Abstract
Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.
Highlights
AND MOTIVATIONShizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are severe psychiatric disorders, conferring lifelong disability (Hyman, 2012; GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, 2016)
We systematically reviewed published studies that examined DNAm in relation to drug response in SCZ, BD, or MDD, using the PubMed, Web of Science, and MEDLINE with the following search builder: (((((((pharmacogenetic) OR pharmacogenomic) OR pharmacoepigenetic) OR drug response) OR treatment) OR drug efficiency) OR #DRUG#) AND ((((DNA methylation) OR methylation) OR epigenetic) OR EWAS) AND (#DISORDER#). #DRUG# is the major drug for each disorder: antipsychotic, mood stabilizer, lithium, antidepressant, selective serotonin reuptake inhibitor (SSRI) and selective norepinephrine reuptake inhibitor (SNRI). #DISORDER# is one of the major psychiatric disorders: SCZ, BD and MDD
We summarize recent findings from pharmacoepigenetic studies in SCZ, BD and MDD to evaluate the reproducibility of drug response-related DNAm changes in these disorders
Summary
AND MOTIVATIONShizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are severe psychiatric disorders, conferring lifelong disability (Hyman, 2012; GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, 2016). The Sequenced Treatment Alternatives to Relieve Depression trial (STAR∗D) study reported that only 35% of patients remit after their primary antidepressant treatment (Rush et al, 2006; Katz et al, 2012). This illustrates the importance of developing biomarkers that can support decisions regarding optimal drug choice, and identify likely poor responders as quickly as possible. This emphasizes the need for a better biomarker-based stratification of patients that could facilitate treatment planning
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