The Epigenetic Code in Depression: Implications for Treatment

Department of Psychiatry, Psychosomatic Medicine & Psychotherapy, Goethe University Frankfurt, Frankfurt, Germany.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.39). 12/2011; 91(2):310-4. DOI: 10.1038/clpt.2011.282
Source: PubMed

ABSTRACT Major depressive disorder (MDD) is a common and disabling disorder that carries both a substantial personal burden as well as a social one. A better understanding of the epigenetic mechanisms in depression might provide a new framework for individually tailored pharmacologic treatment options. In this review we highlight current knowledge about the role of epigenetic mechanisms in the pathogenesis of depression and treatment implications.

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    ABSTRACT: 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. 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. 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. 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. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.