Overall, our findings suggest that the AKT gene is differentially methylated in the skeletal muscle of patients taking atypical antipsychotics or mood stabilizer maintenance therapy. These results may direct future approaches to reduce the harmful adverse effects of atypical antipsychotic treatment.

Atypical antipsychotics (AAPs) are a class of medications associated with significant metabolic side effects, including insulin resistance. The aim of this study was to analyze the skeletal muscle lipidome of patients on AAPs, compared to mood stabilizers, to further understand the molecular changes underlying AAP treatment and side effects. Bipolar patients on AAPs or mood stabilizers underwent a fasting muscle biopsy and assessment of insulin sensitivity. A lipidomic analysis of total fatty acids (TFAs), phosphatidylcholines (PCs) and ceramides (CERs) was performed on the muscle biopsies, then lipid species were compared between treatment groups, and correlation analyses were performed with insulin sensitivity. TFAs and PCs were decreased and CERs were increased in the AAP group relative to those in the mood stabilizer group (FDR q-value <0.05). A larger number of TFAs and PCs were positively correlated with insulin sensitivity in the AAP group compared to those in the mood stabilizer group. In contrast, a larger number of CERs were negatively correlated with insulin sensitivity in the AAP group compared to that in the mood stabilizer group. The findings here suggest that AAPs are associated with changes in the lipid profiles of human skeletal muscle when compared to mood stabilizers and that these changes correlate with insulin sensitivity.

The goal of pharmacogenetic research is to assist clinicians in predicting patient response to medications when genetic variations are identified. The pharmacogenetic variation of antiepileptic drug response and side effects has yielded findings that have been included in drug labeling and guidelines. The goal of this review is to provide a brief overview of the pharmacogenetic research on antiepileptic drugs. It will focus on findings that have been included in drug labeling, guidelines, and candidate pharmacogenetic variation. Overall, several genes have been included in guidelines by national and international organizations; however, much work is needed to implement and evaluate their use in clinical settings.