No interaction of GABAA alpha-1 subunit and dopamine receptor D4 genes in symptomatology of major psychoses

Previously, we have reported an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, despite the strength of the association, it only accounted for 2% of the variance, indicating that contributions from other genes were probable. The interaction of the inhibitory GABA system with the dopaminergic pathway has been recently documented. We then hypothesized that θ-aminobutyric acid type A (GABA_A) receptor alpha-1 subunit gene (GABRA1) variants could be associated with major psychoses symptomatology and could influence the DRD4 association with delusional symptoms. The sample consisted of 461 psychiatric inpatients affected by schizophrenia and mood disorders. The four Symptomatologic factors "Mania," "Depression," "Delusion," and "Disorganization" extracted from the Operational Criteria checklist for psychotic illness were used for assessing the patients. GABRA1 variants were not associated with these Symptomatologic factors, and consideration of possible stratification effects such as sex and psychiatric diagnosis did not reveal any association either. The DRD4-GABRA1 interaction was evaluated initially using a traditional stratification technique: DRD4 association with factors has been repeated considering only, in turn, main GABRA1 variants (GABRA1*4 to GABRA1*8 and GABRA1*12-13; 98% of all variants). None of the main GABRA1 variants influenced the observed association between DRD4*7 and delusional score. We tested both polymorphisms conjunct also through a multiple regression technique but no significant interaction has been observed. Our data do not support an interaction of dopamine and GABA systems on major psychoses symptomatology as evidenced by the DRD4 and GABRA1 markers.