Search

One of the leading biological models of obsessive-compulsive disorder ( OCD) is the frontal-striatal-thalamic model. This study undertakes an extensive exploration of the variability in genes related to the regulation of the frontal-striatal-thalamic system in a sample of early-onset OCD trios. To this end, we genotyped 266 single nucleotide polymorphisms ( SNPs) in 35 genes in 84 OCD probands and their parents. Finally, 75 complete trios were included in the analysis. Twenty SNPs were overtransmitted from parents to early-onset OCD probands and presented nominal pointwise P < 0.05 values. Three of these polymorphisms achieved P < 2 × 10−4, the significant P-value after Bonferroni corrections: rs8190748 and rs992990 localized in GAD2 and rs2000292 in HTR1B. When we stratified our sample according to gender, different trends were observed between males and females. In males, SNP rs2000292 ( HTR1B) showed the lowest P-value ( P = 0.0006), whereas the SNPs in GAD2 were only marginally significant ( P = 0.01). In contrast, in females HTR1B polymorphisms were not significant, whereas rs8190748 ( GAD2) showed the lowest P-value ( P = 0.0006). These results are in agreement with several lines of evidence that indicate a role for the serotonin and γ-Aminobutyric acid ( GABA) pathways in the risk of early-onset OCD and with the gender differences in OCD pathophysiology reported elsewhere. However, our results need to be replicated in studies with larger cohorts in order to confirm these associations. [ABSTRACT FROM AUTHOR]