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卒中发作。然而，目前尚不清楚这种关系是否是因果关系，如果是这样，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，尽管有大量的研究，我们还没有能够建立联系抑郁症和中风的机制。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。它还有助于阐明介导抑郁症和中风之间联系的生理或行为机制，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影响中风的几种可能途径，包括健康行为（例如吸烟，体育活动）或生理过程失调（例如心脏功能的自主调节，炎症反应）。这些机制中的许多将在长期时间尺度上起作用，病理生理学（例如动脉粥样硬化）多年积累。如果只有长期机制将抑郁症和中风联系起来，那么抑郁症状的治疗不会立即降低中风风险;相反，经过多年的成功症状管理，益处会逐渐显现。然而，如果因果机制在短期内发挥作用，中断一些假设的机制可能会通过降低抑郁症状消退后的中风风险而带来几乎立即的益处。此外，目前尚不清楚抗抑郁药物是否会影响中风的风险。关于健康行为和炎症反应的研究还没有最终确定这些因素是否完全介导抑郁症和中风之间的关系。虽然没有先前的研究已经评估是否心房颤动（AF）介导抑郁症和中风之间的关系，越来越多的研究正在研究情绪对AF的影响。作为最常见的心律失常和众所周知的中风危险因素，我们将研究AF作为一个可能的调解人的作用。 我们建议使用两个互补的纵向研究，健康和退休研究（HRS）和心血管健康研究（CHS）的数据，以检查两个目标。该提案的第一个目的是确定抑郁症状的哪些特征（例如持续时间和严重程度）最能预测美国中年和老年人中所有卒中类型的首次发病率。我们的第二个目的是研究房颤作为抑郁症状和缺血性卒中发病之间相关性的部分介导因素。识别抑郁症状的特征，预测中风和潜在的病因，可以帮助健康从业者和识别患者中风的风险更大。确定房颤是否是抑郁症和卒中之间关系的中介因素在临床上很重要，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.