METABOLIC EFFECTS OF ANTIPSYCHOTICS IN CHILDREN

抗精神病药对儿童的代谢影响

• 批准号: 7377227
• 负责人: JOHN W. NEWCOMER
• 金额: $ 0.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377227
• 关键词: METABOLIC; EFFECTS; ANTIPSYCHOTICS; CHILDREN

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 everweight and obesity, insulin resistance, and type 2 diabetes mellitus (T2DM) are increasing in children, with epidemic rates of these conditions in children in the United States (US). Increased adiposity and related reductions in insulin sensitivity, also referred to as insulin resistance, are major risk factors for the development of T2DM, cardiovascular disease (CVD, e.g., risk of myocardial infarction and stroke), other adverse health outcomes, and reduced psychosocial function. Reduction in lifespan attributable to obesity impact younger, at-risk individuals most measurably, with severly obese 20 year-old African American males expected to lose 20 years of life. With the use of atypical antipsychotics for treatment of conduct disorder and other aggressive behavior disorders on the rise, concerns about antipsychotic effects, including weight gain, on glucose, lipids and adiposity have also increased, focusing on the widely-used newer medications, clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin sensitivity and antipsychotics can increase adiposity. However, medication effects on glucose control and insulin action may also occur independent of differences in adiposity. This project aims to a) evaluate effects of selected antipsychotic treatments on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis), b) evaluate effects of selected antipsychotic treatments on insulin secretion c) evaluate effects of selected antipsychotic treatments on abdominal fat mass, total body fat and total fat-free mass d) evaluate effects of selected antipsychotic treatment on resting metabolic rates (carbohydrate and fat oxidation) e) evaluate effects of selected antipsychotic treatments on efficacy for symptoms of aggression. These hypoetheses will be 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 aims will be addressed in non-diabetic child and adolescent patients diagnosed with conduct disorder 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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。儿童中超重和肥胖、胰岛素抵抗和 2 型糖尿病 (T2DM) 的患病率正在增加，这些疾病在美国 (US) 儿童中的流行率更高。肥胖增加和相关的胰岛素敏感性降低（也称为胰岛素抵抗）是发生 T2DM、心血管疾病（CVD，例如心肌梗塞和中风的风险）、其他不良健康结果和心理社会功能下降的主要危险因素。肥胖导致的寿命缩短对年轻、高危人群的影响最为显着，严重肥胖的 20 岁非裔美国男性预计会减少 20 年的寿命。随着使用非典型抗精神病药治疗行为障碍和其他攻击性行为障碍的增加，人们对抗精神病药对血糖、血脂和肥胖的影响（包括体重增加）的担忧也有所增加，重点关注广泛使用的新型药物氯氮平和奥氮平。腹部肥胖增加会继而降低胰岛素敏感性，而抗精神病药物会增加肥胖。然而，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 a) 评估选定的抗精神病药物对骨骼肌（葡萄糖处理）、肝脏（葡萄糖产生）和脂肪组织（脂肪分解）中胰岛素作用的影响，b) 评估选定的抗精神病药物对胰岛素分泌的影响 c) 评估效果选定的抗精神病药物治疗对腹部脂肪量、全身脂肪和总去脂体重的影响 d) 评估选定的抗精神病药物治疗对静息代谢率（碳水化合物和脂肪氧化）的影响 e) 评估选择抗精神病药物治疗攻击性症状的疗效。这些假设将测量 1) 使用“金标准”稳定同位素示踪方法测量全身葡萄糖和脂质动力学，2) 使用双能 X 射线吸收测定法和磁共振成像测量身体成分，以及 3)葡萄糖耐量和血脂状况。这些目标将针对被诊断患有行为​​障碍且从未接受过抗精神病药物治疗的非糖尿病儿童和青少年患者。迫切需要相关数据来开展基础研究、确定长期心血管后果并规划治疗干预措施。