Chronic Inflammation as a Pathway to Cognitive Dysfunction in Adolescents and Young Adults with a History of Elevated Depressive Symptoms

项目摘要/摘要 抑郁障碍是一种非常普遍的、反复发作的、使人衰弱的疾病，通常首先发生在 青春期。事实上，在精神病患者中，超过40%的人因健康不佳、残疾或过早死亡而死亡 物质使用障碍可归因于抑郁症。有确凿的证据表明抑郁 个人在认知功能(例如，记忆、执行功能)方面存在缺陷，当 抑郁症正在缓解。值得注意的是，认知缺陷与脑功能障碍直接相关。 目前和缓解的抑郁症。理论和大量的经验证据表明，慢性炎症 可能是抑郁症患者认知功能障碍的基础。慢性炎症与一种已知的危险因素有关 对于抑郁症(应激性生活事件)，并预测内科、老年人和健康成年人的认知功能障碍 样本。重要的是，抑郁症的认知功能障碍也与慢性炎症直接相关。 然而，尚不清楚慢性炎症是否预示着持续性认知功能障碍。 高度抑郁的情况有所缓解。本提案旨在评估(I)是否有升高的历史 青少年/年轻人的抑郁症状预示着慢性病患者的认知表现较差 炎症和(Ii)抑郁症状升高的病史是否调节了 慢性炎症患者的应激事件和认知功能障碍。拟议的研究将招募 来自226名符合条件的参与者中的100人参加了由NIMH资助的持续R01 青少年抑郁症的纵向研究。符合资格的参与者至少完成了两项评估 外周炎症生物标志物并且没有相关的医学疾病(例如，自身免疫性疾病)， [创伤性脑损伤或目前的抑郁症诊断]。慢性炎症将被定义为 超过全身性外周炎症(C-反应蛋白)的可靠生物标志物的既定界限 在两个或两个以上的场合。抑郁症将使用抑郁症的个人水平轨迹进行操作 症状。参与者将完成两个小时的评估，其中包括对General 认知功能和认知功能的特定领域(例如，情景记忆、执行 功能)。因此，根据NIMH战略目标2.2，本研究建议评估这一关系 炎症、压力、抑郁症状和认知功能障碍之间的关系。这项研究有可能 更好地描述抑郁症的病因，并为抑郁症的一个特征确定干预目标 与严重的功能障碍有关。已经设计了一项培训计划，该计划包括正式的 课堂作业、工作坊、体验式学习和导师指导，以发展申请人在 情绪障碍的病因学、心理神经免疫学、神经心理学评估和纵向数据 分析。这项拟议的研究将在坦普尔大学的临床心理学项目中进行，该项目有一个 开展有影响力的NIMH资助的研究和培训研究科学家的成功记录。

PROJECT SUMMARY/ABSTRACT Depressive disorders are highly prevalent, recurrent, and debilitating conditions that typically first occur in adolescence. In fact, over 40% of days lost to ill-health, disability, or premature death among mental and substance use disorders are attributable to depression. There is substantial evidence that depressed individuals experience deficits in cognitive functioning (e.g., memory, executive functioning) that persist when depression is in remission. Significantly, cognitive deficits are directly associated with functional impairment in current and remitted depression. Theory and substantial empirical evidence suggest that chronic inflammation may underlie cognitive dysfunction in depression. Chronic inflammation is associated with a known risk factor for depression (stressful life events) and predicts cognitive dysfunction in medical, elderly, and healthy adult samples. Importantly, cognitive dysfunction in depression also has been directly linked to chronic inflammation. However, it is unknown whether chronic inflammation is predictive of persistent cognitive dysfunction when high levels of depression have abated. This proposal seeks to evaluate (i) whether a history of elevated depressive symptoms in adolescents/young adults predicts worse cognitive performance for those with chronic inflammation and (ii) whether a history of elevated depressive symptoms mediates the relationship between stressful events and cognitive dysfunction for those with chronic inflammation. The proposed study will recruit 100 individuals from a pool of 226 eligible participants who are taking part in an ongoing, NIMH funded R01 longitudinal study of adolescent depression. Eligible participants have completed at least two assessments of peripheral inflammatory biomarkers and have no pertinent medical disorders (e.g. autoimmune disorder), [traumatic brain injury or current depression diagnosis]. Chronic inflammation will be defined as individuals that exceed an established cut-off of a reliable biomarker of systemic, peripheral inflammation (C-reactive protein) on two or more occasions. Depression will be operationalized using person-level trajectories of depressive symptoms. Participants will complete a two-hour assessment that includes an evaluation of generalized cognitive functioning and specific domains of cognitive functioning (e.g., episodic memory, executive functioning). Thus, in line with NIMH Strategic Objective 2.2, this study proposes evaluating the relationship between inflammation, stress, depressive symptoms, and cognitive dysfunction. This study has the potential to better characterize the etiology of depression and identify intervention targets for a feature of depression that is associated with substantial functional impairment. A training plan has been designed that consists of formal classwork, workshops, experiential learning, and mentorship, to develop the applicant's expertise in the etiology of mood disorders, psychoneuroimmunology, neuropsychological assessment, and longitudinal data analysis. The proposed study will take place in Temple University's clinical psychology program, which has a successful track record of conducting impactful NIMH-funded research and training research scientists.