Risk for Adolescent Depression: Stress, Cognitive Vulnerability, & Inflammation

描述（由申请人提供）：抑郁症状和诊断率在15-18岁之间显着上升。尽管具有科学和公共卫生意义，但青少年抑郁症激增的机制尚未完全了解。认知脆弱性-压力模型对我们理解青春期抑郁症发病率增加做出了重要贡献;然而，这些模型并不能充分解释一些躯体症状或纳入认知脆弱性引起抑郁症的生物应激机制。另一个关于抑郁症免疫相关性的令人兴奋的研究机构强调了促炎通路的作用;然而，只有一些抑郁症患者表现出炎症。这个项目提供了一个新颖的和令人信服的整合认知脆弱性-压力框架和抑郁症的促炎模型应用于青春期。这项研究有可能解决这两种模型在单独考虑时所面临的难题和局限性。这些发现可能有助于解释抑郁症状的全部范围，并确定认知脆弱的个体特别可能表现出细胞因子失调和对压力事件反应性增加的迹象。此外，众所周知，儿童早期的逆境有助于认知脆弱性和促炎偏见的发展。主要目标是确定炎症状态与认知脆弱性，压力和童年逆境相结合的作用，作为青少年抑郁症上升的基础。一项多波、为期4年的前瞻性研究将在现有的、特征良好的300名青少年社区样本中进行，其中包括相似数量的男性和女性、高加索人和非洲裔美国人，这些青少年刚刚达到抑郁症开始急剧上升的临界年龄。我们将每年进行一次抽血，以评估促炎性和调节性细胞因子（7种细胞因子的多细胞因子阵列）和C反应蛋白（CRP），同时每6个月进行一次生活压力、抑郁和焦虑症状的持续评估。认知脆弱性和抑郁症和焦虑症的诊断将每年获得，沿着在这个独特的城市青少年队列的童年逆境的历史。我们还将检查白细胞介素-6（IL- 6）对急性应激源的反应性（特里尔社会应激试验），以确定个体差异如何影响IL-6的表达。 认知反应性转化为增加的IL-6释放。这个项目填补了一个关键的知识 关于青春期免疫力正常发展及其在青少年抑郁症急剧上升中的作用的差距。它可能会导致新的干预抑郁症的目标认知影响细胞因子对压力的反应，以及细胞因子的药理学操作，以解决症状，如疲劳，快感缺乏，和退出。

DESCRIPTION (provided by applicant): Rates of depressive symptoms and diagnoses rise markedly between ages 15-18. Despite the scientific and public health significance, the mechanisms responsible for the adolescent surge in depression are not fully understood. Cognitive vulnerability - stress models have contributed importantly to our understanding of the increased incidence of depression in adolescence; however, these models do not adequately explain some of the somatic symptoms or incorporate biological stress mechanisms through which cognitive vulnerability evokes depression. A separate exciting body of research on immune correlates of depression has highlighted the role of proinflammatory pathways; yet, only some depressed individuals exhibit inflammation. This project provides a novel and compelling integration of the cognitive vulnerability - stress framework and the proinflammatory model of depression as applied to adolescence. The research has the potential to solve puzzles and limitations faced by both models when considered separately. The findings may help to account for the full spectrum of depressive symptoms and identify cognitively vulnerable individuals as especially likely to evince signs of cytokine dysregulation and increased reactivity to stressful events. Moreover, it is known that early childhood adversity contributes to both the development of cognitive vulnerability and a proinflammatory bias. The primary goal is to determine the role of inflammatory states in combination with cognitive vulnerabilities, stress, and childhood adversity as contributors that underlie the rise in adolescent depression. A multiwave, 4-year prospective study will be conducted with an existing, well-characterized community sample of 300 adolescents, including similar numbers of males and females and Caucasians and African-Americans, just reaching the critical age when the dramatic rise in depression begins. We will conduct yearly blood draws to assess proinflammatory and regulatory cytokines (a multicytokine array of 7 cytokines) and C-reactive protein (CRP), in parallel with ongoing assessments of life stress and depression and anxiety symptoms every 6 months. Cognitive vulnerabilities and depression and anxiety diagnoses will be obtained yearly, along with a history of childhood adversity in this unique cohort of urban adolescents. We also will examine interleukin-6 (IL- 6) reactivity to an acute stressor (Trier Social Stress Test) to determine how individual variation in cognitive reactivity translates into increased IL-6 release. This project fills a crucial knowledge gap about normal development of immunity in adolescence and its role in the dramatic rise in adolescent depression. It may lead to novel interventions for depression that target cognitive influences on cytokine responses to stress, as well as pharmacological manipulations of cytokines to address symptoms such as fatigue, anhedonia, and withdrawal.