PSYCHOBIOLOGICAL CORRELATES OF RECOVERY IN DEPRESSION

抑郁症康复的心理生物学相关性

• 批准号: 2245303
• 负责人: MICHAEL E THASE
• 金额: $ 18.29万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2245303
• 关键词: clinical depression; clinical trials; cognitive behavior therapy; electroencephalography; fluoxetine; human subject; human therapy evaluation; hypothalamic pituitary axis; mental disorder chemotherapy; mental disorder diagnosis; pituitary adrenal axis; psychobiology; sleep disorders

Our research over the past 5 years has addressed two interrelated aims: 1) to characterize the psychobiologic correlates of response to cognitive behavior therapy (CBT); and 2) to clarify the state dependence (i.e., reversibility) or state independence (i.e., irreversibility) of selected neurobiologic disturbances across the course of the illness. We have found that clinical severity, an abnormal EEG sleep profile, and increased hypothalamic-pituitary-adrenocortical (HPA) activity are associated with poorer response to CBT. Further, remitted patients showed only partial normalization of these presumably state-dependent abnormalities. These findings suggest that some unipolar depressions are characterized by a level of psychobiological disturbance that requires somatic treatment in order to correct or control dysregulated CNS processes. We now propose to extend this work in a controlled study of 150 depressed outpatients randomly assigned to CBT or double-blind treatment with either fluoxetine (FLX) or placebo (PBO). Patients will be assessed with a comprehensive psychobiological battery after 14-days of single-blind PBO "washout" (T1). Only persistently depressed patients manifesting a prespecified level of EEG sleep disturbance will enter the controlled trial. Psychobiological studies will be repeated after 3 months of acute-phase therapy (T2); treatment responders will receive 6 months of continuation therapy. We predict (Hypothesis 1) that there will be a gradient of treatment efficacy, such that FLX > CBT > PBO. Further, we predict (Hypothesis 1a) that response to CBT and PBO, but not FLX, will be inversely related to measures of HPA activity. We also predict (Hypothesis 2) that the FLX group will show significantly greater changes in selected psychobiologic abnormalities at T2 when compared to both CBT and PBO. In Hypothesis 3, we propose that these neurobiologic disturbances are linked to cognitive/phenomenological changes (i.e., impaired executive cortical function, decreased working memory, blunted mood reactivity, and diminished hedonic capacity) that functionally inhibit patients' ability to use CBT. This proposed research, the first to integrate serial, hypothesis-guided psychobiologic assessments within a PBO-controlled trial of pharmacologic and psychotherapeutic treatments, has substantial conceptual and public health significance.

在过去的5年中，我们的研究已经解决了两个相互关联的目的：1） 表征对认知反应的心理生物学相关性 行为疗法（CBT）； 2）阐明国家依赖性（即 可逆性）或选定的状态独立性（即不可逆性） 整个疾病的神经生物学障碍。我们找到了 临床严重程度，异常脑电图和增加 下丘脑 - 垂体 - 肾上腺皮质（HPA）活性与 对CBT的反应较差。此外，退回的患者仅显示部分 这些可能是状态依赖性异常的归一化。这些 调查结果表明，某些单极凹陷的特征是 需要躯体治疗的心理生物学障碍水平 为了纠正或控制失调的CNS过程。我们现在建议 在150个抑郁门诊患者的对照研究中扩展这项工作 用两种氟西汀随机分配给CBT或双盲处理 （FLX）或安慰剂（PBO）。将通过全面评估患者 14天的单盲PBO“ Washout”（T1）后14天后的心理生物学电池（T1）。 只有持续的抑郁症患者表现出预先指定的水平 脑电睡眠障碍将进入对照试验。心理生物学 急性期治疗3个月后，将重复研究（T2）； 治疗响应者将接受6个月的继续治疗。我们 预测（假设1）将有一定的治疗梯度 功效，使得flx> cbt> pbo。此外，我们预测（假设1a） 对CBT和PBO的反应，而不是FLX，将与 HPA活性的度量。 我们还预测（假设2）FLX 小组将在选定的心理生物学上显示出更大的变化 与CBT和PBO相比，T2的异常。在假设3中，我们 提出这些神经生物学障碍与 认知/现象学变化（即执行皮质受损 功能，工作记忆减少，情绪反应性钝化，并且 享乐能力降低），在功能上抑制患者的能力 使用CBT。 这项拟议的研究，第一个整合串行的研究， PBO控制试验中的假设引导的心理生物学评估 药理学和心理治疗疗法的大量 概念和公共卫生的意义。