Genetics of OCD

2017 ◽  
Author(s):  
Paul Arnold
Keyword(s):  
Genetic Architecture ◽  
Individual Treatment ◽  
Clear Understanding ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Glutamate Signaling ◽  
Gene Environment ◽  
Genome Wide ◽  
Significant Heritability ◽  
Candidate Gene Studies

Obsessive-compulsive disorder (OCD) often runs in families and has been shown to have significant heritability. It is genetically complex, and two decades of genetic work have not converged on a clear understanding of genetic risk factors. However, accelerating progress in recent years has begun to generate some insights into the genetic architecture of the disorder, and greater clarity is likely to emerge in the coming decade. This chapter summarizes several lines of genetic work, including genome-wide genetic and linkage studies; candidate gene studies; and investigations of gene-environment interactions and of pharmacogenetics. One developing theme is that genetic variance in components of the brain’s glutamate signaling system may contribute to the development of OCD. Advancing understanding of the genetics of OCD may lead to new insights into pathobiology and to new tools to optimize individual treatment.

scholarly journals Sex differences in the genetic architecture of obsessive-compulsive disorder

2017 ◽  
Author(s):  
Ekaterina A. Khramtsova ◽  
Raphael Heldman ◽  
Eske M. Derks ◽  
Dongmei Yu ◽  
Lea K. Davis ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Obsessive Compulsive Disorder ◽  
Sex Difference ◽  
Genetic Architecture ◽  
Sexually Dimorphic ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Regulatory Variants ◽  
Specific Risk ◽  
Genome Wide

AbstractObsessive-compulsive disorder (OCD), a highly heritable complex phenotype, demonstrates sexual dimorphism in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome-wide characterization of the sex-specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sexual-dimorphism including a sexually dimorphic liability threshold, the presence of individual sex-specific risk variants on the autosomes and the X chromosome, genetic and phenotypic heterogeneity, and sex-specific pleiotropic effects. We observed a strong genetic correlation between male and female OCD and no evidence for a sexually dimorphic liability threshold model. While we did not detect any sex-specific genome-wide associations, we observed that the SNPs with sexually dimorphic effects showed an enrichment of regulatory variants influencing expression of genes in immune tissues. Furthermore, top sex-specific genome-wide associations were enriched for regulatory variants in different tissues, suggesting evidence for potential sex difference in the biology underlying risk for OCD. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex-specific risk factors for OCD, significantly advancing our understanding of the differences in the genetic basis of sexually dimorphic neuropsychiatric traits.

scholarly journals The genetics of obsessive-compulsive disorder: a review

2010 ◽  
Vol 12 (2) ◽  
pp. 149-163 ◽  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Glutamate Transporter ◽  
Twin Studies ◽  
Future Research ◽  
Multidisciplinary Teams ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide ◽  
Family Aggregation ◽  
Candidate Gene Studies

Obsessive-compulsive disorder (OCD) is a serious psychiatric disorder that affects approximately 2% of the populations of children and adults. Family aggregation studies have demonstrated that OCD is familial, and results from twin studies demonstrate that the familiality is due in part to genetic factors. Only three genome-wide linkage studies have been completed to date, with suggestive but not definitive results. In addition, over 80 candidate gene studies have been published. Most of these studies have focused on genes in the serotonergic and dopaminergic pathways. Unfortunately, none have achieved genome-wide significance, and, with the exception of the glutamate transporter gene, none have been replicated. Future research will require the collaboration of multidisciplinary teams of investigators to (i) achieve sufficiently large samples of individuals with OCD; (ii) apply the state-of-the-art laboratory techniques; and (iii) perform the bioinformatic analyses essential to the identification of risk loci.

scholarly journals Sex differences in the genetic architecture of obsessive-compulsive disorder

2018 ◽  
Vol 180 (6) ◽  
pp. 351-364 ◽  
Author(s):  
Ekaterina A. Khramtsova ◽  
Raphael Heldman ◽  
Eske M. Derks ◽  
Dongmei Yu ◽  
Lea K. Davis ◽  
...  
Keyword(s):  
Sex Differences ◽  
Obsessive Compulsive Disorder ◽  
Genetic Architecture ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

scholarly journals Genome-wide association meta-analysis of childhood and adolescent internalising symptoms

2020 ◽  
Author(s):  
Eshim S Jami ◽  
Anke R Hammerschlag ◽  
Hill F Ip ◽  
Andrea G Allegrini ◽  
Beben Benyamin ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genetic Effects ◽  
Childhood Aggression ◽  
Genome Wide Association ◽  
Childhood And Adolescence ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide

Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INToverall) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, Neffective=132,260). Stratified analyses showed rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Gene-based analyses showed significant associations with three genes: WNT3 (p=1.13×10-06), CCL26 (p=1.88×10-06), and CENPO (p=2.54×10-06). Of these, WNT3 was previously associated with neuroticism, with which INToverall also shared a strong genetic correlation (rg=0.76). Genetic correlations were also observed with adult anxiety, depression, and the wellbeing spectrum (|rg|> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range |rg|=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Overall, childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could explain both the persistence of internalising symptoms over time, and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Before you meet someone with obsessive-compulsive disorder: understanding the problem

2017 ◽  
pp. 1-50
Author(s):  
Victoria Bream ◽  
Fiona Challacombe ◽  
Asmita Palmer ◽  
Paul Salkovskis
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Current Knowledge ◽  
Evidence Base ◽  
Background Information ◽  
Clear Understanding ◽  
Obsessive Compulsive ◽  
Case Examples ◽  
Compulsive Disorder ◽  
Recommended Treatment ◽  
Cognitive Behavioural

This chapter provides detailed background information on obsessive-compulsive disorder (OCD) that will give the therapist a clear understanding of current knowledge about the context and causes of this problem. Research evidence on the epidemiology of OCD, impact, and causal factors is presented. Here we introduce the cognitive-behavioural model of OCD, offering a discussion of the key elements of this model. The chapter will also include case examples to illustrate different manifestations of OCD (including contamination, checking, rumination, just-right feelings) and common processes that are key in the maintenance of obsessional problems (for example, reassurance-seeking and magical thinking). This chapter reviews the evidence base for the treatment of OCD, including medication, and identifies cognitive-behavioural therapy (CBT) as the recommended treatment.

GROUP AND INDIVIDUAL TREATMENT OF COMPULSIVE HOARDING: A PILOT STUDY

2000 ◽  
Vol 28 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Gail Steketee ◽  
Randy O. Frost ◽  
Jeff Wincze ◽  
Kamala A.I. Greene ◽  
Heidi Douglass
Keyword(s):  
Theoretical Model ◽  
Pilot Study ◽  
Obsessive Compulsive Disorder ◽  
Group Treatment ◽  
Behavioral Interventions ◽  
Individual Treatment ◽  
Compulsive Hoarding ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Noticeable Improvement

Treatment of compulsive hoarding has rarely been described in the literature, apart from standard treatments for obsessive compulsive disorder of which hoarding is thought to be a subset. This paper presents preliminary findings from seven patients treated with cognitive and behavioral interventions derived from Frost and Hartl's (1996) theoretical model of hoarding. Six clients attended 15 group treatment sessions over 20 weeks plus individual home treatment sessions and one client received 20 weekly-sessions of individual treatment only. After 20 weeks, treatment resulted in noticeable improvement in several hoarding symptoms for five of the seven patients, especially reduction in excessive acquisition of possessions, although problems with clutter persisted. Three of four clients who continued in treatment for approximately 1 year showed substantial further improvement, although none felt entirely recovered. Findings are discussed in light of the model of hoarding and possible modifications to treatment to enhance motivation and benefits.

scholarly journals Genetics of addictive behavior: the example of nicotine dependence

2017 ◽  
Vol 19 (3) ◽  
pp. 237-245 ◽  
Keyword(s):  
Lung Cancer ◽  
Nicotine Dependence ◽  
Genome Wide Association Study ◽  
Environment Interaction ◽  
Addictive Disorders ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
Significant Heritability ◽  
Parent Monitoring

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

scholarly journals Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS

2014 ◽  
Vol 20 (3) ◽  
pp. 337-344 ◽  
Author(s):  
M Mattheisen ◽  
J F Samuels ◽  
Y Wang ◽  
B D Greenberg ◽  
A J Fyer ◽  
...  
Keyword(s):  
Association Study ◽  
Obsessive Compulsive Disorder ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide

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.

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