title: DNA methylation signatures of mood stabilizers and antipsychotics in bipolar disorder.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Lotte C
authors.initials: LC
authors.lastname: Houtepen
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Annet H
authors.initials: AH
authors.lastname: van Bergen
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Christiaan H
authors.initials: CH
authors.lastname: Vinkers
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Marco P M
authors.initials: MP
authors.lastname: Boks
mesh_terms: D000339:Affect / Q000187:drug effects*; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000187:drug effects; D057890:Epigenomics / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D055106:Genome-Wide Association Study; D006801:Humans; D059467:Transcriptome
chemical_list: D014150:Antipsychotic Agents
keywords: DNA methylation; antidepressant; antipsychotics; bipolar; cell type; medication; mood stabilizer