scholarly journals Testing structural models of psychopathology at the genomic level

2018 ◽  
Author(s):  
Irwin D. Waldman ◽  
Holly E. Poore ◽  
Justin M. Luningham ◽  
Jingjing Yang
Keyword(s):  
Bipolar Disorder ◽  
Eating Disorders ◽  
Psychiatric Disorders ◽  
Genetic Correlations ◽  
Structural Models ◽  
Higher Order ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Best Fitting ◽  
Fitting Model

Genome-wide association studies (GWAS) have revealed hundreds of genetic loci associated with the vulnerability to major psychiatric disorders, and post-GWAS analyses have shown substantial genetic correlations among these disorders. This evidence supports the existence of a higher-order structure of psychopathology at both the genetic and phenotypic levels. Despite recent efforts by collaborative consortia such as the Hierarchical Taxonomy of Psychopathology (HiTOP), this structure remains unclear. In this study, we tested multiple alternative structural models of psychopathology at the genomic level, using the genetic correlations among fourteen psychiatric disorders and related psychological traits estimated from GWAS summary statistics. The best-fitting model included four correlated higher-order factors – externalizing, internalizing, thought problems, and neurodevelopmental disorders – which showed distinct patterns of genetic correlations with external validity variables and accounted for substantial genetic variance in their constituent disorders. A bifactor model including a general factor of psychopathology as well as the four specific factors fit worse than the above model. Several model modifications were tested to explore the placement of some disorders – such as bipolar disorder, obsessive-compulsive disorder, and eating disorders – within the broader psychopathology structure. The best-fitting model indicated that eating disorders and obsessive-compulsive disorder, on the one hand, and bipolar disorder and schizophrenia, on the other, load together on the same thought problems factor. These findings provide support for several of the HiTOP higher-order dimensions and suggest a similar structure of psychopathology at the genomic and phenotypic levels.

scholarly journals Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joey Ward ◽  
Laura M. Lyall ◽  
Richard A. I. Bethlehem ◽  
Amy Ferguson ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Genetic Correlations ◽  
Grey Matter Volume ◽  
Obsessive Compulsive ◽  
Major Depressive ◽  
Compulsive Disorder ◽  
Matter Volume ◽  
Genome Wide

AbstractAnhedonia is a core symptom of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of state anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including orbito-frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of state anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this phenotype as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for state anhedonia influences brain structure, including in regions associated with reward and pleasure processing.

The Co-Occurrence of Mania with Medical and other Psychiatric Disorders

1994 ◽  
Vol 24 (4) ◽  
pp. 305-328 ◽  
Author(s):  
Stephen M. Strakowski ◽  
Susan L. McElroy ◽  
Paul W. Keck ◽  
Scott A. West
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Brain Structures ◽  
Future Research ◽  
Medical Illness ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Medical Disorders ◽  
Current State ◽  
Secondary Mania

Objective: The co-occurrence of mania with other medical and psychiatric disorders has been little studied. The authors reviewed the literature in order to clarify the current state of knowledge of this subject and to identify possible areas of future research. Methods: Published articles which specifically addressed associations of mania with medical disorders and other psychiatric syndromes were identified using the Paperchase® medical literature search system and by cross-referencing from other published work. The articles were then organized into three categories: 1) medical disorders associated with secondary mania; 2) medical comorbidity in bipolar disorder; and 3) psychiatric comorbidity in bipolar disorder. Results: The review of medical illness and secondary mania supports the hypothesis that injuries involving right-side and mid-line brain structures are associated with so-called secondary mania. Additionally, an association between bipolar disorder and migraine is identified. Several psychiatric disorders appear to occur with mania at rates higher than expected including obsessive-compulsive disorder, bulimia nervosa, panic disorder, impulse control disorders, and substance abuse. Conclusions: The authors discuss the potential implications of these findings and suggest research approaches to further examine the relationships between mania and other medical and psychiatric syndromes.

Functional MRI in Psychiatric Disorders

2018 ◽  
pp. 91-118
Author(s):  
Jie Lisa Ji ◽  
Alan Anticevic
Keyword(s):  
Magnetic Resonance Imaging ◽  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Large Scale ◽  
Neural Substrates ◽  
Behavioral Symptoms ◽  
Neural Systems ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Psychiatric Conditions

sSince its introduction to clinical research, functional magnetic resonance imaging (fMRI) has had a pivotal role in understanding the systems-level neural substrates of psychiatric disorders. fMRI is a powerful tool for the field of psychiatry because it is well suited to studying large-scale neural systems and distributed neuropathology, which are thought to underlie many of the behavioral symptoms in psychiatric conditions. This chapter highlights key fMRI findings in four major types of psychiatric disorders: schizophrenia, mood disorders (including major depressive disorder and bipolar disorder), obsessive-compulsive disorder, and posttraumatic stress disorder.

scholarly journals Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure

2019 ◽  
Author(s):  
Joey Ward ◽  
Laura M. Lyall ◽  
Richard A. I. Bethlehem ◽  
Amy Ferguson ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Genetic Correlations ◽  
Grey Matter Volume ◽  
Obsessive Compulsive ◽  
Major Depressive ◽  
Compulsive Disorder ◽  
Matter Volume ◽  
Genome Wide

AbstractAnhedonia is a core feature of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including nucleus accumbens, caudate and medial frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this trait as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for anhedonia influences brain structure, particularly in regions associated with reward and pleasure processing.

Familial coaggregation of major psychiatric disorders among first-degree relatives of patients with obsessive-compulsive disorder: a nationwide study

2020 ◽  
pp. 1-8
Author(s):  
Mao-Hsuan Huang ◽  
Chih-Ming Cheng ◽  
Shih-Jen Tsai ◽  
Ya-Mei Bai ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Obsessive Compulsive Disorder ◽  
Autism Spectrum ◽  
Research Database ◽  
Dependent Manner ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
First Degree Relatives ◽  
Dose Dependent

Abstract Background Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear. Methods Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD. Results FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68–8.57), bipolar disorder (RR 2.85, 95% CI 2.68–3.04), MDD (RR 2.67, 95% CI 2.58–2.76), ASD (RR 2.38, 95% CI 2.10–2.71), ADHD (RR 2.19, 95% CI 2.07–2.32), and schizophrenia (RR 1.97, 95% CI 1.86–2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder. Conclusions The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.

The Orbitofrontal Cortex

2019 ◽  
Author(s):  
Edmund T. Rolls
Keyword(s):  
Bipolar Disorder ◽  
Human Brain ◽  
Obsessive Compulsive Disorder ◽  
Orbitofrontal Cortex ◽  
Multidisciplinary Approach ◽  
Animal Behaviour ◽  
Obsessive Compulsive ◽  
Undergraduate Level ◽  
Compulsive Disorder

The book will be valuable for those in the fields of neuroscience, neurology, psychology, psychiatry, biology, animal behaviour, economics, and philosophy, from the undergraduate level upwards. The book is unique in providing a coherent multidisciplinary approach to understanding the functions of one of the most interesting regions of the human brain, in both health and in disease, including depression, bipolar disorder, autism, and obsessive-compulsive disorder. There is no competing book published in the last 10 years.

Transdiagnostic dimensions in obsessive-compulsive and related disorders: associations with internalizing and externalizing symptoms

2020 ◽  
pp. 1-9
Author(s):  
Ivar Snorrason ◽  
Courtney Beard ◽  
Andrew D. Peckham ◽  
Thröstur Björgvinsson
Keyword(s):  
Internalizing Symptoms ◽  
Externalizing Symptoms ◽  
Higher Order ◽  
Order Structure ◽  
Obsessive Compulsive ◽  
Addictive Disorders ◽  
Compulsive Disorder ◽  
Alcohol Cravings ◽  
Internalizing And Externalizing ◽  
Internalizing And Externalizing Symptoms

Abstract Background Hierarchical structural models of psychopathology rarely extend to obsessive-compulsive spectrum disorders. The current study sought to examine the higher-order structure of the obsessive-compulsive and related disorders (OCRDs) in DSM-5: obsessive-compulsive disorder (OCD), hoarding disorder (HD), body dysmorphic disorder (BDD), trichotillomania (hair-pulling disorder; HPD) and excoriation (skin-picking) disorder (SPD). Methods Adult patients in a partial hospital program (N = 532) completed a dimensional measure of the five OCRDs. We used confirmatory factor analysis to identify the optimal model of the comorbidity structure. We then examined the associations between the transdiagnostic factors and internalizing and externalizing symptoms (i.e. depression, generalized anxiety, neuroticism, and drug/alcohol cravings). Results The best fitting model included two correlated higher-order factors: an obsessions-compulsions (OC) factor (OCD, BDD, and HD), and a body-focused repetitive behavior (BFRB) factor (HPD and SPD). The OC factor, not the BFRB factor, had unique associations with internalizing symptoms (standardized effects = 0.42–0.66) and the BFRB factor, not the OC factor, had small marginally significant unique association with drug/alcohol cravings (standardized effect = 0.22, p = 0.088). Conclusions The results mirror findings from twin research and indicate that OCD, BDD, and HD share liability that is significantly associated with internalizing symptoms, but this liability may be relatively less important for BFRBs. Further research is needed to better examine the associations between BFRBs and addictive disorders.

Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders

2010 ◽  
Vol 22 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Cilly Klüger Issler ◽  
Emel Serap Monkul ◽  
José Antonio de Mello Siqueira Amaral ◽  
Renata Sayuri Tamada ◽  
Roseli Gedanke Shavitt ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Obsessive Compulsive Disorder ◽  
Impulse Control ◽  
Severe Form ◽  
Impulse Control Disorders ◽  
Tic Disorders ◽  
Obsessive Compulsive ◽  
Residual Symptoms ◽  
Compulsive Disorder ◽  
Depressive Episodes

Issler CK, Monkul ES, Amaral JAMS, Tamada RS, Shavitt RG, Miguel EC, Lafer B. Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders.Objective:Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD.Method:We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking.Results:The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders.Conclusion:Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden.

Obsessive–compulsive disorder in bipolar disorder patients with first manic episode

2006 ◽  
Vol 94 (1-3) ◽  
pp. 151-156 ◽  
Author(s):  
A PASHINIAN ◽  
S FARAGIAN ◽  
A LEVI ◽  
M YEGHIYAN ◽  
K GASPARYAN ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Obsessive Compulsive Disorder ◽  
Manic Episode ◽  
Obsessive Compulsive ◽  
Compulsive Disorder
Sign in / Sign up

Export Citation Format

Share Document