Epigenome-Wide Studies of Antipsychotics: A Systematic Review and Pathway Meta-Analysis

Abstract

Background&methods: Researchers have aimed to understand the mechanisms of antipsychotics through epigenetics to inform interindividual response rates. However, findings have widely varied across studies, making advancement in the field difficult. Materials&methods: A systematic review was performed to include all epigenome-wide studies of antipsychotic treatment in humans. Methylation sites were used for a pathway and enrichment map analysis was conducted. Results&conclusion: Seven studies were included and 82 methylation sites were used for the exploratory pathway meta-analysis that identified six pathway clusters. The findings here demonstrate that studies of the epigenome and antipsychotic treatment are highly heterogeneous in nature and could inform future work to target cross-cutting gene sets and pathways.

Plain language summary

Antipsychotics are a medication used for the treatment of individuals with schizophrenia and bipolar disorder. Antipsychotics work well, but some patients do not respond to treatment and some get side effects from the treatment, and we are not sure why. A possible reason could be how marks on our DNA interact with antipsychotics in a process called epigenetics. This area of research has been ongoing but requires a summary and report of the results together. This review aims to provide such a report so that one day antipsychotic treatment can be improved so that more patients respond and fewer get side effects.

Keywords::

• antipsychotic
• methylation
• pathway
• review
• systematic

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0222

All authors made substantial contributions to the work including conception, design, acquisition and interpretation. All authors contributed to drafting and gave final approval of the work including accountability for all aspects of the work.

Financial disclosure

This work was supported in part by grants from NIH/NIDDK K23DK118199 (to KJ Burghardt) and L30DK110823 (to KJ Burghardt). 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity 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.

Writing disclosure

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