Depression and Insulin Resistance in Adolescents

描述(申请人提供)：2型糖尿病(T2D)是一种慢性疾病，伴有严重健康并发症的高风险，如心血管和外周血管疾病、中风、失明和肾功能衰竭。T2D在青少年和年轻人中的表现令人震惊地上升，给公共卫生带来了巨大的负担。胰岛素抵抗(IR)是T2D的主要生理前兆。因此，针对IR的可改变危险因素的预防工作有可能显著降低发生T2D的风险。抑郁症状通常首先出现在青春期，与青少年和成人的胰岛素抵抗相关，预测成人发病的T2D，并导致T2D死亡和发病率的增加，超出了抑郁症与肥胖的相互关系。抑郁症状和胰岛素抵抗之间联系的潜在机制尚不清楚。从理论上讲，抑郁症状通过促进应激诱导的行为(改变饮食、降低体能)和上调生理应激机制(皮质醇、神经肽Y)来诱发胰岛素抵抗。抑郁症的心理治疗改善了成人的胰岛素抵抗，但改善抑郁症状是否能阻止有T2D风险的青少年胰岛素抵抗的进展尚不确定。这项建议的目的是：1)评估6周认知行为(CB)抑郁症预防组与6周标准护理健康教育(HE)组在减轻抑郁症状和改善IR方面的效果；2)评估与压力相关的行为和生理因素，调节抑郁症状的减少和IR的改善；以及3)试点向T2D风险少女提供基于正念的压力减轻(MBSR)组。这位名叫Lauren Shomaker的儿童心理学家是一位儿童临床心理学家，他在青少年发展/精神病理学、饮食行为和儿童肥胖/肥胖相关健康并存方面的背景非常适合推进本提案中的目标。在K99阶段，Shomaker博士将接受培训，以增强她在以下方面的专业知识：1)在青少年中进行随机对照试验(RCT)，ii)IR测量，以及iii)心血管健康评估。Shomaker博士组建了一支强大的导师和顾问团队，他们在以下领域拥有专长：儿童肥胖和胰岛素抵抗随机对照试验(共同导师：Marian Tanofsy-Kraff，PhD，Jack Yanovski，MD，PhD)，CB抑郁干预(Eric Stices，PhD，Marjan Holloway，PhD)，心血管健身(Kong Chen，PhD)，压力生理学(Zofia Zukowska，MD，PhD)，高级统计分析(Cara Olsen，PhD)和MBSR(Kirk Brown，PhD)。拟议的K99/R00应用程序是促进Shomaker博士过渡到独立职业生涯的最终目标的理想工具，该目标专注于青少年心理社会发展和身体健康之间的相互联系，以及心理社会因素和身体健康之间联系的潜在机制。 公共卫生相关性：2型糖尿病(T2D)是我国最常见的慢性病之一。它影响了美国7.8%的人口，每年的社会成本为900亿美元。在过去，T2D被认为是一种仅限于老年人的疾病。然而，它在青少年和年轻人中的表现出现了令人震惊的上升。早发的T2D与终末期肾病和死亡的风险更高，预期寿命更短，为15-27岁。胰岛素抵抗(IR)是T2D的主要生理前兆。以青春期为特征的IR的正常上升可能使青春期处于敏感期，在有T2D风险的青少年中触发IR恶化的进展。青春期也是女孩抑郁症状加重的高峰期。超过25%的青少年抑郁症状加重。即使在缺乏严重抑郁障碍(MDD)的完整标准的情况下，青少年的抑郁症状也与相当大的心理社会和行为障碍相关，患MDD的风险要高出2-4倍。在青少年和成人中，抑郁症状也与胰岛素抵抗相关，并预测T2D的发病。因此，改善有T2D风险的青春期女孩抑郁症状的升高有可能改善相当一部分年轻人的IR和T2D风险。

DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) is a chronic disease accompanied by heightened risk for severe health complications such as cardiovascular and peripheral vascular disease, stroke, blindness, and renal failure. The alarming rise in the manifestation of T2D among adolescents and young adults poses an enormous public health burden. Insulin resistance (IR) is a major physiological precursor to T2D. Thus, prevention efforts targeting modifiable risk factors for IR have the potential to diminish the risk of developing T2D significantly. Depressive symptoms often first appear during adolescence, are associated with IR in adolescents and adults, predict adult-onset T2D, and contribute to increased risk for T2D mortality and morbidity, beyond the interrelationship of depression with obesity. The mechanisms underlying the link between depressive symptoms and IR are unclear. Depressive symptoms theoretically induce IR by promoting stress-induced behaviors (altered eating, lowered fitness) and up regulating physiological stress mechanisms (cortisol, neuropeptide Y). Psychotherapy for depression improves IR in adults, but it is uncertain whether ameliorating depressive symptoms prevent progression of IR in adolescents at risk for T2D. The aims of this proposal are: 1) to assess the effects of a 6-wk cognitive-behavioral (CB) depression prevention group vs. a 6-wk standard-of-care health education (HE) group on reducing depressive symptoms and improving IR in adolescent girls at risk for T2D; 2) to assess the stress-related behavioral and physiological factors that mediate the relationship underlying decreases in depressive symptoms and improvements in IR; and 3) to pilot delivery of a mindfulness-based stress reduction (MBSR) group to adolescents girls at risk for T2D. The PI, Dr. Lauren Shomaker, is a child clinical psychologist whose background in adolescent development/psychopathology, eating behavior, and pediatric obesity/obesity related health co-morbidities is uniquely suited to advance the aims in this proposal. During the K99 phase, Dr. Shomaker will obtain training to enhance her expertise in: 1) conduct of randomized controlled trials (RCTs) in adolescents, ii) measurement of IR, and iii) assessment of cardiovascular fitness. Dr. Shomaker has assembled a strong mentoring and consultant team with expertise in RCTs for pediatric obesity and IR (Co- Mentors: Marian Tanofsy-Kraff, PhD, Jack Yanovski, MD, PhD), CB depression interventions (Eric Stice, PhD, Marjan Holloway, PhD), cardiovascular fitness (Kong Chen, PhD), stress physiology (Zofia Zukowska, MD, PhD), advanced statistical analysis (Cara Olsen, PhD), and MBSR (Kirk Brown, PhD). The proposed K99/R00 application is the ideal vehicle to promote Dr. Shomaker's ultimate goal of transitioning to an independent career focused upon the interconnections between adolescent psychosocial development and physical health, and the putative mechanisms underlying the links between psychosocial factors and physical well-being. PUBLIC HEALTH RELEVANCE: Type 2 diabetes (T2D) is one of our nation's most common chronic diseases. It affects >7.8% of the U.S., and the societal cost is >$90 billion/yr. In the past, T2D was considered a disease limited to older adults. Yet, there has been an alarming rise in its manifestation among adolescents and young adults. Early onset T2D has been associated with greater risk of end-stage renal disease and death and a shorter life expectancy of 15-27 yrs. Insulin resistance (IR) is a major physiological precursor to T2D. The normative rise in IR that characterizes puberty may render adolescence a sensitive period, triggering the progression of worsening IR among adolescents at risk for T2D. Adolescence also marks a peak period for the onset of elevated depressive symptoms among girls. Elevated depressive symptoms affect over 25% of adolescents. Even in the absence of full criteria for major depressive disorder (MDD), adolescent depressive symptoms are associated with considerable psychosocial and behavioral impairment and a 2-4-fold greater risk of developing MDD. Depressive symptoms also are associated with IR in adolescents and adults and predict T2D onset. Therefore, amelioration of elevated depressive symptoms in adolescent girls who are at risk for T2D has the potential to improve IR and risk for T2D in a considerable subset of youth.