title: Epigenetics of depression.
abstract: Major depressive disorder (MDD) is a leading cause of disability worldwide and is associated with poor psychological, medical, and socioeconomic outcomes. Although much has been learned about the etiology and treatment options of MDD over the past decade, there remain unanswered questions that pose challenges to improving acute and chronic outcomes for those with MDD. MDD is a clinically heterogeneous disorder. Genetic studies to date have indicated a number of genes, including transporters, neurotransmitters, neurotrophins, and their associated signaling networks that may predispose individuals to MDD and may also predict treatment outcomes. However, twin studies indicate that genes account for only a small degree of the variation in MDD. Thus, other mechanisms, through epigenetic marks, may act to form a molecular memory of previous gene-to-environment interactions and to establish vulnerabilities (or, conversely, resistance) to MDD. Current evidence supports a role for pre-, peri-, and early postnatal adversities and stressful life events into adulthood affecting epigenetic patterns, providing a mechanistic foundation to develop epigenetic marks as biomarkers for MDD. This review presents the evidence supporting a role for epigenetic effects in MDD and in treatment response. We also discuss the controversy behind modulating epigenetic mechanisms in long-term antidepressant pharmacotherapy.
authors.affiliation: Department of Psychiatry, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
authors.forename: Sermsak
authors.initials: S
authors.lastname: Lolak
authors.affiliation: Department of Genetics, Mid-Atlantic Permanente Medical Group, Rockville, Maryland, USA.
authors.forename: Pim
authors.initials: P
authors.lastname: Suwannarat
authors.affiliation: Inova Neurosciences Institute, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, The Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lipsky
mesh_terms: D001483:Base Sequence; D003865:Major Depressive Disorder / Q000235:genetics*; D044127:Epigenesis, Genetic; D056726:Genetic Association Studies; D006801:Humans; D008969:Molecular Sequence Data
keywords: Chromatin; DNA methylation; Epigenetics; Gene; Histone; Major depression; Treatment response