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Abstract
Aim: The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response. Methods: Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs. Results:In vitro data demonstrated that antipsychotic drugs induce epigenetic response by downregulating miRNA that target DNA methyltransferases, resulting in global hypermethylation. Similar trend was observed in clinical setting too and alterations were markedly associated with drug response rather than disease pathogenesis. Conclusion: Study demonstrates that antipsychotic drugs can influence host methylome and thereby indicating its role in mediating a strong pharmacoepigenomic response.
Financial & competing interests disclosure
The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2017-0086