METABOLIC EFFECTS OF ANTIPSYCHOTICS IN CHILDREN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 超重和肥胖、胰岛素抵抗和2型糖尿病(T2 DM)在儿童中的患病率正在上升，美国的流行率也在上升。肥胖增加和相关的胰岛素敏感性降低是导致T2 DM、心血管疾病、寿命缩短和其他不利健康和心理社会后果的主要危险因素。随着非典型抗精神病药物用于攻击性行为障碍的使用增加，人们对抗精神病药物效果的担忧也加剧了，包括体重增加对血糖、血脂和肥胖症的影响。腹部肥胖增加会降低胰岛素敏感性，抗精神病药物会增加肥胖。药物对血糖控制和胰岛素作用的影响也可能与肥胖的差异无关。该项目旨在评估选定的抗精神病药物对a)骨骼肌(葡萄糖处理)、肝脏(葡萄糖产生)和脂肪组织(脂肪分解)的胰岛素作用，b)胰岛素分泌，c)腹部脂肪质量，全身脂肪和总脱脂质量，d)静息代谢率(碳水化合物和脂肪氧化)e)攻击症状的疗效。这些假说将通过1)使用金标准稳定同位素示踪方法测量全身葡萄糖和脂肪动力学，2)使用双能量X射线吸收和磁共振成像测量身体成分，以及3)糖耐量和脂肪分布的纵向变化来评估。这一目标将针对被诊断为有攻击性行为的非糖尿病儿童和青少年，他们从未接受过抗精神病药物治疗。迫切需要相关数据来瞄准基础研究，确定长期心血管后果，并计划治疗干预措施。

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.