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Moving pharmacoepigenetics tools for depression toward clinical use.

Laura M Hack1, Gabriel R Fries2, Harris A Eyre3

  • 1Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Palo Alto, CA 94305, USA; Sierra Pacific Mental Illness Research Education and Clinical Centers, VA Palo Alto Health Care System, Palo Alto, CA, USA.

Journal of Affective Disorders
|February 26, 2019
PubMed
Summary

Pharmacoepigenetics shows promise for predicting antidepressant response by combining genetic and environmental factors. Further research is needed to overcome challenges and develop clinically useful tools for precision psychiatry.

Keywords:
AntidepressantsDNA methylationDecision support tools (DSTs)DepressionHistonesPharmacoepigenetics

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Major depressive disorder (MDD) is a leading cause of global disability, with over half of patients not achieving remission after initial antidepressant treatment.
  • Despite a known genetic basis for MDD, validated biomarkers for treatment response are lacking in clinical practice.
  • Pharmacoepigenetics offers a novel approach to integrate genetic and environmental factors for personalized psychiatric treatment.

Purpose of the Study:

  • To review the emerging field of pharmacoepigenetics in the context of antidepressant treatment response.
  • To explore the potential of epigenetic modifications as biomarkers for predicting treatment outcomes in depression.

Main Methods:

  • A narrative review of English-language studies was conducted using PubMed, Google Scholar, PsychINFO, and Ovid Medicine.
  • Literature search focused on DNA methylation and histone modifications in human and animal models of depression.
  • Studies were included from inception through January 2019.

Main Results:

  • Emerging evidence suggests epigenetic marks like DNA methylation and histone modifications may predict antidepressant response.
  • Challenges include patient heterogeneity, locus variability, lack of replication, tissue specificity, and environmental influences.
  • These factors pose significant hurdles for developing reliable pharmacoepigenetic tools.

Conclusions:

  • Pharmacoepigenetics holds potential for precision psychiatry but is still in its early stages.
  • Future development requires genome-wide approaches, reproducible assays, careful tissue selection, and integration of genetic and clinical data.
  • These advancements could lead to clinically useful predictive tests for antidepressant response.