Short and long term depressive symptoms and arrhythmic pathways to stroke

描述（由申请人提供）：新出现的证据表明，抑郁症状升高可预测中风发作。然而，目前尚不清楚这种关系是否有因果关系，如果有因果关系，这种影响是否会因抑郁症状的持续时间或强度而改变。此外，尽管进行了大量的研究，我们仍无法确定抑郁症和中风之间的联系机制。解决这些研究问题对于告知抑郁症状的临床管理至关重要。它也有助于阐明生理或行为机制调解抑郁症和中风之间的联系，以确定其他干预机会。先前的研究表明，抑郁或抑郁症状可能通过几种途径影响中风，包括健康行为（如吸烟、体育活动）或生理过程失调（如心功能的自主调节、炎症反应）。这些机制中的许多将在长期的时间尺度上运作，病理生理（如动脉粥样硬化）积累多年。如果只有长期机制将抑郁和中风联系起来，那么对抑郁症状的治疗就不能立即降低中风的风险；相反，益处将在多年成功的症状管理中发展。然而，如果因果机制在短期内发挥作用，一些假设机制的中断可能会在抑郁症状消退后通过降低中风风险而获得几乎立竿见影的好处。此外，目前尚不清楚抗抑郁药物是否会影响中风的风险。健康行为和炎症反应的研究尚未最终确定这些因素是否完全介导抑郁和中风之间的关系。虽然之前没有研究评估房颤（AF）是否介导抑郁和中风之间的关系，但越来越多的研究正在研究情绪对房颤的影响。作为最常见的心律失常和卒中的已知危险因素，我们将研究房颤作为可能的中介的作用。我们建议使用两个互补的纵向研究，健康与退休研究（HRS）和心血管健康研究（CHS）的数据来检验两个目标。该建议的第一个目的是确定哪些特征（如持续时间和严重程度）的抑郁症状最好地预测所有类型的中风在美国中老年人的首次发病率。我们的第二个目的是检查心房颤动作为抑郁症状和缺血性中风发作之间的关联的部分中介。识别抑郁症状的特征，预测中风和潜在的病因，可以帮助卫生从业人员和识别患者更大的中风风险。确定心房颤动是否是抑郁症和中风之间关系的中介因素具有重要的临床意义，因为它可以为高危患者的治疗计划提供信息。

DESCRIPTION (provided by applicant): Emerging evidence suggests that elevated depressive symptoms predict stroke onset. However, it remains unclear whether this relationship is causal and, if so, whether the effects are modified by the duration or intensity of depressive symptoms. Furthermore, despite substantial research, we have not been able to establish the mechanisms linking depression and stroke. Addressing these research questions is critical to inform clinical management of depressive symptoms. It also is useful in elucidating the physiological or behavioral mechanisms mediating the link between depression and stroke to identify other opportunities for intervention. Previous research suggests several possible pathways via which depression or depressive symptoms could influence stroke, including health behaviors (e.g. smoking, physical activity) or dysregulation of physiologic processes (e.g. autonomic regulation of cardiac function, inflammatory responses). Many of these mechanisms would operate over a long term time-scale, with pathophysiology (e.g. atherosclerosis) accumulating over years. If only long-term mechanisms link depression and stroke, treatment of depressive symptoms would not be expected to reduce stroke risk immediately; benefits would instead develop over years of successful symptom management. However, if causal mechanisms exert their effects in the short term, interruption of some hypothesized mechanisms might allow nearly immediate benefits by reducing stroke risk after resolution of depressive symptoms. Furthermore, it remains unclear if antidepressant medication affects the risk of stroke. The research on health behaviors and inflammation response has not conclusively established whether these factors fully mediate the relationship between depression and stroke. While no prior research has assessed whether atrial fibrillation (AF) mediates the relationship between depression and stroke, a growing number of studies are examining the impact of mood on AF. As the most common cardiac arrhythmia and a well-known risk factor of stroke, we will examine AF's role as a possible mediator. We propose using data from two complementary longitudinal studies, the Health and Retirement Study (HRS) and the Cardiovascular Health Study (CHS), to examine two aims. The first aim of this proposal is to determine what characteristics (e.g. duration and severity) of depressive symptoms best predict first incidence of all stroke types among middle aged and elderly individuals in the United States. Our second aim is to examine atrial fibrillation as a partial mediator of the association between depressive symptoms and onset of ischemic stroke. The identification of characteristics of depressive symptoms that predict stroke and the underlying etiology can help health practitioners and identify patients at greater risk for stroke. Indentifying whether atrial fibrillation is a mediating factor in the relationship between depression and stroke is clinically important as it may inform treatment plans of at risk patients.