Daily stress processes and sympathetic reactivity in depression

项目摘要/摘要 严重抑郁障碍(MDD)是一个惊人的公共卫生挑战，在美国约10%的成年人中表现出来 这对美国和对全球疾病和残疾的负担都有很大贡献。考虑到不断增加的 MDD的流行，特别是在青壮年，了解其病理生理学是至关重要的 在广泛的职能范围内建立MDD基础，以确定个性化的预防措施 和治疗性干预。鉴于压力和MDD之间的密切相互联系，更好地理解 MDD应激系统功能障碍的潜在机制可能为临床提供相关的洞察力 治疗策略。这一提议的中心科学前提是MDD是一个脆弱性因素 这敏感并放大了日常心理社会应激过程和急性发作之间的功能联系 交感神经应激反应。因此，确定交感神经血管后果 自然主义的日常心理社会应激暴露可能有助于深入了解MDD在应激状态下的发病机制。 易感个体，代表MDD的一种新的生物特征。目标1将检查每日的效果 心理社会应激暴露对MDD患者急性交感应激反应的影响。目标2将决定这一关系 负性情感反应与日常心理社会压力暴露之间(即，负性情感的增加 应激反应)和MDD的急性交感应激反应。我们的综合多管齐下的技术 方法结合了对累积暴露和情绪反应的全面评估，以 自然主义的日常心理社会压力源(基于日记本的方法) 急性情绪和精神障碍时交感神经反应性(显微神经学)的测量 认知压力源。符合研究领域标准(RDoC)框架，并确保 评估所有功能的应激反应，我们将测试患有MDD的成年人是否有广泛的 症状严重程度的范围，以及健康的非抑郁症成年人。确定两者之间的功能链接 MDD患者的日常应激源和交感反应性是未来研究的必要第一步 检查新的靶向治疗和预防策略，以诱导情绪、认知和生理 对压力的恢复力，从而缓解当前-并降低对未来-精神疾病的敏感性， 脑血管疾病和神经认知疾病。

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.