An Integrative Psychobiological Investigation of Comorbid Depression and Anxiety

共病抑郁和焦虑的综合心理生物学调查

• 批准号: 7432762
• 负责人: IAN H GOTLIB
• 金额: $ 22.52万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7432762
• 关键词: Acute; Adolescence; Affect; Affective; Alleles; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Attention; Biological; Brain; Cognitive; Comorbidity; Condition; Cues; Depressive disorder; Development; Diagnosis; Disease; Dorsal; Emotional; Emotions; Etiology; Exhibits; Facial Expression; Functional disorder; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Processes; Genotype; Hydrocortisone; Impairment; Individual; Individual Differences; Investigation; Laboratories; Lead; Maintenance; Major Depressive Disorder; Measures; Medial; Memory; Mental Depression; Mental disorders; Moods; Nature; Neurophysiology - biologic function; Neurosecretory Systems; Occupational; Outcome; Participant; Patient Self-Report; Patients; Pattern; Persons; Process; Public Health; Purpose; Rate; Recording of previous events; Recovery; Regulation; Relapse; Reporting; Risk Factors; Role; Salivary; Severities; Stimulus; Stress; Stressful Event; Structure; Symptoms; Variant; Ventral Striatum; avoidance behavior; emotion regulation; emotional stimulus; experience; hypothalamic-pituitary-adrenal axis; intervention program; negative mood; neuroimaging; psychobiologic; psychologic; psychological stressor; relating to nervous system; response; reward circuitry; serotonin transporter; social; stimulus processing; stressor; suicidal risk; theories

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.

描述（由申请人提供）：抑郁和焦虑是所有精神疾病中最常见的。近年来，越来越明显的是，抑郁症和焦虑症高度共存。重度抑郁症（MDD）和社交焦虑症（SAD）的合并症尤其有害：与非合并症患者相比，患有这种合并症的人遭受的痛苦程度更高，回避行为更严重，社交和职业功能受损更大，自杀风险更高。尽管 MDD 和 SAD 的共存率很高，但很少有研究探讨这种合并症的性质。例如，我们不知道共病患者与诊断上更纯粹或无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，或者已发现的预测焦虑和抑郁症病程的因素是否也与了解其共病相关。就本提案而言，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。压力反应性、压力恢复和情绪失调的结构都与理解 MDD 和 SAD 的本质有关，尽管它们是分开的。我们假设这些结构对于理解这些疾病的共病也至关重要。因此，在这个项目中，我们建议检查和整合被诊断患有非共病MDD、非共病SAD、共病MDD/SAD以及无精神疾病史的参与者的自我报告测量、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遗传多态性。更具体地说，我们建议在一个项目中检查仔细诊断的共病和非共病参与者的作用：（a）定向和摆脱负面刺激； (b) 神经内分泌对心理压力源的反应和恢复； (c) 响应情绪刺激的神经激活模式； (d) 对积极材料的反应和利用来调节消极影响； (e) 血清素转运蛋白基因的等位基因多态性。该项目的研究结果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MDD和SAD共病中压力反应、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之间的相互作用，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常见的。近年来，越来越明显的是，抑郁和焦虑是高度共存的，并且这种共存与严重的不良后果相关，包括高自杀风险。该项目旨在研究抑郁和焦虑共病中应激反应、神经内分泌功能、情绪调节、认知过程和大脑功能模式之间的相互作用。该项目的研究结果有望确定功能障碍的关键领域，作为针对这种衰弱状况的干预计划的目标。