DNA methylation and clinical response to antidepressant medication in major depressive disorder: A review and recommendations

•Research into the role that epigenetic mechanisms play in Major Depressive Disorder has grown rapidly over the last decade.•Studies examining epigenetic mechanisms in psychiatric treatment response are rapidly emerging.•We examine articles investigating DNA methylation and clinical antidepressant response in Major Depressive Disorder.•Conclusions include a summary of current limitations and suggestions for future directions. Antidepressant medications are the most common treatment for major depression and related disorders. Pharmacogenetic studies have demonstrated that response to these medications is associated with genetic variation. While these studies have been invaluable they have yet to explain why a significant number of patients do not respond to their initial medication. The epigenetic modification known as DNA methylation has recently been studied in the context of antidepressant treatment response. As such, the purpose of this article is to review the advances made in the relatively new field of pharmaco-epigenetics of antidepressant response. We included all published articles examining DNA methylation in association with antidepressant treatment response in Major Depressive Disorder from April 2006 to June 2016 using the PubMed, Medline, PsychInfo and Web of Science databases. At the present time, although original articles are limited, epigenetic modifications of SLC6A4, BDNF, and IL11 genes are showing promising results as biomarkers for prediction of antidepressant response. However, research methods and results are heterogeneous and additional studies are required before results are generalizable. At the end of this review we provide recommendations for study design and analytic approaches.