An Integrative Psychobiological Investigation of Comorbid Depression and Anxiety

描述（由申请人提供）：抑郁和焦虑是所有精神疾病中最普遍的。近年来，越来越明显的是抑郁和焦虑是高度共病的。重度抑郁障碍（MDD）和社交焦虑障碍（SAD）的共病是特别有害的：与非共病个体相比，具有这种共病模式的人报告了更高水平的痛苦，更严重的回避行为，更严重的社会和职业功能障碍，以及更高的自杀风险。尽管MDD和SAD的共病率很高，但很少有研究检查这种共病的性质。例如，我们不知道共病患者与诊断上更纯的或非共病的患者有何不同。目前还不清楚共病和非共病患者的复发率是否不同，或者已经发现的预测焦虑和抑郁障碍病程的因素是否也与理解其共病有关。最重要的是，我们对与合并症相关的遗传学或心理和生物功能障碍知之甚少。结构的压力反应，压力恢复，情绪失调都有牵连，虽然分开，在了解MDD和SAD的性质，我们假设，这些结构是至关重要的，也了解这些疾病的合并症。因此，在这个项目中，我们建议检查和整合自我报告的措施，认知的措施，指标下丘脑-垂体-肾上腺轴功能，神经反应的情绪刺激和情绪调节，和基因多态性的参与者诊断为非共病MDD，非共病SAD，共病MDD/SAD，并没有精神疾病史。更具体地说，我们建议在一个单独的项目中仔细诊断共病和非共病参与者的作用：（a）定向和脱离负面刺激;（B）神经内分泌反应和恢复的心理应激;（c）神经激活模式，以响应情绪刺激;（d）的反应，并利用积极的材料，以调节负面影响;（e）神经内分泌功能的变化。和（e）5-羟色胺转运蛋白基因上的等位基因多态性。该项目的发现将为抑郁和焦虑共病的综合心理生物学理论的发展做出重要贡献，并有望阐明压力反应，神经内分泌功能，情绪调节，认知过程，遗传学和共病MDD和SAD中神经反应模式的相互作用，并确定功能障碍的关键领域作为这种衰弱状况的干预计划的目标。公共卫生相关性：抑郁和焦虑是所有精神疾病中最普遍的。近年来，越来越明显的是抑郁和焦虑是高度共病的，并且这种共病与显著的不良后果相关，包括自杀的高风险。本研究旨在探讨抑郁症与焦虑症共病时，压力反应、神经内分泌功能、情绪调节、认知过程与脑功能模式之间的相互作用。该项目的结果有望确定功能障碍的关键领域，作为这种衰弱状况的干预计划的目标。

DESCRIPTION (provided by applicant): Depression and anxiety are among the most prevalent of all psychiatric disorders. In recent years it has become increasingly apparent that depression and anxiety are highly comorbid. The comorbidity of Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD) is particularly pernicious: compared to non-comorbid individuals, persons with this pattern of comorbidity report higher levels of suffering, greater severity of avoidance behavior, greater impairment in social and occupational functioning, and higher risk of suicide. Despite the high co-occurrence of MDD and SAD, few studies have examined the nature of this comorbidity. We do not know, for example, how comorbid patients differ from their diagnostically purer, or non-comorbid, counterparts. It is also unclear whether relapse rates differ for comorbid and non-comorbid patients, or whether the factors that have been found to predict the course of anxiety and depressive disorders are also relevant for understanding their comorbidity. And most important for the purposes of this proposal, we know little about the genetics, or the psychological and biological dysfunctions that are associated with comorbidity. The constructs of stress reactivity, stress recovery, and emotion dysregulation all have been implicated, albeit separately, in understanding the nature of MDD and SAD; we postulate that these constructs are critical in also understanding the comorbidity of these disorders. Thus, in this project we propose to examine and integrate self-report measures, cognitive measures, indicators of hypothalamic-pituitary-adrenal axis functioning, neural responses to emotional stimuli and emotion regulation, and a genetic polymorphism in participants diagnosed with non-comorbid MDD, with non-comorbid SAD, with comorbid MDD/SAD, and with no history of psychiatric disorder. More specifically, we propose to examine in a single project with carefully diagnosed comorbid and non-comorbid participants the roles of: (a) orienting towards and disengaging from negative stimuli; (b) neuroendocrine responses to and recovery from a psychological stressor; (c) patterns of neural activation in response to emotional stimuli; (d) responsivity to, and utilization of, positive material to regulate negative affect; and (e) allele polymorphism on the serotonin transporter gene. Findings from this project will represent important contributions to the development of an integrative psychobiological theory of the comorbidity of depression and anxiety, and promise to elucidate the interplay of stress reactivity, neuroendocrine functioning, emotion regulation, cognitive processes, genetics, and patterns of neural reactivity in comorbid MDD and SAD, and to identify critical areas of dysfunction as targets for intervention programs for this debilitating condition. PUBLIC HEALTH RELEVANCE: Depression and anxiety are among the most prevalent of all psychiatric disorders. In recent years it has become increasingly apparent both that depression and anxiety are highly comorbid, and that this comorbidity is associated with significant adverse outcomes, including a high risk of suicide. This project is proposed to examine the interplay of stress reactivity, neuroendocrine functioning, emotion regulation, cognitive processes, and patterns of brain function in comorbid depression and anxiety. Findings from this project promise to identify critical areas of dysfunction as targets for intervention programs for this debilitating condition.