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Updated: Mar 26, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
DNA methylation signatures of mood stabilizers and antipsychotics in bipolar disorder
Lotte C Houtepen1, Annet H van Bergen1, Christiaan H Vinkers1
1Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
Aim:
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.
Experimental Procedures:
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.
Conclusion:
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.
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The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...