Atypical Antipsychotics and the Human Skeletal Muscle Lipidome.

Kyle Burghardt,Berhane Seyoum,Zhengping Yi,Bradley Howlett,Kristen Ward,Elani Sanders

doi:10.3390/metabo8040064

Abstract

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.

Highlights

Bipolar Disorder is a severe mental illness estimated to affect approximately 3% of the United States adults each year and carries with it significant social, economic and disability burden [1,2,3,4]
We investigated lipidsensitivity composition of several in lipid features asthe wellskeletal as somemuscle opposingTFA, correlations with insulin patients with bipolar disorder on either a maintenance regimen of Atypical antipsychotics (AAPs) or mood stabilizers
We identified elevated levels of skeletal muscle CERs in the AAP group relative to those in the mood stabilizer group, which may align with studies in the metabolic literature that have demonstrated increased skeletal muscle CERs with insulin resistance [53]

Summary

Introduction

Bipolar Disorder is a severe mental illness estimated to affect approximately 3% of the United States adults each year and carries with it significant social, economic and disability burden [1,2,3,4]. Treatment of bipolar disorder includes both non-pharmacologic and pharmacologic strategies. Approximately 50% of bipolar disorder patients become non-adherent on long-term treatment [5,6,7]. The atypical antipsychotics (AAPs) carry significant risk for metabolic side effects, including weight gain, insulin resistance, and metabolic syndrome, which is thought to be partly responsible for non-adherence [8]. In addition to non-adherence, the metabolic side effects of AAPs contribute to the elevated rates of cardiovascular mortality within the severely mentally ill when

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