Measurement of Cardiometabolic Risk in Antipsychotic-Treated Children

抗精神病药物治疗儿童心脏代谢风险的测量

• 批准号: 8030396
• 负责人: Ginger Ellen Nicol
• 金额: $ 16.44万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-24 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8030396
• 关键词: Adherence; Adult; Age; Antipsychotic Agents; Area; Award; Behavioral; Biological Markers; Body Composition; Body mass index; C-reactive protein; Cardiac; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Child; Child Psychiatry; Childhood; DEXA; Development; Diabetes Mellitus; Drug or chemical Tissue Distribution; Education; Effectiveness of Interventions; Epidemic; Event; Fasting; Fatty Liver; Fatty acid glycerol esters; Fibrinogen; Gender; General Population; Glucose; Goals; Heart; Hepatic; Housing; Insulin; Insulin Resistance; Intervention; Knowledge; Life Expectancy; Lipids; Magnetic Resonance Spectroscopy; Matched Group; Measurable; Measurement; Measures; Mental Health; Mental disorders; Mentally Ill Persons; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Methods; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Onset of illness; Outcome; Overweight; Participant; Particle Size; Persons; Pharmaceutical Preparations; Population; Premature Mortality; Prevalence; Public Sector; Qualifying; Randomized; Reporting; Research; Research Personnel; Research Priority; Research Project Grants; Resources; Risk; Risk Factors; Sampling Studies; Screening procedure; Techniques; Testing; Thick; Tissues; Training; Triglycerides; Ultrasonography; Very low density lipoprotein; Vulnerable Populations; Youth; adiponectin; cardiovascular disorder risk; cardiovascular risk factor; career; career development; case control; diabetes risk; diet and exercise; disorder risk; high risk; innovation; insulin sensitivity; intima media; liver imaging; metabolic abnormality assessment; mortality; obesity in children; obesity risk; prevent; research study; weight loss intervention

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. ) PUBLIC HEALTH RELEVANCE: Childhood onset of obesity and type 2 diabetes, both predictors of cardiometabolic risk have increased to epidemic proportions in recent decades, and children with mental illness treated with antipsychotic medications are at additional risk for obesity, type 2 diabetes and early mortality related to cardiovascular disease. Techniques exist for the early, noninvasive study of metabolic risk, such as imaging of liver and heart lipid content, and carotid artery wall plaques, but have not been studied in the high-risk population of mentally ill children. This K23 award will sponsor the career development of a candidate uniquely qualified to further study obesity and metabolic risk in children with mental health disorders by supporting an innovative research project that evaluates the use of these sensitive, early biomarkers of carbiometabolic risk in children with mental health disorders.

描述（由申请人提供）：本 K23 奖项申请与最近的 IOM 研究优先列表中的多个主题领域以及最近的 IOM 报告摘要和关注儿童肥胖问题的白宫“让我们行动起来”运动相关。该奖项将为候选人提供指导、教学培训和其他职业发展活动，特别适合培养患有精神健康障碍的儿童的肥胖和代谢风险领域的专业知识。申请人的近期职业目标是进一步发展测量肥胖和心脏代谢风险的代谢机制的专业知识。申请人的长期职业目标是将自己定位为研究儿童肥胖和精神病人群心脏代谢风险的独立研究者。计划中的活动将产生的专业综合知识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、服务不足的主题领域所需的研究提供资源。近几十年来，美国儿童期肥胖和 2 型糖尿病（这两种心血管风险的预测因素）的患病率已上升到流行病的程度。患有精神疾病的儿童，尤其是那些接受抗精神病药物治疗的儿童，面临着肥胖和相关风险状况的额外风险。尽管已知与肥胖相关的结果增加，包括与儿童期发病与成人发病的肥胖相关的过早死亡，但人们仍然低估了儿童的这些风险。多种评估心脏代谢风险的无创技术已开始应用于儿童，包括通过超声测量颈动脉内膜中层厚度（IMT），以及通过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、无创研究。不幸的是，这些有希望的方法都没有应用于患有精神疾病的儿童高危人群，并且根本没有对儿童的心脏甘油三酯含量进行评估，从而阻碍了对风险的准确描述或降低这一弱势群体风险的干预措施的有效性。该应用的研究部分侧重于使用疾病风险的敏感早期生物标志物，包括肝脏甘油三酯含量 (HTGC)、心脏甘油三酯含量 (CTGC) 和颈动脉 IMT，分别与糖尿病和心血管疾病风险直接相关。这项两项研究计划的总体目标是使用这些敏感标记物来描述已治疗和未治疗的精神健康障碍儿童的可测量风险水平，并评估使用这些生物标记物在接受完善的行为减肥干预的儿童中可以观察到的风险变化幅度。这将通过两项研究来完成：1）对年龄、性别和体重指数（BMI）百分位数匹配的三组超重/肥胖儿童的 CTGC、HTCG 和 IMT 值进行病例对照横断面比较：接受抗精神病药物治疗的精神疾病儿童；未接受抗精神病药物治疗的精神疾病儿童和未接受治疗的无精神疾病儿童（还将包括一小部分瘦健康参与者的参考组）和 2) 一项随机对照试验，研究 12 周行为减肥干预（相对于饮食和运动教育）对超重/肥胖抗精神病药物治疗儿童的 CTGC、HTGC 和 IMT 的影响（一小部分健康超重/肥胖儿童参考组将接受积极治疗） 仅干预）。主要分析计划将分别利用方差分析和方差分析来测试一组集中的假设，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志物。 ） 公共卫生相关性：肥胖和 2 型糖尿病的儿童发病率，这两种心脏代谢风险的预测因素在近几十年来已增加到流行病的程度，并且接受抗精神病药物治疗的患有精神疾病的儿童面临肥胖、2 型糖尿病和与心血管疾病相关的早期死亡的额外风险。存在用于代谢风险的早期无创研究的技术，例如肝脏和心脏脂质含量以及颈动脉壁斑块的成像，但尚未在精神疾病儿童的高危人群中进行研究。该 K23 奖项将赞助一个具有独特资格的候选人的职业发展，该候选人通过支持一个创新研究项目，评估这些敏感的早期碳生物代谢风险生物标志物在患有精神健康障碍的儿童中的使用情况，以进一步研究患有精神健康障碍的儿童的肥胖和代谢风险。