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

描述（由申请人提供）：抑郁症状和诊断的比率在15-18岁之间显著上升。尽管在科学和公共卫生方面具有重要意义，但导致青少年抑郁症激增的机制尚不完全清楚。认知脆弱性-压力模型对我们理解青少年抑郁症发病率的增加做出了重要贡献；然而，这些模型不能充分解释一些躯体症状或纳入生物应激机制，通过认知脆弱性引起抑郁。另一项令人兴奋的关于抑郁症免疫相关因素的研究强调了促炎途径的作用；然而，只有一些抑郁的人表现出炎症。这个项目提供了一个新的和引人注目的整合认知脆弱性-压力框架和抑郁症的促炎模型，适用于青少年。这项研究有可能解决两种模型在单独考虑时面临的难题和局限性。这一发现可能有助于解释抑郁症的所有症状，并识别出认知脆弱的个体，因为这些个体特别可能表现出细胞因子失调的迹象，对压力事件的反应性增加。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，这些因素是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300名青少年中进行，其中包括数量相近的男性和女性、高加索人和非裔美国人，这些青少年刚刚达到抑郁开始急剧上升的关键年龄。我们将每年抽血评估促炎和调节细胞因子（由7种细胞因子组成的多细胞因子阵列）和c反应蛋白（CRP），同时每6个月持续评估生活压力、抑郁和焦虑症状。每年都会获得认知脆弱性、抑郁和焦虑的诊断，以及这一独特的城市青少年群体的童年逆境史。我们还将检查白细胞介素-6 （IL- 6）对急性应激源的反应（特里尔社会压力测试），以确定个体差异如何

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.