METABOLIC EFFECTS OF ANTIPSYCHOTICS IN CHILDREN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The prevalence of overweight and obesity, insulin resistance, and type 2 diabetes mellitus (T2DM) are increasing in children, with epidemic rates in the US. Increased adiposity and related reductions in insulin sensitivity, are major risk factors for T2DM, cardiovascular disease, lifespan reductions and other adverse health and psychosocial out-comes. With the use of atypical antipsychotics for aggressive behavior disorders on the rise, concerns about antipsychotic effects, including weight gain, on glucose, lipids and adiposity have also intensified. Increased abdominal adiposity can decrease insulin sensitivity and antipsychotics can increase adiposity. Medication effects on glucose control and insulin action may also occur independent of differences in adiposity. This project aims to evaluate effects of selected antipsychotic treatments on a) insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis), b) insulin secretion c) abdominal fat mass, total body fat and total fat-free mass, d) resting metabolic rates (carbohydrate and fat oxidation) e) efficacy for symptoms of aggression. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of gold standard stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aim will be addressed in non-diabetic children and adolescents diagnosed with aggressive behavior who have never been treated with an antipsychotic medication. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.