HPA Reactivity and Diurnal Patterns Associated with Adolescent Anxiety/Depression

描述（由申请人提供）：拟议的研究旨在系统地调查青少年焦虑，抑郁及其合并症与下丘脑-垂体-肾上腺（HPA）功能的关系，考虑背景，性别，早期生活经历和个人生物行为因素的潜在差异。研究设计和方法：该项目将特别关注HPA反应（唾液皮质醇指数）的急性心理社会应激。使用新开发的可导出的青少年版本的特里尔社会压力测试（TSST），本研究将区分反应期的预期，任务，和恢复期，在不熟悉与熟悉的情况下。在12年级（约18岁）期间，将从威斯康星州家庭和工作研究（一项儿童/青少年发育的纵向社区研究）（N=417）中招募青少年（n=96）。根据9、10和11年级的平均焦虑和/或抑郁症状水平，一半（n=48）将被选为高水平的焦虑和/或抑郁症状;另一半（n=48）将从两个分布的下半部分随机选择。每组48名受试者将被随机分配到实验室（不熟悉的环境; n=24）或家中（熟悉的环境; n=24）进行评估，性别平衡。还将在3天内评估HPA基础活性，以表征昼夜模式。与青少年及其母亲的访谈和问卷调查将确定最近的生活压力，青少年认知归因/偏见，青少年心理健康症状和障碍。将获得完整的诊断性精神病评估（K-SADS）。具体目标：（1）调查（a）HPA昼夜模式的关联（皮质醇的总体水平和每日斜率）和对急性心理社会应激源（TSST）的反应性，区分预期、任务和恢复成分，以及（B）背景差异（陌生实验室vs熟悉家庭）和性别;（2）调查（a）HPA活动与（目标1中定义的昼夜和反应性）与青少年焦虑和/或抑郁的关系，以及（B）环境和性别的差异;（3）探讨（a）青少年早期压力暴露史、HPA昼夜模式和气质抑制与目标1和目标2相关性的差异，以及（B）情境和性别差异。本申请符合PAR-06-473“焦虑和抑郁关系的转化研究”的目标。它是跨学科的，解决的问题整合生物，神经内分泌应激反应系统与上下文和个人因素;它是探索性的，包括一个新开发的青少年版本的TSST是可出口到外地设置;和，它是翻译，整合基础科学研究与青少年心理健康的研究。公共卫生相关性：通过观察下丘脑-垂体-肾上腺（HPA）功能，拟议的项目将深入了解青春期焦虑和抑郁共病的潜在病理生理学，这与开发有效的药理学和其他治疗方法有关。此外，通过利用威斯康星州家庭和工作研究中的纵向数据，拟议的项目可以研究共病焦虑/抑郁症的发展，以及早期经历和儿童特征是这些后期过程的风险因素，这对早期预防工作的发展很重要。

DESCRIPTION (provided by applicant): The proposed research aims to systematically investigate the associations of adolescent anxiety, depression, and their comorbidity with hypothalamic-pituitary-adrenal (HPA) function, considering potential differences by context, gender, early life experiences, and individual biobehavioral factors. Research design and methods: This project will focus especially on HPA reactivity (indexed by salivary cortisol) to an acute psychosocial stressor. Using a newly-developed exportable adolescent version of the Trier Social Stress Test (TSST), this study will distinguish reactivity during anticipatory, task, and recovery periods and in unfamiliar vs. familiar contexts. During Grade 12 (approximate age 18 years), adolescents (n=96) will be recruited from the Wisconsin Study of Families and Work, a longitudinal community study of child/adolescent development (N=417). Based on levels of anxiety and/or depression symptoms averaged over Grades 9, 10 and 11, half (n=48) will be selected for high levels of anxiety and/or depression symptoms; the other half (n=48) will be randomly selected from the lower half of both distributions. Each group of 48 will be randomly assigned to assessments conducted either in the laboratory (unfamiliar context; n=24) or home (familiar context; n=24), balanced for gender. HPA basal activity also will be assessed over 3 days to characterize diurnal patterns. Interviews and questionnaires with adolescents and their mothers will ascertain recent life stressors, adolescent cognitive attributions/biases, and adolescent mental health symptoms and impairments. Full diagnostic psychiatric evaluations (K-SADS) will be obtained. Specific aims: (1) to investigate (a) the associations of HPA diurnal patterns (overall levels and daily slope of cortisol) and reactivity to an acute psychosocial stressor (TSST), differentiating anticipatory, task, and recovery components, and (b) differences by context (unfamiliar laboratory vs familiar home) and gender; (2) to investigate (a) the associations of HPA activity (diurnal and reactive, as defined in Aim 1) with adolescent anxiety and/or depression, and (b) differences by context and gender; and (3) to explore (a) differences in the associations found in Aims 1 and 2 by adolescents' earlier histories of stress exposure, HPA diurnal patterns, and temperamental inhibition, and (b) differences by context and gender. This application is consistent with the goals of PAR-06-473, "Translational Research on the Relationship of Anxiety and Depression". It is interdisciplinary, addressing questions integrating biological, neuroendocrine stress-response systems with contextual and individual factors; it is exploratory, including a newly-developed adolescent version of the TSST that is exportable to field settings; and, it is translational, integrating basic science research with the study of adolescent mental health. PUBLIC HEALTH RELEVANCE: By looking at hypothalamic-pituitary-adrenal (HPA) function, the proposed project will provide insight into the underlying pathophysiology of comorbid anxiety and depression in adolescence, which has relevance for the development of effective pharmacological and other treatments. Further, by taking advantage of the longitudinal data available in the Wisconsin Study of Families and Work, the proposed project can look at the development of comorbid anxiety/depression and what early experiences and child characteristics are risk factors for these later processes, work that is important for the development of early prevention efforts.