POSTER NO: 474

Molecular Genetic Studies of Obsessive-Compulsive Disorder

¹Lan Zhang, ¹Xiehe Liu, ¹Tao Li, ¹Yanchun Yang, ²Xun Hu, ²David Collier
¹Institute of Mental Health, West China Hospital, Sichuan University, No.7 Xiao Xue Road, Chengdu 610041, P.R. China, ²Institute of Psychiatry, 1 Windsor Walk, Denmark Hill, London SE5 8AF, U.K.

Backgroud: Obsessive-compulsive disorder (OCD) is a chronic and disabling mental disorder with the onset in adolescent. The lifetime prevalence of OCD in American population is 2-3%. The previous findings have indicated a dysfunction of the serotonergic and dopaminergic systems involved the etiology of OCD. Methods: We studied the association between OCD and six candidate genes encoding important components of the serotonergic and dopaminergic pathways in 120 nuclear trios using TDT, HTDT, and correlation analysis of quantitative traits. Polymorphisms in the following genes were studied: serotonin 2A receptor (5-HT2A), serotonin transportor (5-HTT), dopamine D2 receptor (DRD2), dopamine D4 receptor (DRD4), catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA). Results : (1) For overall sample, there was no evidence for linkage disequilibrium between six genes and OCD. (2) We found linkage disequilibrium between DRD2 -141Del/Ins and early-onset OCD, linkage disequilibrium between COMT Val/Met and late-onset OCD. These two loci were also correlated with the onset age according to the correlation analysis taken. (3) We failed to replicate the linkage disequilibrium between COMTVal/Met and different gender patients. (4) There was the evidence for linkage disequilibrium between DRD2 -141Del/Ins and OCD patients without family histories. (5) We didn't find linkage disequilibrium between sixes genes and drug responders or non-responders. However, there was significant difference between drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus. (6) In symptom subtypes according to Y-BOCS Symptom Checklist, we observed that DRD4 VNTR was correlated with factor 1 (perfectionism) and DRD2 -141Del/Ins is correlated with factor 4 (checking). COMT Val/Met was correlated with the severity of obsession. Conclusions: The interesting results suggest that OCD is highly heterogeneous in both phenotype and genotype and multiple minor effect genes in the serotonergic and dopaminergic systems may be involved in the genetic etiology of OCD.