HPA Reactivity and Diurnal Patterns Associated with Adolescent Anxiety/Depression

描述（由申请人提供）：本研究旨在系统探讨青少年焦虑、抑郁及其与下丘脑-垂体-肾上腺（HPA）功能共病的关系，并考虑环境、性别、早期生活经历和个体生物行为因素的潜在差异。研究设计和方法：本项目将特别关注HPA对急性社会心理应激源的反应性（以唾液皮质醇为指标）。本研究使用新开发的可输出青少年版的Trier社会压力测试（TSST），将区分预期期、任务期和恢复期以及在不熟悉和熟悉环境下的反应性。在12年级（大约18岁），青少年（n=96）将从威斯康星州家庭和工作研究中招募，这是一项儿童/青少年发展的纵向社区研究（n= 417）。根据9年级、10年级和11年级的平均焦虑和/或抑郁症状水平，将选择一半（n=48）为高水平焦虑和/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人将被随机分配到实验室（不熟悉的环境，n=24）或家庭（熟悉的环境，n=24）进行评估，性别平衡。HPA基础活动也将在3天内进行评估，以表征昼夜模式。对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源、青少年认知归因/偏见以及青少年心理健康症状和损伤。将获得全面的诊断性精神病学评估（K-SADS）。具体目的：(1)调查(a) HPA日模式（皮质醇的总体水平和每日斜率）与对急性心理社会应激源（TSST）的反应性的关联，区分预期、任务和恢复成分，以及(b)不同背景（陌生实验室与熟悉家庭）和性别的差异；(2)调查(a) HPA活动（如目标1所定义的昼夜活动和反应性活动）与青少年焦虑和/或抑郁的关系，以及(b)不同背景和性别的差异；(3)探讨(a)青少年早期应激暴露史、HPA日模式和气质抑制在目标1和目标2中的关联差异，以及(b)环境和性别的差异。本申请符合PAR-06-473“焦虑与抑郁关系的转化研究”的目标。它是跨学科的，解决整合生物学，神经内分泌应激反应系统与环境和个体因素的问题；它是探索性的，包括新开发的青少年版TSST，可导出到实地设置；而且，它是转化性的，将基础科学研究与青少年心理健康研究结合起来。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少年共病焦虑和抑郁的潜在病理生理学，这与开发有效的药物和其他治疗方法有关。此外，通过利用威斯康星家庭和工作研究中可用的纵向数据，拟议的项目可以研究共病焦虑/抑郁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.