title: Epigenetics and depressive disorders: a review of current progress and future directions.
abstract: BACKGROUND
  Several broad lines of evidence support the involvement of epigenetic processes in neurodevelopment and psychiatric disorders. Epigenetic disruption also provides a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes.
  
  
  METHODS
  A review of the literature was performed with keywords 'depression', 'depressive disorder' or 'antidepressants' and 'DNA methylation', or 'epigenetics' in humans. Citations were limited to those written in English and published prior to July 2014.
  
  
  RESULTS
  We present a summary of results to date. Most studies have focused on DNA methylation in various CNS or peripheral tissue, with almost universally small sample sizes. Although seven epigenome-wide association studies have now been reported, the majority of studies have used a candidate-gene approach. Three genes (SLC6A4, BDNF, NR3C1) have been investigated in more than one study, but replication of findings is generally lacking.
  
  
  CONCLUSIONS
  Recent evidence provides insights to epigenetic processes in psychiatric disorders; however, replication is lacking and care must be taken in the interpretation of current findings. This applies to epigenetic epidemiology generally, which is subject to various limitations that no single approach can address in isolation. Due to limited focus of most depression studies to date, placing the findings within the broader context of mood disorder pathophysiology may prove challenging. However, identifying peripheral biomarkers for depressive disorder remains a tantalising possibility, especially given the potential for carefully-designed longitudinal studies with multiple biospecimens and ongoing advances in epigenetic technologies.
authors.affiliation: Cancer & Disease Epigenetics, Murdoch Childrens Research Institute, & Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia and joanne.ryan@mcri.edu.au.
authors.forename: Vania
authors.initials: V
authors.lastname: Januar
authors.affiliation: Cancer & Disease Epigenetics, Murdoch Childrens Research Institute, & Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia and.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: Cancer & Disease Epigenetics, Murdoch Childrens Research Institute, & Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia and Inserm U1061, Hopital La Colombiere & Universite Montpellier, Montpellier, France joanne.ryan@mcri.edu.au.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D019175:DNA Methylation; D003863:Depression / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C579455:BDNF protein, human
keywords: CNS tissue; DNA methylation; Epigenetics; biomarker; causation; confounding; depression; gene-environment; major depressive disorder; tissue heterogeneity