Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers.

Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PPARGC1A) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses.

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

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.

Personal genotyping and student outcomes in genetic and pharmacogenetic teaching: a systematic review and meta-analysis.

Aim: Teaching of genetics and pharmacogenetics with personal genotyping (PGT) is becoming commonplace. We aimed to perform a systematic review and meta-analysis to understand the effects of PGT on student outcomes. Methods: A systematic review was performed on studies that reported the effects of PGT on student attitudes, perceptions or knowledge. Extracted data were summarized qualitatively and when possible, quantitatively. Results: Student PGT has a positive effect on student attitude and perceptions survey responses in studies without a control group (p = 0.009) and in studies with a control group (p = 0.025). Knowledge increased after the use of PGT (p < 0.001) in studies without a control group. Conclusion: The findings here suggest that perceptions, attitudes and knowledge increase with PGT in the classroom.

Bibliometric data based on the Pharm.D. and Ph.D. degree in United States research-intensive colleges of pharmacy.

OBJECTIVES: The objective of this work was to compare bibliometrics based on doctoral degrees within United States colleges of pharmacy to understand productivity differences. Secondary objectives were to provide quantitative data based on degree that could be utilized by individual faculty, administration and other key stakeholders in academic pharmacy. METHODS: Bibliometric indices were obtained from Scopus and Web of Science for faculty from research-intensive United States pharmacy schools. Scholarly metrics that included publication number, total citations, highest cited article and H-index were compared between degrees using multivariate regression adjusted for academic rank and years since first publication. A correction for multiple testing was applied. KEY FINDINGS: All collected scholarly metrics were higher for Ph.D.-only and Pharm.D./Ph.D. faculty when compared to Pharm.D.-only faculty. Ph.D.-only faculty significantly differed compared to Pharm.D./Ph.D. faculty for Web of Science average citations per document. CONCLUSIONS: Differences are apparent between the major doctoral degrees at research-intensive, federally funded colleges of pharmacy; however, these differences were primarily identified for Pharm.D.-only compared to the other doctoral degree types Future work should analyse the potential variables that explain the scholarly metrics differences between degrees and aim to analyse other areas of faculty impact beyond scholarly metrics.

A bibliometric analysis of the top 50 NIH-Funded colleges of pharmacy using two databases.

BACKGROUND: Scholarly productivity is an essential component of college of pharmacy activities and may depend on university rank, faculty type, faculty rank and department. Bibliometric measures provide a means to analyze scholarly productivity from colleges of pharmacy while accounting for these various factors. OBJECTIVES: To analyze bibliometric data from two databases based on Carnegie Research Classification and NIH-funding rank; provide descriptions of bibliometric data based on department type and faculty classification; and examine the distribution of publications in the top 50 NIH-funded Colleges of Pharmacy. METHODS: Faculty rosters were gathered for the top 50 NIH-funded colleges of pharmacy, and names were searched in Scopus and Web of Science to establish bibliometric records. Bibliometric indices were compared based on Carnegie Basic Classification and between the NIH funding ranks 1-25 versus 26-50 using WOS bibliometric data. Descriptive statistics were presented, and Pareto distributions were developed for total publications across all schools included. RESULTS: Schools in the top 25 for NIH funding and schools with a Carnegie R1 classification had significantly higher bibliometric measures compared to schools ranked 26-50 and schools classified as R2, respectively. For faculty members with a bibliometric record (i.e., at least one publication), 20% provide approximately 60% of the publications. Additionally, approximately 90% of publications are provided by 50% of faculty records. Faculty records from basic science departments, as compared to clinical pharmacy departments, represent the highest contributing groups in the Pareto analysis. CONCLUSION: Bibliometric indices are higher at colleges of pharmacy with greater NIH funding or an R1 Carnegie classification. A minority of faculty provides most publications in colleges of pharmacy, which is composed of members from basic science departments. The descriptive data provided here is useful for understanding readily available bibliometric data based on department type and faculty classification and rank.

Skeletal muscle DNA methylation modifications and psychopharmacologic treatment in bipolar disorder.

Both severe mental illness and atypical antipsychotics have been independently associated with insulin resistance and weight gain. Altered regulation of skeletal muscle DNA methylation may play a role. We aimed to evaluate DNA methylation modifications in human skeletal muscle samples to further understand its potential role in the metabolic burden observed in psychiatric patients and psychopharmacologic treatment. Subjects were included in our study if they had a bipolar diagnosis and were currently treated with a mood stabilizer or atypical antipsychotic. A healthy control group free of psychiatric or physical disease was also included for comparisons. Anthropometric, BMI and hemoglobin A1C (HbA1C%) were measured. Fasting skeletal muscle biopsies were obtained and methylation levels of 5-methycytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 5-formylcytosine (5-fC) were measured. Skeletal muscle global methylation of 5-mC and 5-fC were significantly higher in bipolar subjects compared to healthy controls. 5-mC was significantly higher in the AAP group compared to the mood stabilizer group. Significant correlations were observed between 5-fC methylation and HbA1C%. Our findings suggest that psychiatric disease and treatment may influence some methylation measures in the skeletal muscle of patients with bipolar disorder, which may be further influenced by medication treatment.

Atypical Antipsychotics and the Human Skeletal Muscle Lipidome.

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.