Metabolic Signature of Antipsychotics used in the Treatment of Autism
Abstract
Atypical antipsychotics (AAP) are prescribed to numerous autistic patients to treat symptoms of agitation, stereotypic behavior, temper tantrums and self-injury. Despite their ability to ameliorate many behavioral problems, AAP have serious metabolic side-effects which include weight gain, insulin resistance, and increased risk of diabetes and cardiovascular disease. The main therapeutic targets of AAP are the dopamine (DAR) and serotonin (5-HTR) receptors. The general consensus is that AAP cause metabolic disturbances by an exclusive action on the brain. Preliminary Data: We discovered functional DAR and 5-HTR subtypes in human adipose tissue and found that incubation of adipose explants and adipocytes with olanzapine, risperidone and ziprasidone suppressed leptin and adiponectin and alter inteleukin-6 (IL-6) release. Oral delivery of olanzapine to female rats caused a rapid and robust suppression of leptin, a satiety hormone, concomitant with increased food intake and weight gain. Hypothesis and Objectives: We hypothesized that activation of DAR and/or 5-HTR subtypes in adipose tissue contributes to the metabolic side-effects caused by AAP. The overall objective was to establish adipose tissue as a critical target of AAP and elucidate some of the mechanisms by which the drugs alter adipose tissue functions leading to weight gain and the metabolic syndrome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA591182
Entities
People
- Nira Ben-jonathan
Organizations
- University of Cincinnati