METABOLIC AND HORMONAL ABNORMALITIES IN CHILDREN TREATED WITH RISPERIDONE

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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. In a number of pediatric double-blind randomized controlled trials, risperidone, an atypical antipsychotic medication, was markedly superior to placebo at controlling behavioral problems, aggression, and irritability. Disruptive behavior and aggression being leading causes for evaluation and hospitalization in child psychiatry, the apparent efficacy of risperidone has led to its widespread use in the young population. Unfortunately, data regarding the long-term safety in minors remain, at best, limited. In the proposed study, these investigators seek to characterize the metabolic and hormonal abnormalities associated with long-term treatment with risperidone in minors. They suspect that the clinical impact of these abnormalities become significant only after prolonged exposure. Therefore, only minors who have taken risperidone for at least six months will be recruited. Information related to demographics, general health, stage of sexual development, level of physical activity, dietary and calcium intake, and psychiatric treatment history will be collected. They will genotype the serotonin receptor (5-HT2c) and leptin genes and measure prolactin, sex steroids, insulin, glucose, and a lipid profile. Finally, spinal bone mineral density will be measured using dual energy x-ray absorptiometry (DEXA) and forearm bone density using peripheral quantitative computerized tomography (pQCT). These investigators hypothesize that treatment with risperidone will be associated with an elevated rate of weight gain. They also expect that subjects with dyslipidemia, insulin resistance, or glucose intolerance will have gained more weight compared to those without these metablic abnormalities. Furthermore, they predict that the T allele of the 5-HT2c receptor gene and the A allele of the leptin gene will be protective against risperidone-induced weight gain. Finally, they expect to find a negative correlation between BMD and prolactin level and a positive correlation between BMD and sex steroid level even when controlling for cofounders such as height, duration of risperidone treatment, calcium intake, and level of physical activity.