Modification of the association between early adversity and obsessive-compulsive disorder by polymorphisms in the MAOA, MAOB and COMT genes. (30th December 2016)

• Record Type: Journal Article
• Authors: McGregor, N.W.; Hemmings, S.M.J.; Erdman, L.; Calmarza-Font, I.; Stein, D.J.; Lochner, C.
• Is Part Of: Psychiatry research. Volume 246(2016)
• Page Start: 527
• Page End: 532
• Publication Date: 2016-12-30
• Subjects: Obsessive-compulsive disorder -- Monoamine oxidase A (MAOA) -- Monoamine oxidase B (MAOB) -- Catechol-O-methyltransferase (COMT) -- Genetics -- Neuropsychiatry -- Gene-by-environment interaction (GxE); Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2016.10.044
• Languages: English
• ISSNs: 0165-1781

Abstract

Abstract: The monoamine oxidases (MAOA/B) and catechol-O-methyltransferase (COMT) enzymes break down regulatory components within serotonin and dopamine pathways, and polymorphisms within these genes are candidates for OCD susceptibility. Childhood trauma has been linked OCD psychopathology, but little attention has been paid to the interactions between genes and environment in OCD aetiology. This pilot study investigated gene-by-environment interactions between childhood trauma and polymorphisms in the MAOA, MAOB and COMT genes in OCD. Ten polymorphisms ( MAOA : 3 variants, MAOB : 4 variants, COMT : 3 variants) were genotyped in a cohort of OCD patients and controls. Early-life trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Gene-by-gene (GxG) and gene-by-environment interactions (GxE) of the variants and childhood trauma were assessed using logistic regression models. Significant GxG interactions were found between rs362204 ( COMT ) and two independent polymorphisms in the MAOB gene (rs1799836 and rs6651806). Haplotype associations for OCD susceptibility were found for MAOB . Investigation of GxE interactions indicated that the sexual abuse sub-category was significantly associated with all three genes in haplotype x environment interaction analyses. Preliminary findings indicate that polymorphisms within the MAOB and COMT genes interact resulting in risk for OCD. Childhood trauma interacts with haplotypes in COMT, MAOA and MAOB, increasing risk for OCD. Highlights: Significant GxG was found between rs362204 ( COMT ) and rs1799836 ( MAOB ) ( p =0.0004; OR=0.883) Significant GxG was found between rs362204 ( COMT ) and rs6651806 ( MAOB ) ( p =0.001; OR=0.867) The severity of childhood trauma modifies the association of variants in MAOA, MAOB and COMT with OCD The severity of childhood trauma increases the risk for OCD MAOB may play a more prominent role in OCD psychopathology than previously thought