Metabolic Signature of Antipsychotics used in the Treatment of Autism
Annual rept. 30 Sep 2012-29 Sep 2013
CINCINNATI UNIV OH
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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 andor 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.
- Anatomy and Physiology
- Medicine and Medical Research