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水平远远大于机会，并且在共病形式中比非共病形式严重得多，持久性和致残性。然而，尽管共病对于理解、预防和治疗情感痛苦至关重要，但人们对它的了解却很少。一个有前途 解释共病的起点是广泛性焦虑障碍（GAD）和重性抑郁障碍（MDD）之间的关系。证据表明，广泛性焦虑症和抑郁症共享几乎所有的遗传风险提示存在共同的过程，增加脆弱性的两种疾病的过程，这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遗传了什么，也没有人解释容易患焦虑或抑郁的人的焦虑或抑郁的存在。这个项目的主要目的是评估3种生物行为机制，这些机制被假设为导致GAD（威胁敏感性），MDD（奖励反应性）或其合并症（持续性思维）。这些候选机制将在4组GAD，MDD，共病GAD-MDD和健康对照组中进行研究，以测试机制与疾病关系的特定预测。机制将被评估“在线”，因为它们自然发生的威胁和奖励的经验，在实验室（使用实验范例）和日常生活中（使用生态瞬时评估）。三项研究将描述障碍组的机制，解决有关GAD和MDD中断形式的未解决问题，并探索他们与环境相互作用以维持情绪障碍的途径。这项工作的发现预计将为干预措施提供信息，通过以更高的精度针对常见和特定的疾病过程，有可能改善共病疾病的结局。这将是解决焦虑情绪共病及其相关负担的重要一步。

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.