Mechanisms of Comorbidity and Specificity for Generalized Anxiety and Depression

描述(由申请人提供)：焦虑和情绪障碍共同发生的程度远远大于偶然性，并且在共病中比非共病形式更严重、更持久和更致残。然而，尽管共病对于理解、预防和治疗情绪痛苦是至关重要的，但人们对其了解很少。一个有希望的人 解释共病的起点是广泛性焦虑症(GAD)和严重抑郁障碍(MDD)之间的关系。GAD和MDD几乎所有遗传风险的证据表明，存在增加这两种疾病易感性的共同过程--这一过程可能是研究和治疗的有力目标。然而，还没有人试图确定这些疾病的风险人群到底遗传了什么，也没有人试图确定同时患有这两种疾病的人存在焦虑或抑郁的原因。这个项目的中心目标是评估三种生物行为机制，它们被假设为有助于GAD(威胁敏感性)、MDD(奖励反应)或它们的共病(持之以恒的思维)。这些候选机制将在4组中进行研究-GAD、MDD、共病GAD-MDD和健康对照组-允许对机制与疾病的关系进行具体预测。将对机制进行“在线”评估，因为它们是在实验室(使用实验范例)和日常生活(使用生态学瞬时评估)对威胁和奖励经验作出反应时自然发生的。三项研究将描述障碍群体的机制，解决关于它们在GAD和MDD中的破坏形式的悬而未决的问题，并探索它们与环境相互作用以维持情绪障碍的途径。这项工作的发现有望告知干预措施，通过更精确地针对常见和特定于障碍的过程，有可能改善共病障碍的结果。这将代表着在解决焦虑-情绪共病及其相关负担方面向前迈出的重要一步。

DESCRIPTION (provided by applicant): Anxiety and mood disorders co-occur at levels far greater than chance and are considerably more severe, persistent, and disabling in the comorbid than the noncomorbid form. However, although comorbidity is vitally important for efforts to understand, prevent, and treat emotional suffering, it is poorly understood. A promising starting point for explaining comorbidity is the relationship between generalized anxiety disorder (GAD) and major depressive disorder (MDD). Evidence that GAD and MDD share nearly all of their genetic risk hints at the existence of common processes that increase vulnerability for both disorders-processes which may represent potent targets for research and treatment. However, no one has yet attempted to determine just what is inherited by persons at risk for these disorders, nor what accounts for the presence of anxiety or depression in persons vulnerable to both. The central aim of this project is to evaluate 3 biobehavioral mechanisms that are hypothesized to contribute to GAD (threat sensitivity), MDD (reward responsiveness), or their comorbidity (perseverative thought). These candidate mechanisms will be studied in 4 groups-GAD, MDD, comorbid GAD-MDD, and healthy controls-that allow specific predictions to be tested about the relations of mechanisms to disorders. Mechanisms will be assessed "on-line" as they occur naturally in response to threat and reward experiences in the laboratory (using experimental paradigms) and in daily life (using ecological momentary assessment). Three studies will characterize the mechanisms in the disorder groups, address unresolved questions about the form of their disruption in GAD and MDD, and explore pathways through which they interact with the environment to maintain emotional disturbance. Discoveries resulting from this work are expected to inform interventions that, by targeting common as well as disorder-specific processes with increased precision, have the potential to improve outcomes for comorbid disorders. This would represent a significant step forward in addressing anxiety-mood comorbidity and its associated burden.