social cognition, neurocognitive performance and psychosocial functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Subpopulations of Older Foster Youths With Differential Risk of Diagnosis for Alcohol Abuse or Dependence*

PubMed Central

Keller, Thomas E.; Blakeslee, Jennifer E.; Lemon, Stephenie C.; Courtney, Mark E.

2010-01-01

Objective: Distinctive combinations of factors are likely to be associated with serious alcohol problems among adolescents about to emancipate from the foster care system and face the difficult transition to independent adulthood. This study identifies particular subpopulations of older foster youths that differ markedly in the probability of a lifetime diagnosis for alcohol abuse or dependence. Method: Classification and regression tree (CART) analysis was applied to a large, representative sample (N = 732) of individuals, 17 years of age or older, placed in the child welfare system for more than 1 year. CART evaluated two exploratory sets of variables for optimal splits into groups distinguished from each other on the criterion of lifetime alcohol-use disorder diagnosis. Results: Each classification tree yielded four terminal groups with different rates of lifetime alcohol-use disorder diagnosis. Notable groups in the first tree included one characterized by high levels of both delinquency and violence exposure (53% diagnosed) and another that featured lower delinquency but an independent-living placement (21% diagnosed). Notable groups in the second tree included African American adolescents (only 8% diagnosed), White adolescents not close to caregivers (40% diagnosed), and White adolescents closer to caregivers but with a history of psychological abuse (36% diagnosed). Conclusions: Analyses incorporating variables that could be comorbid with or symptomatic of alcohol problems, such as delinquency, yielded classifications potentially useful for assessment and service planning. Analyses without such variables identified other factors, such as quality of caregiving relationships and maltreatment, associated with serious alcohol problems, suggesting opportunities for prevention or intervention. PMID:20946738

Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among adult eating disorder patients.

PubMed

Svedlund, Nils Erik; Norring, Claes; Ginsberg, Ylva; von Hausswolff-Juhlin, Yvonne

2017-01-17

Very little is known about the prevalence of ADHD symptoms in Bulimia Nervosa and Binge Eating Disorder and even less in other eating disorders. This knowledge gap is of clinical importance since stimulant treatment is proven effective in Binge Eating Disorder and discussed as a treatment possibility for Bulimia Nervosa. The objective of this study was to explore the prevalence and types of self-reported ADHD symptoms in an unselected group of eating disorder patients assessed in a specialized eating disorder clinic. In total 1165 adults with an eating disorder were assessed with a battery of standardized instruments, for measuring inter alia ADHD screening, demographic variables, eating disorder symptoms and psychiatric comorbidity. Chi-square tests were used for categorical variables and Kruskal-Wallis tests for continuous variables. Almost one third (31.3 %) of the patients scored above the screening cut off indicating a possible ADHD. The highest prevalence rates (35-37 %) were found in Bulimia Nervosa and Anorexia Nervosa bingeing/purging subtype, while Eating Disorder Not Otherwise Specified type 1-4 and Binge Eating Disorder patients reported slightly below average (26-31 %), and Anorexia Nervosa restricting subtype patients even lower (18 %). Presence of binge eating, purging, loss of control over eating and non-anorectic BMI were related to results indicating a possible ADHD. Psychiatric comorbidity correlated to ADHD symptoms without explaining the differences between eating disorder diagnoses. There is a high frequency of ADHD symptoms in patients with binge eating/purging eating disorders that motivates further studies, particularly concerning the effects of ADHD medication. The finding that the frequency of ADHD symptoms in anorexia nervosa with binge eating/purging is as high as in bulimia nervosa highlights the need also for this group.

The MAOA promoter polymorphism, disruptive behavior disorders, and early onset substance use disorder: gene-environment interaction.

PubMed

Vanyukov, Michael M; Maher, Brion S; Devlin, Bernie; Kirillova, Galina P; Kirisci, Levent; Yu, Ling-Mei; Ferrell, Robert E

2007-12-01

Conduct, oppositional defiant, and attention deficit hyperactivity disorders, reflecting early antisociality and behavior dysregulation, are predictive of substance use disorders. Liabilities to these disorders share genetic and environmental variance. Parenting characteristics have been shown to influence development of antisociality, moderated by variation at the MAOA gene, which has also been associated with the risk for substance use disorders. To extend these findings, we tested the relationships between the MAOA promoter polymorphism (variable number tandem repeat), indices of child's perception of paternal and maternal parenting, and disruptive behavior disorders and substance use disorders. A sample of 148 European-American males was assessed prospectively at ages from 10-12 to 18-19 years and genotyped for the monoamine oxidase A variable number tandem repeat. The Diagnostic and statistical manual of mental disorder-III-R diagnoses were obtained using standard methodology. Parenting was assessed using a scale summarizing the child's evaluation of the parenting style (parent's behavior toward him, parental emotional distance and involvement). Correlation, logistic regression, and Cox proportional hazard regression analysis was used to determine the relationships between the variables. The strength of association between parenting index and conduct and attention deficit hyperactivity disorders depended on the MAOA genotype. Unlike earlier findings, the parenting-risk relationships were observed in the 'high-' rather than 'low-activity' genotypes. The strength and direction of relationships depended on the parental sex. The MAOA polymorphism's association with the risk for substance use disorders was detected when parenting was controlled for. The results are consistent with the contribution of the MAOA gene, parenting style and their interactions to variation in the risk for early onset behavior disorders and liability to substance use disorders.

Dynamic Resting-State Functional Connectivity in Major Depression.

PubMed

Kaiser, Roselinde H; Whitfield-Gabrieli, Susan; Dillon, Daniel G; Goer, Franziska; Beltzer, Miranda; Minkel, Jared; Smoski, Moria; Dichter, Gabriel; Pizzagalli, Diego A

2016-06-01

Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.

Association between family history of mood disorders and clinical characteristics of bipolar disorder: results from the Brazilian bipolar research network.

PubMed

Berutti, Mariangeles; Nery, Fabiano G; Sato, Rodrigo; Scippa, Angela; Kapczinski, Flavio; Lafer, Beny

2014-06-01

To compare clinical characteristics of bipolar disorder (BD) in patients with and without a family history of mood disorders (FHMD) in a large sample from the Brazilian Research Network of Bipolar Disorders. Four-hundred eighty-eight DSM-IV BD patients participating in the Brazilian Research Network of Bipolar Disorders were included. Participants were divided between those with FHMD (n=230) and without FHMD (n=258). We compared these two groups on demographic and clinical variables and performed a logistic regression to identify which variables were most strongly associated with positive family history of mood disorders. BD patients with FHMD presented with significantly higher lifetime prevalence of any anxiety disorder, obsessive-compulsive disorder, social phobia, substance abuse, and were more likely to present history of suicide attempts, family history of suicide attempts and suicide, and more psychiatric hospitalizations than BD patients without FHMD. Logistic regression showed that the variables most strongly associated with a positive FHMD were any comorbid anxiety disorder, comorbid substance abuse, and family history of suicide. Cross-sectional study and verification of FHMD by indirect information. BD patients with FHMD differ from BD patients without FHMD in rates of comorbid anxiety disorder and substance abuse, number of hospitalizations and suicide attempts. As FHMD is routinely assessed in clinical practice, these findings may help to identify patients at risk for particular manifestations of BD and may point to a common, genetically determined neurobiological substrate that increases the risk of conditions such as comorbidities and suicidality in BD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Discrete subgroups of adolescents diagnosed with borderline personality disorder: a latent class analysis of personality features.

PubMed

Ramos, Vera; Canta, Guilherme; de Castro, Filipa; Leal, Isabel

2014-08-01

Research suggests that borderline personality disorder (BPD) can be diagnosed in adolescents and is marked by considerable heterogeneity. This study aimed to identify personality features characterizing adolescents with BPD and possible meaningful patterns of heterogeneity that could lead to personality subgroups. The authors analyzed data on 60 adolescents, ages 15 to 18 years, who met DSM criteria for a BPD diagnosis. The authors used latent class analysis (LCA) to identify subgroups based on the personality pattern scales from the Millon Adolescent Clinical Inventory (MACI). LCA indicated that the best-fitting solution was a two-class model, identifying two discrete subgroups of BPD adolescents that were described as internalizing and externalizing. The subgroups were then compared on clinical and sociodemographic variables, measures of personality dimensions, DSM BPD criteria, and perception of attachment styles. Adolescents with a BPD diagnosis constitute a heterogeneous group and vary meaningfully on personality features that can have clinical implications for treatment.

Diabetes mellitus in a girl with thyroid hormone resistance syndrome: a little recognized interaction between the two diseases.

PubMed

Stagi, Stefano; Manoni, Cristina; Cirello, Valentina; Covelli, Danila; Giglio, Sabrina; Chiarelli, Francesco; Seminara, Salvatore; de Martino, Maurizio

2014-01-01

The syndrome of resistance to thyroid hormone (RTH) is characterized by elevated serum free thyroid hormones (FT4 and FT3) in the presence of unsuppressed TSH levels, reflecting resistance to the normal negative feedback mechanisms in the hypothalamus and pituitary. The degree of resistance within peripheral tissues determines whether thyrotoxic clinical features are associated with this condition. Classic features include attention deficit hyperactivity disorder, growth delay, tachycardia, and goiter. However, other features, such as frequent ear, nose and throat infections, hearing deficit, and decreased bone mass have recently been recognized. The phenotype of RTH is variable, with most patients presenting with mild to moderate symptoms. In this report we describe a girl with familiar RTH and diabetes mellitus. This is, to our knowledge, the first report regarding this association. Nearly one year after long-term triiodothyroacetic acid (Triac) therapy, we observed a reduction of thyroid hormone levels with an amelioration of insulin resistance. The possible interactions between these disorders are discussed.

Kindler syndrome.

PubMed

Ashton, G H S

2004-03-01

Kindler syndrome is a rare, autosomal recessive skin fragility disorder characterized by blistering in infancy, followed by photosensitivity and progressive poikiloderma. Ultrastructural examination reveals marked basement membrane reduplication and variable levels of cleavage at the dermal-epidermal junction. The molecular pathology underlying Kindler syndrome has recently been shown to involve loss-of-function mutations in a novel gene, KIND1, encoding kindlin-1. Immunofluorescence, gene expression and cell biology studies have shown that kindlin-1 is expressed mainly in basal keratinocytes and plays a role in the attachment of the actin cytoskeleton via focal contacts to the extracellular matrix. Thus, Kindler syndrome is the first genodermatosis caused by a defect in actin-extracellular matrix linkage rather than the classic keratin-extracellular matrix linkage underlying the pathology of other inherited skin fragility disorders such as epidermolysis bullosa. This article reviews the clinical features as well as the molecular and cellular pathology of Kindler syndrome and highlights the importance of the new protein, kindlin-1, in cell-matrix adhesion and its intriguing link to photosensitivity.

A Latent Growth Mixture Modeling Approach to PTSD Symptoms in Rape Victims.

PubMed

Armour, Cherie; Shevlin, Mark; Elklit, Ask; Mroczek, Dan

2012-03-01

The research literature has suggested that longitudinal changes in posttraumatic stress disorder (PTSD) could be adequately described in terms of one universal trajectory, with individual differences in baseline levels (intercept) and rate of change (slope) being negligible. However, not everyone who has experienced a trauma is diagnosed with PTSD, and symptom severity levels differ between individuals exposed to similar traumas. The current study employed the latent growth mixture modeling technique to test for multiple trajectories using data from a sample of Danish rape victims (N = 255). In addition, the analysis aimed to determine whether a number of explanatory variables could differentiate between the trajectories (age, acute stress disorder [ASD], and perceived social support). Results concluded the existence of two PTSD trajectories. ASD was found to be the only significant predictor of one trajectory characterized by high initial levels of PTSD symptomatology. The present findings confirmed the existence of multiple trajectories with regard to PTSD symptomatology in a way that may be useful to clinicians working with this population.

[Steinert disease].

PubMed

Bouhour, Françoise; Bost, Muriel; Vial, Christophe

2007-06-01

Steinert disease, also known as myotonic dystrophy type 1, is a muscle disease characterized by myotonia and by multiorgan damage that combines various degrees of muscle weakness, arrhythmia and/or cardiac conduction disorders, cataract, endocrine damage, sleep disorders and baldness. It is the most frequent of the adult-onset muscular dystrophies; its prevalence is estimated at 1/20,000 inhabitants. Diagnosis is confirmed by the demonstration of an abnormality at the 19q13-2 locus, with the use of molecular genetic techniques. Its transmission is autosomal dominant, and anticipation may occur, that is, disease may be more severe and occur earlier in offspring. Genetic counseling is often delicate for this condition because of the great variability of clinical expression, both within and between families. Prenatal diagnosis is proposed especially for maternal transmission because of the severity of the possible neonatal forms. Management ideally includes multidisciplinary annual follow-up. Disease course is usually slowly progressive but rapid deterioration may sometimes be observed. Life expectancy is reduced by the increased mortality associated with the pulmonary and cardiac complications.

Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor.

PubMed

Molek, Peter; Vodnik, Miha; Strukelj, Borut; Bratkovič, Tomaž

2014-09-26

Initially considered the main endogenous anorexigenic factor, fat-derived leptin turned out to be a markedly pleiotropic hormone, influencing diverse physiological processes. Moreover, hyperleptinemia in obese individuals has been linked to the onset or progression of serious disorders, such as cancer, autoimmune diseases, and atherosclerosis, and antagonizing peripheral leptin's signalization has been shown to improve these conditions. To develop an antibody-based leptin antagonist we have devised a tailored panning procedure and screened two phage display libraries of single chain variable antibody fragments (scFvs) against recombinant leptin receptor. One of the scFvs was expressed in Escherichia coli and its interaction with leptin receptor was characterized in more detail. It was found to recognize a discontinuous epitope and to compete with leptin for receptor binding with IC50 and Kd values in the nanomolar range. The reported scFv represents a lead for development of leptin antagonists that may ultimately find use in therapy of various hyperleptinemia-related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Developmental disorders of the hypothalamus and pituitary gland associated with congenital hypopituitarism.

PubMed

Mehta, Ameeta; Dattani, Mehul T

2008-02-01

The pituitary gland is a complex organ secreting six hormones from five different cell types. It is the end product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of congenital hypopituitarism. These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, PITX1, PITX2, SOX2 and SOX3. The expression pattern of these transcription factors dictates the phenotype that results when the gene encoding the relevant transcription factor is mutated. The highly variable phenotype may consist of isolated hypopituitarism or more complex disorders such as septo-optic dysplasia and holoprosencephaly. However, the overall incidence of mutations in known transcription factors in patients with hypopituitarism is low, indicating that many genes remain to be identified; characterization of these will further elucidate the pathogenesis of this complex condition and also shed light on normal pituitary development and function.

A Latent Growth Mixture Modeling Approach to PTSD Symptoms in Rape Victims

PubMed Central

Armour, Cherie; Shevlin, Mark; Elklit, Ask; Mroczek, Dan

2012-01-01

The research literature has suggested that longitudinal changes in posttraumatic stress disorder (PTSD) could be adequately described in terms of one universal trajectory, with individual differences in baseline levels (intercept) and rate of change (slope) being negligible. However, not everyone who has experienced a trauma is diagnosed with PTSD, and symptom severity levels differ between individuals exposed to similar traumas. The current study employed the latent growth mixture modeling technique to test for multiple trajectories using data from a sample of Danish rape victims (N = 255). In addition, the analysis aimed to determine whether a number of explanatory variables could differentiate between the trajectories (age, acute stress disorder [ASD], and perceived social support). Results concluded the existence of two PTSD trajectories. ASD was found to be the only significant predictor of one trajectory characterized by high initial levels of PTSD symptomatology. The present findings confirmed the existence of multiple trajectories with regard to PTSD symptomatology in a way that may be useful to clinicians working with this population. PMID:22661909

Discovery of serum biomarkers predicting development of a subsequent depressive episode in social anxiety disorder.

PubMed

Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

2015-08-01

Although social anxiety disorder (SAD) is strongly associated with the subsequent development of a depressive disorder (major depressive disorder or dysthymia), no underlying biological risk factors are known. We aimed to identify biomarkers which predict depressive episodes in SAD patients over a 2-year follow-up period. One hundred sixty-five multiplexed immunoassay analytes were investigated in blood serum of 143 SAD patients without co-morbid depressive disorders, recruited within the Netherlands Study of Depression and Anxiety (NESDA). Predictive performance of identified biomarkers, clinical variables and self-report inventories was assessed using receiver operating characteristics curves (ROC) and represented by the area under the ROC curve (AUC). Stepwise logistic regression resulted in the selection of four serum analytes (AXL receptor tyrosine kinase, vascular cell adhesion molecule 1, vitronectin, collagen IV) and four additional variables (Inventory of Depressive Symptomatology, Beck Anxiety Inventory somatic subscale, depressive disorder lifetime diagnosis, BMI) as optimal set of patient parameters. When combined, an AUC of 0.86 was achieved for the identification of SAD individuals who later developed a depressive disorder. Throughout our analyses, biomarkers yielded superior discriminative performance compared to clinical variables and self-report inventories alone. We report the discovery of a serum marker panel with good predictive performance to identify SAD individuals prone to develop subsequent depressive episodes in a naturalistic cohort design. Furthermore, we emphasise the importance to combine biological markers, clinical variables and self-report inventories for disease course predictions in psychiatry. Following replication in independent cohorts, validated biomarkers could help to identify SAD patients at risk of developing a depressive disorder, thus facilitating early intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Is major depressive episode related to anxiety disorders in anorexics and bulimics?

PubMed

Godart, Nathalie T; Perdereau, Fabienne; Curt, Florence; Rein, Zoé; Lang, François; Venisse, Jean Luc; Halfon, Olivier; Bizouard, Paul; Loas, Gwenole; Corcos, Maurice; Jeammet, Philippe; Flament, Martine F

2006-01-01

To determine whether the presence of anxiety disorders is related to depressive comorbidity in subjects with eating disorders (ED), while taking into account certain variables that may be related to depression (subjects' age, ED duration, prior incidents of anorexia nervosa in bulimic subjects, inpatient or outpatient status, nutritional state [as measured by body mass index]). We evaluated the frequency of depressive disorders in 271 subjects presenting with a diagnosis of either anorexia nervosa or bulimia, using the Mini International Neuropsychiatric Interview, DSM-IV version. A multivariate analysis reveals that anxiety disorders do not all have the same influence in terms of risk of onset of major depressive episode in anorexics and bulimics when adjusted on variables related to depression. Depression in subjects with ED can be explained in part by comorbidity with obsessive-compulsive disorder, generalized anxiety, social phobia, and panic disorder.

Cognitive factors in panic disorder, agoraphobic avoidance and agoraphobia.

PubMed

Berle, David; Starcevic, Vladan; Hannan, Anthony; Milicevic, Denise; Lamplugh, Claire; Fenech, Pauline

2008-02-01

There remains a lack of consensus regarding the possibility that especially high levels of panic-related cognitions characterise panic disorder with agoraphobia. We administered the Anxiety Sensitivity Index, the Agoraphobic Cognitions Questionnaire and the Anxious Thoughts and Tendencies Scale as well as measures of agoraphobic avoidance to patients diagnosed with panic disorder with agoraphobia (n=75) and without agoraphobia (n=26). Patients with panic disorder with agoraphobia did not score significantly higher on any of the cognitive variables than did panic disorder patients without agoraphobia. However, most of the cognitive variables showed small to moderate-strength correlations with self-report measures of agoraphobic avoidance. Our findings suggest that anxiety sensitivity, catastrophising of the consequences of panic and a general anxiety-prone cognitive style, although to some extent associated with agoraphobic avoidance, do not discriminate panic disorder with agoraphobia from panic disorder without agoraphobia.

Associated and mediating variables related to quality of life among service users with mental disorders.

PubMed

Fleury, Marie-Josée; Grenier, Guy; Bamvita, Jean-Marie

2018-02-01

This study aimed to identify variables associated with quality of life (QoL) and mediating variables among 338 service users with mental disorders in Quebec (Canada). Data were collected using nine standardized questionnaires and participant medical records. Quality of life was assessed with the Satisfaction with Life Domains Scale. Independent variables were organized into a six-block conceptual framework. Using structural equation modeling, associated and mediating variables related to QoL were identified. Lower seriousness of needs was the strongest variable associated with QoL, followed by recovery, greater service continuity, gender (male), adequacy of help received, not living alone, absence of substance use or mood disorders, and higher functional status, in that order. Recovery was the single mediating variable linking lower seriousness of needs, higher service continuity, and reduced alcohol use with QoL. Findings suggest that greater service continuity creates favorable conditions for recovery, reducing seriousness of needs and increasing QoL among service users. Lack of recovery-oriented services may affect QoL among alcohol users, as substance use disorders were associated directly and negatively with QoL. Decision makers and mental health professionals should promote service continuity, and closer collaboration between primary care and specialized services, while supporting recovery-oriented services that encourage service user involvement in their treatment and follow-up. Community-based organizations should aim to reduce the seriousness of needs particularly for female service users and those living alone.

Intra-Individual Reaction Time Variability in Schizophrenia, Depression and Borderline Personality Disorder

ERIC Educational Resources Information Center

Kaiser, Stefan; Roth, Alexander; Rentrop, Mirjam; Friederich, Hans-Christoph; Bender, Stephan; Weisbrod, Matthias

2008-01-01

Intra-individual reaction time variability (IIV) in neuropsychological task performance reflects short term fluctuations in performance. Increased IIV has been reported in patients with schizophrenia and could be related to a deficient neural timing mechanism, but the role of IIV in adult patients with other psychiatric disorders has not been…

Atypical Pupillary Light Reflex and Heart Rate Variability in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Daluwatte, Chathuri; Miles, Judith H.; Christ, Shawn E.; Beversdorf, David Q.; Takahashi, T. Nicole; Yao, Gang

2013-01-01

We investigated pupillary light reflex (PLR) in 152 children with ASD, 116 typically developing (TD) children, and 36 children with non-ASD neurodevelopmental disorders (NDDs). Heart rate variability (HRV) was measured simultaneously to study potential impairments in the autonomic nervous system (ANS) associated with ASD. The results showed that…

Phonetic Variability in Residual Speech Sound Disorders: Exploration of Subtypes

ERIC Educational Resources Information Center

Preston, Jonathan L.; Koenig, Laura L.

2011-01-01

Purpose: To explore whether subgroups of children with residual speech sound disorders (R-SSDs) can be identified through multiple measures of token-to-token phonetic variability (changes in one spoken production to the next). Method: Children with R-SSDs were recorded during a rapid multisyllabic picture naming task and an oral diadochokinetic…

Does Response Variability Predict Distractibility among Adults with Attention-Deficit/Hyperactivity Disorder?

ERIC Educational Resources Information Center

Adams, Zachary W.; Roberts, Walter M.; Milich, Richard; Fillmore, Mark T.

2011-01-01

Increased intraindividual variability in response time (RTSD) has been observed reliably in attention-deficit/hyperactivity disorder (ADHD) and has often been used as a measure of inattention. RTSD is assumed to reflect attentional lapses and distractibility, though evidence for the validity of this connection is lacking. We assessed whether RTSD…

Robotic set-up to quantify hand-eye behavior in motor execution and learning of children with autism spectrum disorder.

PubMed

Casellato, Claudia; Gandolla, Marta; Crippa, Alessandro; Pedrocchi, Alessandra

2017-07-01

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder characterized by a persistence of social and communication impairment, and restricted and repetitive behaviors. However, motor disorders have also been described, but not objectively assessed. Most studies showed inefficient eye-hand coordination and motor learning in children with ASD; in other experiments, mechanisms of acquisition of internal models in self-generated movements appeared to be normal in autism. In this framework, we have developed a robotic protocol, recording gaze and hand data during upper limb tasks, in which a haptic pen-like handle is moved along specific trajectories displayed on the screen. The protocol includes trials of reaching under a perturbing force field and catching moving targets, with or without visual availability of the whole path. We acquired 16 typically-developing scholar-age children and one child with ASD as a case study. Speed-accuracy tradeoff, motor performance, and gaze-hand spatial coordination have been evaluated. Compared to typically developing peers, in the force field sequence, the child with ASD showed an intact but delayed learning, and more variable gazehand patterns. In the catching trials, he showed less efficient movements, but an intact capability of exploiting the available a-priori plan. The proposed protocol represents a powerful tool, easily tunable, for quantitative (longitudinal) assessment, and for subject-tailored training in ASD.

The Therapeutic Potential of Cannabinoids for Movement Disorders

PubMed Central

Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

2014-01-01

Background There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and particularly for neurologic conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science, preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. Results The pharmacology of cannabis is complex with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits but more consistently suggest potential neuroprotective effects in several animal models of Parkinson’s (PD) and Huntington’s disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia or ataxia and nonexistent for myoclonus or restless legs syndrome. Conclusions Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological and therapeutic effects of this class of drugs in movement disorders. PMID:25649017

Diminished heart rate complexity in adolescent girls: a sign of vulnerability to anxiety disorders?

PubMed

Fiol-Veny, Aina; De la Torre-Luque, Alejandro; Balle, Maria; Bornas, Xavier

2018-07-01

Diminished heart rate variability has been found to be associated with high anxiety symptomatology. Since adolescence is the period of onset for many anxiety disorders, this study aimed to determine sex- and anxiety-related differences in heart rate variability and complexity in adolescents. We created four groups according to sex and anxiety symptomatology: high-anxiety girls (n = 24) and boys (n = 25), and low-anxiety girls (n = 22) and boys (n = 24) and recorded their cardiac function while they performed regular school activities. A series of two-way (sex and anxiety) MANOVAs were performed on time domain variability, frequency domain variability, and non-linear complexity. We obtained no multivariate interaction effects between sex and anxiety, but highly anxious participants had lower heart rate variability than the low-anxiety group. Regarding sex, girls showed lower heart rate variability and complexity than boys. The results suggest that adolescent girls have a less flexible cardiac system that could be a marker of the girls' vulnerability to developing anxiety disorders.

Eating Disorders and Their Associated Risk Factors among Iranian Population – A Community Based Study

PubMed Central

Garrusi, Behshid; Baneshi, Mohammad Reza

2013-01-01

Backgrounds: Many socio cultural variables could be affect eating disorders in Asian countries. In Iran, there are few researches regarding eating disorders and their contributing factors. The aim of this study is to explore frequency of eating disorders and their risk factors in an Iranian population. Materials and Methods: About 1204 participants were selected aged between fourteen to 55 years. Frequency of eating disorders and effects of variables such as demographic characteristics, Body Mass Index (BMI), use of media, body dissatisfaction, self-esteem, social comparison and social pressure for thinness in individuals with and without eating disorders, were assessed. Findings: The prevalence of eating disorders was 11.5% that included 0.8% anorexia nervosa, 6.2% full threshold bulimia nervosa, 1.4% sub threshold anorexia nervosa and 30% sub threshold binge eating disorder. Symptoms of bulimic syndrome were greater in males. Conclusion: In Iran, eating disorders and related problems are new issue that could be mentioned seriously The identification of these disorders and their related contributing factors are necessity of management and preventive programs planning. PMID:23283053

Differentiating among singular and comorbid obsessive-compulsive disorder and social phobia symptomology.

PubMed

Rudy, Brittany M; May, Anna C; Whiting, Sara E; Davis, Thompson E; Jenkins, Whitney S; Reuther, Erin T

2014-01-01

Social phobia is a frequent co-occurring diagnosis with obsessive-compulsive disorder (OCD); however, co-occurring OCD in those with social phobia is less common. Genetic, environmental, and cognitive traits are common risk factors for anxiety disorders broadly. It is plausible that shared variables related to OCD and/or social phobia could provide insight into the co-occurrence of these two disorders. The current study explored differences in fear of negative evaluation (FNE) and perfectionism among four groups: those with (1) elevated social phobia symptoms, (2) elevated OCD symptoms, (3) elevated symptoms of OCD and social phobia, and those who were (4) asymptomatic as a control group. A non-clinical sample of 196 participants completed several online questionnaires about social phobia and OCD symptomology. Results identified three cognitive variables (i.e., FNE, total perfectionism, and concern over mistakes) as differential variables in comorbid symptom presentation of OCD and social phobia. A fourth variable (i.e., doubts about actions) was identified as a potential dual risk factor, and four subsequent variables (i.e., parental criticism, personal standards, parental expectations, and organization) were not implicated in differential symptom presentation. Given the different rates of OCD and social phobia co-occurrence, identification of differentiating variables could aid in better understanding of potential risk factors, which may enhance preventative and therapeutic techniques. Study implications, limitations, and future recommendations are discussed.

Performance on a computerized shopping task significantly predicts real world functioning in persons diagnosed with bipolar disorder.

PubMed

Laloyaux, Julien; Pellegrini, Nadia; Mourad, Haitham; Bertrand, Hervé; Domken, Marc-André; Van der Linden, Martial; Larøi, Frank

2013-12-15

Persons diagnosed with bipolar disorder often suffer from cognitive impairments. However, little is known concerning how these cognitive deficits impact their real world functioning. We developed a computerized real-life activity task, where participants are required to shop for a list of grocery store items. Twenty one individuals diagnosed with bipolar disorder and 21 matched healthy controls were administered the computerized shopping task. Moreover, the patient group was assessed with a battery of cognitive tests and clinical scales. Performance on the shopping task significantly differentiated patients and healthy controls for two variables: Total time to complete the shopping task and Mean time spent to consult the shopping list. Moreover, in the patient group, performance on these variables from the shopping task correlated significantly with cognitive functioning (i.e. processing speed, verbal episodic memory, planning, cognitive flexibility, and inhibition) and with clinical variables including duration of illness and real world functioning. Finally, variables from the shopping task were found to significantly explain 41% of real world functioning of patients diagnosed with bipolar disorder. These findings suggest that the shopping task provides a good indication of real world functioning and cognitive functioning of persons diagnosed with bipolar disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Homework compliance counts in cognitive-behavioral therapy.

PubMed

Lebeau, Richard T; Davies, Carolyn D; Culver, Najwa C; Craske, Michelle G

2013-01-01

Prior research has demonstrated that there is some association between treatment engagement and treatment outcome in behavioral therapy for anxiety disorders. However, many of these investigations have been limited by weak measurement of treatment engagement variables, failure to control for potentially important baseline variables, and failure to consider various treatment engagement variables simultaneously. The purpose of the present study is to examine the relationship between two treatment engagement variables (treatment expectancy and homework compliance) and the extent to which they predict improvement from cognitive-behavioral therapy (CBT) for anxiety disorders. 84 adults with a DSM-IV-defined principal anxiety disorder took part in up to 12 sessions of CBT or acceptance and commitment therapy. Pre- and post-treatment disorder severity was assessed using clinical severity ratings from a semi-structured diagnostic interview. Participants made ratings of treatment expectancy after the first session. Homework compliance was assessed each session by the treating clinician. Contrary to hypotheses, treatment expectancy and homework compliance were poorly correlated. Regression analyses revealed that homework compliance, but not treatment expectancy, predicted a significant portion of the variance in treatment outcome (10%). The present research suggests that although treatment expectation and homework compliance likely represent unique constructs of treatment engagement, homework compliance may be the more important treatment engagement variable for outcomes. The present research suggests that improvement of homework compliance has the potential to be a highly practical and effective way to improve clinical outcomes in CBT targeting anxiety disorders.

Longitudinal Changes in Functioning and Disability in Patients with Disorders of Consciousness: The Importance of Environmental Factors

PubMed Central

Willems, Michelle; Sattin, Davide; Vingerhoets, Ad J.J.M.; Leonardi, Matilde

2015-01-01

Disorders of consciousness are neurological conditions associated with low levels of functioning which pose a serious challenge to public health systems. The current study aimed to examine longitudinal changes in functioning in patients with disorders of consciousness and to identify associated biopsychosocial factors using the International Classification of Functioning, Disability, and Health. An Italian sample of 248 patients was assessed longitudinally. Differences in relative variability (an index of change that controls for baseline levels) between acute and chronic patients and predictors of relative variability in “Activities & Participation” were examined. Results showed that there were subgroups of patients whose functioning improved over time. The number of problems in “Activities & Participation” decreased in acute patients over time, whereas in chronic patients, an increase was found. The significant difference in relative variability for the environmental factor “support and relationships” reflects the increase in facilitators in acute patients, whereas the number of facilitators in chronic patients remained unchanged over time. Age at event, time from event, and relative variability in “Environmental Factors” were significant predictors of relative variability in “Activities & Participation”. It is of clinical relevance that patients with disorders of consciousness are kept in a supportive and facilitative environment, in order to prevent a decline in their functioning. Moreover, caregivers should receive tailored support in order to enhance and facilitate appropriate care of patients with disorders of consciousness. PMID:25837348

Systematic review of the neural basis of social cognition in patients with mood disorders.

PubMed

Cusi, Andrée M; Nazarov, Anthony; Holshausen, Katherine; Macqueen, Glenda M; McKinnon, Margaret C

2012-05-01

This review integrates neuroimaging studies of 2 domains of social cognition--emotion comprehension and theory of mind (ToM)--in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were "fMRI," "emotion comprehension," "emotion perception," "affect comprehension," "affect perception," "facial expression," "prosody," "theory of mind," "mentalizing" and "empathy" in combination with "major depressive disorder," "bipolar disorder," "major depression," "unipolar depression," "clinical depression" and "mania." Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Studies that did not include control tasks or a comparator group were included in this review. Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks under lying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders.

Association Between Childhood to Adolescent Attention Deficit/Hyperactivity Disorder Symptom Trajectories and Late Adolescent Disordered Eating.

PubMed

Yilmaz, Zeynep; Javaras, Kristin N; Baker, Jessica H; Thornton, Laura M; Lichtenstein, Paul; Bulik, Cynthia M; Larsson, Henrik

2017-08-01

Disordered eating is more prevalent among adolescents with attention deficit/hyperactivity disorder. Both inattention and hyperactivity/impulsivity symptoms show strong associations with disordered eating, but few investigations of these associations have been longitudinal. Thus, we examined the effect of childhood to adolescent inattention and hyperactivity/impulsivity symptom trajectories on late adolescent disordered eating. We used growth mixture modeling to identify distinct inattention and hyperactivity/impulsivity symptom trajectories (called "classes") across three time points (ages 8-9, 13-14, and 16-17 years) in the Swedish Twin study of CHild and Adolescent Development. The resulting classes were used to predict Eating Disorder Inventory-2 Bulimia, Drive for Thinness, and Body Dissatisfaction subscales at age 16-17 years, with adjustment for sex and body mass index at age 16-17 years. The combined inattention and hyperactivity/impulsivity symptom trajectory classes included: a "low symptom" class characterized by low inattention and hyperactivity/impulsivity throughout childhood/adolescence; a "predominantly inattention" class characterized by elevated inattention, but not hyperactivity/impulsivity, throughout childhood/adolescence; a "predominantly hyp/imp" class characterized by elevated hyperactivity/impulsivity, but not inattention, throughout childhood/adolescence; and a "both inattention and hyp/imp" class characterized by elevated inattention and hyperactivity/impulsivity throughout childhood/adolescence. After adjusting for sex and body mass index or sex and anxiety/depression symptoms, the "both inattention and hyp/imp" (vs. "low symptom") class predicted significantly higher Eating Disorder Inventory-2 subscale scores during late adolescence. Increased vigilance for disordered eating among children who have both inattention and hyperactivity/impulsivity symptoms throughout childhood and adolescence could aid in early identification of eating disorders. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Categories versus dimensions in personality and psychopathology: a quantitative review of taxometric research.

PubMed

Haslam, N; Holland, E; Kuppens, P

2012-05-01

Taxometric research methods were developed by Paul Meehl and colleagues to distinguish between categorical and dimensional models of latent variables. We have conducted a comprehensive review of published taxometric research that included 177 articles, 311 distinct findings and a combined sample of 533 377 participants. Multilevel logistic regression analyses have examined the methodological and substantive variables associated with taxonic (categorical) findings. Although 38.9% of findings were taxonic, these findings were much less frequent in more recent and methodologically stronger studies, and in those reporting comparative fit indices based on simulated comparison data. When these and other possible confounds were statistically controlled, the true prevalence of taxonic findings was estimated at 14%. The domains of normal personality, mood disorders, anxiety disorders, eating disorders, externalizing disorders, and personality disorders (PDs) other than schizotypal yielded little persuasive evidence of taxa. Promising but still not definitive evidence of psychological taxa was confined to the domains of schizotypy, substance use disorders and autism. This review indicates that most latent variables of interest to psychiatrists and personality and clinical psychologists are dimensional, and that many influential taxonic findings of early taxometric research are likely to be spurious.

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Montplaisir, Jacques; Lanfranchi, Paola; Blais, Hélène; Rompré, Sylvie; Colombo, Roberto; Gagnon, Jean-François

2011-07-01

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder. Copyright © 2011 Movement Disorder Society.

Social functioning as a predictor of the use of mental health resources in patients with severe mental disorder.

PubMed

Bellido-Zanin, Gloria; Pérez-San-Gregorio, María Ángeles; Martín-Rodríguez, Agustín; Vázquez-Morejón, Antonio J

2015-12-15

Previous studies have tried to determine the factors causing greater use of health resources by patients with mental disorders. These studies have essentially focused on socio-economic variables. Nevertheless, many other variables, such as social functioning, have not yet been explored. This study aims to assess the effect of social functioning on mental health service use in a sample of patients with severe mental disorder (schizophrenia, other psychotic disorders or bipolar affective disorder) in an area of Spain. The Social Functioning Scale (SFS) was administered to 172 family members of patients with a severe mental disorder who were receiving care at a community mental health unit. Analysis of bivariate logistic regression identified specific areas as predictors of the use of mental health resources over a 12-month follow-up period. The overall social functioning score predicted need for hospital admissions. In addition, interpersonal behaviour had a major role in the number of outpatient visits, while social isolation significantly predicted the need for hospitalization. These results point out the necessity for including psychosocial variables, such as social functioning in current mental health resource use models. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of social cognitive impairment on speech disorder in schizophrenia.

PubMed

Docherty, Nancy M; McCleery, Amanda; Divilbiss, Marielle; Schumann, Emily B; Moe, Aubrey; Shakeel, Mohammed K

2013-05-01

Disordered speech in schizophrenia impairs social functioning because it impedes communication with others. Treatment approaches targeting this symptom have been limited by an incomplete understanding of its causes. This study examined the process underpinnings of speech disorder, assessed in terms of communication failure. Contributions of impairments in 2 social cognitive abilities, emotion perception and theory of mind (ToM), to speech disorder were assessed in 63 patients with schizophrenia or schizoaffective disorder and 21 nonpsychiatric participants, after controlling for the effects of verbal intelligence and impairments in basic language-related neurocognitive abilities. After removal of the effects of the neurocognitive variables, impairments in emotion perception and ToM each explained additional variance in speech disorder in the patients but not the controls. The neurocognitive and social cognitive variables, taken together, explained 51% of the variance in speech disorder in the patients. Schizophrenic disordered speech may be less a concomitant of "positive" psychotic process than of illness-related limitations in neurocognitive and social cognitive functioning.

Association between Magnesium Disorders and Hypocalcemia following Thyroidectomy.

PubMed

Nellis, Jason C; Tufano, Ralph P; Gourin, Christine G

2016-09-01

To identify factors associated with postoperative hypocalcemia after thyroid surgery and to understand the relationship among hypocalcemia, length of hospitalization, and costs of care. Retrospective database analysis. Discharge data from the Nationwide Inpatient Sample for 620,744 patients who underwent thyroid surgery from 2001 to 2010 were analyzed through cross-tabulations and multivariate regression modeling. Hypocalcemia, length of stay, and costs were examined as dependent variables. Secondary independent variables included magnesium and phosphate metabolism disorders, vitamin D deficiency, menopause, sex, extent of surgery, malignancy, and surgeon volume. Hypocalcemia was reported in 6% of patients and was significantly more common for the following variables: women, age <65 years, patients from the Northeast, total thyroidectomy ± neck dissection patients, low-volume surgical care, malignancy, recurrent laryngeal nerve injury, and patients with disorders of magnesium or phosphate metabolism (P < .001). Magnesium and phosphate disorders were present in <1% of patients. Magnesium disorders were significantly more likely for patients with hypocalcemia (7%; P < .001), and hypocalcemia was present in 52% of patients with magnesium disorders (P < .001). On multiple logistic regression analysis, the odds of hypocalcemia were greatest for patients with magnesium disorders (odds ratio, 12.71; 95% confidence interval, 8.59-18.82). This relationship was not attenuated by high-volume surgical care. Hypocalcemia and magnesium disorders were both associated with increased length of stay and costs, with a greater effect for magnesium disorders than for hypocalcemia (P < .001). Disorders of magnesium metabolism are an independent risk factor for postthyroidectomy hypocalcemia and are associated with significantly increased costs and length of stay. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Relation of Psychiatric Symptoms with Epilepsy, Asthma, and Allergy in Youth with ASD vs. Psychiatry Referrals.

PubMed

Weber, Rebecca J; Gadow, Kenneth D

2017-08-01

The present study aimed to characterize the association of psychopathology with the clinical correlates of epilepsy, asthma, and allergy within and between neurobehavioral syndromes. Participants were consecutively evaluated youth (6-18 years, 75 % male) with autism spectrum disorder (ASD; n = 589) and non-ASD outpatient psychiatry referrals (n = 653). Informants completed a background questionnaire (parents) and a psychiatric symptom severity rating scale (parents, teachers). Youth with ASD had higher rates of epilepsy and allergy but not asthma than psychiatry referrals, even when analyses were limited to youth with IQ ≥ 70. Somatic conditions evidenced variable associations with medical services utilization, educational interventions, family income, and maternal education. Youth with ASD with versus without epilepsy had more severe ASD social deficits (parents' ratings) and less severe ASD repetitive behaviors (teachers' ratings). Epilepsy was associated with more severe depression, mania, and schizophrenia symptoms in youth with ASD. Youth with allergy (psychiatry referrals only) had more severe anxiety and depression symptoms (parents' ratings) but less severe aggression (teachers' ratings) thus providing evidence of both context- and diagnostic-specificity. Youth with ASD versus non-ASD psychiatry referrals evidence a variable pattern of relations between somatic conditions and a range of clinical correlates, which suggests that the biologic substrates and psychosocial concomitants of neurodevelopmental disorders and their co-occurring somatic conditions may interact to produce unique clinical phenotypes.

Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8.

PubMed

Boycott, Kym M; Beaulieu, Chandree L; Kernohan, Kristin D; Gebril, Ola H; Mhanni, Aziz; Chudley, Albert E; Redl, David; Qin, Wen; Hampson, Sarah; Küry, Sébastien; Tetreault, Martine; Puffenberger, Erik G; Scott, James N; Bezieau, Stéphane; Reis, André; Uebe, Steffen; Schumacher, Johannes; Hegele, Robert A; McLeod, D Ross; Gálvez-Peralta, Marina; Majewski, Jacek; Ramaekers, Vincent T; Nebert, Daniel W; Innes, A Micheil; Parboosingh, Jillian S; Abou Jamra, Rami

2015-12-03

Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Lack of Breastfeeding: A Potential Risk Factor in the Multifactorial Genesis of Borderline Personality Disorder and Impaired Maternal Bonding.

PubMed

Schwarze, Cornelia E; Hellhammer, Dirk H; Stroehle, Verena; Lieb, Klaus; Mobascher, Arian

2015-10-01

Borderline personality disorder (BPD) is characterized by a pattern of intense but unstable interpersonal relationships. These interpersonal dysfunctions may originate from impaired bonding and attachment that is determined during early life. Remarkably, it has been reported that the quality of mother-infant relationship is influenced by the feeding mode. Thus, bottle feeding instead of breastfeeding and possible lack of maternal bonding-related behavior may increase the risk for later psychopathology and attachment problems as seen in BPD. A total of 100 BPD patients and 100 matched healthy controls underwent semistructured interviews, based on retrospective information about early risk factors and breastfeeding during infancy. The authors' analyses revealed that BPD patients were significantly less breastfed compared to healthy controls (no breastfeeding in BPD: 42.4%; no breastfeeding in controls: 18.2%; p < .001). The BPD diagnosis was significantly predicted by the variable "no breastfeeding" (p < .001; odds ratio [OR] = 3.32; confidence interval [CI] [1.74, 6.34]), even after adjustment for childhood trauma and several confounding factors (p = .001). The variable "no breastfeeding" accounts for 9.1% of the variance of the BPD diagnosis and is associated with low perceived maternal bonding (p = .006). Breastfeeding may act as an early indicator of the mother-infant relationship that seems to be relevant for bonding and attachment later in life.

Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme

PubMed Central

Dhalla, F; da Silva, S P; Lucas, M; Travis, S; Chapel, H

2011-01-01

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immunodeficiencies in adults. They comprise a heterogeneous group of pathologies, with frequent non-infectious complications in addition to the bacterial infections that usually characterize their presentation. Complications include a high risk of malignancy, especially lymphoma and gastric cancer. Helicobacter pylori infection and pernicious anaemia are risk predictors for gastric cancer in the general population and probably in patients with CVIDs. Screening for gastric cancer in a high-risk population appears to improve survival. Given the increased risk of gastric cancer in patients with CVIDs and prompted by a case of advanced gastric malignancy in a patient with a CVID and concomitant pernicious anaemia, we performed a review of the literature for gastric cancer and conducted a cohort study of gastric pathology in 116 patients with CVIDs under long-term follow-up in Oxford. Regardless of the presence of pernicious anaemia or H. pylori infection, patients with CVIDs have a 10-fold increased risk of gastric cancer and are therefore a high-risk population. Although endoscopic screening of all patients with CVIDs could be considered, a more selective approach is appropriate and we propose a surveillance protocol that should reduce modifiable risk factors such as H. pylori, in order to improve the management of patients with CVIDs at risk of gastric malignancy. PMID:21470209

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

PubMed Central

Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

2016-01-01

ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

Response time intra-subject variability: commonalities between children with autism spectrum disorders and children with ADHD

PubMed Central

Adamo, Nicoletta; Huo, Lan; Adelsberg, Samantha; Petkova, Eva; Castellanos, F. Xavier

2013-01-01

Despite the common co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) in individuals with autism spectrum disorders (ASD), the underlying mechanisms are under-explored. A potential candidate for investigation is response time intra-subject variability (RT-ISV), a hypothesized marker of attentional lapses. Direct comparisons of RT-ISV in ASD versus ADHD are limited and contradictory. We aimed to examine whether distinct fluctuations in RT-ISV characterize children with ASD and with ADHD relative to typically developing children (TDC). We applied both a priori-based and data-driven strategies to RT performance of 46 children with ASD, 46 with ADHD, and 36 TDC (aged 7–11.9 years). Specifically, we contrasted groups relative to the amplitude of four preselected frequency bands as well as to 400 frequency bins from 0.006 to 0.345 Hz. In secondary analyses, we divided the ASD group into children with and without substantial ADHD symptoms (ASD+ and ASD−, respectively). Regardless of the strategy employed, RT-ISV fluctuations at frequencies between 0.20 and 0.345 Hz distinguished children with ADHD, but not children with ASD, from TDC. Children with ASD+ and those with ADHD shared elevated amplitudes of RT-ISV fluctuations in frequencies between 0.18 and 0.345 Hz relative to TDC. In contrast, the ASD− subgroup did not differ from TDC in RT-ISV frequency fluctuations. RT-ISV fluctuations in frequencies 0.18–0.345 Hz (i.e., periods between 3 and 5 s) are associated with ADHD symptoms regardless of categorical diagnosis and may represent a biomarker. These results suggest that children with ADHD and those with ASD+ share common underlying pathophysiological mechanisms of RT-ISV. PMID:23716135

Reductions in the diurnal rigidity of anxiety predict treatment outcome in cognitive behavioral therapy for generalized anxiety disorder.

PubMed

Fisher, Aaron J; Newman, Michelle G

2016-04-01

Generalized anxiety disorder (GAD) is a chronic and disabling disorder which is characterized by worrisome mentation about future outcomes. Because the evocative stimuli in GAD are largely internally derived, the feared outcomes contained in worry episodes can be invoked--and responded to--regardless of external context. We hypothesized that individuals with GAD would be entrained to internally-regulated, fixed patterns of anxiety on a day-to-day basis and that successful therapeutic intervention would serve to mitigate this entrainment. Thus, the present study examined the constructs of flexibility and rigidity as they apply to the daily fluctuation of anxious symptoms in individuals with GAD. We aimed to demonstrate that an apparently variable system can be conceptualized as rigid when the variability maps onto stable and predictable periodic oscillations. Sixty-nine individuals completed cognitive-behavioral treatment for GAD. Average age was 36.62 years (SD = 11.56), and participants were mostly Caucasian (89.5%) and female (68.4%). Daily-diary data indicating level of anxiety on a 0 to 100-point scale and collected four times per day were subjected to spectral analysis in order to determine the spectral power attributable to daily oscillations--which was related to the degree of rigidity in daily anxiety. Diurnal rigidity decreased throughout therapy and the degree to which rigidity was reduced significantly predicted reliable change at post-treatment. Thus, symptom rigidity can be conceptualized as stable periodic fluctuation and is discernible from other metrics of volatility in repeated measures data. Moreover, diurnal rigidity is significantly reduced during treatment, facilitating flexible responding to environmental demands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dysregulation of objectively assessed 24-hour motor activity patterns as a potential marker for bipolar I disorder: results of a community-based family study

PubMed Central

Shou, H; Cui, L; Hickie, I; Lameira, D; Lamers, F; Zhang, J; Crainiceanu, C; Zipunnikov, V; Merikangas, K R

2017-01-01

There has been a growing number of studies that have employed actigraphy to investigate differences in motor activity in mood disorders. In general, these studies have shown that people with bipolar disorders (BPDs) tend to exhibit greater variability and less daytime motor activity than controls. The goal of this study was to examine whether patterns of motor activity differ in euthymic individuals across the full range of mood disorder subtypes (Bipolar I (BPI), Bipolar II (BPII) and major depression (MDD)) compared with unaffected controls in a community-based family study of mood spectrum disorders. Minute-to-minute activity counts derived from actigraphy were collected over a 2-week period for each participant. Prospective assessments of the level, timing and day-to-day variability of physical activity measures were compared across diagnostic groups after controlling for a comprehensive list of potential confounding factors. After adjusting for the effects of age, sex, body mass index (BMI) and medication use, the BPI group had lower median activity intensity levels across the second half of the day and greater variability in the afternoon compared with controls. Those with a history of BPII had increased variability during the night time compared with controls, indicating poorer sleep quality. No differences were found in the average intensity, variability or timing of activity in comparisons between other mood disorder subgroups and controls. Findings confirm evidence from previous studies that BPI may be a manifestation of a rhythm disturbance that is most prominent during the second half of the day. The present study is the largest study to date that included the full range of mood disorder subgroups in a nonclinical sample that increases the generalizability of our findings to the general community. The manifestations of activity patterns outside of acute episodes add to the accumulating evidence that dysregulation of patterns of activity may constitute a potential biomarker for BPD. PMID:28892068

Dysregulation of objectively assessed 24-hour motor activity patterns as a potential marker for bipolar I disorder: results of a community-based family study.

PubMed

Shou, H; Cui, L; Hickie, I; Lameira, D; Lamers, F; Zhang, J; Crainiceanu, C; Zipunnikov, V; Merikangas, K R

2017-08-22

There has been a growing number of studies that have employed actigraphy to investigate differences in motor activity in mood disorders. In general, these studies have shown that people with bipolar disorders (BPDs) tend to exhibit greater variability and less daytime motor activity than controls. The goal of this study was to examine whether patterns of motor activity differ in euthymic individuals across the full range of mood disorder subtypes (Bipolar I (BPI), Bipolar II (BPII) and major depression (MDD)) compared with unaffected controls in a community-based family study of mood spectrum disorders. Minute-to-minute activity counts derived from actigraphy were collected over a 2-week period for each participant. Prospective assessments of the level, timing and day-to-day variability of physical activity measures were compared across diagnostic groups after controlling for a comprehensive list of potential confounding factors. After adjusting for the effects of age, sex, body mass index (BMI) and medication use, the BPI group had lower median activity intensity levels across the second half of the day and greater variability in the afternoon compared with controls. Those with a history of BPII had increased variability during the night time compared with controls, indicating poorer sleep quality. No differences were found in the average intensity, variability or timing of activity in comparisons between other mood disorder subgroups and controls. Findings confirm evidence from previous studies that BPI may be a manifestation of a rhythm disturbance that is most prominent during the second half of the day. The present study is the largest study to date that included the full range of mood disorder subgroups in a nonclinical sample that increases the generalizability of our findings to the general community. The manifestations of activity patterns outside of acute episodes add to the accumulating evidence that dysregulation of patterns of activity may constitute a potential biomarker for BPD.

Threat-Related Attention Bias Variability and Posttraumatic Stress.

PubMed

Naim, Reut; Abend, Rany; Wald, Ilan; Eldar, Sharon; Levi, Ofir; Fruchter, Eyal; Ginat, Karen; Halpern, Pinchas; Sipos, Maurice L; Adler, Amy B; Bliese, Paul D; Quartana, Phillip J; Pine, Daniel S; Bar-Haim, Yair

2015-12-01

Threat monitoring facilitates survival by allowing one to efficiently and accurately detect potential threats. Traumatic events can disrupt healthy threat monitoring, inducing biased and unstable threat-related attention deployment. Recent research suggests that greater attention bias variability, that is, attention fluctuations alternating toward and away from threat, occurs in participants with PTSD relative to healthy comparison subjects who were either exposed or not exposed to traumatic events. The current study extends findings on attention bias variability in PTSD. Previous measurement of attention bias variability was refined by employing a moving average technique. Analyses were conducted across seven independent data sets; in each, data on attention bias variability were collected by using variants of the dot-probe task. Trauma-related and anxiety symptoms were evaluated across samples by using structured psychiatric interviews and widely used self-report questionnaires, as specified for each sample. Analyses revealed consistent evidence of greater attention bias variability in patients with PTSD following various types of traumatic events than in healthy participants, participants with social anxiety disorder, and participants with acute stress disorder. Moreover, threat-related, and not positive, attention bias variability was correlated with PTSD severity. These findings carry possibilities for using attention bias variability as a specific cognitive marker of PTSD and for tailoring protocols for attention bias modification for this disorder.

Gene-Specific Demethylation as Targeted Therapy in MDS

DTIC Science & Technology

2017-07-01

SUPPLEMENTARY NOTES 14. ABSTRACT Myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic disorders characterized by bone marrow failure and...clonal hematopoietic disorders characterized by bone marrow failure and risk of progression to Acute Myeloid Leukemia (AML) in approximately 30 percent

The impact of DSM-5 on the diagnosis and severity indicator of eating disorders in a treatment-seeking sample.

PubMed

Nakai, Yoshikatsu; Nin, Kazuko; Noma, Shun'ichi; Teramukai, Satoshi; Fujikawa, Kei; Wonderlich, Stephen A

2017-11-01

To examine the impact of the DSM-5 on the diagnoses and severity indicators of eating disorders, we conducted a comparative study on the classification of eating disorders including subtypes of anorexia nervosa (AN) between the DSM-IV and DSM-5 criteria. In addition, we studied the association of the DSM-5 severity criteria and clinical variables. Participants were 304 outpatients, aged 16-45 years, with eating disorders, diagnosed using semi-structured clinical interviews and the eating disorder examination questionnaire (EDE-Q). The severity of AN, bulimia nervosa (BN), and binge-eating disorder (BED) was rated from mild to extreme using the DSM-5 severity criteria. The DSM-5 remarkably reduced the number of diagnoses in the residual category from 37.5% to 9.2% and effectively differentiated the diagnostic groups in eating disorder psychopathology. Unexpectedly, however, the scores of all the EDE-Q subscales significantly decreased as severity ratings increased in the DSM-5 AN. Furthermore, while the AN binge-eating/purging group reported significantly lower severity ratings than the AN restricting group, the former displayed more severe eating disorder psychopathology than the latter. In the BN and BED groups, the level of eating concern increased as severity ratings increased, but the severity groups did not differ on other eating pathology variables. The DSM-5 effectively reduced the reliance on residual categories and differentiated the diagnostic groups in eating disorder psychopathology. However, our findings show limited support for the DSM-5 severity specifiers for eating disorders. It is necessary to test additional clinical or functional variables for severity specifiers across eating disorders. © 2017 Wiley Periodicals, Inc.

Family breakup and adolescents' psychosocial maladjustment: public health implications of family disruptions.

PubMed

Roustit, Christelle; Chaix, Basile; Chauvin, Pierre

2007-10-01

Recent changes in family structure are associated with an increase in psychosocial maladjustment in adolescents. We examined, from a public health intervention perspective, the association between family breakup and psychosocial maladjustment in adolescents and assessed the mediating role of family-functioning variables. We analyzed data from the Social and Health Survey of Children and Adolescents in Quebec, Montreal, Canada, which was conducted in 1999. Sample-weighted logistic regression analyses were performed to determine the risk of internalizing disorders, externalizing disorders, substance abuse, and alcohol consumption in relation to family breakups and family-functioning variables, after adjusting for socioeconomic factors. All 4 of the indicators of psychosocial maladjustment were significantly associated with family breakup. The association between family breakups and internalizing disorders was mediated by parental psychological distress and low paternal emotional support. Independently, the witnessing of interparental violence was also strongly associated with internalizing disorders. For the other 3 outcomes, that is, externalizing disorders, substance abuse, and alcohol consumption, family breakup and family-functioning variables had independent effects. Family-based interventions and social approaches are complementary support modalities for adolescents experiencing family disruptions.

Psychopathologic differences between cannabis-induced psychoses and recent-onset primary psychoses with abuse of cannabis.

PubMed

Rubio, Gabriel; Marín-Lozano, Jesús; Ferre, Francisco; Martínez-Gras, Isabel; Rodriguez-Jimenez, Roberto; Sanz, Javier; Jimenez-Arriero, Miguel Angel; Carrasco, José Luis; Lora, David; Jurado, Rosa; López-Trabada, José Ramón; Palomo, Tomás

2012-11-01

The study aims to identify psychopathologic variables in cannabis-induced psychosis and recent-onset primary psychoses using the Symptom Checklist-90-R and the Psychiatric Research Interview for Substance and Mental Disorders. A sample of 181 subjects with psychotic symptoms and cannabis use referred to the psychiatry inpatient units of 3 university general hospitals were assessed. The final sample included 50 subjects with a diagnosis of cannabis-induced psychotic disorder (CIPD) and 104 subjects with primary psychotic disorders. Using receiver operating characteristic curves, the most efficient psychopathologic variables for classifying CIPD were interpersonal sensitivity, "depression," phobic anxiety, and Scale to Assess Unawareness of Mental Disorders subscales. The area under the receiver operating characteristic curve of the model including depression and "misattribution" scores was 96.78% (95% confidence interval, 94.43-99.13). Depressive symptoms could be used to distinguish CIPD from other primary psychotic disorders. Clinical variables related to "neurotic" symptoms could be involved in the susceptibility to cannabis-induced psychosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Association of ADHD, Tics, and Anxiety with Dopamine Transporter ("DAT1") Genotype in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Gadow, Kenneth D.; Roohi, Jasmin; DeVincent, Carla J.; Hatchwell, Eli

2008-01-01

Background: Autism spectrum disorder (ASD) is associated with high rates of psychiatric disturbance to include attention-deficit/hyperactivity disorder (ADHD), tic disorder, and anxiety disorders. The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism located in the…

Genetics Home Reference: PPM-X syndrome

MedlinePlus

... a condition characterized by psychotic disorders (most commonly bipolar disorder ), a pattern of movement abnormalities known as parkinsonism, ... Additional Information & Resources MedlinePlus (4 links) Health Topic: Bipolar Disorder Health Topic: Developmental Disabilities Health Topic: Movement Disorders ...

Gorlin-Goltz syndrome and neoplasms: a case study.

PubMed

Lopes, Nilza N F; Caran, Eliana M; Lee, Maria Lucia; Silva, Nasjla Saba; Rocha, André Caroli; Macedo, Carla R D

2010-01-01

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms, such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Bifid ribs as well as mandibular and maxillar OKC were also diagnosed Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations nd malignant neoplasias.

[Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature].

PubMed

Castro-Mujica, María Del Carmen; Barletta-Carrillo, Claudia; Poterico, Julio A; Acosta, Marisa; Valer, Jesús; Cruz, Miguel De La

2017-01-01

Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature.

[TREATMENT DILEMMAS IN BEHÇET'S SYNDROME].

PubMed

Zeller, Lior; Ling, Edoard; Abu-Shakra, Mahmoud

2016-02-01

Behçet's disease is an inflammatory systemic disorder, characterized by a relapsing and remitting course, it manifests with oral and genital ulcerations, skin lesions, uveitis, vasculitis, central nervous system and gastrointestinal involvement. The main histopathological finding is widespread vasculitis of the arteries and veins. Therapy is variable and depends largely on the severity of the disease and organ involvement. There is common practice to treat with anticoagulation in patients suffering from vessel thrombosis, but there are no control trials to support this tendency. Anticoagulation treatment can cause major bleeding events in patients suffering from aneurysms. In this case report we describe a treatment dilemma in a patient suffering from deep vein thrombosis and pulmonary aneurysms.

mtDNA Deletion in an Iranian Infant with Pearson Marrow Syndrome.

PubMed

Arzanian, Mohammad Taghi; Eghbali, Aziz; Karimzade, Parvaneh; Ahmadi, Mitra; Houshmand, Massoud; Rezaei, Nima

2010-03-01

Pearson syndrome (PS) is a rare multisystem mitochondrial disorder of hematopoietic system, characterized by refractory sideroblastic anemia, pancytopenia, exocrine pancreatic insufficiency, and variable neurologic, hepatic, renal, and endocrine failure. We describe a six-month-old female infant with Pearson marrow syndrome who presented with neurological manifestations. She had several episodes of seizures. Hematopoietic abnormalities were macrocytic anemia and neutropenia. Bone marrow aspiration revealed a cellular marrow with marked vacuolization of erythroid and myeloid precursors. Analysis of mtDNA in peripheral blood showed 8.5 kb deletion that was compatible with the diagnosis of PS. PS should be considered in infants with neurologic diseases, in patients with cytopenias, and also in patients with acidosis or refractory anemia.

Performance Variability, Impulsivity Errors and the Impact of Incentives as Gender-Independent Endophenotypes for ADHD

ERIC Educational Resources Information Center

Uebel, Henrik; Albrecht, Bjorn; Asherson, Philip; Borger, Norbert A.; Butler, Louise; Chen, Wai; Christiansen, Hanna; Heise, Alexander; Kuntsi, Jonna; Schafer, Ulrike; Andreou, Penny; Manor, Iris; Marco, Rafaela; Miranda, Ana; Mulligan, Aisling; Oades, Robert D.; van der Meere, Jaap; Faraone, Stephen V.; Rothenberger, Aribert; Banaschewski, Tobias

2010-01-01

Background: Attention-deficit hyperactivity disorder (ADHD) is one of the most common and highly heritable child psychiatric disorders. There is strong evidence that children with ADHD show slower and more variable responses in tasks such as Go/Nogo tapping aspects of executive functions like sustained attention and response control which may be…

The Latent Structure of Dietary Restraint, Body Dissatisfaction, and Drive for Thinness: A Series of Taxometric Analyses

ERIC Educational Resources Information Center

Holm-Denoma, Jill M.; Richey, J. Anthony; Joiner, Thomas E., Jr.

2010-01-01

Although the latent structure of various eating disorders has been explored in previous studies, no published studies have examined the latent structure of theoretically relevant variables that have been shown to cut across eating disorder diagnoses. The current study examined 3 such variables (dietary restraint, body dissatisfaction, and drive…

Eating disorder pathology among overweight treatment-seeking youth: clinical correlates and cross-sectional risk modeling.

PubMed

Eddy, Kamryn T; Tanofsky-Kraff, Marian; Thompson-Brenner, Heather; Herzog, David B; Brown, Timothy A; Ludwig, David S

2007-10-01

Preliminary research suggests that pediatric overweight is associated with increased eating disorder pathology, however, little is known about which overweight youth are most vulnerable to eating disorder pathology. We therefore investigated 122 overweight treatment-seeking youth to describe eating disorder pathology and mental health correlates, and to identify psychopathological constructs that may place overweight youth at increased risk for eating disorder pathology. Youth participated in a comprehensive assessment of eating disorders, mood and anxiety disorders, general psychopathology, and risk variables involving semi-structured clinical interviews and self- and parent-report questionnaires prior to the initiation of weight-loss treatment. Ten youth met criteria for an eating disorder, and over one-third endorsed recent binge eating. Eating disorder pathology was associated with depressive and anxious symptoms (p's<0.001). Structural equation modeling indicated increased negative affect, teasing experience, and thin-ideal internalization, and decreased perfectionism were associated with increased eating disorder pathology. Findings corroborate earlier work indicating that eating disorder pathology is elevated and clinically significant in overweight treatment-seeking youth, bolstering the need for mental health assessment of such individuals. Cross-sectional modeling proposed key variables that relate to eating disorder pathology in overweight treatment-seeking youth, which following prospective replication, may inform the development of effective interventions for overweight and eating disorders.

Skin Hyperpigmentation in Indian Population: Insights and Best Practice

PubMed Central

Nouveau, Stephanie; Agrawal, Divya; Kohli, Malavika; Bernerd, Francoise; Misra, Namita; Nayak, Chitra Shivanand

2016-01-01

Skin pigmentation is one of the most strikingly variable phenotypes in humans, therefore making cutaneous pigmentation disorders frequent symptoms manifesting in a multitude of forms. The most common among them include lentigines, postinflammatory hyperpigmentation, dark eye circles, and melasma. Variability of skin tones throughout the world is well-documented, some skin tones being reported as more susceptible to pigmentation disorders than others, especially in Asia and India. Furthermore, exposure to ultraviolet radiation is known to trigger or exacerbate pigmentation disorders. Preventive strategies for photoprotection and treatment modalities including topical and other medical approaches have been adopted by dermatologists to mitigate these disorders. This review article outlines the current knowledge on pigmentation disorders including pathophysiology, molecular profiling, and therapeutic options with a special focus on the Indian population. PMID:27688436

The Eating Disorders Continuum, Self-Esteem, and Perfectionism

ERIC Educational Resources Information Center

Peck, Lisa D.; Lightsey, Owen Richard

2008-01-01

Among 261 undergraduate women, increased severity of eating disorders along a continuum was associated with decreased self-esteem, increased perfectionism, and increased scores on 7 subscales of the Eating Disorders Inventory-2. Women with eating disorders differed from both symptomatic women and asymptomatic women on all variables, whereas…

Sleep variability in military-related PTSD: a comparison to primary insomnia and healthy controls.

PubMed

Straus, Laura D; Drummond, Sean P A; Nappi, Carla M; Jenkins, Melissa M; Norman, Sonya B

2015-02-01

Sleep disturbances are prevalent in posttraumatic stress disorder (PTSD) and are associated with a number of adverse health consequences. Few studies have used comprehensive assessment methods to characterize sleep in Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OEF/OIF/OND) veterans with PTSD. OEF/OIF/OND veterans with PTSD and sleep disturbance (n = 45) were compared to patients with primary insomnia (n = 25) and healthy control subjects (n = 27). Participants were assessed using questionnaire-based measures as well as daily subjective and objective measures of sleep. The 3 groups were compared with regard to (a) group means, (b) intraindividual (i.e., night-to-night) variability of sleep, and (c) interindividual (i.e., within-group) variability of sleep. In terms of group means, only objective sleep efficiency was significantly worse with PTSD than with primary insomnia (d = 0.54). Those with PTSD differed from those with primary insomnia on measures of intraindividual as well as interindividual variability (d = 0.48-0.73). These results suggested sleep symptoms in OEF/OIF/OND veterans with PTSD are more variable across nights and less consistent across patients relative to sleep symptoms in insomnia patients without PTSD. These findings have implications for research, as well as for personalizing treatment for individuals with PTSD. Published 2015. This article is a US Government work and is in the public domain in the USA.

Clinical Significance of Mobile Health Assessed Sleep Duration and Variability in Bipolar Disorder

PubMed Central

Kaufmann, Christopher N.; Gershon, Anda; Eyler, Lisa T.; Depp, Colin A.

2016-01-01

OBJECTIVE Sleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect. METHODS Forty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect. RESULTS Greater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7-8 hours were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect. CONCLUSIONS Greater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder. PMID:27451108

Clinical significance of mobile health assessed sleep duration and variability in bipolar disorder.

PubMed

Kaufmann, Christopher N; Gershon, Anda; Eyler, Lisa T; Depp, Colin A

2016-10-01

Sleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect. Forty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect. Greater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7-8 h were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect. Greater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune Disorder HSCT Protocol

ClinicalTrials.gov

2017-11-17

Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait.

PubMed

Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

2015-10-01

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N=1316). Using both single-nucleotide polymorphism (SNP)- and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.

The future prospects of pharmacogenetics in oral anticoagulation therapy

PubMed Central

Kamali, Farhad; Pirmohamed, Munir

2006-01-01

Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? A mini-review of the evidence.

PubMed

Fluegge, Keith

2016-10-01

Neurodevelopmental disorders are increasing in prevalence worldwide. Previous work suggests that exposure to the environmental air pollutant and greenhouse gas - nitrous oxide (N 2 O) - may be an etiological factor in neurodevelopmental disorders through the targeting of several neural correlates. While a number of recent systematic reviews have addressed the role of general anesthesia in the surgical setting and neurodevelopmental outcomes, a narrative mini-review was conducted to first define and characterize the relevant variables (i.e., N 2 O, attention-deficit hyperactivity disorder [ADHD] and autism spectrum disorders [ASD]) and their potential interactions into a coherent, hypothesis-generating work. The narrative mini-review merges basic principles in environmental science, anesthesiology, and psychiatry to more fully develop the novel hypotheses that neurodevelopmental impairment found in conditions like ADHD and ASD may be due to exposure to the increasing air pollutant, N 2 O. The results of the present mini-review indicate that exposure to N 2 O, even at non-toxic doses, may modulate central neurotransmission and target many neural substrates directly implicated in neurodevelopmental disorders, including the glutamatergic, opioidergic, cholinergic, and dopaminergic systems. Epidemiological studies also indicate that early and repeated exposure to general anesthesia, including N 2 O, may contribute to later adverse neurodevelopmental outcomes in children. The current evidence and subsequent hypotheses suggest that a renewed interest be taken in the toxicological assessment of environmental N 2 O exposure using validated biomarkers and psychiatric endpoints. Given the relevance of N 2 O as a greenhouse gas, societies may also wish to engage in a more robust monitoring and reporting of N 2 O levels in the environment for climactic benefit as well. Copyright © 2016 Elsevier B.V. All rights reserved.

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

PubMed

Nakajima, N; Sato, H; Takahashi, K; Hasegawa, G; Mizuno, K; Hashimoto, S; Sato, Y; Terai, S

2017-03-01

Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium. © 2016 John Wiley & Sons Ltd.

The relationship between affective state and the rhythmicity of activity in bipolar disorder.

PubMed

Gonzalez, Robert; Tamminga, Carol A; Tohen, Mauricio; Suppes, Trisha

2014-04-01

The aim of this study was to test the relationships between mood state and rhythm disturbances as measured via actigraphy in bipolar disorder by assessing the correlations between manic and depressive symptoms as measured via Young Mania Rating Scale (YMRS) and 30-item Inventory for Depressive Symptomatology, Clinician-Rated (IDS-C-30) scores and the actigraphic measurements of rhythm, the 24-hour autocorrelation coefficient and circadian quotient. The research was conducted at the University of Texas Southwestern Medical Center at Dallas from February 2, 2009, to March 30, 2010. 42 patients with a DSM-IV-TR diagnosis of bipolar I disorder were included in the study. YMRS and the IDS-C-30 were used to determine symptom severity. Subjects wore the actigraph continuously for 7 days. The 24-hour autocorrelation coefficient was used as an indicator of overall rhythmicity. The circadian quotient was used to characterize the strength of a circadian rhythm. A greater severity of manic symptoms correlated with a lower degree of rhythmicity and less robust rhythms of locomotor activity as indicated by lower 24-hour autocorrelation (r = -0.3406, P = .03) and circadian quotient (r = -0.5485, P = .0002) variables, respectively. No relationship was noted between the degree of depression and 24-hour autocorrelation scores (r = -0.1190, P = .45) or circadian quotient (r = 0.0083, P = .96). Correlation was noted between the 24-hour autocorrelation and circadian quotient scores (r = 0.6347, P < .0001). These results support the notion that circadian rhythm disturbances are associated with bipolar disorder and that these disturbances may be associated with clinical signatures of the disorder. Further assessment of rhythm disturbances in bipolar disorder is warranted. © Copyright 2014 Physicians Postgraduate Press, Inc.

Development and characterization of a camelid single-domain antibody directed to human CD22 biomarker.

PubMed

Faraji, Fatemeh; Tajik, Nader; Behdani, Mahdi; Shokrgozar, Mohammad Ali; Zarnani, Amir Hassan; Shahhosseini, Fatemeh; Habibi-Anbouhi, Mahdi

2018-03-15

CD22 is a B-cell-specific trans-membrane glycoprotein, which is found on the surface of the most B cells and modulates their function, survival, and apoptosis. Recently, targeting this cell surface biomarker in B-cell malignancies and disorders has attracted a lot of attention. The variable domain of camelid single-chain antibodies (VHH, nanobody) is a form of antibodies with novel properties including small size (15-17 kDa), thermal and chemical stability, high affinity and homology to human antibody sequences. In this study, a novel anti-CD22-specific VHH (Nb) has been developed and characterized by the screening of an immunized phage display library and its binding to CD22 + B cells is evaluated. Produced anti-CD22 VHH had a single protein band about 17 kDa of molecular size in Western blotting and its binding affinity was approximately 9 × 10 -9  M. Also, this product had high specificity and it was able to recognize the natural CD22 antigen in CD22+ cell lysate as well as on the cell surface (93%). This anti-CD22 VHH with both high affinity and specificity recognizes CD22 antigen well and can be used in diagnosis and treatment of B cell disorders and malignancies. © 2018 International Union of Biochemistry and Molecular Biology, Inc.

Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome.

PubMed

Pannone, Luca; Bocchinfuso, Gianfranco; Flex, Elisabetta; Rossi, Cesare; Baldassarre, Giuseppina; Lissewski, Christina; Pantaleoni, Francesca; Consoli, Federica; Lepri, Francesca; Magliozzi, Monia; Anselmi, Massimiliano; Delle Vigne, Silvia; Sorge, Giovanni; Karaer, Kadri; Cuturilo, Goran; Sartorio, Alessandro; Tinschert, Sigrid; Accadia, Maria; Digilio, Maria C; Zampino, Giuseppe; De Luca, Alessandro; Cavé, Hélène; Zenker, Martin; Gelb, Bruce D; Dallapiccola, Bruno; Stella, Lorenzo; Ferrero, Giovanni B; Martinelli, Simone; Tartaglia, Marco

2017-04-01

Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu 261 , Leu 262 , and Arg 265 in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. Structural data predicted a gain-of-function role of substitutions at residues Leu 262 and Arg 265 exerted by disruption of the N-SH2/PTP autoinhibitory interaction. Molecular dynamics simulations suggested a more complex behavior for changes affecting Leu 261 , with possible impact on SHP2's catalytic activity/selectivity and proper interaction of the PTP domain with the regulatory SH2 domains. Consistent with that, biochemical data indicated that substitutions at codons 262 and 265 increased the catalytic activity of the phosphatase, while those affecting codon 261 were only moderately activating but impacted substrate specificity. Remarkably, these mutations underlie a relatively mild form of NS characterized by low prevalence of cardiac defects, short stature, and cognitive and behavioral issues, as well as less evident typical facial features. © 2017 WILEY PERIODICALS, INC.

Variable patterns of ectopic mineralization in Enpp1asj-2J mice, a model for generalized arterial calcification of infancy

PubMed Central

Siu, Sarah Y.; Dyment, Nathaniel A.; Rowe, David W.; Sundberg, John P.; Uitto, Jouni; Li, Qiaoli

2016-01-01

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular system. The classical forms of GACI are caused by mutations in the ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a spontaneous mutation in the Enpp1 gene has been characterized as a model for GACI. These mutant mice develop ectopic mineralization in skin and vascular connective tissues as well as in cartilage and collagen-rich tendons and ligaments. This study examined in detail the temporal ectopic mineralization phenotype of connective tissues in this mouse model, utilizing a novel cryo-histological method that does not require decalcification of bones. The wild type, heterozygous, and homozygous mice were administered fluorescent mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and 11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and examined for progression of mineralization. The results revealed differential timeline for disease initiation and progression in various tissues of this mouse model. It also highlights the advantages of cryo-histological fluorescent imaging technique to study mineral deposition in mouse models of ectopic mineralization disorders. PMID:27863377

Heart Rate Variability During a Joint Attention Task in Toddlers With Autism Spectrum Disorders

PubMed Central

Billeci, Lucia; Tonacci, Alessandro; Narzisi, Antonio; Manigrasso, Zaira; Varanini, Maurizio; Fulceri, Francesca; Lattarulo, Caterina; Calderoni, Sara; Muratori, Filippo

2018-01-01

Background: Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders featuring early impairments in social domain, with autonomic nervous system (ANS) unbalance possibly representing a useful marker for such disturbances. Impairments in joint attention (JA) are one of the earliest markers of social deficits in ASD. In this study, we assessed the feasibility of using wearable technologies for characterizing the ANS response in ASD toddlers during the presentation of JA stimuli. Methods: Twenty ASD toddlers and 20 age- and gender-matched typically developed (TD) children were recorded at baseline and during a JA task through an unobtrusive chest strap for electrocardiography (ECG). Specific algorithms for feature extraction, including Heart Rate (HR), Standard Deviation of the Normal-to-Normal Intervals (SDNN), Coefficient of Variation (CV), pNN10 as well as low frequency (LF) and high frequency (HF), were applied to the ECG signal and a statistical comparison between the two groups was performed. Results: As regards the single phases, SDNN (p = 0.04) and CV (p = 0.021) were increased in ASD at baseline together with increased LF absolute power (p = 0.034). Moreover, CV remained higher in ASD during the task (p = 0.03). Considering the phase and group interaction, LF increased from baseline to task in TD group (p = 0.04) while it decreased in the ASD group (p = 0.04). Conclusions: The results of this study indicate the feasibility of characterizing the ANS response in ASD toddlers through a minimally obtrusive tool. Our analysis showed an increased SDNN and CV in toddlers with ASD particularly at baseline compared to TD and lower LF during the task. These findings could suggest the possibility of using the proposed approach for evaluating physiological correlates of JA response in young children with ASD. PMID:29765335

Treatment implications of high-resolution manometry findings: options for patients with esophageal dysmotility.

PubMed

Bolkhir, Ahmed; Gyawali, C Prakash

2014-03-01

High-resolution manometry (HRM) has significantly impacted diagnosis and management of achalasia in particular, and has improved characterization of other motor disorders. Achalasia, the most profound esophageal motor disorder, is characterized by esophageal outflow obstruction from abnormal relaxation of the lower esophageal sphincter (LES) during swallowing, and presents with transit symptoms (dysphagia, regurgitation). Esophageal body motor disorders include both inhibitory nerve dysfunction associated with hypermotility or spasm, and hypomotility disorders with poor contraction. The implications of hypermotility disorders are both perceptive and obstructive. On the other hand, hypomotility disorders have reflux implications because of abnormal barrier function at the LES, and abnormal bolus clearance. Esophageal outflow obstruction in achalasia responds favorably to disruption of the LES, and outcome may be predicted by HRM subtyping of achalasia. Identification of dominant (perceptive vs. obstructive) mechanisms of symptom generation help direct therapy of hypermotility disorders, while hypomotility disorders typically require management of concurrent reflux disease.

Body weight concerns: Cross-national study and identification of factors related to eating disorders.

PubMed

Silva, Wanderson Roberto da; Santana, Moema de Souza; Maroco, João; Maloa, Benvindo Felismino Samuel; Campos, Juliana Alvares Duarte Bonini

2017-01-01

Body weight concerns are common among individuals with eating disorders, and this construct can be assessed using psychometric instruments. The Weight Concerns Scale (WCS) is commonly used to assess body weight concerns. To evaluate the psychometric properties of the WCS with Brazilian, Portuguese, and Mozambican female college students; to estimate body weight concerns; and to identify factors related to eating disorders. Confirmatory factor analysis was performed. Factorial, convergent, concurrent, and divergent validity, as well as reliability, were assessed. Cross-national invariance was tested by means of multigroup analysis. Structural models were tested using the WCS as the dependent variable, while demographic and academic variables and body mass index were used as independent variables. Logistic models were tested to estimate the likelihood of eating disorders being developed in specific groups. Participants were 2,068 female students. The psychometric properties of the WCS were adequate for the Portuguese sample; however, for the Brazilian and Mozambican samples, it was necessary to correlate the errors of two items to improve model fit. The WCS did not show cross-national invariance. The variables "thoughts about dropping out of college," "medication use because of studies," "medication and supplements use for body change," "body mass index," "socioeconomic status," "age," and "performance in course" were significant predictors of body weight concerns. Overall, 24.4% (95% confidence interval = 22.9-26.7) of the students were likely to develop eating disorders. Students under 21 years old, who use medication and supplements for body change, and who were classified as overweight/obese have increased likelihood of developing eating disorders. The WCS showed good psychometric properties with Brazilian, Portuguese, and Mozambican students; however, it did not show cross-national invariance. We identified important aspects for investigating body weight concerns and factors related to eating disorders.

Cognitive variability in bipolar II disorder: who is cognitively impaired and who is preserved.

PubMed

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Del Mar Bonnin, Caterina; Torres, Imma; Reinares, María; Priego, Ángel; Salamero, Manel; Colom, Francesc; Varo, Cristina; Vieta, Eduard; Martínez-Arán, Anabel

2016-05-01

Although it is well established that euthymic patients with bipolar disorder can have cognitive impairment, substantial heterogeneity exists and little is known about the extent and severity of impairment within the bipolar II disorder subtype. Therefore, the main aim of this study was to analyze cognitive variability in a sample of patients with bipolar II disorder. The neuropsychological performance of 116 subjects, including 64 euthymic patients with bipolar II disorder and 52 healthy control subjects, was examined and compared by means of a comprehensive neurocognitive battery. Neurocognitive data were analyzed using a cluster analysis to examine whether there were specific groups based on neurocognitive patterns. Subsequently, subjects from each cluster were compared on demographic, clinical, and functional variables. A three-cluster solution was identified with an intact neurocognitive group (n = 29, 48.3%), an intermediate or selectively impaired group (n = 24, 40.0%), and a globally impaired group (n = 7, 11.6%). Among the three clusters, statistically significant differences were observed in premorbid intelligence quotient (p = 0.002), global functional outcome (p = 0.021), and leisure activities (p = 0.001), with patients in the globally impaired cluster showing the lowest attainments. No differences in other clinical characteristics were found among the groups. These results confirm that neurocognitive variability is also present among patients with bipolar II disorder. Approximately one-half of the patients with bipolar II disorder were cognitively impaired, and among them 12% were severely and globally impaired. The identification of different cognitive profiles may help to develop cognitive remediation programs specifically tailored for each cognitive profile. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiple comorbidities of 21 psychological disorders and relationships with psychosocial variables: a study of the online assessment and diagnostic system within a web-based population.

PubMed

Al-Asadi, Ali M; Klein, Britt; Meyer, Denny

2015-02-26

While research in the area of e-mental health has received considerable attention over the last decade, there are still many areas that have not been addressed. One such area is the comorbidity of psychological disorders in a Web-based sample using online assessment and diagnostic tools, and the relationships between comorbidities and psychosocial variables. We aimed to identify comorbidities of psychological disorders of an online sample using an online diagnostic tool. Based on diagnoses made by an automated online assessment and diagnostic system administered to a large group of online participants, multiple comorbidities (co-occurrences) of 21 psychological disorders for males and females were identified. We examined the relationships between dyadic comorbidities of anxiety and depressive disorders and the psychosocial variables sex, age, suicidal ideation, social support, and quality of life. An online complex algorithm based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, was used to assign primary and secondary diagnoses of 21 psychological disorders to 12,665 online participants. The frequency of co-occurrences of psychological disorders for males and females were calculated for all disorders. A series of hierarchical loglinear analyses were performed to examine the relationships between the dyadic comorbidities of depression and various anxiety disorders and the variables suicidal ideation, social support, quality of life, sex, and age. A 21-by-21 frequency of co-occurrences of psychological disorders matrix revealed the presence of multiple significant dyadic comorbidities for males and females. Also, for those with some of the dyadic depression and the anxiety disorders, the odds for having suicidal ideation, reporting inadequate social support, and poorer quality of life increased for those with two-disorder comorbidity than for those with only one of the same two disorders. Comorbidities of several psychological disorders using an online assessment tool within a Web-based population were similar to those found in face-to-face clinics using traditional assessment tools. Results provided support for the transdiagnostic approaches and confirmed the positive relationship between comorbidity and suicidal ideation, the negative relationship between comorbidity and social support, and the negative relationship comorbidity and quality of life. Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).

Multiple Comorbidities of 21 Psychological Disorders and Relationships With Psychosocial Variables: A Study of the Online Assessment and Diagnostic System Within a Web-Based Population

PubMed Central

Klein, Britt; Meyer, Denny

2015-01-01

Background While research in the area of e-mental health has received considerable attention over the last decade, there are still many areas that have not been addressed. One such area is the comorbidity of psychological disorders in a Web-based sample using online assessment and diagnostic tools, and the relationships between comorbidities and psychosocial variables. Objective We aimed to identify comorbidities of psychological disorders of an online sample using an online diagnostic tool. Based on diagnoses made by an automated online assessment and diagnostic system administered to a large group of online participants, multiple comorbidities (co-occurrences) of 21 psychological disorders for males and females were identified. We examined the relationships between dyadic comorbidities of anxiety and depressive disorders and the psychosocial variables sex, age, suicidal ideation, social support, and quality of life. Methods An online complex algorithm based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, was used to assign primary and secondary diagnoses of 21 psychological disorders to 12,665 online participants. The frequency of co-occurrences of psychological disorders for males and females were calculated for all disorders. A series of hierarchical loglinear analyses were performed to examine the relationships between the dyadic comorbidities of depression and various anxiety disorders and the variables suicidal ideation, social support, quality of life, sex, and age. Results A 21-by-21 frequency of co-occurrences of psychological disorders matrix revealed the presence of multiple significant dyadic comorbidities for males and females. Also, for those with some of the dyadic depression and the anxiety disorders, the odds for having suicidal ideation, reporting inadequate social support, and poorer quality of life increased for those with two-disorder comorbidity than for those with only one of the same two disorders. Conclusions Comorbidities of several psychological disorders using an online assessment tool within a Web-based population were similar to those found in face-to-face clinics using traditional assessment tools. Results provided support for the transdiagnostic approaches and confirmed the positive relationship between comorbidity and suicidal ideation, the negative relationship between comorbidity and social support, and the negative relationship comorbidity and quality of life. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG) PMID:25803420

Extralinguistic speech characteristics of children with conduct and anxiety disorders.

PubMed

Kotsopoulos, S; Mellor, C

1986-01-01

Nine children with conduct and nine with anxiety disorder participated in the study. The subjects were requested to respond to verbal tasks (counting, picture description, story telling). Disturbance of conduct was associated with short initial hesitation before speaking. It is suggested that the initial hesitation variables are measures of reflection and cognitive planning. Anxiety across subjects was associated with increased breath rate and lower output of speech per breath. It is suggested speech breath variables are reliable measures of anxiety. Implication for the diagnosis and management of child psychiatric disorders are discussed.

Patterns of co-occurring addictions, posttraumatic stress disorder, and major depressive disorder in detoxification treatment seekers: Implications for improving detoxification treatment outcomes.

PubMed

Anderson, RaeAnn E; Hruska, Bryce; Boros, Alec P; Richardson, Christopher J; Delahanty, Douglas L

2018-03-01

Poly-substance use and psychiatric comorbidity are common among individuals receiving substance detoxification services. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are the most common co-occurring psychiatric disorders with substance use disorder (SUD). Current treatment favors a one-size-fits-all approach to treating addiction focusing on one substance or one comorbidity. Research examining patterns of substance use and comorbidities can inform efforts to effectively identify and differentially treat individuals with co-occurring conditions. Using latent class analysis, the current study identified four patterns of PTSD, MDD, and substance use among 375 addiction treatment seekers receiving medically supervised detoxification. The four identified classes were: 1) a PTSD-MDD-Poly SUD class characterized by PTSD and MDD occurring in the context of opioid, cannabis, and tobacco use disorders; 2) an MDD-Poly SUD class characterized by MDD and alcohol, opioid, tobacco, and cannabis use disorders; 3) an alcohol-tobacco class characterized by alcohol and tobacco use disorders; and 4) an opioid-tobacco use disorder class characterized by opioid and tobacco use disorders. The observed classes differed on gender and clinical characteristics including addiction severity, trauma history, and PTSD/MDD symptom severity. The observed classes likely require differing treatment approaches. For example, people in the PTSD-MDD-Poly SUD class would likely benefit from treatment approaches targeting anxiety sensitivity and distress tolerance, while the opioid-tobacco class would benefit from treatments that incorporate motivational interviewing. Appropriate matching of treatment to class could optimize treatment outcomes for polysubstance and comorbid psychiatric treatment seekers. These findings also underscore the importance of well-developed referral networks to optimize outpatient psychotherapy for detoxification treatment-seekers to enhance long-term recovery, particularly those that include transdiagnostic treatment components. Copyright © 2017. Published by Elsevier Inc.

Disgust, Fear, and the Anxiety Disorders: A Critical Review

PubMed Central

Cisler, Josh M.; Olatunji, Bunmi O.; Lohr, Jeffrey M.

2010-01-01

Anxiety disorders have traditionally been conceptualized as reflecting the emotions of fear and anxiety. A developing program of research demonstrates a relation between disgust and three specific anxiety disorders: blood-injection-injury (BII) phobia, spider phobia, and contamination-related obsessive-compulsive disorder (OCD). This review serves three purposes. First, the authors review the response patterns predicted to be observed if the emotional response in these disorders involved disgust versus fear. The review suggests specific response patterns that characterize disgust and fear in the domains of heart rate, facial expression, neural activity, and cognitive processes. Second, the authors review extant research employing measures of these domains in spider phobia, BII phobia, and contamination-related OCD. The evidence suggests that both fear and disgust characterize each of these disorders, but the magnitude at which the emotions characterize the disorders may depend on the response domain measured. For example, disgust may be more involved in spider phobia in appraisals and facial expression, but less involved in neural correlates or heart rate domains. Third, the authors suggest guidelines for future research, including concurrent use of specific measures as well as examining whether the different emotions in different response domains respond to similar interventions (e.g., exposure). PMID:18977061

Physiological and behavioral indices of emotion dysregulation as predictors of outcome from cognitive behavioral therapy and acceptance and commitment therapy for anxiety.

PubMed

Davies, Carolyn D; Niles, Andrea N; Pittig, Andre; Arch, Joanna J; Craske, Michelle G

2015-03-01

Identifying for whom and under what conditions a treatment is most effective is an essential step toward personalized medicine. The current study examined pre-treatment physiological and behavioral variables as predictors and moderators of outcome in a randomized clinical trial comparing cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. Sixty individuals with a DSM-IV defined principal anxiety disorder completed 12 sessions of either CBT or ACT. Baseline physiological and behavioral variables were measured prior to entering treatment. Self-reported anxiety symptoms were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. Higher pre-treatment heart rate variability was associated with worse outcome across ACT and CBT. ACT outperformed CBT for individuals with high behavioral avoidance. Subjective anxiety levels during laboratory tasks did not predict or moderate treatment outcome. Due to small sample sizes of each disorder, disorder-specific predictors were not tested. Future research should examine these predictors in larger samples and across other outcome variables. Lower heart rate variability was identified as a prognostic indicator of overall outcome, whereas high behavioral avoidance was identified as a prescriptive indicator of superior outcome from ACT versus CBT. Investigation of pre-treatment physiological and behavioral variables as predictors and moderators of outcome may help guide future treatment-matching efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Parental bonding and adult psychopathology: results from the US National Comorbidity Survey.

PubMed

Enns, M W; Cox, B J; Clara, I

2002-08-01

Research using the parental bonding instrument (PBI) has suggested that lack of parental care and/or overprotection may be important risk factors for adult mental disorders. Much of this research, however, has relied on clinical populations with one or two disorders, or has used highly select community samples. The association between parenting experiences and the occurrence of 13 common mental disorders in adulthood was evaluated in the US National Comorbidity Survey (N = 5877). The effect of sociodemographic variables (age, education, income) was statistically controlled and the effects of six parenting variables (maternal and paternal care, overprotection and authoritarianism) were examined simultaneously. The effects in men and women were examined separately. Lack of care was the parenting variable most consistently associated with adult psychopathology. Parenting experiences with one's mother were more consistently associated with adult mental disorders. In general the impact of parenting was diagnostically non-specific. However, there appeared to be some unique effects for externalizing disorders (substance use disorders and antisocial personality disorder) in males; paternal overprotection and authoritarianism conferred a reduced risk of externalizing disorders in adult males. The overall impact of parenting as assessed by the PBI was modest, accounting for about 1 to 5 % of the variance in the occurrence of adult mental disorders. Parenting experiences, particularly lack of care, are potentially causally related in a non-specific manner to a wide variety of forms of adult psychopathology in both men and women. The overall magnitude of the effect is small but statistically significant in a nationally representative US sample.

First-principles quantum transport method for disordered nanoelectronics: Disorder-averaged transmission, shot noise, and device-to-device variability

NASA Astrophysics Data System (ADS)

Yan, Jiawei; Wang, Shizhuo; Xia, Ke; Ke, Youqi

2017-03-01

Because disorders are inevitable in realistic nanodevices, the capability to quantitatively simulate the disorder effects on electron transport is indispensable for quantum transport theory. Here, we report a unified and effective first-principles quantum transport method for analyzing effects of chemical or substitutional disorder on transport properties of nanoelectronics, including averaged transmission coefficient, shot noise, and disorder-induced device-to-device variability. All our theoretical formulations and numerical implementations are worked out within the framework of the tight-binding linear muffin tin orbital method. In this method, we carry out the electronic structure calculation with the density functional theory, treat the nonequilibrium statistics by the nonequilbrium Green's function method, and include the effects of multiple impurity scattering with the generalized nonequilibrium vertex correction (NVC) method in coherent potential approximation (CPA). The generalized NVC equations are solved from first principles to obtain various disorder-averaged two-Green's-function correlators. This method provides a unified way to obtain different disorder-averaged transport properties of disordered nanoelectronics from first principles. To test our implementation, we apply the method to investigate the shot noise in the disordered copper conductor, and find all our results for different disorder concentrations approach a universal Fano factor 1 /3 . As the second test, we calculate the device-to-device variability in the spin-dependent transport through the disordered Cu/Co interface and find the conductance fluctuation is very large in the minority spin channel and negligible in the majority spin channel. Our results agree well with experimental measurements and other theories. In both applications, we show the generalized nonequilibrium vertex corrections play a determinant role in electron transport simulation. Our results demonstrate the effectiveness of the first-principles generalized CPA-NVC for atomistic analysis of disordered nanoelectronics, extending the capability of quantum transport simulation.

A comparison of disordered eating attitudes and behaviors among Filipino and American college students.

PubMed

Madanat, H N; Hawks, S R; Novilla, M L

2006-09-01

The purpose of this study was to compare the levels of eating disordered attitudes and behaviors among college students in the United States and the Philippines. A convenience-based cross-sectional survey. General education classes in one college in Manila and another in the Western US. 340 college students. A paper-pencil survey was given to the students in the classroom consisting of Eating Attitudes Test (EAT-26) and demographic variables. Eating disordered attitudes and behaviors (scoring 20 or more on EAT-26) was the dependent variable, while gender and country of residence were the two main independent variables. Frequency distributions, chi-squares, and logistic regression analysis were employed to summarize and analyze the data. Filipino students were 10.9 times (p-value <0.0001) more likely to have eating disordered attitudes and behaviors than their American counterparts controlling for the demographics collected. This relationship remained significant when regression models were done for each gender separately. In addition, married students and more specifically married female students were more likely to have eating disordered attitudes and behaviors than single students or single females. Arguments are made as to why higher levels of eating disordered attitudes and behaviors are observed among Filipino college students. These results provide important information about the levels of eating disordered attitudes and behaviors in the Philippines and may be useful for developing future education programs.

Emotional Stimuli and Motor Conversion Disorder

ERIC Educational Resources Information Center

Voon, Valerie; Brezing, Christina; Gallea, Cecile; Ameli, Rezvan; Roelofs, Karin; LaFrance, W. Curt, Jr.; Hallett, Mark

2010-01-01

Conversion disorder is characterized by neurological signs and symptoms related to an underlying psychological issue. Amygdala activity to affective stimuli is well characterized in healthy volunteers with greater amygdala activity to both negative and positive stimuli relative to neutral stimuli, and greater activity to negative relative to…

Heart Rate and Treatment Effect in Children with Disruptive Behavior Disorders

ERIC Educational Resources Information Center

Stadler, Christina; Grasmann, Dorte; Fegert, Jorg M.; Holtmann, Martin; Poustka, Fritz; Schmeck, Klaus

2008-01-01

Objective: To examine whether children with disruptive behavior disorders (DBDs; hyperkinetic conduct disorder, conduct disorder, hyperkinetic disorder) characterized by low heart rate profit less from an intensive cognitive behavioral intervention aimed at reducing impulsive, oppositional and aggressive behavior problems. Method: Basal heart rate…

Diagnostic classification of eating disorders in children and adolescents: How does DSM-IV-TR compare to empirically-derived categories?

PubMed Central

Eddy, Kamryn T.; le Grange, Daniel; Crosby, Ross D.; Hoste, Renee Rienecke; Doyle, Angela Celio; Smyth, Angela; Herzog, David B.

2009-01-01

Objective The purpose of this study was to empirically derive eating disorder phenotypes in a clinical sample of children and adolescents using latent profile analysis (LPA) and compare these latent profile (LP) groups to the DSM-IV-TR eating disorder categories. Method Eating disorder symptom data collected from 401 youth (ages 7–19; mean 15.14 ± 2.35y) seeking eating disorder treatment were included in LPA; general linear models were used to compare LP groups to DSM-IV-TR eating disorder categories on pre-treatment and outcome indices. Results Three LP groups were identified: LP1 (n=144), characterized binge eating and purging (“Binge/purge”); LP2 (n=126), characterized by excessive exercise and extreme eating disorder cognitions (“Exercise-extreme cognitions”); and LP3 (n=131), characterized by minimal eating disorder behaviors and cognitions (“Minimal behaviors/cognitions”). Identified LPs imperfectly resembled DSM-IV-TR eating disorders. LP1 resembled bulimia nervosa; LP2 and LP3 broadly resembled anorexia nervosa with a relaxed weight criterion, differentiated by excessive exercise and severity of eating disorder cognitions. LP groups were more differentiated than the DSM-IV-TR categories across pre-treatment eating disorder and general psychopathology indices, as well as weight change at follow-up. Neither LP nor DSM-IV-TR categories predicted change in binge/purge behaviors. Validation analyses suggest these empirically-derived groups improve upon the current DSM-IV-TR categories. Conclusions In children and adolescents, revisions for DSM-V should consider recognition of patients with minimal cognitive eating disorder symptoms. PMID:20410717

Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder.

PubMed

Badin, M S; Graf, L; Iyer, J K; Moffat, K A; Seecharan, J L; Hayward, C P M

2016-12-01

Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate (ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once. Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program (HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015. A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder. The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders. © 2016 John Wiley & Sons Ltd.

Attachment styles and personality disorders: their connections to each other and to parental divorce, parental death, and perceptions of parental caregiving.

PubMed

Brennan, K A; Shaver, P R

1998-10-01

Attachment theory was explored as a means of understanding the origins of personality disorders. We investigated whether adult attachment styles and personality disorders share a common underlying structure, and how both kinds of variables relate to family background factors, including parental death, parental divorce, and current representations of childhood relationships with parents. A nonclinical group of 1407 individuals, mostly adolescents and young adults, were surveyed about their attachment styles, parental marital status, parental mortality status, perceptions of treatment by parents in childhood, and 13 personality disorders. Results indicated substantial overlap between attachment and personality-disorder measures. Two of the personality-disorder dimensions are related to the two dimensions of the attachment space; that is, there is a two-dimensional space in which both the attachment patterns and most of the personality disorders can be arrayed. The one personality-disorder factor that is unrelated to attachment appears akin to psychopathy. Both personality disorders and attachment styles were associated with family-of-origin variables. Results are discussed in terms of encouraging further research to test the idea that insecure attachment and most of the personality disorders share similar developmental antecedents.

[Suicidal Behavior and Attention Decifit Hyperactivity Disorder in Adolescents of Medellin (Colombia), 2011-2012].

PubMed

Restrepo-Bernal, Diana; Bonfante-Olivares, Laura; Torres de Galvis, Yolanda; Berbesi-Fernández, Dedsy; Sierra-Hincapié, Gloria

2014-01-01

Suicide is a public health problem. In Colombia, teenagers are considered a group at high risk for suicidal behavior. To explore the possible association between suicidal behavior and attention deficit hyperactivity disorder in adolescents of Medellin. Observational, cross-sectional, analytical study. The Composite International Diagnostic Interview was applied to a total of 447 adolescents and the sociodemographic, clinical, familiar, and life event variables of interest were analyzed. The descriptive analysis of qualitative variables are presented as absolute values and frequencies, and the age was described with median [interquartile range]. A logistic regression model was constructed with explanatory variables that showed statistical association. Data were analyzed with SPSS® software version 21.0. Of the total, 59.1% were female, and the median age was 16 [14-18] years. Suicidal behavior was presented in 31% of females and 23% of males. Attention deficit was present in 6.3% of adolescents. The logistic regression analysis showed that the variables that best explained the suicidal behavior of adolescents were: female sex, post-traumatic stress disorder, panic disorder, and cocaine use. The diagnosis and early intervention of attention deficit hyperactivity disorder in children may be a useful strategy in the prevention of suicidal behavior in adolescents. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

PubMed

Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

PubMed Central

Panas, Marios; Paraskevas, George P.; Bougea, Anastasia M.; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family. PMID:25349749

Characterization of naturally developing small intestinal bacterial overgrowth in 16 German shepherd dogs.

PubMed

Willard, M D; Simpson, R B; Fossum, T W; Cohen, N D; Delles, E K; Kolp, D L; Carey, D P; Reinhart, G A

1994-04-15

Sixteen German Shepherd Dogs were found, via quantitative microbial culture of intestinal fluid samples, to have small intestinal bacterial overgrowth (IBO) over an 11-month period. All dogs were deficient in serum IgA. Consistent clinical signs suggestive of an alimentary tract disorder were not observed. Serum cobalamin determinations were not helpful in detecting IBO. Serum folate concentrations had variable sensitivity and specificity for detecting dogs from which we could culture > or = 1 x 10(5) bacterial/ml from intestinal fluid samples in the nonfed state. Histologic and intestinal mucosal cytologic examinations were not useful in detecting IBO. Substantial within-dog and between-dog variation was found in the numbers and species of bacteria in the intestines. The difficulty in diagnosing IBO, the variability in organisms found in individual dogs on repeated sampling, the likelihood that intestinal fluid microbial cultures failed to diagnose IBO in some dogs, and the potential of IBO to be clinically inapparent were the most important findings in this study.

Mutations in riboflavin transporter present with severe sensory loss and deafness in childhood.

PubMed

Srour, Myriam; Putorti, Maria Lisa; Schwartzentruber, Jeremy; Bolduc, Véronique; Shevell, Michael Israel; Poulin, Chantal; O'ferrall, Erin; Buhas, Daniela; Majewski, Jacek; Brais, Bernard

2014-11-01

We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood-onset recessive sensory loss associated with deafness and variable optic atrophy. Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals. WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown-Vialetto-Van-Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement. Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability. © 2014 Wiley Periodicals, Inc.

Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date

PubMed Central

Gaddi, Antonio; Cicero, AFG; Odoo, FO; Poli A, A; Paoletti, R

2007-01-01

Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%–2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines. PMID:18200807

Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date.

PubMed

Gaddi, Antonio; Cicero, A F G; Odoo, F O; Poli, A A; Paoletti, R

2007-01-01

Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes.

PubMed

Martinez de LaPiscina, Idoia; de Mingo, Carmen; Riedl, Stefan; Rodriguez, Amaia; Pandey, Amit V; Fernández-Cancio, Mónica; Camats, Nuria; Sinclair, Andrew; Castaño, Luis; Audi, Laura; Flück, Christa E

2018-01-01

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes

PubMed Central

Martinez de LaPiscina, Idoia; de Mingo, Carmen; Riedl, Stefan; Rodriguez, Amaia; Pandey, Amit V.; Fernández-Cancio, Mónica; Camats, Nuria; Sinclair, Andrew; Castaño, Luis; Audi, Laura; Flück, Christa E.

2018-01-01

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms. PMID:29670578

Effect of rivastigmine on mobility of patients with higher-level gait disorder: a pilot exploratory study.

PubMed

Gurevich, Tanya; Balash, Yacov; Merims, Doron; Peretz, Chava; Herman, Talia; Hausdorff, Jeffrey M; Giladi, Nir

2014-06-01

Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD. The aim of this study was to compare gait and cognitive performance before and after the use of rivastigmine in patients with HLGD, free from cognitive impairment or Parkinsonism. Fifteen non-demented patients with HLGD (age 79.2 ± 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3 ± 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label, pilot study. They were assessed before and after treatment (week 0 and week 12), and after a 4-week washout period (week 16). Assessments included the Mindstreams computerized neuropsychological battery, Activities-specific Balance Confidence Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go (TUG) test, gait speed and stride time variability. One-way multiple analysis of variance tests for repeated measures were used, and Pillai's trace test was considered as robust to investigate significant differences. The mean dose of rivastigmine during the 8-12 week period was 5.1 ± 2.3 mg/day. A positive effect was observed on the Mindstreams memory subscale and anxiety scores [Pillai's trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p = 0.006, respectively, over the course of the study] as well as on mobility (TUG test) [Pillai's trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and stride time variability did not change. The use of relatively low-dose rivastigmine did not affect gait speed and stride time variability; however, the general mobility and anxiety were improved. These preliminary results warrant a larger, randomized, placebo-controlled study.

A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models.

PubMed

Coghill, D R; Seth, S; Matthews, K

2014-07-01

Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning. The neuropsychological functioning of 83 medication-naive boys with well-characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks. Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)]. The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment.

Increased intra-individual reaction time variability in cocaine-dependent subjects: role of cocaine-related cues.

PubMed

Liu, Shijing; Lane, Scott D; Schmitz, Joy M; Green, Charles E; Cunningham, Kathryn A; Moeller, F Gerard

2012-02-01

Neuroimaging data suggest that impaired performance on response inhibition and information processing tests in cocaine-dependent subjects is related to prefrontal and frontal cortical dysfunction and that dysfunction in these brain areas may underlie some aspects of cocaine addiction. In subjects with attention-deficit hyperactivity disorder and other psychiatric disorders, the Intra-Individual Reaction Time Variability (IIRTV) has been associated with frontal cortical dysfunction. In the present study, we evaluated IIRTV parameters in cocaine-dependent subjects vs. controls using a cocaine Stroop task. Fifty control and 123 cocaine-dependent subjects compiled from three studies completed a cocaine Stroop task. Standard deviation (SD) and coefficient of variation (CV) for reaction times (RT) were calculated for both trials with neutral and trials with cocaine-related words. The parameters mu, sigma, and tau were calculated using an ex-Gaussian analysis employed to characterize variability in RTs. The ex-Gaussian analysis divides the RTs into normal (mu, sigma) and exponential (tau) components. Using robust regression analysis, cocaine-dependent subjects showed greater SD, CV and Tau on trials with cocaine-related words compared to controls (p<0.05). However, in trials with neutral words, there was no evidence of group differences in any IIRTV parameters (p>0.05). The Wilcoxon matched-pairs signed-rank test showed that for cocaine-dependent subjects, both SD and tau were larger in trials with cocaine-related words than in trials with neutral words (p<0.05). The observation that only cocaine-related words increased IIRTV in cocaine-dependent subjects suggests that cocaine-related stimuli might disrupt information processing subserved by prefrontal and frontal cortical circuits. Copyright © 2011 Elsevier Ltd. All rights reserved.

Family Distress and Eating Disorders among Undergraduate Students of University of Port Harcourt, Rivers State, Nigeria

ERIC Educational Resources Information Center

Iruloh, Betty-Ruth Ngozi; Wilson, Chukwu Juliet U.

2017-01-01

The study investigated the relative relationship between family distress and eating disorders among undergraduate students of University of Port Harcourt. The study was guided by three research questions and three null hypotheses to test the tenability of the independent variables on the dependent variable at 0.05 level of significance. The study…

Understanding Variability in Reading Comprehension in Adolescents with Autism Spectrum Disorders: Interactions with Language Status and Decoding Skill

ERIC Educational Resources Information Center

Norbury, Courtenay; Nation, Kate

2011-01-01

Although it is well recognized that reading skills vary in people with autism spectrum disorders (ASD), reasons for this variability are not well understood. We used the simple view of reading model to investigate both word decoding and text comprehension processes in two well-established subtypes within the autism spectrum, those with…

Variability in Classroom Social Communication: Performance of Children with Fetal Alcohol Spectrum Disorders and Typically Developing Peers

ERIC Educational Resources Information Center

Kjellmer, Liselotte; Olswang, Lesley B.

2013-01-01

Purpose: In this study, the authors examined how variability in classroom social communication performance differed between children with fetal alcohol spectrum disorders (FASD) and pair-matched, typically developing peers. Method: Twelve pairs of children were observed in their classrooms, 40 min per day (20 min per child) for 4 days over a…

Do Cognitive Models Help in Predicting the Severity of Posttraumatic Stress Disorder, Phobia, and Depression After Motor Vehicle Accidents? A Prospective Longitudinal Study

PubMed Central

Ehring, Thomas; Ehlers, Anke; Glucksman, Edward

2008-01-01

The study investigated the power of theoretically derived cognitive variables to predict posttraumatic stress disorder (PTSD), travel phobia, and depression following injury in a motor vehicle accident (MVA). MVA survivors (N = 147) were assessed at the emergency department on the day of their accident and 2 weeks, 1 month, 3 months, and 6 months later. Diagnoses were established with the Structured Clinical Interview for DSM–IV. Predictors included initial symptom severities; variables established as predictors of PTSD in E. J. Ozer, S. R. Best, T. L. Lipsey, and D. S. Weiss's (2003) meta-analysis; and variables derived from cognitive models of PTSD, phobia, and depression. Results of nonparametric multiple regression analyses showed that the cognitive variables predicted subsequent PTSD and depression severities over and above what could be predicted from initial symptom levels. They also showed greater predictive power than the established predictors, although the latter showed similar effect sizes as in the meta-analysis. In addition, the predictors derived from cognitive models of PTSD and depression were disorder-specific. The results support the role of cognitive factors in the maintenance of emotional disorders following trauma. PMID:18377119

Rapid improvements in emotion regulation predict intensive treatment outcome for patients with bulimia nervosa and purging disorder.

PubMed

MacDonald, Danielle E; Trottier, Kathryn; Olmsted, Marion P

2017-10-01

Rapid and substantial behavior change (RSBC) early in cognitive behavior therapy (CBT) for eating disorders is the strongest known predictor of treatment outcome. Rapid change in other clinically relevant variables may also be important. This study examined whether rapid change in emotion regulation predicted treatment outcomes, beyond the effects of RSBC. Participants were diagnosed with bulimia nervosa or purging disorder (N = 104) and completed ≥6 weeks of CBT-based intensive treatment. Hierarchical regression models were used to test whether rapid change in emotion regulation variables predicted posttreatment outcomes, defined in three ways: (a) binge/purge abstinence; (b) cognitive eating disorder psychopathology; and (c) depression symptoms. Baseline psychopathology and emotion regulation difficulties and RSBC were controlled for. After controlling for baseline variables and RSBC, rapid improvement in access to emotion regulation strategies made significant unique contributions to the prediction of posttreatment binge/purge abstinence, cognitive psychopathology of eating disorders, and depression symptoms. Individuals with eating disorders who rapidly improve their belief that they can effectively modulate negative emotions are more likely to achieve a variety of good treatment outcomes. This supports the formal inclusion of emotion regulation skills early in CBT, and encouraging patient beliefs that these strategies are helpful. © 2017 Wiley Periodicals, Inc.

On the association between diabetes and mental disorders in a community sample: results from the German National Health Interview and Examination Survey.

PubMed

Kruse, Johannes; Schmitz, Norbert; Thefeld, Wolfgang

2003-06-01

To determine the relationship between mental disorders and diabetes in a representative community sample. This was a cross-sectional study. Data on diabetes and HbA(1c) values were obtained by structured questionnaires and by laboratory assessments. Current psychiatric disorders were diagnosed by a modified version of the Composite International Diagnostic Interview (CIDI). People with diabetes (PWD) were not more likely to meet Diagnostic and Statistical Manual of Psychiatric Disorders, 4th edition (DSM-IV) criteria for at least one mental disorder than were individuals without diabetes. However, a different diagnostic pattern occurred compared with the general population: odds ratios (ORs) for anxiety disorders in PWD were higher (OR 1.93, 95% CI 1.19-3.14). Although PWD had higher prevalence rates of affective disorders, the relationship between diabetes and affective disorders was not statistically significant after controlling for age, sex, marital status, and socioeconomic status. In contrast, the relationship between diabetes and anxiety disorders remained significant after controlling for these variables. In contrast to individuals without mental disorders, PWD with affective or anxiety disorders more frequently had adequate glycemic control. Diabetes was associated with an increased likelihood of anxiety disorders. The association between mental disorders, diabetes, and glycemic control should be evaluated carefully in terms of potentially confounding sociodemographic variables, sample characteristics, and definitions of the disorders.

Depression or Endocrine Disorder?: What Mental Health Counselors Need to Know about Hypothyroidism.

ERIC Educational Resources Information Center

Stanley, Paula Helen

1997-01-01

Describes hypothyroidism, an endocrine disorder characterized by symptoms that resemble those of depression. Discusses features of the disorder, types and grades of hypothyroidism, causes, valuative techniques for the disorder, and implications of hypothyroidism in counseling and in treating patients suffering from this disorder. (RJM)

Subthreshold Depressive Disorder in Adolescents: Predictors of Escalation to Full-Syndrome

ERIC Educational Resources Information Center

Klein, Daniel N.; Shankman, Stewart A.; Lewinsohn, Peter M.; Seeley, John R.

2009-01-01

The risk for the onset of full-syndrome depressive disorders from the subtreshold depressive disorder in adolescents is found to be at 67 percent. The variables that predict the progression to the full onset are: severity of depressive symptoms, medical conditions/ symptoms, history of suicidal ideation, history of anxiety disorder, and familial…

Family Intervention with a Case of Bipolar I Disorder with Family Conflict

ERIC Educational Resources Information Center

Sahu, Kamlesh Kumar

2013-01-01

Bipolar disorder is a major mental illness. Inherited treatment of bipolar disorder has been focused on pharmacological treatments. Though, psychosocial variables appear to be important antecedents of bipolar disorder, poor drug compliance, expressed emotion or faulty communication and life events play a vital role in relapse. Conflict is commonly…

Tics and Tourette Syndrome in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Canitano, Roberto; Vivanti, Giacomo

2007-01-01

Autism spectrum disorders (ASDs) are more frequently associated with tic disorders than expected by chance. Variable rates of comorbidity have been reported and common genetic and neurobiological factors are probably involved. The aim of this study was to determine the rate of tic disorders in a clinical sample (n = 105) of children and…

Aggression, impulsivity, and psychopathic traits in combined antisocial personality disorder and substance use disorder.

PubMed

Alcorn, Joseph L; Gowin, Joshua L; Green, Charles E; Swann, Alan C; Moeller, F Gerard; Lane, Scott D

2013-01-01

Aggression, impulsivity, and psychopathic traits are prominent in both antisocial personality disorder (ASPD) and substance use disorders (SUD), but have rarely been examined collectively. The authors' results show that all three variables were elevated in adults with comorbid ASPD/SUD, relative to SUD-only and control subjects.

Examination of Predictors and Moderators for Self-help Treatments of Binge Eating Disorder

PubMed Central

Masheb, Robin M.; Grilo, Carlos M.

2008-01-01

Predictors and moderators of outcomes were examined in 75 overweight patients with binge eating disorder (BED) who participated in a randomized clinical trial of guided self-help treatments. Age variables, psychiatric and personality disorder comorbidity and clinical characteristics were tested as predictors and moderators of treatment outcomes. Current age and age of BED onset did not predict outcomes. Key dimensional outcomes (binge frequency, eating psychopathology, and negative affect) were predominately predicted, but not moderated, by their respective pretreatment levels. Presence of personality disorders, particularly Cluster C, predicted both post-treatment negative affect and eating disorder psychopathology. Negative affect, but not major depressive disorder, predicted attrition, and post-treatment negative affect and eating disorder psychopathology. Despite the prognostic significance of these findings for dimensional outcomes, none of the variables tested were predictive of binge remission (i.e., a categorical outcome). No moderator effects were found. The present study found poorer prognosis for patients with negative affect and personality disorders suggesting that treatment outcomes may be enhanced by attending to the cognitive and personality styles of these patients. PMID:18837607

Posttraumatic stress disorder in adult attention-deficit/hyperactivity disorder: clinical features and familial transmission.

PubMed

Antshel, Kevin M; Kaul, Prashant; Biederman, Joseph; Spencer, Thomas J; Hier, Bridget O; Hendricks, Kaitlin; Faraone, Stephen V

2013-03-01

Attention-deficit/hyperactivity disorder (ADHD) is characterized by clinically significant functional impairment due to symptoms of inattention and/or hyperactivity and impulsivity. Previous research suggests a link, in child samples, between ADHD and posttraumatic stress disorder (PTSD), which is characterized by (1) chronically reexperiencing a traumatic event, (2) hyperarousal, and (3) avoiding stimuli associated with the trauma while exhibiting numbed responsiveness. This study sought to address the link between ADHD and PTSD in adults by providing a comprehensive comparison of ADHD patients with and without PTSD across multiple variables including demographics, patterns of psychiatric comorbidities, functional impairments, quality of life, social adjustment, and familial transmission. Participants in our controlled family study conducted between 1998 and 2003 were 190 adults with DSM-IV ADHD who were attending an outpatient mental health clinic in Boston, Massachusetts; 16 adults with DSM-IV ADHD who were recruited by advertisement from the greater Boston area; and 123 adult controls without ADHD who were recruited by advertisement from the greater Boston area. All available first-degree relatives also participated. Subjects completed a large battery of self-report measures (the Quality of Life Enjoyment and Satisfaction Questionnaire, items from the Current Behavior Scale, the Social Adjustment Scale Self-Report, and the Four Factor Index of Social Status) designed to assess various psychiatric and functional parameters. Diagnoses were made using data obtained from structured psychiatric interviews (Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version, and the Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Epidemiologic Version). The lifetime prevalence of PTSD was significantly higher among adults with ADHD compared with controls (10.0% vs 1.6%; P = .004). Participants with ADHD and those with ADHD + PTSD did not differ in core symptoms of ADHD nor in age at onset, but those with ADHD + PTSD had higher rates of psychiatric comorbidity than those with ADHD only (including higher lifetime rates of major depressive disorder, oppositional defiant disorder, social phobia, agoraphobia, and generalized anxiety disorder) and worse quality of life ratings for all domains. Familial risk analysis revealed that relatives of ADHD probands without PTSD had elevated rates of both ADHD (51%) and PTSD (12%) that significantly differed from rates among relatives of controls (7% [P ≤ .001] and 0% [P ≤ .05], respectively). A similar pattern of elevated risk for ADHD and PTSD (80% and 40%) was observed in relatives of probands with ADHD + PTSD (P ≤ .001 for both conditions). The comorbidity of PTSD and ADHD in adults leads to greater clinical severity in terms of psychiatric comorbidity and psychosocial functioning. The familial coaggregation of the 2 disorders suggests that these disorders share familial risk factors and that their co-occurrence is not due to diagnostic errors. © Copyright 2013 Physicians Postgraduate Press, Inc.

Intrusive thoughts in obsessive-compulsive disorder and eating disorder patients: a differential analysis.

PubMed

García-Soriano, Gemma; Roncero, Maria; Perpiñá, Conxa; Belloch, Amparo

2014-05-01

The present study aims to compare the unwanted intrusions experienced by obsessive-compulsive (OCD) and eating disorder (ED) patients, their appraisals, and their control strategies and analyse which variables predict the intrusions' disruption and emotional disturbance in each group. Seventy-nine OCD and 177 ED patients completed two equivalent self-reports designed to assess OCD-related and ED-related intrusions, their dysfunctional appraisals, and associated control strategies. OCD and ED patients experienced intrusions with comparable frequency and emotional disturbance, but OCD patients experienced greater disruption. Differences appeared between groups on some appraisals and control strategies. Intolerance to uncertainty (OCD group) and thought importance (ED group) predicted their respective emotional disturbance and disruption. Additionally, control importance (OCD group) and thought-action fusion moral (OCD and ED groups) predicted their emotional disturbance. OCD and ED share the presence of intrusions; however, different variables explain why they are disruptive and emotionally disturbing. Cognitive intrusions require further investigation as a transdiagnostic variable. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Dynamic brain connectivity is a better predictor of PTSD than static connectivity.

PubMed

Jin, Changfeng; Jia, Hao; Lanka, Pradyumna; Rangaprakash, D; Li, Lingjiang; Liu, Tianming; Hu, Xiaoping; Deshpande, Gopikrishna

2017-09-01

Using resting-state functional magnetic resonance imaging, we test the hypothesis that subjects with post-traumatic stress disorder (PTSD) are characterized by reduced temporal variability of brain connectivity compared to matched healthy controls. Specifically, we test whether PTSD is characterized by elevated static connectivity, coupled with decreased temporal variability of those connections, with the latter providing greater sensitivity toward the pathology than the former. Static functional connectivity (FC; nondirectional zero-lag correlation) and static effective connectivity (EC; directional time-lagged relationships) were obtained over the entire brain using conventional models. Dynamic FC and dynamic EC were estimated by letting the conventional models to vary as a function of time. Statistical separation and discriminability of these metrics between the groups and their ability to accurately predict the diagnostic label of a novel subject were ascertained using separate support vector machine classifiers. Our findings support our hypothesis that PTSD subjects have stronger static connectivity, but reduced temporal variability of connectivity. Further, machine learning classification accuracy obtained with dynamic FC and dynamic EC was significantly higher than that obtained with static FC and static EC, respectively. Furthermore, results also indicate that the ease with which brain regions engage or disengage with other regions may be more sensitive to underlying pathology than the strength with which they are engaged. Future studies must examine whether this is true only in the case of PTSD or is a general organizing principle in the human brain. Hum Brain Mapp 38:4479-4496, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A psychometric investigation of gender differences and common processes across Borderline and Antisocial Personality Disorders

PubMed Central

Chun, Seokjoon; Harris, Alexa; Carrion, Margely; Rojas, Elizabeth; Stark, Stephen; Lejuez, Carl; Lechner, William V.; Bornovalova, Marina A.

2016-01-01

The comorbidity between Borderline Personality Disorder (BPD) and Antisocial Personality Disorder (ASPD) is well-established, and the two disorders share many similarities. However, there are also differences across disorders: most notably, BPD is diagnosed more frequently in females and ASPD in males. We investigated if a) comorbidity between BPD and ASPD is attributable to two discrete disorders or the expression of common underlying processes, and b) if the model of comorbidity is true across sex. Using a clinical sample of 1400 drug users in residential substance abuse treatment, we tested three competing models to explore whether the comorbidity of ASPD and BPD should be represented by a single common factor, two correlated factors, or a bifactor structure involving a general and disorder-specific factors. Next, we tested whether our resulting model was meaningful by examining its relationship with criterion variables previously reported to be associated with BPD and ASPD. The bifactor model provided the best fit and was invariant across sex. Overall, the general factor of the bifactor model significantly accounted for a large percentage of the variance in criterion variables, whereas the BPD and AAB specific factors added little to the models. The association of the general and specific factor with all criterion variables was equal for males and females. Our results suggest common underlying vulnerability accounts for both the comorbidity between BPD and AAB (across sex), and this common vulnerability drives the association with other psychopathology and maladaptive behavior. This in turn has implications for diagnostic classification systems and treatment. General scientific summary This study found that, for both males and females, borderline and antisocial personality disorders show a large degree of overlap, and little uniqueness. The commonality between BPD and ASPD mainly accounted for associations with criterion variables. This suggests that BPD and ASPD show a large common core that accounts for their comorbidity. PMID:27808543

Smartphone Application for the Analysis of Prosodic Features in Running Speech with a Focus on Bipolar Disorders: System Performance Evaluation and Case Study.

PubMed

Guidi, Andrea; Salvi, Sergio; Ottaviano, Manuel; Gentili, Claudio; Bertschy, Gilles; de Rossi, Danilo; Scilingo, Enzo Pasquale; Vanello, Nicola

2015-11-06

Bipolar disorder is one of the most common mood disorders characterized by large and invalidating mood swings. Several projects focus on the development of decision support systems that monitor and advise patients, as well as clinicians. Voice monitoring and speech signal analysis can be exploited to reach this goal. In this study, an Android application was designed for analyzing running speech using a smartphone device. The application can record audio samples and estimate speech fundamental frequency, F0, and its changes. F0-related features are estimated locally on the smartphone, with some advantages with respect to remote processing approaches in terms of privacy protection and reduced upload costs. The raw features can be sent to a central server and further processed. The quality of the audio recordings, algorithm reliability and performance of the overall system were evaluated in terms of voiced segment detection and features estimation. The results demonstrate that mean F0 from each voiced segment can be reliably estimated, thus describing prosodic features across the speech sample. Instead, features related to F0 variability within each voiced segment performed poorly. A case study performed on a bipolar patient is presented.

Metabolic cutis laxa syndromes.

PubMed

Mohamed, Miski; Kouwenberg, Dorus; Gardeitchik, Thatjana; Kornak, Uwe; Wevers, Ron A; Morava, Eva

2011-08-01

Cutis laxa is a rare skin disorder characterized by wrinkled, redundant, inelastic and sagging skin due to defective synthesis of elastic fibers and other proteins of the extracellular matrix. Wrinkled, inelastic skin occurs in many cases as an acquired condition. Syndromic forms of cutis laxa, however, are caused by diverse genetic defects, mostly coding for structural extracellular matrix proteins. Surprisingly a number of metabolic disorders have been also found to be associated with inherited cutis laxa. Menkes disease was the first metabolic disease reported with old-looking, wrinkled skin. Cutis laxa has recently been found in patients with abnormal glycosylation. The discovery of the COG7 defect in patients with wrinkled, inelastic skin was the first genetic link with the Congenital Disorders of Glycosylation (CDG). Since then several inborn errors of metabolism with cutis laxa have been described with variable severity. These include P5CS, ATP6V0A2-CDG and PYCR1 defects. In spite of the evolving number of cutis laxa-related diseases a large part of the cases remain genetically unsolved. In metabolic cutis laxa syndromes the clinical and laboratory features might partially overlap, however there are some distinct, discriminative features. In this review on metabolic diseases causing cutis laxa we offer a practical approach for the differential diagnosis of metabolic cutis laxa syndromes.

Smartphone Application for the Analysis of Prosodic Features in Running Speech with a Focus on Bipolar Disorders: System Performance Evaluation and Case Study

PubMed Central

Guidi, Andrea; Salvi, Sergio; Ottaviano, Manuel; Gentili, Claudio; Bertschy, Gilles; de Rossi, Danilo; Scilingo, Enzo Pasquale; Vanello, Nicola

2015-01-01

Bipolar disorder is one of the most common mood disorders characterized by large and invalidating mood swings. Several projects focus on the development of decision support systems that monitor and advise patients, as well as clinicians. Voice monitoring and speech signal analysis can be exploited to reach this goal. In this study, an Android application was designed for analyzing running speech using a smartphone device. The application can record audio samples and estimate speech fundamental frequency, F0, and its changes. F0-related features are estimated locally on the smartphone, with some advantages with respect to remote processing approaches in terms of privacy protection and reduced upload costs. The raw features can be sent to a central server and further processed. The quality of the audio recordings, algorithm reliability and performance of the overall system were evaluated in terms of voiced segment detection and features estimation. The results demonstrate that mean F0 from each voiced segment can be reliably estimated, thus describing prosodic features across the speech sample. Instead, features related to F0 variability within each voiced segment performed poorly. A case study performed on a bipolar patient is presented. PMID:26561811

Sensory texture analysis of thickened liquids during ingestion.

PubMed

Chambers, Edgar; Jenkins, Alicia; Mertz Garcia, Jane

2017-12-01

Practitioners support the use of thickened liquids for many patients with disordered swallowing. Although physical measures have highlighted differences among products there are questions about the ability of the measures to fully explain the sensory texture effects during swallowing of thickened liquids. This study used a trained sensory panel to describe the textural aspects of liquids during ingestion and swallowing. The lexicon was able to characterize differences in beverages, thickeners, and thickness levels with the most important attribute being viscosity, which loaded heavily in the almost one-dimensional space that resulted from the sensory analysis of these beverages. Other effects, such as slipperiness provided some minimal additional information on the products. Trained sensory panelists were shown to be useful in the measurement of differences in thickened liquid products prescribed for patients with dysphagia. They were able to differentiate products based on perceived differences related to flow speed, viscosity, and other parameters suggesting their use in further studies of swallowing behavior and for development of products for disordered swallowing should be considered. Understanding how these variables might relate to clinical decision making about product selection or modification to best meet the nutritional needs of a person with disordered swallowing could be helpful. This is especially true given the difficulties in measuring texture instrumentally in these products. © 2017 Wiley Periodicals, Inc.

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

Lindsay, E.A.; Grillo, A.; Ferrero, G.B.

The microphthalmia with linear skin defects (MLS) syndrome (MIM309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 305050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here the authors report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanningmore » the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. The authors propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, they cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome). 24 refs., 4 figs., 1 tab.« less

Mixed, melancholic, and anxious features in depression: a cross-sectional study of sociodemographic and clinical correlates.

PubMed

Zaninotto, Leonardo; Souery, Daniel; Calati, Raffaella; Scudellari, Paolo; Janiri, Luigi; Montgomery, Stuart; Kasper, Siegfried; Zohar, Joseph; Mendlewicz, Julien; Serretti, Alessandro

2014-11-01

Major depression (MD) is currently viewed as a heterogeneous condition, characterized by different psychopathological dimensions. Our sample was composed of 1,289 nonpsychotic bipolar/unipolar depressed patients. Participants were divided into mixed (MXD), melancholic (MEL), and anxious (ANX) depressed, according to a hierarchical functional model. Sociodemographic and clinical variables were compared across depressive subtypes by χ2 test and analysis of variance. The Young Mania Rating Scale (YMRS) and 2 subscales (melancholic [MEL-S] and psychic-somatic anxiety [PSOM-ANX]) from the Hamilton Depression Rating Scale also served as continuous outcome measures. MXD patients more frequently had bipolar I disorder (BD I), younger age of onset, and a higher familial load for mood disorders. MEL and ANX patients were more frequently diagnosed with major depressive disorder and reported a higher suicide risk. YMRS scores in depression was associated with BD I diagnosis (P < .0001) and manic polarity of the last episode (P < .0001), while a depressive polarity of the last episode (P < .0001) was associated with higher MEL-S score. No specific predictor was associated with PSOM-ANX score. Overall, our findings suggest that mixed depressive features are associated with significant hallmarks of bipolarity, and melancholic features may be influenced by previous depressive polarity. The symptom domain of anxiety appears to have no specific predictor.

Clumsiness in Children: Developmental Coordination Disorder.

ERIC Educational Resources Information Center

Fox, Mervyn A.

1998-01-01

Explores the diagnostic criteria of developmental coordination disorder, a condition that is characterized by motor awkwardness and has a strong association with psychiatric disorders and learning disabilities. Delineates the nature of developmental coordination disorder and discusses its treatment through occupational therapy and cognitive…

Intraindividual variability in basic reaction time predicts middle-aged and older pilots' flight simulator performance.

PubMed

Kennedy, Quinn; Taylor, Joy; Heraldez, Daniel; Noda, Art; Lazzeroni, Laura C; Yesavage, Jerome

2013-07-01

Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots. Two-hundred and thirty-six pilots (40-69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%-12% of the negative age effect on initial flight performance. IIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance.

Intraindividual Variability in Basic Reaction Time Predicts Middle-Aged and Older Pilots’ Flight Simulator Performance

PubMed Central

2013-01-01

Objectives. Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots. Method. Two-hundred and thirty-six pilots (40–69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. Results. Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%–12% of the negative age effect on initial flight performance. Discussion. IIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance. PMID:23052365

Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial disease model

PubMed Central

Foriel, Sarah; Eidhof, Ilse

2018-01-01

ABSTRACT Mitochondrial diseases are associated with a wide variety of clinical symptoms and variable degrees of severity. Patients with such diseases generally have a poor prognosis and often an early fatal disease outcome. With an incidence of 1 in 5000 live births and no curative treatments available, relevant animal models to evaluate new therapeutic regimes for mitochondrial diseases are urgently needed. By knocking down ND-18, the unique Drosophila ortholog of NDUFS4, an accessory subunit of the NADH:ubiquinone oxidoreductase (Complex I), we developed and characterized several dNDUFS4 models that recapitulate key features of mitochondrial disease. Like in humans, the dNDUFS4 KD flies display severe feeding difficulties, an aspect of mitochondrial disorders that has so far been largely ignored in animal models. The impact of this finding, and an approach to overcome it, will be discussed in the context of interpreting disease model characterization and intervention studies. This article has an associated First Person interview with the first author of the paper. PMID:29590638

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

2010-12-01

Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

Socio-neuro risk factors for suicidal behavior in criminal offenders with psychotic disorders.

PubMed

Harenski, Carla L; Brook, Michael; Kosson, David S; Bustillo, Juan R; Harenski, Keith A; Caldwell, Michael F; Van Rybroek, Gregory J; Koenigs, Michael; Decety, Jean; Thornton, David M; Calhoun, Vince D; Kiehl, Kent A

2017-01-01

Relative to the general population, individuals with psychotic disorders have a higher risk of suicide. Suicide risk is also elevated in criminal offenders. Thus, psychotic-disordered individuals with antisocial tendencies may form an especially high-risk group. We built upon prior risk analyses by examining whether neurobehavioral correlates of social cognition were associated with suicidal behavior in criminal offenders with psychotic disorders. We assessed empathic accuracy and brain structure in four groups: (i) incarcerated offenders with psychotic disorders and past suicide attempts, (ii) incarcerated offenders with psychotic disorders and no suicide attempts, (iii) incarcerated offenders without psychotic disorders and (iv) community non-offenders without psychotic disorders. Established suicide risk variables were examined along with empathic accuracy and gray matter in brain regions implicated in social cognition. Relative to the other groups, offenders with psychotic disorders and suicide attempts had lower empathic accuracy and smaller temporal pole volumes. Empathic accuracy and temporal pole volumes were significantly associated with suicide attempts independent of other risk variables. The results indicate that brain and behavioral correlates of social cognition may add incremental value to models of suicide risk. © The Author (2017). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Socio-neuro risk factors for suicidal behavior in criminal offenders with psychotic disorders

PubMed Central

Brook, Michael; Kosson, David S.; Bustillo, Juan R.; Harenski, Keith A.; Caldwell, Michael F.; Van Rybroek, Gregory J.; Koenigs, Michael; Decety, Jean; Thornton, David M.; Calhoun, Vince D.; Kiehl, Kent A.

2017-01-01

Abstract Relative to the general population, individuals with psychotic disorders have a higher risk of suicide. Suicide risk is also elevated in criminal offenders. Thus, psychotic-disordered individuals with antisocial tendencies may form an especially high-risk group. We built upon prior risk analyses by examining whether neurobehavioral correlates of social cognition were associated with suicidal behavior in criminal offenders with psychotic disorders. We assessed empathic accuracy and brain structure in four groups: (i) incarcerated offenders with psychotic disorders and past suicide attempts, (ii) incarcerated offenders with psychotic disorders and no suicide attempts, (iii) incarcerated offenders without psychotic disorders and (iv) community non-offenders without psychotic disorders. Established suicide risk variables were examined along with empathic accuracy and gray matter in brain regions implicated in social cognition. Relative to the other groups, offenders with psychotic disorders and suicide attempts had lower empathic accuracy and smaller temporal pole volumes. Empathic accuracy and temporal pole volumes were significantly associated with suicide attempts independent of other risk variables. The results indicate that brain and behavioral correlates of social cognition may add incremental value to models of suicide risk. PMID:28065894

Effects of depression, anxiety, comorbidity, and antidepressants on resting-state heart rate and its variability: an ELSA-Brasil cohort baseline study.

PubMed

Kemp, Andrew H; Brunoni, Andre R; Santos, Itamar S; Nunes, Maria A; Dantas, Eduardo M; Carvalho de Figueiredo, Roberta; Pereira, Alexandre C; Ribeiro, Antonio L P; Mill, José G; Andreão, Rodrigo V; Thayer, Julian F; Benseñor, Isabela M; Lotufo, Paulo A

2014-12-01

Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen's d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen's d, 0.42-0.95) and other antidepressants (Cohen's d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

Differential sensory fMRI signatures in autism and schizophrenia: Analysis of amplitude and trial-to-trial variability.

PubMed

Haigh, Sarah M; Gupta, Akshat; Barb, Scott M; Glass, Summer A F; Minshew, Nancy J; Dinstein, Ilan; Heeger, David J; Eack, Shaun M; Behrmann, Marlene

2016-08-01

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Nonlinear digital signal processing in mental health: characterization of major depression using instantaneous entropy measures of heartbeat dynamics.

PubMed

Valenza, Gaetano; Garcia, Ronald G; Citi, Luca; Scilingo, Enzo P; Tomaz, Carlos A; Barbieri, Riccardo

2015-01-01

Nonlinear digital signal processing methods that address system complexity have provided useful computational tools for helping in the diagnosis and treatment of a wide range of pathologies. More specifically, nonlinear measures have been successful in characterizing patients with mental disorders such as Major Depression (MD). In this study, we propose the use of instantaneous measures of entropy, namely the inhomogeneous point-process approximate entropy (ipApEn) and the inhomogeneous point-process sample entropy (ipSampEn), to describe a novel characterization of MD patients undergoing affective elicitation. Because these measures are built within a nonlinear point-process model, they allow for the assessment of complexity in cardiovascular dynamics at each moment in time. Heartbeat dynamics were characterized from 48 healthy controls and 48 patients with MD while emotionally elicited through either neutral or arousing audiovisual stimuli. Experimental results coming from the arousing tasks show that ipApEn measures are able to instantaneously track heartbeat complexity as well as discern between healthy subjects and MD patients. Conversely, standard heart rate variability (HRV) analysis performed in both time and frequency domains did not show any statistical significance. We conclude that measures of entropy based on nonlinear point-process models might contribute to devising useful computational tools for care in mental health.

Language and Communication Skills in Preschool Children with Autism Spectrum Disorders: Contribution of Cognition, Severity of Autism Symptoms, and Adaptive Functioning to the Variability

ERIC Educational Resources Information Center

Kjellmer, Liselotte; Hedvall, Asa; Fernell, Elisabeth; Gillberg, Christopher; Norrelgen, Fritjof

2012-01-01

This study examined the contribution of cognitive function, severity of autism, and adaptive functioning to the variability in language and communication skills in 129 preschool children (aged 24-63 months) with autism spectrum disorder (ASD). Participants were selected from a representative research cohort of 208 preschool children on the basis…

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour.

PubMed

Lesch, Klaus-Peter; Araragi, Naozumi; Waider, Jonas; van den Hove, Daniel; Gutknecht, Lise

2012-09-05

Aggression, which comprises multi-faceted traits ranging from negative emotionality to antisocial behaviour, is influenced by an interaction of biological, psychological and social variables. Failure in social adjustment, aggressiveness and violence represent the most detrimental long-term outcome of neurodevelopmental disorders. With the exception of brain-specific tryptophan hydroxylase-2 (Tph2), which generates serotonin (5-HT) in raphe neurons, the contribution of gene variation to aggression-related behaviour in genetically modified mouse models has been previously appraised (Lesch 2005 Novartis Found Symp. 268, 111-140; Lesch & Merschdorf 2000 Behav. Sci. Law 18, 581-604). Genetic inactivation of Tph2 function in mice led to the identification of phenotypic changes, ranging from growth retardation and late-onset obesity, to enhanced conditioned fear response, increased aggression and depression-like behaviour. This spectrum of consequences, which are amplified by stress-related epigenetic interactions, are attributable to deficient brain 5-HT synthesis during development and adulthood. Human data relating altered TPH2 function to personality traits of negative emotionality and neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation are based on genetic association and are therefore not as robust as the experimental mouse results. Mouse models in conjunction with approaches focusing on TPH2 variants in humans provide unexpected views of 5-HT's role in brain development and in disorders related to negative emotionality, aggression and antisocial behaviour.

Social Aspects of the Workplace Among Individuals With Bipolar Disorder.

PubMed

O'Donnell, Lisa; Himle, Joseph A; Ryan, Kelly; Grogan-Kaylor, Andrew; McInnis, Melvin G; Weintraub, Jenna; Kelly, Marisa; Deldin, Patricia

2017-01-01

Bipolar disorder (BD) is characterized by recurrent mood episodes and profound impairments in psychosocial functioning. Occupational disability is one of the most problematic impairments for individuals with BD due to high rates of unemployment and work impairments. Current evidence indicates that social stressors at work-such as social isolation, conflict with others, and stigmas-are common experiences for employed individuals with BD. Yet, few studies have examined the relationship between social stressors at work and overall occupational functioning, instead focusing on individual clinical features of the disorder. This cross-sectional study employed logistic and linear regressions to determine which demographic variables, mood symptoms, and social aspects of the work environment (exclusion, conflict, social support, stigma) were associated with work status (working vs. not working) and work functioning for individuals with bipolar disorder I and II. Greater stigma and exclusion at work ( p < .05) are associated with unemployment among adult individuals with BD, and higher degrees of depression and conflict at work ( p < .05) are associated with work impairments for employed individuals. By examining two distinct measures of work outcomes (work status and work functioning) within the same group of participants, this study provides a unique insight, revealing that predictors of occupational functioning vary based on the specific measure of work outcomes used. This study also emphasizes the need for treatments that address the clinical features of BD and intervene in the work environment to improve functioning and prevent unemployment among individuals with BD.

Predictive Model for Anxiety and Depression in Spanish Patients with Stable Chronic Obstructive Pulmonary Disease.

PubMed

González-Gutiérrez, María Victoria; Guerrero Velázquez, José; Morales García, Concepción; Casas Maldonado, Francisco; Gómez Jiménez, Francisco Javier; González Vargas, Francisco

2016-03-01

The association between chronic obstructive pulmonary disease (COPD) and anxiety and depression is not yet completely characterized, and differences between countries may exist. We used a predictive model to assess this association in a Spanish population. Prospective transversal descriptive study of 204 patients with stable COPD. Concomitant anxiety or depression were diagnosed by psychiatric assessment, using the diagnostic criteria of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Sociodemographic, clinical and lung function parameters were analyzed. In total, 36% of stable COPD patients had psychiatric comorbidities, but 76% were unaware of their diagnosis. Nineteen percent had a pure anxiety disorder, 9.8% had isolated depression, and 7.3% had a mixed anxiety-depression disorder. Predictive variables in the multivariate analysis were younger age, higher educational level, lack of home support, higher BODE index, and greater number of exacerbations. The ROC curve of the model had an AUC of 0.765 (P<0.001). In COPD, concomitant psychiatric disorders are significantly associated with sociodemographic factors. Anxiety disorders are more common than depression. Patients with more severe COPD, according to BODE, younger patients and those with a higher educational level have a greater risk of being diagnosed with anxiety or depression in a structured psychiatric interview. In our population, most patients with psychiatric comorbidities remain unidentified. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

Psychiatric disorders in a cohort of individuals with Prader-Willi syndrome.

PubMed

Shriki-Tal, L; Avrahamy, H; Pollak, Y; Gross-Tsur, V; Genstil, L; Hirsch, H J; Benarroch, F

2017-07-01

Psychiatric manifestations in Prader-Willi Syndrome (PWS) are common and often are the most debilitating problem in these individuals. We present an epidemiological nation-wide survey of psychiatric diagnoses in the PWS population, based on full-range psychiatric interviews. We studied the distribution of psychiatric diagnoses (as opposed to a symptom-based approach) in the Israel national cohort of adolescents and adults with PWS. There was a total of 53 (32 males) ages 12 years and older. All individuals and their caretakers were interviewed using standardized psychiatric questionnaires. Demographic and clinical variables, Clinical Global Impression (CGI) score, IQ, severity of hyperphagia and quality of life (QOL) were also assessed and correlations with NPD (number of psychiatric diagnoses) calculated. An overwhelming majority (89%) of the study participants had at least one psychiatric diagnosis. The most common were disruptive behavior disorders (DBD) (68%), obsessive compulsive disorder (OCD) (45%) and skin picking (35%). Individuals with DBD were at increased risk for OCD and skin picking. Psychotic disorders were found in 11%. NPD had a significant negative influence on QOL. There was no correlation between NPD and BMI, IQ, hyperphagia severity, hormonal profile or genetic subtypes. Psychiatric diagnoses are very frequent in PWS and strongly influence QOL. Furthermore, characterizing the profile of psychiatric comorbidity in PWS is crucial for planning effective interventions. Precise behavioral phenotyping in PWS in combination with a well-defined genetic etiology may aid biological research linking biological correlates to behavior. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hypogammaglobulinemia factitia- Munchausen syndrome masquerading as common variable immune deficiency

PubMed Central

2013-01-01

Background We describe the first case of a patient with factitious disorder who closely simulated a primary immune deficiency disorder – Common Variable Immune Deficiency (CVID), by surreptitiously ingesting non-steroidal anti-inflammatory agents. Case description He was treated with several expensive and potentially dangerous drugs before the diagnosis was established through collateral information. In retrospect he did not meet the proposed new criteria for CVID. These criteria may prove useful in distinguishing cases of CVID from secondary hypogammaglobulinemia. Conclusion It is imperative clinicians recognise patients with factitious disorder at the earliest opportunity to prevent iatrogenic morbidity and mortality. PMID:24341706

Children with Comorbid Speech Sound Disorder and Specific Language Impairment Are at Increased Risk for Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

McGrath, Lauren M.; Hutaff-Lee, Christa; Scott, Ashley; Boada, Richard; Shriberg, Lawrence D.; Pennington, Bruce F.

2008-01-01

This study focuses on the comorbidity between attention-deficit/hyperactivity disorder (ADHD) symptoms and speech sound disorder (SSD). SSD is a developmental disorder characterized by speech production errors that impact intelligibility. Previous research addressing this comorbidity has typically used heterogeneous groups of speech-language…

An Initial Report of Sleep Disorders in Women in the U.S. Military.

PubMed

Capener, Dale C; Brock, Matthew S; Hansen, Shana L; Matsangas, Panagiotis; Mysliwiec, Vincent

2018-02-07

Sleep disorders are increasingly recognized in active duty service members (ADSM). While there are multiple studies in male ADSM, there are limited data regarding sleep disorders in women in the military. The purpose of this study was to characterize sleep disorders in female ADSM referred for clinical evaluation to provide a better understanding of this unique population. We conducted a retrospective review of female ADSM who underwent a sleep medicine evaluation and an attended polysomnogram (PSG). Demographic and polysomnogram variables, as well as medical records, were reviewed. Associated illnesses to include post-traumatic stress disorder, pain disorders, anxiety, and depression, were recorded. The cohort consisted of 101 women. The average age was 33.9 ± 9.0 years and body mass index was 27.3 ± 4.5, with an average Epworth Sleepiness Scale score of 12.9 ± 5.2, and Insomnia Severity Index score of 17.6 ± 5.7. Overall, 36.6% were diagnosed with insomnia only, 14.9% with obstructive sleep apnea (OSA) only, and 34.7% met diagnostic criteria for both insomnia and OSA. The average apnea-hypopnea index for the entire cohort was 5.37 ± 7.04/h whereas it was 10.34 ± 3.14/h for those meeting diagnostic criteria for OSA. The women referred for sleep evaluations had the following rates of associated illnesses: pain disorders (59.4%), anxiety (48.5%), depression (46.5%), and post-traumatic stress disorder (21.8%). For patients with OSA, the relative risk of having post-traumatic stress disorder was 2.72 (95% confidence interval 1.16-6.39). Women in the U.S. military who have sleep disorders have a high rate of behavioral medicine and pain disorders. Interestingly, nearly 50% of active duty females referred for a sleep study have OSA while not necessarily manifesting the typical signs of obesity or increased age. The reasons for this finding are not completely understood, though factors related to military service may potentially contribute. The findings from our study indicate a need for increased awareness and evaluation of sleep disorders in women in the military, especially those with behavioral medicine disorders. Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

External Validity of Childhood Disintegrative Disorder in Comparison with Autistic Disorder

ERIC Educational Resources Information Center

Kurita, Hiroshi; Osada, Hirokazu; Miyake, Yuko

2004-01-01

To examine the external validity of DSM-IV childhood disintegrative disorder (CDD), 10 children (M = 8.2 yrs) with CDD and 152 gender- and age-matched children with autistic disorder (AD) were compared on 24 variables. The CDD children had a significantly higher rate of epilepsy, significantly less uneven intellectual functioning, and a tendency…

Academic Achievements, Behavioral Problems, and Loneliness as Predictors of Social Skills among Students with and without Learning Disorders

ERIC Educational Resources Information Center

Zach, Sima; Yazdi-Ugav, Orly; Zeev, Aviva

2016-01-01

This study aimed to examine to what extent academic achievements, learning disorders, behavior problems and loneliness explain the variance of students' social skills. The differences between students diagnosed with learning disorders and students without learning disorders in all four variables were examined. Participants were 733 elementary…

Major depressive disorder, personality disorders, and coping strategies are independent risk factors for lower quality of life in non-metastatic breast cancer patients.

PubMed

Brunault, Paul; Champagne, Anne-Laure; Huguet, Grégoire; Suzanne, Isabelle; Senon, Jean-Louis; Body, Gilles; Rusch, Emmanuel; Magnin, Guillaume; Voyer, Mélanie; Réveillère, Christian; Camus, Vincent

2016-05-01

Our aim was to identify risk factors for lower quality of life (QOL) in non-metastatic breast cancer patients. Our study included 120 patients from the University Hospital Centers of Tours and Poitiers. This cross-sectional study was conducted 7 months after patients' breast cancer diagnosis and assessed QOL (Quality of Life Questionnaire Core 30 = QLQ-C30), socio-demographic characteristics, coping strategies (Brief-COPE), physiological and biological variables (e.g., initial tumor severity and types of treatment received), the existence of major depressive disorder (Mini International Neuropsychiatric Interview), and pain severity (Questionnaire de Douleur Saint Antoine). We assessed personality disorders 3 months after diagnosis (Vragenlijst voor Kenmerken van de Persoonlijkheid questionnaire). We used multiple linear regression models to determine which factors were associated with physical, emotional, and global QOL. Lower physical QOL was associated with major depressive disorder, younger age, a more severe initial tumor stage, and the use of the behavioral disengagement coping. Lower emotional QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, and lower use of acceptance coping strategies. Lower global QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, lower use of positive reframing coping strategies, and an absence of hormone therapy. Lower QOL scores were more strongly associated with variables related to the individual's premorbid psychological characteristics and the manner in which this individual copes with the cancer (e.g., depression, personality, and coping) than to cancer-related variables (e.g., treatment types and cancer severity). Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Systematic review of the neural basis of social cognition in patients with mood disorders

PubMed Central

Cusi, Andrée M.; Nazarov, Anthony; Holshausen, Katherine; MacQueen, Glenda M.; McKinnon, Margaret C.

2012-01-01

Background This review integrates neuroimaging studies of 2 domains of social cognition — emotion comprehension and theory of mind (ToM) — in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Methods Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were “fMRI,” “emotion comprehension,” “emotion perception,” “affect comprehension,” “affect perception,” “facial expression,” “prosody,” “theory of mind,” “mentalizing” and “empathy” in combination with “major depressive disorder,” “bipolar disorder,” “major depression,” “unipolar depression,” “clinical depression” and “mania.” Results Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Limitations Studies that did not include control tasks or a comparator group were included in this review. Conclusion Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks underlying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders. PMID:22297065

[Factors Associated With Suicide Attempts and Nonsuicidal Self-Injurious Behaviors in Patients With Eating Disorders].

PubMed

Rodríguez Guarín, Maritza; Rodríguez Malagón, Nelcy; Gempeler Rueda, Juanita; Garzón, Daniel Felipe

2013-01-01

Suicide attempt (SA) and non-suicidal self-injurious behaviors (NSSI) have been described in patients with eating disorders (ED), and they have been associated with increased morbidity and poor prognosis. To explore the presence of SA and NSSI in patients attending an outpatient ED program, as well as to evaluate the associated variables and the correlation between both types of behaviors. A total of 908 patients of both sexes attending the Equilibrio outpatient program in Bogotá were studied. The histories of SA and NSSI were systematically examined in the development of medical history by direct and structured questions to the patient, and then validated during interviews with the family. Sociodemographic and clinical variables, as well as history of traumatic experiences, were also studied. Simple frequencies were calculated, and a bivariate analysis was performed between SA, NSSI, and the other variables of the study. Finally, two models of association were designed for the multivariate analysis, using variables of clinical importance and statistical significance. SA sometime in their lives was reported by 13% of the patients, and 26% of them reported NSSI. The variables associated with SA were bipolar disorder (OR: 3.86, 95% CI; 2.4-6.1), borderline personality, purgative subtype of ED, and self-injury. Sexual abuse was associated with NSSI (OR: 3.48, 95%CI; 2.2-5.4), as well as bipolar disorder, trichotillomania, and suicide attempt. SA and NSSI are frequent in patients with eating disorders with multiple comorbidities, increased impulsivity and emotional dysregulation, and they should be explored and treated. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Adults with Asperger Syndrome: A Childhood Disorder Grows Up

ERIC Educational Resources Information Center

Wilkinson, Lee A.

2007-01-01

Asperger syndrome is a chronic developmental disorder characterized by problems in social relatedness, empathic communication and understanding, and circumscribed interests. The inclusion of Asperger's Disorder (Asperger syndrome) in the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-IV; American Psychiatric Association, 1994), has…

Changes in heart rate variability during TOVA testing in patients with major depressive disorder.

PubMed

Shen, Tsu-Wang; Liu, Fang-Chih; Chen, Shaw-Ji; Chen, Shao-Tsu

2013-01-01

The aim of this study was to identify major depressive disorder (MDD) based on heart rate variability (HRV) during tests of variables of attention (TOVA). Forty-five MDD patients without cardiovascular disease and 45 controls matched by age and gender participated in this study. Compared to the controls, the MDD group had lower resting HRV parameters, more omissions and variability and longer response times on TOVA, and failure of attention employment to decrease HRV. The resting HRV parameters may provide easily measured, clinically useful ways to identify patients with MDD and to monitor their progress in treatment. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Genetics Home Reference: ADNP syndrome

MedlinePlus

... disorder, which is characterized by impaired communication and social interaction. Affected individuals also have distinctive facial features and ... spectrum disorder, including repetitive behaviors and difficulty with social interactions. ADNP syndrome is also associated with mood disorders ...

Neuropsychiatric disorders in Cushing's syndrome

PubMed Central

Pivonello, Rosario; Simeoli, Chiara; De Martino, Maria Cristina; Cozzolino, Alessia; De Leo, Monica; Iacuaniello, Davide; Pivonello, Claudia; Negri, Mariarosaria; Pellecchia, Maria Teresa; Iasevoli, Felice; Colao, Annamaria

2015-01-01

Endogenous Cushing's syndrome (CS), a rare endocrine disorder characterized by cortisol hypersecretion, is associated with psychiatric and neurocognitive disorders. Major depression, mania, anxiety, and neurocognitive impairment are the most important clinical abnormalities. Moreover, patients most often complain of impairment in quality of life, interference with family life, social, and work performance. Surprisingly, after hypercortisolism resolution, despite the improvement of the overall prevalence of psychiatric and neurocognitive disorders, the brain volume loss at least partially persists and it should be noted that some patients may still display depression, anxiety, panic disorders, and neurocognitive impairment. This brief review aimed at describing the prevalence of psychiatric and neurocognitive disorders and their characterization both during the active and remission phases of CS. The last section of this review is dedicated to quality of life, impaired during active CS and only partially resolved after resolution of hypercortisolism. PMID:25941467

Is Reaction Time Variability in ADHD Mainly at Low Frequencies?

ERIC Educational Resources Information Center

Karalunas, Sarah L.; Huang-Pollock, Cynthia L.; Nigg, Joel T.

2013-01-01

Background: Intraindividual variability in reaction times (RT variability) has garnered increasing interest as an indicator of cognitive and neurobiological dysfunction in children with attention deficit hyperactivity disorder (ADHD). Recent theory and research has emphasized specific low-frequency patterns of RT variability. However, whether…

Dynamic Patterns in Mood Among Newly Diagnosed Patients With Major Depressive Episode or Panic Disorder and Normal Controls

PubMed Central

Katerndahl, David; Ferrer, Robert; Best, Rick; Wang, Chen-Pin

2007-01-01

Objective: The purpose of this pilot study was to compare the dynamic patterns of hourly mood variation among newly diagnosed primary care patients with major depressive disorder or panic disorder with patterns in patients with neither disorder. Method: Five adult patients with major depressive episode, 5 with panic disorder, and 5 with neither disorder were asked to complete hourly self-assessments of anxiety and depression (using 100-mm visual analog scales) for each hour they were awake during a 30-day period. Time series were analyzed using ARIMA (autoregression, integration, moving average) modeling (to assess periodicity), Lyapunov exponents (to assess sensitivity to initial conditions indicative of chaotic patterns), and correlation dimension saturation (to assess whether an attractor is limiting change). The study was conducted from March to June 2003. Results: Controls displayed circadian rhythms with underlying chaotic variability. Depressed patients did not display circadian rhythm, but did show chaotic dynamics. Panic disorder patients showed circadian rhythms, but 2 of the 4 patients completing the self-assessments displayed nonchaotic underlying patterns. Conclusions: Patients with major depressive disorder or panic disorder may differ from controls and from each other in their patterns of mood variability. There is a need for more research on the dynamics of mood among patients with mental disorders. PMID:17632650

Hypochondriasis, somatoform disorders, and anxiety disorders: sociodemographic variables, general psychopathology, and naturalistic treatment effects.

PubMed

Gropalis, Maria; Bleichhardt, Gaby; Witthöft, Michael; Hiller, Wolfgang

2012-05-01

The question of whether hypochondriasis (HYP) should be considered a somatoform disorder (SFD) or classified as an anxiety disorder (ANX) has recently been raised. To empirically provide information on this issue, we compared patients with HYP (n = 65) with those with other SFDs (n = 94) and those with ANX (n = 224) regarding sociodemographic and biographical variables, general psychopathology, and naturalistic cognitive-behavioral therapy treatment effects. Compared with SFD, patients with HYP were younger and had fewer comorbid affective disorders and less impaired life domains, suggesting a closer connection between HYP and ANX. Regarding cognitive-behavioral therapy treatment effects, all diagnostic groups showed comparable significant improvement (d = 0.44-0.64). According to level of anxiety, the SFD sample had significantly lower pretreatment scores than did the ANX and the HYP samples. The results suggest that patients with HYP have an interim position between SFD and ANX, with slightly closer connections to ANX.

Nonequilibrium thermodynamics in sheared hard-sphere materials.

PubMed

Lieou, Charles K C; Langer, J S

2012-06-01

We combine the shear-transformation-zone (STZ) theory of amorphous plasticity with Edwards' statistical theory of granular materials to describe shear flow in a disordered system of thermalized hard spheres. The equations of motion for this system are developed within a statistical thermodynamic framework analogous to that which has been used in the analysis of molecular glasses. For hard spheres, the system volume V replaces the internal energy U as a function of entropy S in conventional statistical mechanics. In place of the effective temperature, the compactivity X=∂V/∂S characterizes the internal state of disorder. We derive the STZ equations of motion for a granular material accordingly, and predict the strain rate as a function of the ratio of the shear stress to the pressure for different values of a dimensionless, temperature-like variable near a jamming transition. We use a simplified version of our theory to interpret numerical simulations by Haxton, Schmiedeberg, and Liu, and in this way are able to obtain useful insights about internal rate factors and relations between jamming and glass transitions.

Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability.

PubMed

Tatton-Brown, Katrina; Seal, Sheila; Ruark, Elise; Harmer, Jenny; Ramsay, Emma; Del Vecchio Duarte, Silvana; Zachariou, Anna; Hanks, Sandra; O'Brien, Eleanor; Aksglaede, Lise; Baralle, Diana; Dabir, Tabib; Gener, Blanca; Goudie, David; Homfray, Tessa; Kumar, Ajith; Pilz, Daniela T; Selicorni, Angelo; Temple, I Karen; Van Maldergem, Lionel; Yachelevich, Naomi; van Montfort, Robert; Rahman, Nazneen

2014-04-01

Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142 individuals with overgrowth. The mutations alter residues in functional DNMT3A domains, and protein modeling suggests that they interfere with domain-domain interactions and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P < 0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancies.

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing.

PubMed

Yuan, Lamei; Wu, Song; Xu, Hongbo; Xiao, Jingjing; Yang, Zhijian; Xia, Hong; Liu, An; Hu, Pengzhi; Lu, Anjie; Chen, Yulan; Xu, Fengping; Deng, Hao

2015-01-01

Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.

Role of Genetic Factors in the Pathogenesis of Radial Deficiencies in Humans

PubMed Central

Elmakky, Amira; Stanghellini, Ilaria; Landi, Antonio; Percesepe, Antonio

2015-01-01

Radial deficiencies (RDs), defined as under/abnormal development or absence of any of the structures of the forearm, radial carpal bones and thumb, occur with a live birth incidence ranging from 1 out of 30,000 to 1 out 6,000 newborns and represent about one third/one fourth of all the congenital upper limb anomalies. About half of radial disorders have a mendelian cause and pattern of inheritance, whereas the remaining half appears sporadic with no known gene involved. In sporadic forms certain anomalies, such as thumb or radial hypoplasia, may occur either alone or in association with systemic conditions, like vertebral abnormalities or renal defects. All the cases with a mendelian inheritance are syndromic forms, which include cardiac defects (in Holt-Oram syndrome), bone marrow failure (in Fanconi anemia), platelet deficiency (in thrombocytopenia-absent-radius syndrome), ocular motility impairment (in Okihiro syndrome). The genetics of radial deficiencies is complex, characterized by genetic heterogeneity and high inter- and intra-familial clinical variability: this review will analyze the etiopathogenesis and the genotype/phenotype correlations of the main radial deficiency disorders in humans. PMID:26962299

A small molecule mitigates hearing loss in a mouse model of Usher syndrome III.

PubMed

Alagramam, Kumar N; Gopal, Suhasini R; Geng, Ruishuang; Chen, Daniel H-C; Nemet, Ina; Lee, Richard; Tian, Guilian; Miyagi, Masaru; Malagu, Karine F; Lock, Christopher J; Esmieu, William R K; Owens, Andrew P; Lindsay, Nicola A; Ouwehand, Krista; Albertus, Faywell; Fischer, David F; Bürli, Roland W; MacLeod, Angus M; Harte, William E; Palczewski, Krzysztof; Imanishi, Yoshikazu

2016-06-01

Usher syndrome type III (USH3), characterized by progressive deafness, variable balance disorder and blindness, is caused by destabilizing mutations in the gene encoding the clarin-1 (CLRN1) protein. Here we report a new strategy to mitigate hearing loss associated with a common USH3 mutation CLRN1(N48K) that involves cell-based high-throughput screening of small molecules capable of stabilizing CLRN1(N48K), followed by a secondary screening to eliminate general proteasome inhibitors, and finally an iterative process to optimize structure-activity relationships. This resulted in the identification of BioFocus 844 (BF844). To test the efficacy of BF844, we developed a mouse model that mimicked the progressive hearing loss associated with USH3. BF844 effectively attenuated progressive hearing loss and prevented deafness in this model. Because the CLRN1(N48K) mutation causes both hearing and vision loss, BF844 could in principle prevent both sensory deficiencies in patients with USH3. Moreover, the strategy described here could help identify drugs for other protein-destabilizing monogenic disorders.

A Transactional Systems Model of Autism Services

PubMed Central

Cuvo, Anthony J; Vallelunga, Lori R

2007-01-01

There has been an escalation in the number of children identified with autism spectrum disorders in recent years. To increase the likelihood that treatments for these children are effective, interventions should be derived from sound theory and research evidence. Absent this supportive foundation, intervention programs could be inconsequential if not harmful. Although atypical, the development of children with autism should be considered initially from the perspective of the same variables that affect the development of typical children. In addition, the developmental deviations that characterize autism must be considered when developing intervention programs. Behavioral systems models describe both typical and atypical development and emphasize dynamic multidirectional person–environment transactions. The environment is viewed as having multiple levels, from the individuals with autism themselves, to larger societal and cultural levels. Behavioral systems models of human development can be generalized to a transactional systems model of services for children with autism. This model is the foundational theoretical position of the Southern Illinois University Center for Autism Spectrum Disorders. The center's programs are described to illustrate the application of the model to multiple levels of the social ecology. PMID:22478495

Exceptional bone metastasis of basal cell carcinoma in Gorlin-Goltz syndrome.

PubMed

Lamon, Tatiana; Gerard, Stephane; Meyer, Nicolas; Losfeld, Benjamin; Abellan van Kan, Gabor; Balardy, Laurent; Vellas, Bruno

2010-01-01

Basal cell carcinoma (BCC), the most prevalent form of cancer worldwide, is a malignant skin neoplasm. It is locally invasive, with an exceptional incidence of reported metastasis. It can also be part of the Gorlin-Goltz syndrome, an autosomal dominant genetic disorder with high penetrance and variable expressivity, which is principally characterized by cutaneous BCC, odontogenic keratocysts, palmar and/or plantar pits, and falx cerebri calcification. We report the exceptional clinical observation of a 54-year-old man presenting bone metastasis from BCC in Gorlin-Goltz syndrome. Less than 300 cases of metastatic BCC have been reported in the literature. The present case is the second associated with Gorlin-Goltz syndrome. Copyright 2009 S. Karger AG, Basel.

Update on the therapy of Behçet disease

PubMed Central

Saleh, Zeinab

2014-01-01

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials. PMID:24790727

Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

PubMed

Mathur, Deepan; Somashekar, Santhosh; Navarrete, Cristina; Rodriguez, Maria M

2014-08-01

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

The contribution of Raman spectroscopy to the analysis of phase transformations in pharmaceutical compounds.

PubMed

Hédoux, Alain; Guinet, Yannick; Descamps, Marc

2011-09-30

We show in this paper the contribution of the whole Raman spectrum including the phonon spectrum, to detect, identify and characterize polymorphic forms of molecular compounds, and study their stability and transformation. Obtaining these kinds of information is important in the area of pharmaceutical compounds. Two different polymorphic systems are analyzed through investigations in indomethacin and caffeine exposed to variable environmental conditions and various stresses, as possibly throughout the production cycle of the active pharmaceutical ingredient. It is shown the capability of the low-frequency Raman spectroscopy to reveal disorder in the crystalline state, to detect small amorphous or crystalline material, and to elucidate ambiguous polymorphic or polyamorphic situations. Copyright © 2011 Elsevier B.V. All rights reserved.

A novel mutation in the Norrie disease gene.

PubMed

Ott, S; Patel, R J; Appukuttan, B; Wang, X; Stout, J T

2000-04-01

Norrie disease is an X-linked recessive disorder characterized by congenital blindness and in some cases mental retardation and deafness.(1) The variability of signs among patients often complicates diagnosis. Signs such as an ocular pseudoglioma, progressive deafness, and mental disturbance are considered classic features.(2) Only one third of patients with Norrie disease have sensorineural deafness, and approximately one half of the affected individuals exhibit mental retardation, often with psychotic features.(3) Histologic analysis has suggested that retinal dysgenesis occurs early in eye development and involves cells in the inner wall of the optic cup.(4) The gene associated with Norrie disease was identified in 1992. (5,6) We report a novel mutation identified in a patient in whom Norrie disease was diagnosed.

Relationship of Personality Disorders to the Course of Major Depressive Disorder in a Nationally Representative Sample

PubMed Central

Skodol, Andrew E.; Grilo, Carlos M.; Keyes, Katherine; Geier, Timothy; Grant, Bridget F.; Hasin, Deborah S.

2011-01-01

Objective The purpose of this study was to examine the effects of specific personality disorder co-morbidity on the course of major depressive disorder in a nationally-representative sample. Method Data were drawn from 1,996 participants in a national survey. Participants who met criteria for major depressive disorder at baseline in face-to-face interviews (2001–2002) were re-interviewed three years later (2004–2005) to determine persistence and recurrence. Predictors included all DSM-IV personality disorders. Control variables included demographic characteristics, other Axis I disorders, family and treatment histories, and previously established predictors of the course of major depressive disorder. Results 15.1% of participants had persistent major depressive disorder and 7.3% of those who remitted had a recurrence. Univariate analyses indicated that avoidant, borderline, histrionic, paranoid, schizoid, and schizotypal personality disorders all elevated the risk for persistence. With Axis I co-morbidity controlled, all but histrionic personality disorder remained significant. With all other personality disorders controlled, borderline and schizotypal remained significant predictors. In final, multivariate analyses that controlled for age at onset of major depressive disorder, number of previous episodes, duration of current episode, family history, and treatment, borderline personality disorder remained a robust predictor of major depressive disorder persistence. Neither personality disorders nor other clinical variables predicted recurrence. Conclusions In this nationally-representative sample of adults with major depressive disorder, borderline personality disorder robustly predicted persistence, a finding that converges with recent clinical studies. Personality psychopathology, particularly borderline personality disorder, should be assessed in all patients with major depressive disorder, considered in prognosis, and addressed in treatment. PMID:21245088

Social Responsiveness and Competence in Prader-Willi Syndrome: Direct Comparison to Autism Spectrum Disorder

ERIC Educational Resources Information Center

Dimitropoulos, Anastasia; Ho, Alan; Feldman, Benjamin

2013-01-01

Prader-Willi syndrome (PWS), a neurodevelopmental disorder primarily characterized by hyperphagia and food preoccupations, is caused by the absence of expression of the paternally active genes in the proximal arm of chromosome 15. Although maladaptive behavior and the cognitive profile in PWS have been well characterized, social functioning has…

Characterizing Community-Based Mental Health Services for Children with Autism Spectrum Disorders and Disruptive Behavior Problems

ERIC Educational Resources Information Center

Brookman-Frazee, Lauren I.; Taylor, Robin; Garland, Ann F.

2010-01-01

This study describes the characteristics of children with autism spectrum disorders (ASD) with disruptive behavior problems served in community-based mental health clinics, characterizes psychotherapy process and outcome, and examines differences between children with ASD and a non-ASD comparison group. Results indicate that children with ASD…

Predictors and moderators of response to cognitive behavioral therapy and medication for the treatment of binge eating disorder.

PubMed

Grilo, Carlos M; Masheb, Robin M; Crosby, Ross D

2012-10-01

To examine predictors and moderators of response to cognitive behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). 108 BED patients in a randomized double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout, and posttreatment. Demographic factors, psychiatric and personality disorder comorbidity, eating disorder psychopathology, psychological features, and 2 subtyping methods (negative affect, overvaluation of shape/weight) were tested as predictors and moderators for the primary outcome of remission from binge eating and 4 secondary dimensional outcomes (binge-eating frequency, eating disorder psychopathology, depression, and body mass index). Mixed-effects models analyzed all available data for each outcome variable. In each model, effects for baseline value and treatment were included with tests of both prediction and moderator effects. Several demographic and clinical variables significantly predicted and/or moderated outcomes. One demographic variable signaled a statistical advantage for medication only (younger participants had greater binge-eating reductions), whereas several demographic and clinical variables (lower self-esteem, negative affect, and overvaluation of shape/weight) signaled better improvements if receiving CBT. Overvaluation was the most salient predictor/moderator of outcomes. Overvaluation significantly predicted binge-eating remission (29% of participants with vs. 57% of participants without overvaluation remitted). Overvaluation was especially associated with lower remission rates if receiving medication only (10% vs. 42% for participants without overvaluation). Overvaluation moderated dimensional outcomes: Participants with overvaluation had significantly greater reductions in eating disorder psychopathology and depression levels if receiving CBT. Overvaluation predictor/moderator findings persisted after controlling for negative affect. Our findings have clinical utility for prescription of CBT and medication and implications for refinement of the BED diagnosis. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Predictors and Moderators of Response to Cognitive Behavioral Therapy and Medication for the Treatment of Binge Eating Disorder

PubMed Central

Grilo, Carlos. M.; Masheb, Robin M.; Crosby, Ross D.

2012-01-01

Objective To examine predictors and moderators of response to cognitive-behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). Method 108 BED patients in a randomized double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout-, and post-treatment. Demographic factors, psychiatric and personality-disorder co-morbidity, eating-disorder psychopathology, psychological features, and two sub-typing methods (negative-affect, overvaluation of shape/weight) were tested as predictors and moderators for the primary outcome of remission from binge-eating and four secondary dimensional outcomes (binge-eating frequency, eating-disorder psychopathology, depression, and body mass index). Mixed-effects-models analyzed all available data for each outcome variable. In each model, effects for baseline value and treatment were included with tests of both prediction and moderator effects. Results Several demographic and clinical variables significantly predicted and/or moderated outcomes. One demographic variable signaled a statistical advantage for medication-only (younger participants had greater binge-eating reductions) whereas several demographic and clinical variables (lower self-esteem, negative-affect, and overvaluation of shape/weight) signaled better improvements if receiving CBT. Overvaluation was the most salient predictor/moderator of outcomes. Overvaluation significantly predicted binge-eating remission (29% of participants with versus 57% of participants without overvaluation remitted). Overvaluation was especially associated with lower remission rates if receiving medication-only (10% versus 42% for participants without overvaluation). Overvaluation moderated dimensional outcomes: participants with overvaluation had significantly greater reductions in eating-disorder psychopathology and depression levels if receiving CBT. Overvaluation predictor/moderator findings persisted after controlling for negative-affect. Conclusions Our findings have clinical utility for prescription of CBT and medication and implications for refinement of the BED diagnosis. PMID:22289130

Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action.

PubMed

Ullah, Anwar; Masood, Rehana; Ali, Ijaz; Ullah, Kifayat; Ali, Hamid; Akbar, Haji; Betzel, Christian

2018-07-15

Snake venom thrombin-like enzymes (SVTLEs) constitute the major portion (10-24%) of snake venom and these are the second most abundant enzymes present in the crude venom. During envenomation, these enzymes had shown prominently the various pathological effects, such as disturbance in hemostatic system, fibrinogenolysis, fibrinolysis, platelet aggregation, thrombosis, neurologic disorders, activation of coagulation factors, coagulant, procoagulant etc. These enzymes also been used as a therapeutic agent for the treatment of various diseases such as congestive heart failure, ischemic stroke, thrombotic disorders etc. Although the crystal structures of five SVTLEs are available in the Protein Data Bank (PDB), there is no single article present in the literature that has described all of them. The current work describes the structural aspects, structure-based mechanism of action, processing and inhibition of these enzymes. The sequence analysis indicates that these enzymes show a high sequence identity (57-85%) with each other and low sequence identity with trypsin (36-43%), human alpha-thrombin (29-36%) and other snake venom serine proteinases (57-85%). Three-dimensional structural analysis indicates that the loops surrounding the active site are variable both in amino acids composition and length that may convey variable substrate specificity to these enzymes. The surface charge distributions also vary in these enzymes. Docking analysis with suramin shows that this inhibitor preferably binds to the C-terminal region of these enzymes and causes the destabilization of their three-dimensional structure. Copyright © 2018 Elsevier B.V. All rights reserved.

Genotype and phenotype spectrum of NRAS germline variants.

PubMed

Altmüller, Franziska; Lissewski, Christina; Bertola, Debora; Flex, Elisabetta; Stark, Zornitza; Spranger, Stephanie; Baynam, Gareth; Buscarilli, Michelle; Dyack, Sarah; Gillis, Jane; Yntema, Helger G; Pantaleoni, Francesca; van Loon, Rosa LE; MacKay, Sara; Mina, Kym; Schanze, Ina; Tan, Tiong Yang; Walsh, Maie; White, Susan M; Niewisch, Marena R; García-Miñaúr, Sixto; Plaza, Diego; Ahmadian, Mohammad Reza; Cavé, Hélène; Tartaglia, Marco; Zenker, Martin

2017-06-01

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c.35G>A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c.34G>C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.

A parallel SNP array study of genomic aberrations associated with mental retardation in patients and general population in Estonia.

PubMed

Männik, Katrin; Parkel, Sven; Palta, Priit; Zilina, Olga; Puusepp, Helen; Esko, Tõnu; Mägi, Reedik; Nõukas, Margit; Veidenberg, Andres; Nelis, Mari; Metspalu, Andres; Remm, Maido; Ounap, Katrin; Kurg, Ants

2011-01-01

The increasing use of whole-genome array screening has revealed the important role of DNA copy-number variations in the pathogenesis of neurodevelopmental disorders and several recurrent genomic disorders have been defined during recent years. However, some variants considered to be pathogenic have also been observed in phenotypically normal individuals. This underlines the importance of further characterization of genomic variants with potentially variable expressivity in both patient and general population cohorts to clarify their phenotypic consequence. In this study whole-genome SNP arrays were used to investigate genomic rearrangements in 77 Estonian families with idiopathic mental retardation. In addition to this family-based approach, phenotype and genotype data from a cohort of 1000 individuals in the general population were used for accurate interpretation of aberrations found in mental retardation patients. Relevant structural aberrations were detected in 18 of the families analyzed (23%). Fifteen of those were in genomic regions where clinical significance has previously been established. In 3 families, 4 novel aberrations associated with intellectual disability were detected in chromosome regions 2p25.1-p24.3, 3p12.1-p11.2, 7p21.2-p21.1 and Xq28. Carriers of imbalances in 15q13.3, 16p11.2 and Xp22.31 were identified among reference individuals, affirming the variable phenotypic consequence of rare variants in some genomic regions considered as pathogenic. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Factors associated with poor functional outcome in bipolar disorder: sociodemographic, clinical, and neurocognitive variables.

PubMed

Sanchez-Moreno, J; Bonnin, C M; González-Pinto, A; Amann, B L; Solé, B; Balanzá-Martinez, V; Arango, C; Jiménez, E; Tabarés-Seisdedos, R; Garcia-Portilla, M P; Ibáñez, A; Crespo, J M; Ayuso-Mateos, J L; Martinez-Aran, A; Torrent, C; Vieta, E

2018-05-03

The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a sample of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Role of Individual and Social Variables in Predicting Body Dissatisfaction and Eating Disorder Symptoms among Iranian Adolescent Girls: An Expanding of the Tripartite Influence Mode.

PubMed

Shahyad, Shima; Pakdaman, Shahla; Shokri, Omid; Saadat, Seyed Hassan

2018-01-12

The aim of the present study was to examine the causal relationships between psychological and social factors, being independent variables and body image dissatisfaction plus symptoms of eating disorders as dependent variables through the mediation of social comparison and thin-ideal internalization. To conduct the study, 477 high-school students from Tehran were recruited by method of cluster sampling. Next, they filled out Rosenberg Self-esteem Scale (RSES), Physical Appearance Comparison Scale (PACS), Self-Concept Clarity Scale (SCCS), Appearance Perfectionism Scale (APS), Eating Disorder Inventory (EDI), Multidimensional Body Self Relations Questionnaire (MBSRQ) and Sociocultural Attitudes towards Appearance Questionnaire (SATAQ-4). In the end, collected data were analyzed using structural equation modeling. Findings showed that the assumed model perfectly fitted the data after modification and as a result, all the path-coefficients of latent variables (except for the path between self-esteem and thin-ideal internalization) were statistically significant (p>0.05). Also, in this model, 75% of scores' distribution of body dissatisfaction was explained through psychological variables, socio-cultural variables, social comparison and internalization of the thin ideal. The results of the present study provid experimental basis for the confirmation of proposed causal model. The combination of psychological, social and cultural variables could efficiently predict body image dissatisfaction of young girls in Iran.

Can the Five Factor Model of Personality Account for the Variability of Autism Symptom Expression? Multivariate Approaches to Behavioral Phenotyping in Adult Autism Spectrum Disorder

ERIC Educational Resources Information Center

Schwartzman, Benjamin C.; Wood, Jeffrey J.; Kapp, Steven K.

2016-01-01

The present study aimed to: determine the extent to which the five factor model of personality (FFM) accounts for variability in autism spectrum disorder (ASD) symptomatology in adults, examine differences in average FFM personality traits of adults with and without ASD and identify distinct behavioral phenotypes within ASD. Adults (N = 828;…

Executive Functioning Differences between Adults with Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder in Initiation, Planning and Strategy Formation

ERIC Educational Resources Information Center

Bramham, Jessica; Ambery, Fiona; Young, Susan; Morris, Robin; Russell, Ailsa; Xenitidis, Kiriakos; Asherson, Philip; Murphy, Declan

2009-01-01

Executive functioning deficits characterize the neuropsychological profiles of the childhood neurodevelopmental disorders of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). This study sought to determine whether similar impairments exist in adults with ADHD (N = 53) and ASD (N = 45) in comparison with a…

Substance-Related and Addictive Disorders as a Risk Factor of Suicide and Homicide among Patients with ADHD: A Mini Review.

PubMed

Yoshimasu, Kouichi

2016-01-01

To discuss the role of substance-related and addictive disorders (SRAD) that lead patients with attention-deficit hyperactivity disorder (ADHD) to suicide and homicide. Relevant articles were searched via PubMed using several keywords related to this issue. Most of the articles included in this review were published after 2000. Patients with ADHD often fall into crises of catastrophic life events such as suicide or homicide. SRAD play an important role in leading ADHD patients to such events. Because ADHD is characterized by inattentiveness and impulsivity, any kinds of substances, legal or illegal, can deteriorate ADHD symptoms, leading ADHD patients to such catastrophic events. There are several pathways that connect ADHD with SRAD, which are roughly divided into two ways: internalizing mental disorders and externalizing mental disorders. The former includes depression and anxiety disorders characterized by self-inhibition or withdrawal. The latter typically includes conduct disorder or oppositional defiant disorder, as well as antisocial personality disorder, characterized by aggressive or antisocial behaviors or emotions towards others. These comorbid psychiatric disorders are apt to lead ADHD patients to SRAD, and once these patients suffer from SRAD, risk of catastrophic life events seems to increase due to the irreversibility of their adverse mentality. Comorbid mental disorders with ADHD can act, at least partially, as mediators from ADHD to SRAD. SRAD can be a critical risk factor of suicide and homicide among patients with ADHD. Early interventions for families with ADHD and psychiatric comorbidities may work as effective preventive strategies against such events. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Differential Diagnosis of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder by Means of Inhibitory Control and "Theory of Mind"

ERIC Educational Resources Information Center

Buhler, Eva; Bachmann, Christian; Goyert, Hannah; Heinzel-Gutenbrunner, Monika; Kamp-Becker, Inge

2011-01-01

Autism spectrum disorders (ASD) and attention deficit hyperactivity disorders (ADHD) are both associated with deficits in executive control and with problems in social contexts. This study analyses the variables inhibitory control and theory of mind (ToM), including a developmental aspect in the case of the latter, to differentiate between the…

[Night-to-night variability of the obstructive sleep apnoea-hypopnoea syndrome].

PubMed

Mjid, M; Ouahchi, Y; Toujani, S; Snen, H; Ben Salah, N; Ben Hmida, A; Louzir, B; Mhiri, N; Cherif, J; Beji, M

2016-11-01

The apnoea-hypopnoea index (AHI) is the primary measurement used to characterize the obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Despite its popularity, there are limiting factors to its application such as night-to-night variability. To evaluate the variability of AHI in the OSAHS. A prospective study was designed in our university hospital's sleep unit. Adults with clinical suspicion of OSAHS underwent 2 consecutive nights of polysomnographic recording. The population was divided in two groups according to an AHI>or<10. Patients with psychiatric disorders or professions that might result in sleep deprivation or an altered sleep/wake cycle were excluded. Twenty patients were enrolled. The mean age was 50.6±9.3 years. OSAHS was mild in 4 cases, moderate in 6 cases and severe in 8 cases. AHI was less than 5 in two cases. AHI values were not significantly altered throughout both recording nights (33.2 vs. 31.8 events/h). A significant positive correlation was found between AHI measured on the first and the second night. However, a significant individual variability was noted. Comparison between both patient's groups showed a correlation between AHI and the body mass index. This study demonstrates that the AHI in OSAHS patients is well correlated between two consecutive nights. However, a significant individual variability should be taken into consideration, especially when AHI is used in the classification of OSAHS or as a criterion of therapeutic success. Copyright © 2016. Published by Elsevier Masson SAS.

Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case.

PubMed

Thurm, Audrey; Himelstein, Daniel; DʼSouza, Precilla; Rennert, Owen; Jiang, Susanqi; Olatunji, Damilola; Longo, Nicola; Pasquali, Marzia; Swedo, Susan; Salomons, Gajja S; Carrillo, Nuria

2016-05-01

Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders. Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.

[Mental health service utilization among borderline personality disorder patients inpatient].

PubMed

Cailhol, L; Thalamas, C; Garrido, C; Birmes, P; Lapeyre-Mestre, M

2015-04-01

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability and impulsivity. Several North American prospective studies support the high level of mental health care utilization in this population. There is little data in other systems of health organization, such as France. Furthermore, little is known on the variables associated with the mental health service utilization among BPD patients. The main objective was to compare the utilization of mental health care among BPD patients, to the general population and patients with another personality disorder (PD) and to describe the demographic and clinical factors associated with the group of patients who use the most health care. A multi-center (5 public and private centers), epidemiological study. Data were collected prospectively (database of an insurance fund covering 80% of the population) and viewed, retrospectively. We used the data collected during the five years previously to the inclusion. Inclusion criteria were age (18-60 years) and membership in the health insurance fund targeted. Patients on legal protection, forced hospitalization, with a chronic psychotic disorder, manic, mental retardation, or not reading French were excluded. First, four groups were composed: BPD, other PD, control groups for PD and other PD. The first two groups were recruited from a screening of inpatients including a self-administered questionnaire (Personality Disorder Questionnaire 4+). Assessment by a psychologist including the Structured Interview for DSM-IV Personality Disorders (SIDP-IV) was given straight to those who had a score above 28. This questionnaire allowed us to distinguish one group of subjects with BPD and a group with other PD (without BPD). Clinical evaluation included Axis I (MINI), Axis II (SIDP-IV), psychopathological features (YSQ-I, DSQ-40), demographic variables and therapeutic alliance (Haq-II). Matched controls (age, sex) composed the 3rd and 4th group (BPD control and other PD control). They were randomly chosen in the health database insurance previously used. One hundred and thirty-seven (95.8%) screened patients agreed to answer the psychological assessment. In this sample, 44 (32.1%) had BPD, 39 (28.5%) other PD and another 39 (28.5%) did not have PD. The BPD group was compared to a sample of 165 matched subjects and the other group PD to a sample of 123 matched controls. There was no difference between BPD and other PD groups regarding the mental health utilization. However, there was an increased use of hospitalizations and deliverances of nervous system drugs in both clinical groups compared to their controls. The analysis of drugs supplied in pharmacies for BPD patients showed that the first two drugs were opiate substitutes (12.3% methadone, buprenorphine 6.7%). No anticonvulsants or atypical antipsychotics appear in the top 20 of treatments delivered. A composite variable (hospitalization for more than 6 months during previous five years and 500 supplied drugs) allowed the discrimination of two groups among patients with BPD: heavy users of care and low care users. No variables (demographics, Axis I, Axis II, self-aggressiveness, DSQ-40, Haq-II, YSQ-I) could discriminate the two groups except the number of previous psychotherapies (heavy users: n=0.4 (SD 0.5) vs low users: n=1.8 (SD 2.1) P=0.0054). This study confirms the important use of the service of BPD patients in France, as well as the possible moderating role of psychotherapy. We found a mismatch between these uses and recommendations. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Reduced benzodiazepine sensitivity in patients with panic disorder: comparison with patients with obsessive-compulsive disorder and normal subjects.

PubMed

Roy-Byrne, P; Wingerson, D K; Radant, A; Greenblatt, D J; Cowley, D S

1996-11-01

The authors sought to replicate their previous finding of reduced response to diazepam in patients with panic disorder, to test whether this effect was specific for panic disorder, and to determine whether this reduced response was merely an artifact of resistance to sedation from anxiety-related overarousal. The effects of four increasing intravenous doses of diazepam on saccadic eye movement velocity and accuracy (the latter being a saccadic variable that is unaffected by sedation), short-term memory, and self- and observer-rated sedation were assessed in 18 patients with panic disorder, 15 patients with obsessive-compulsive disorder, and 14 normal comparison subjects. The ratios of effect to blood level areas under the curve for both ascending and descending limbs of the effect/blood level curves were compared for each variable. Patients with panic disorder showed significantly less diazepam effect on saccadic velocity and accuracy for the ascending limb of the blood level curve than comparison subjects. Patients with obsessive-compulsive disorder showed similar differences from comparison subjects but only for saccadic velocity. There were no group differences in diazepam effects on memory and sedation. Patients with panic disorder are less sensitive than comparison subjects to diazepam. Although this difference is not an artifact of resistance to sedation, it may not be specific for panic disorder but rather may reflect a more nonspecific aspect of anxiety disorders.

Lexical and phonological variability in preschool children with speech sound disorder.

PubMed

Macrae, Toby; Tyler, Ann A; Lewis, Kerry E

2014-02-01

The authors of this study examined relationships between measures of word and speech error variability and between these and other speech and language measures in preschool children with speech sound disorder (SSD). In this correlational study, 18 preschool children with SSD, age-appropriate receptive vocabulary, and normal oral motor functioning and hearing were assessed across 2 sessions. Experimental measures included word and speech error variability, receptive vocabulary, nonword repetition (NWR), and expressive language. Pearson product–moment correlation coefficients were calculated among the experimental measures. The correlation between word and speech error variability was slight and nonsignificant. The correlation between word variability and receptive vocabulary was moderate and negative, although nonsignificant. High word variability was associated with small receptive vocabularies. The correlations between speech error variability and NWR and between speech error variability and the mean length of children's utterances were moderate and negative, although both were nonsignificant. High speech error variability was associated with poor NWR and language scores. High word variability may reflect unstable lexical representations, whereas high speech error variability may reflect indistinct phonological representations. Preschool children with SSD who show abnormally high levels of different types of speech variability may require slightly different approaches to intervention.