A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention.

Elad Lax,David Ohana,Gal Warhaftig,Paola Roska,Alexander M Ponizovsky,Rachel Maayan,Yael Delayahu,Moshe Szyf,Gal Yadid,Abraham Weizman

doi:10.3389/fnmol.2018.00322

Abstract

Previous studies in animal models of cocaine craving have delineated broad changes in DNA methylation profiles in the nucleus accumbens. A crucial factor for progress in behavioral and mental health epigenetics is the discovery of epigenetic markers in peripheral tissues. Several studies in primates and humans have associated differences in behavioral phenotypes with changes in DNA methylation in T cells and brain. Herein, we present a pilot study (n = 27) showing that the T cell DNA methylation profile differentiates persons with a substance use disorder from controls. Intervention with dehydroepiandrosterone (DHEA), previously shown to have a long-term therapeutic effect on human addicts herein resulted in reversal of DNA methylation changes in genes related to pathways associated with the addictive state.

Highlights

Several lines of evidence suggest a crucial role for epigenetic modification in forming and maintaining the drug-addicted state (Maze and Nestler, 2011; Xu et al, 2016)
Previous studies have shown a broad signature of addiction in DNA methylation in the NAc of rats during cocaine craving (Massart et al, 2015), it is unknown whether addiction is associated with a similar altered DNA methylation signature in humans
If DNA methylation profiles are altered in addicts, this could provide a rationale for considering epigenetic based interventions

Summary

Introduction

Several lines of evidence suggest a crucial role for epigenetic modification in forming and maintaining the drug-addicted state (Maze and Nestler, 2011; Xu et al, 2016). The DNA methylation landscape was shown to be altered in different animal models for drug addiction (Maze and Nestler, 2011; Itzhak et al, 2015; Wright et al, 2015). Dehydroepiandrosterone (DHEA), an endogenous neurosteroid, negatively modulates the levels of the stress hormone cortisol (Flood et al, 1988), reduces anxiety and restores stable mood, as demonstrated both in animal models (Melchior and Ritzmann, 1994; Genud et al, 2009) and in humans (Morales et al, 1994; Wolkowitz et al, 1999). In humans, reduced DHEA levels during drug abstinence

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Conclusion