Influence of genetic polymorphisms in the glutamatergic and GABAergic systems and their interactions with environmental stressors on antidepressant response

Aim: To investigate the role of genetic polymorphisms in glutamatergic and GABAergic genes and their interactions with environmental stressors in antidepressant response. Methods: A set of 114 SNPs of 34 glutamatergic and GABAergic genes, mainly in promoter and coding regions, were genotyped in 281 Chinese Han major depressive disorder patients. The 17-item Hamilton Depression Rating Scale was used to evaluate the symptom severity and therapeutic efficacy. Childhood Trauma Questionnaire and Life Events Scale were used for assessing early-onset and recent stressful life events, respectively. Results: The single SNPs rs1954787 (GRIK4), rs1992647 (GABRA6), rs10036156 (GABRP) and rs3810651 (GABRQ) were significantly associated with antidepressant response, as were haplotypes in GRIK4 and GABRP genes. A genetic interaction between rs11542313 (GAD1), rs13303344 (GABRD) and rs2256882 (GABRE) was identified as impacting therapeutic response. SNPs in GRIA3 demonstrated interactions with early-onset adverse events and recent negative life stress that influence treatment outcome. Conclusion: Genetic polymorphisms in the glutamatergic and GABAergic systems and certain genetic interactions, as well as gene–environment interactions, are associated with antidepressant response. Original submitted 9 July 2012; Revision submitted 1 January 2013