title: DNA methylation and clinical response to antidepressant medication in major depressive disorder: A review and recommendations.
abstract: 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.
authors.affiliation: Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lisoway
authors.affiliation: Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.affiliation: Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: jim.kennedy@camh.ca.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D019175:DNA Methylation; D003863:Depression / Q000188:drug therapy / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D044127:Epigenesis, Genetic; D057890:Epigenomics; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C508611:IL11 protein, human; D017370:Interleukin-11; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C579455:BDNF protein, human
keywords: Antidepressant response; DNA methylation; Major depressive disorder; Pharmaco-epigenetics; Pharmacological treatment; Psychiatry; Treatment response