Affiliation:
1. Centre for Addiction and Mental Health, Toronto, Canada
2. Department of Psychiatry, University of Toronto, Canada
3. St. Michael’s Hospital, Toronto, Canada
Abstract
Abstract
Introduction The relationship between genetic polymorphisms of
antipsychotic drug-metabolizing agents and drug receptors has been often
investigated. DNA methylation is a form of epigenetic modification that
regulates gene expression. Few studies have analyzed the relationship between
genome-wide methylation patterns and antipsychotic dosage. The primary aim of
this pilot study was to investigate the association between antipsychotic dosage
and genome-wide DNA methylation in patients with schizophrenia (SCZ).
Methods Current dosage of antipsychotic medications was assessed in 136
patients with SCZ. Dosage was standardized using three different methods:
chlorpromazine equivalent dose (CPZe), defined daily dose (DDD), and percentage
of Lexicomp maximum dose (PM%). DNA methylation was measured in white
blood cells. Antipsychotic dosage was the primary outcome variable in a model,
including genome-wide methylation status as the main predictor.
Results This study did not show any association between DNA methylation
and dosage variation for CPZe, PM%, and DDD. However, the probe
cg271403389 was consistently associated with antipsychotic dosage across the
three standardization methods. When looking at the genomic location of the most
significant probes, we found that 15% were intergenic, 23% were
in the distal promoter, 9% in the 3′untranslated region,
32% in the gene body, 3% in the 5′ untranslated region,
15% in the proximal promoter, and 3% in the first exon.
Discussion This study shows the importance of investigating the
relationship between DNA methylation and optimal antipsychotic dosage to
personalize treatment in SCZ. Future studies require larger prescription
databases to build on the results of this analysis.
Subject
Pharmacology (medical),Psychiatry and Mental health,General Medicine
Cited by
1 articles.
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