METABOLIC AND HORMONAL ABNORMALITIES IN CHILDREN TREATED WITH RISPERIDONE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。在一些儿科双盲随机对照试验中，利培酮（一种非典型抗精神病药物）在控制行为问题、攻击性和易怒方面明显上级安慰剂。破坏性行为和攻击性是儿童精神病学评估和住院的主要原因，利培酮的明显疗效导致其在年轻人群中广泛使用。不幸的是，有关未成年人长期安全的数据充其量仍然有限。在拟议的研究中，这些研究人员试图描述未成年人长期接受利培酮治疗相关的代谢和激素异常。他们怀疑这些异常的临床影响只有在长时间暴露后才会变得显著。因此，只有服用利培酮至少6个月的未成年人才会被招募。将收集与人口统计学、一般健康状况、性发育阶段、体力活动水平、饮食和钙摄入量以及精神病治疗史相关的信息。他们将对血清素受体（5-HT 2c）和瘦素基因进行基因分型，并测量催乳素、性类固醇、胰岛素、葡萄糖和血脂。最后，将使用双能X线吸收法（DEXA）测量脊柱骨密度，使用外周定量计算机断层扫描（pQCT）测量前臂骨密度。这些研究者假设利培酮治疗与体重增加率升高有关。他们还预计，与没有这些代谢异常的受试者相比，患有血脂异常、胰岛素抵抗或葡萄糖耐受不良的受试者体重增加更多。此外，他们预测5-HT 2c受体基因的T等位基因和瘦素基因的A等位基因将对利培酮诱导的体重增加具有保护作用。最后，他们希望发现骨密度和催乳素水平之间的负相关性和骨密度和性类固醇水平之间的正相关性，即使在控制了共同因素，如身高，利培酮治疗时间，钙摄入量和体力活动水平。

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.