Daily stress processes and sympathetic reactivity in depression

项目总结/摘要 重度抑郁症（MDD）是一个令人震惊的公共卫生挑战，在美国约10%的成年人中表现出来。 美国，并大大增加了全球疾病和残疾的负担。考虑到日益 MDD的患病率，特别是在年轻的成年人中，了解其病理生理学是至关重要的。 MDD在广泛的功能范围内的基础，以确定个性化的预防性 和治疗干预。考虑到压力和MDD之间的密切相互联系， MDD中应激系统功能障碍的潜在机制可能提供临床相关的见解， 治疗策略。这个建议的核心科学前提是MDD作为一个脆弱性因素 敏感和放大日常心理社会压力过程和急性 交感神经应激反应因此，确定交感神经血管的后果， 自然主义的日常心理社会压力暴露可能提供对压力下MDD发病机制的深入了解- 易感个体，代表MDD的新生物特征。目标1将检查每日 心理社会应激暴露对MDD急性交感神经应激反应的影响目标2将决定关系 在对日常心理社会压力暴露的负面情感反应（即，负面影响增加， 应激反应）和急性交感神经应激反应。我们的一体化多管齐下的技术 这种方法结合了对累积暴露和情绪反应的综合评估， 自然主义的日常心理社会压力源（基于门诊日记的方法）， 在急性实验室应用的情绪和 认知压力源符合研究领域标准（RDoC）框架，并确保 为了评估整个功能范围内的应激反应，我们将测试具有广泛功能的MDD成人， 症状严重程度的范围，以及健康的非抑郁症成年人。确定以下方面的职能联系： MDD中的日常应激源和交感神经反应是未来研究的必要的第一步， 检查新的靶向治疗和预防策略，以诱导情感，认知和生理 对压力的适应力，从而减轻当前的精神病，并减少对未来精神病的易感性， 脑血管和神经认知疾病。

PROJECT SUMMARY/ABSTRACT Major depressive disorder (MDD) is a staggering public health challenge, manifesting in ~10% of adults in the US and contributing substantially to the global burden of disease and disability. Considering the increasing prevalence of MDD, particularly in young adulthood, it is critical to understand the pathophysiological underpinnings of MDD across a broad spectrum of function in order to identify individually-tailored preventive and therapeutic interventions. Given the intimate reciprocal link between stress and MDD, a better understanding of the mechanisms underlying stress system dysfunction in MDD may provide clinically relevant insight into such treatment strategies. The central scientific premise of this proposal is that MDD serves as a vulnerability factor that sensitizes and amplifies the functional link between daily psychosocial stress processes and acute sympathetic stress reactivity. Accordingly, determining the sympathetic neurovascular consequences of naturalistic daily psychosocial stress exposure may provide insight into the pathogenesis of MDD in stress- susceptible individuals, representing a novel biosignature of MDD. Aim 1 will examine the effect of daily psychosocial stress exposure on acute sympathetic stress reactivity in MDD. Aim 2 will determine the relation between negative affective reactivity to daily psychosocial stress exposure (i.e., increase in negative affect in response to stress) and acute sympathetic stress reactivity in MDD. Our integrative multi-pronged technical approach combines the comprehensive assessment of cumulative exposure and emotional responsiveness to naturalistic everyday psychosocial stressors (ambulatory daily diary-based approach) with the direct measurement of sympathetic reactivity (microneurography) during acute laboratory-applied emotional and cognitive stressors. Consistent with the Research Domain Criteria (RDoC) framework and to ensure the assessment of stress reactivity across a full spectrum of function, we will test adults with MDD having a broad range of symptom severity, as well as healthy non-depressed adults. Identification of the functional link between daily stressors and sympathetic reactivity in MDD is the necessary first step for future studies designed to examine novel targeted treatment and preventative strategies to induce emotional, cognitive, and physiological resilience to stress, thereby mitigating current—and reducing susceptibility toward future—psychiatric, cerebrovascular, and neurocognitive diseases.