Profiling the Skeletal Muscle Proteome in Patients on Atypical Antipsychotics and Mood Stabilizers

Abstract

Atypical antipsychotics (AAP) are used in the treatment of severe mental illness. They are associated with several metabolic side effects including insulin resistance. The skeletal muscle is the primary tissue responsible for insulin-stimulated glucose uptake. Dysfunction of protein regulation within the skeletal muscle following treatment with AAPs may play a role in the associated metabolic side effects. The objective of this study was to measure protein abundance in the skeletal muscle of patients on long-term AAP or mood stabilizer treatment. Cross-sectional muscle biopsies were obtained from patients with bipolar disorder and global protein abundance was measured using stable isotope labeling by amino acid (SILAC) combined with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Sixteen patients completed muscle biopsies and were included in the proteomic analyses. A total of 40 proteins were significantly different between the AAP group and the mood stabilizer group. In-silico pathway analysis identified significant enrichment in several pathways including glucose metabolism, cell cycle, apoptosis, and folate metabolism. Proteome abundance changes also differed based on protein biological processes and function. In summary, significant differences in proteomic profiles were identified in the skeletal muscle between patients on AAPs and mood stabilizers. Future work is needed to validate these findings in prospectively sampled populations.

Keywords: antipsychotic; mood stabilizer; proteomic; skeletal muscle.

Figure 1

Pie chart representation of protein location and function for identified protein abundance differences between patients on atypical antipsychotics (AAP) and mood stabilizers. This figure depicts the location and function (as determined by the Molecule Module of Ingenuity Pathway Analysis Software) of protein abundancies that were determined to be significantly different in the skeletal muscle of AAP-treated subjects versus mood stabilizer-treated subjects. The top half of the panel depicts protein location (a,b) and the bottom half of the panel shows the distribution of annotated function for each identified protein (c,d). The increased abundance and decreased abundance refer to increases or decreases in the AAP group relative to the mood stabilizer group.