An Integrative Psychobiological Investigation of Comorbid Depression and Anxiety

描述(由申请人提供)：抑郁症和焦虑症是所有精神疾病中最常见的。近年来，抑郁和焦虑高度并存的现象变得越来越明显。严重抑郁障碍(MDD)和社交焦虑障碍(SAD)的共病尤其有害：与非共病个体相比，患有这种共病模式的人报告的痛苦程度更高，回避行为更严重，社会和职业功能受损更大，自杀风险更高。尽管MDD和SAD的发生率很高，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为更纯粹或非共病的患者有何不同。目前也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过程的因素是否也与理解他们的共病有关。最重要的是，对于这项建议的目的，我们对与共病相关的遗传学或心理和生物功能障碍知之甚少。应激反应、应激恢复和情绪失调的结构都与理解MDD和SAD的本质有关，尽管是分开的；我们假设这些结构对于理解这些障碍的共病也是关键的。因此，在这个项目中，我们建议检查和整合自我报告测量、认知测量、下丘脑-垂体-肾上腺轴功能指标、对情绪刺激和情绪调节的神经反应，以及被诊断为非共病MDD、非共病SAD、共病MDD/SAD和无精神障碍病史的参与者的基因多态。更具体地说，我们建议在一个有仔细诊断的共病和非共生参与者的单一项目中检查：(A)定向和脱离负面刺激；(B)对心理应激源的神经内分泌反应和恢复；(C)对情绪刺激的神经激活模式；(D)对积极材料的反应性和对调节负面情绪的利用；以及(E)5-羟色胺转运体基因的等位基因多态。该项目的发现将对发展抑郁和焦虑共病的综合心理生物学理论做出重要贡献，并有望阐明应激反应、神经内分泌功能、情绪调节、认知过程、遗传学和神经反应模式在MDD和SAD共病中的相互作用，并确定关键的功能障碍区域作为这种衰弱疾病干预计划的目标。公共卫生相关性：抑郁症和焦虑症是所有精神疾病中最普遍的两种。近年来，越来越明显的是，抑郁症和焦虑症高度并存，这种共病与严重的不良后果有关，包括自杀的高风险。该项目旨在研究应激反应、神经内分泌功能、情绪调节、认知过程和大脑功能模式在抑郁和焦虑共病中的相互作用。这一项目的发现有望确定关键的功能障碍区域作为这种衰弱疾病干预计划的目标。

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.