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The Genetics of Obsessive-Compulsive Disorder.

ABSTRACT: OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a significant cause of disability worldwide. Family studies indicate that OCD has a significant hereditable component, with relatives of OCD cases being 4 times more likely to develop the disorder than the general population. Linkage studies in OCD have generally been underpowered and have failed to reach the statistical threshold for genome-wide significance, but they have nevertheless been useful for revealing potential regions of interest for future candidate gene studies. Candidate gene studies in OCD have thus far focused on genes involved in the serotonergic, dopaminergic, and glutamatergic pathways. These studies have been for the most part inconclusive, and failures to replicate have been the norm until very recently. The only genetic association replicated by multiple groups was with a glutamate transporter gene (SLC1A1). Genome-wide association studies in OCD are in progress, but final results have not yet been reported. As with the study of many other psychiatric disorders, an improved understanding of OCD will only be achieved (1) with larger collaborative efforts involving more probands, (2) the use of probands and controls drawn from epidemiologically-based populations rather than clinical samples, (3) developing a more precise phenotypic description of OCD and (4) measuring important environmental influences that affect OCD pathogenesis and severity.

SUBMITTER: Bloch MH

PROVIDER: S-EPMC3747631 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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The Genetics of Obsessive-Compulsive Disorder.

Bloch Michael H MH Pittenger Christopher C

Current psychiatry reviews 20100501 2

OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a significant cause of disability worldwide. Family studies indicate that OCD has a significant hereditable component, with relatives of OCD cases being 4 times more likely to develop the disorder than the general population. Linkage studies in OCD have generally been underpowered and have failed to reach the statistical threshold for genome-wide significance, but they have nevertheless been useful for revealing potential re ...[more]

PMID: 23970845

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Project description:Objective: To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Methods: Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL). Results: Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1-5.2]% vs. 1.0%-2.0%, z?=?1.491, p?<?0.001, n?=?1389), encephalitis or meningitis (1.4 [0.9-2.1]% vs. 0.1%-0.4%, z?=?5.913, p?<?0.001, n?=?1393), rheumatoid arthritis (1.1 [0.6-2.0]% vs. 0.2%-0.4%, z?=?3.416, p?<?0.001, n?=?949) and rheumatic fever (0.6 [0.3-1.2]% vs. 0.1%-0.2%, z?=?3.338, p?<?0.001, n?=?1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5?±?0.9 vs. 2.3?±?1.0, t?=?3.183, p?=?0.002, n?=?822). Conclusion: These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.

Dataset Information

The Genetics of Obsessive-Compulsive Disorder.

Publications

The Genetics of Obsessive-Compulsive Disorder.

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