Dataset Information

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

ABSTRACT:

Objective

Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.

Methods

Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.

Results

OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.

Conclusions

The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.

SUBMITTER: Sampaio AS

PROVIDER: S-EPMC4368617 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

Sampaio Aline Santos AS Hounie Ana Gabriela AG Petribú Kátia K Cappi Carolina C Morais Ivanil I Vallada Homero H do Rosário Maria Conceição MC Stewart S Evelyn SE Fargeness Jesen J Mathews Carol C Arnold Paul P Hanna Gregory L GL Richter Margaret M Kennedy James J Fontenelle Leonardo L de Bragança Pereira Carlos Alberto CA Pauls David L DL Miguel Eurípedes Constantino EC

PloS one 20150320 3

<h4>Objective</h4>Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has ident ...[more]

PMID: 25793616

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Project description:Cognitive behavior therapy (CBT) has been established as efficacious for obsessive-compulsive disorder (OCD) among older children and adolescents, yet its effect on young children has not been evaluated sufficiently.To examine the relative efficacy of family-based CBT (FB-CBT) involving exposure plus response prevention vs an FB relaxation treatment (FB-RT) control condition for children 5 to 8 years of age.A 14-week randomized clinical trial (Pediatric Obsessive-Compulsive Disorder Treatment Study for Young Children [POTS Jr]) conducted at 3 academic medical centers between 2006 and 2011, involving 127 pediatric outpatients 5 to 8 years of age who received a primary diagnosis of OCD and a Children's Yale-Brown Obsessive Compulsive Scale total score of 16 or higher.Participants were randomly assigned to 14 weeks of (1) FB-CBT, including exposure plus response prevention, or (2) FB-RT.Responder status defined as an independent evaluator-rated Clinical Global Impression-Improvement scale score of 1 (very much improved) or 2 (much improved) and change in independent evaluator-rated continuous Children's Yale-Brown Obsessive Compulsive Scale total score. RESULTS Family-based CBT was superior to FB-RT on both primary outcome measures. The percentages of children who were rated as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale at 14 weeks were 72% for FB-CBT and 41% for FB-RT. The effect size difference between FB-CBT and FB-RT on the Clinical Global Impression-Improvement scale was 0.31 (95% CI, 0.17-0.45). The number needed to treat (NNT) with FB-CBT vs FB-RT was estimated as 3.2 (95% CI, 2.2-5.8). The effect size difference between FB-CBT and FB-RT on the Children's Yale-Brown Obsessive Compulsive Scale at week 14 was 0.84 (95% CI, 0.62-1.06).A comprehensive FB-CBT program was superior to a relaxation program with a similar format in reducing OCD symptoms and functional impairment in young children (5-8 years of age) with OCD.clinicaltrials.gov Identifier: NCT00533806.

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

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

Objective

Methods

Results

Conclusions

Publications

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

Similar Datasets

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