Research Article

DNA methylation signatures of mood stabilizers and antipsychotics in bipolar disorder

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands

^‡Authors contributed equally

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Annet H van Bergen^‡

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands

^‡Authors contributed equally

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Christiaan H Vinkers

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands

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Marco PM Boks

*Author for correspondence:

E-mail Address: M.P.M.Boks@umcutrecht.nl

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands

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Published Online:21 Jan 2016https://doi.org/10.2217/epi.15.98

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Abstract

Aim: In view of the potential effects of psychiatric drugs on DNA methylation, we investigated whether medication use in bipolar disorder is associated with DNA methylation signatures. Experimental procedures: Blood-based DNA methylation patterns of six frequently used psychotropic drugs (lithium, quetiapine, olanzapine, lamotrigine, carbamazepine, and valproic acid) were examined in 172 bipolar disorder patients. After adjustment for cell type composition, we investigated gene networks, principal components, hypothesis-driven genes and epigenome-wide individual loci. Results: Valproic acid and quetiapine were significantly associated with altered methylation signatures after adjustment for drug-related changes on celltype composition. Conclusion: Psychiatric drugs influence DNA methylation patterns over and above cell type composition in bipolar disorder. Drug-related changes in DNA methylation are therefore not only an important confounder in psychiatric epigenetics but may also inform on the biological mechanisms underlying drug efficacy.

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Financial & competing interests disclosure

This study was made possible by a NARSAD Young Investigator Grant to MPM Boks. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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