Measurement of Cardiometabolic Risk in Antipsychotic-Treated Children

描述(申请人提供)：这份K23奖项申请与最近国际移民组织研究优先列表中的多个主题领域相关，以及最近国际移民组织报告简报和白宫专注于儿童肥胖症的“让我们行动”活动。该奖项将支持为一名候选人提供指导、教学培训和其他职业发展活动，该候选人特别适合在患有心理健康障碍的儿童的肥胖和代谢风险领域发展专门知识。申请人的直接职业目标是进一步发展在测量肥胖和心脏代谢风险的代谢机制方面的专业知识。申请者的长期职业目标是将自己确立为一名独立的研究员，研究精神疾病人群中儿童肥胖和心脏代谢风险。计划开展的活动将产生专门的综合专门知识，这在儿童精神病学领域将是独一无二的，并将为未来几十年这一高度优先、服务不足的专题领域所需的研究提供资源。近几十年来，美国儿童期肥胖症和2型糖尿病的患病率已经上升到流行水平，这两种疾病都是心血管风险的预测指标。患有精神疾病的儿童，特别是那些接受抗精神病药物治疗的儿童，患肥胖症和相关风险状况的风险更高。尽管与儿童期肥胖和成人肥胖症相关的肥胖相关结果，包括过早死亡的已知增加，但对儿童的这些风险仍然认识不足。各种评估心脏代谢风险的非侵入性技术已开始应用于儿童，包括超声测量颈动脉内膜中层厚度(IMT)，以及1H磁共振波谱(MRS)测量肝脏和心脏甘油三酯含量。这些措施允许对代谢风险进行早期、非侵入性研究。不幸的是，这些有希望的方法都没有应用到患有精神障碍的儿童的高危人群中，而且根本没有对儿童的心脏甘油三酯含量进行评估，这阻碍了对风险的准确表征或降低这一脆弱人群风险的干预措施的有效性。该应用的研究部分侧重于使用敏感的早期疾病风险生物标志物，包括肝脏甘油三酯含量(HTGC)以及心脏甘油三酯含量(CTGC)和颈动脉内膜厚度，分别与糖尿病和心血管疾病风险直接相关。这项由两项研究组成的研究计划的总体目标是，使用这些敏感的标记物来表征治疗和未治疗的精神健康障碍儿童的可测量风险水平，并评估在接受良好的行为减肥干预的儿童中，使用这些生物标记物可以观察到的风险变化的程度。这将通过两项研究来完成：1)病例对照横断面比较三组超重/肥胖儿童的CTGC、HTCG和IMT值，这些儿童的年龄、性别和体重指数(BMI)百分位数匹配：接受抗精神病药物治疗的精神病儿童；(2)一项为期12周的行为减肥干预(与饮食和运动教育相比)对超重/肥胖抗精神病药物治疗儿童的CTGC、HTGC和IMT影响的随机对照测试(一小部分健康超重/肥胖儿童仅接受积极干预)。主要的分析计划将分别利用方差分析和方差分析来测试一组有重点的假设，这些假设涉及研究样本中的心脏代谢风险水平，以及已知的减肥干预措施可以在多大程度上改变这些敏感的风险生物标记物。)

DESCRIPTION (provided by applicant): This K23 award application is relevant to multiple topic areas in the recent IOM research priority list, as well as the recent IOM report brief and White House "Let's Move" Campaign focused on childhood obesity. The award will support mentoring, didactic training and additional career development activities for a candidate uniquely suited to develop expertise in the area of obesity and metabolic risk in children with mental health disorders. The applicant's immediate career goals are to further develop expertise in the measurement of metabolic mechanisms underlying obesity and cardiometabolic risk. The applicant's long-term career goal is to establish herself as an independent investigator studying childhood obesity and cardiometabolic risk in psychiatric populations. The specialized combined expertise that will emerge from the planned activities will be unique in the field of child psychiatry and will provide a resource for needed research in this high-priority, underserved topic area for decades to come. The US prevalence of childhood-onset obesity and type 2 diabetes, both predictors of cardiovascular risk, have increased to epidemic proportions in recent decades. Children with mental illness, especially those treated with antipsychotic medications, are at additional risk for obesity and related risk conditions. Despite known increases in obesity-related outcomes, including premature mortality, associated with childhood-onset versus adult-onset obesity, there remains an under-appreciation of these risks in children. A variety of noninvasive techniques to assess cardiometabolic risk have begun to be applied in children, including carotid intima media thickness (IMT) measured by ultrasound, and hepatic and cardiac triglyceride content measured by 1H Magnetic Resonance Spectroscopy (MRS). These measures allow for the early, noninvasive study of metabolic risk. Unfortunately, none of these promising methods have been applied to the high-risk population of children with psychiatric disorders, and cardiac triglyceride content has not been evaluated in children at all, preventing accurate characterization of risk or the effectiveness of interventions the reduce risk in this vulnerable population. The research portion of this application focuses on the use of sensitive, early biomarkers of disease risk, including hepatic triglyceride content (HTGC), as well as cardiac triglyceride content (CTGC) and carotid IMT, directly relevant to diabetes and cardiovascular disease risk, respectively. The overall aim of this two-study research plan is to characterize the level of measurable risk using these sensitive markers in treated and untreated children with mental health disorders, and to evaluate the magnitude of change in risk that can be observed using these biomarkers in children receiving a well- established behavioral weight-loss intervention. This will be accomplished using two studies: 1) A case control cross sectional comparison of CTGC, HTCG and IMT values in three groups of overweight/obese children who are age-, gender- and body mass index (BMI) percentile-matched: antipsychotic treated mentally ill children; mentally ill children not treated with antipsychotics and untreated children with no mental illness (a small reference group of lean healthy participants will also be included) and 2) A randomized controlled test of the effects of a 12-week behavioral weight loss intervention (versus diet and exercise education) on CTGC, HTGC and IMT in overweight/obese antipsychotic-treated children (a small reference group of healthy overweight/obese children will receive the active intervention only). The primary analytic plan will utilize ANOVA and ANCOVA, respectively, to test a focused set of hypotheses concerning the level of cardiometabolic risk in the study samples and the extent to which known weight loss interventions can modify these sensitive risk biomarkers. )