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Abstract
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
Acknowledgements
The authors thank colleagues involved in collecting clinical data: C Wang of Beijing Anding Hospital (Beijing, China); L Li and Z Liu of the Second Xiangya Hospital of Central South University (Changsha, China); C Wang of Huaian No. 3 People‘s Hospital (Huaian, China); X Zhang, Y Zhang and H Zhou of Yangzhou Wutaishang Hospital (Yangzhou, China). The authors thank N Sun and K Zhang from the First Hospital of Shanxi Medical University (Taiyuan, China) for providing control group information. The authors thank Q Wang and X Liu of West China Hospital (Chengdu, China), H Guo of JiangSu Province Center for Disease Control and Prevention (Nanjing, China) and J Dai of Nanjing Medical University (Nanjing, China) for statistical advice and analyses.
Financial & competing interests disclosure
The study has been partly supported by the National Basic Research Program of China (973 Program, No. 2007CB512308 Z Zhang), National Nature Science Foundation of China for the Excellent Young Scientist (No. 30825014 Z Zhang), International Cooperation and Exchange of the National Natural Science Foundation of China (No. 81061120529 Z Zhang), National Natural Science Foundation of China (No. 30900482 X Zhang) and National Key Science & Technology Program in the 12th Five Year Plan of China (The Project of New Drug Formulation, No. 2012ZX09506-001-009 Z Zhang). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.