NCT02374996

Pharmacoepigenetics of Bipolar Disorder Treatment

Pharmacoepigenetics of Second Generation Antipsychotic-Induced Insulin Resistance in Bipolar Disorder

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 40 (actual)
• Sponsor: Wayne State University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Insulin is a hormone produced by the body to regulate blood sugar. Insulin resistance is a state when the body is not using insulin correctly, and more insulin is needed to maintain normal blood sugar. Insulin resistance is common in bipolar patients and even more common in bipolar patients treated with antipsychotics. Insulin resistance from antipsychotics can lead to type 2 diabetes, metabolic syndrome and cardiovascular disease and is known to lead to worse psychiatric outcomes (less mood stability) and lower life expectancies in bipolar disorder. Abnormal regulation of the folate cycle is known to play a role in antipsychotic-induced insulin resistance and the main endpoint to the folate cycle is the production of methyl donors for DNA methylation. DNA methylation is critical as it regulates how genes are expressed. Thus, changes in DNA methylation may play a role in the disease process of antipsychotic-induced insulin resistance. The purpose of this study is to examine the differences in the DNA methylation of candidate tissues known to have a role in the development of insulin resistance. The three groups of bipolar patients to be studied are 1) antipsychotic treated patients with impaired glucose tolerance, 2) antipsychotic treated patients with normal glucose tolerance and 3) lithium treated patients with normal glucose tolerance. Group 1 will be compared to groups 2 and 3 in order to assess how DNA methylation in the skeletal muscle and fat tissue changes due to medication effects (group 2 vs. 3) and medication side effects (group 1 vs. 2). Secondary analyses include the analysis of how fats are processed in skeletal muscle and fat tissue in relation to antipsychotic-induced insulin resistance and the correlation of DNA methylation across different tissues. The investigators hypothesize that antipsychotic-induced insulin resistance is to due changes in the way DNA is expressed (through epigenetic changes) which causes further changes in the way fats are processed in the body eventually leading to insulin resistance. This work is based on preliminary findings however further work is needed to identify the true mechanisms behind antipsychotic-induced insulin resistance and in particular, the main tissue in which this mechanism occurs.

Detailed description

This study will be composed of 2 visits. The first visit will be used as a screening visit for inclusion of the three groups of patients for the second visit where the outcomes will be collected (e.g., tissue samples for DNA methylation and lipidomic analysis).

Conditions

• Antipsychotic Agents
• Bipolar Disorder

Timeline

• Start date: 2015-11-01
• Primary completion: 2017-09-01
• Completion: 2017-09-01
• First posted: 2015-03-02
• Last updated: 2018-02-14

Locations

1 site across 1 country: United States