The GABAA-Receptor γ2 (GABRG2) Gene in obsessive-compulsive disorder

Objective: The gamma-aminobutyric acid type A (GABA(A)) system may be implicated in obsessive-compulsive disorder, based on its major role in modulation of anxiety and its function as the principal inhibitory neurotransmitter system in the cortex. In addition, glutamatergic/GABAergic mechanisms appear to play a role in the pathophysiology of obsessive-compulsive disorder, making the GABA(A) receptor-gamma(2) (GAB rho gamma 2) gene a good candidate for susceptibility in this disorder. Method: 118 probands meeting DSM-IV criteria for primary obsessive-compulsive disorder and their available parents were recruited for participation in this study and informed consent was obtained. An NciI restriction site polymorphism in the second intron was genotyped and data was analyzed using the Transmission Disequilibrium Test. Results: In total, 61 of the participating families were informative (i.e., with at least one heterozygous parent). No biases were observed in the transmission of either of the two alleles (chi(2) = 0.016, 1 d.f., p = 0.898) to the affected probands in the total sample. Conclusion/Discussion: While these results do not provide support for a major role for the GABA(A) receptor-gamma 2 in obsessive-compulsive disorder, further investigations of this gene in larger samples are warranted.