Accession Number : ADA591182


Title :   Metabolic Signature of Antipsychotics used in the Treatment of Autism


Descriptive Note : Annual rept. 30 Sep 2012-29 Sep 2013


Corporate Author : CINCINNATI UNIV OH


Personal Author(s) : Ben-Jonathan, Nira


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a591182.pdf


Report Date : Oct 2013


Pagination or Media Count : 10


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.


Descriptors :   *MENTAL DISORDERS , *METABOLISM , ADIPOSE TISSUE , BEHAVIOR , FOOD CONSUMPTION , HORMONES , SEROTONIN , SIGNS AND SYMPTOMS , WEIGHT


Subject Categories : Psychology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE