Influence of Genetic Polymorphisms in the Glutamatergic and GABAergic Systems and Their Interactions with Environmental Stressors on Antidepressant Response

• DOI: 10.2217/pgs.13.1
• Publication Date: 2013-02-11T12:49:17Z
• Authors: Mengjia Pu; Zhijun Zhang; Zhi Xu; Yanyan Shi; Leiyu Geng; Yonggui Yuan; Xiangrong Zhang; Gavin P Reynolds
• Keywords: Adult; Male; Depressive Disorder, Major; Adolescent; Glutamic Acid; Middle Aged; Polymorphism, Single Nucleotide; Antidepressive Agents; 3. Good health; Life Change Events; 03 medical and health sciences; Logistic Models; 0302 clinical medicine; Humans; Female; Gene-Environment Interaction; Promoter Regions, Genetic; gamma-Aminobutyric Acid

To investigate the role of genetic polymorphisms in glutamatergic and GABAergic genes and their interactions with environmental stressors in antidepressant response.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.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.Genetic polymorphisms in the glutamatergic and GABAergic systems and certain genetic interactions, as well as gene-environment interactions, are associated with antidepressant response.