Optimizing Long-Term Outcomes for Winter Depression with CBT-SAD and Light Therapy: Confirming the Targets, Mechanisms, and Treatment Sequence

通过 CBT-SAD 和光疗法优化冬季抑郁症的长期结果：确认目标、机制和治疗顺序

• 批准号: 10348155
• 负责人: KELLY J. ROHAN
• 金额: $ 66.59万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10348155
• 关键词: Acute; Adult; Affect; Aftercare; Algorithms; American; Behavioral; Belief; Biological; Biological Markers; Chronic; Cognitive Therapy; Data; Development; Disease remission; Economic Burden; Electroencephalography; Emotional; Exposure to; Future; Intervention; Investigational Therapies; Light; Lighting; Major Depressive Disorder; Maps; Mediator of activation protein; Melatonin; Mental Depression; Mental Health; Mydriasis; National Institute of Mental Health; Nature; Outcome; Patient Self-Report; Patients; Phase; Phototherapy; Population; Prevention; Probability; Public Health; Pupil; Randomized; Recurrence; Research Domain Criteria; Retina; Risk; Seasonal Affective Disorder; Seasons; Sleep; Specificity; Stimulus; Symptoms; Testing; Time; Treatment outcome; Work; base; candidate marker; circadian; clinical decision-making; clinical practice; cost; depressive symptoms; disability; efficacy testing; efficacy trial; falls; follow-up; improved; indexing; melanopsin; personalized medicine; precision medicine; primary outcome; recurrent depression; response; single episode major depressive disorder; social; symptomatic improvement; targeted treatment; treatment effect; young adult

Winter seasonal affective disorder (SAD) is a subtype of recurrent depression involving major depressive episodes during the fall and/or winter months that remit each spring. The central public health challenge in the management of SAD is prevention of winter depression recurrences. This application focuses on two SAD treatments that each work for some patients: light therapy (LT) and a SAD-tailored group cognitive-behavioral therapy (CBT-SAD). LT is the acute SAD treatment with the most substantial evidence to support its efficacy. Correction of circadian phase is LT's established target and mechanism. In our recently completed R01-level efficacy trial, post-treatment outcomes for CBT-SAD and LT were very similar, but CBT-SAD was associated with fewer depression recurrences over 2-year followup than LT (27.3% in CBT- SAD vs. 45.6% in LT). CBT-SAD engaged and altered a specific mechanism of action, seasonal beliefs, which improved at twice the rate during CBT-SAD compared to LT, and this improvement was associated with lower risk for recurrence following CBT-SAD. This confirmatory efficacy R01 will apply the experimental therapeutics approach to determine how each treatment works when it is effective and to identify the best candidates for each. We will ascertain whether theoretically-derived candidate biomarkers of each treatment's target and effect are prescriptive of better outcomes in that treatment vs. the other. Biomarkers of LT's target and effect include circadian phase angle difference (PAD) and the post-illumination pupil response (PIPR). Biomarkers of CBT-SAD's target and effect include pupil dilation and sustained gamma band EEG responses to seasonal words, which are hypothesized to reflect less engagement with seasonal stimuli following CBT-SAD and corroborate with the established target of seasonal beliefs. In addition to determining change mechanisms, we will test the efficacy of a “switch” decision rule upon recurrence to inform clinical decision-making in practice. We will randomize 160 adults with SAD to 6-weeks of CBT-SAD or LT in Winter 1; follow subjects in Winter 2; and, if a depression recurrence occurs, cross them over into the alternate treatment (i.e., switch from LTCBT-SAD or CBT-SADLT). All subjects will be followed in Winter 3. Biomarker assessments will occur at pre- and post-treatment in Winter 1, at Winter 2 followup (and again at post-treatment for those crossed-over), and at Winter 3 followup. Consistent with NIMH's priorities for demonstrating target engagement at the level of RDoC-relevant biomarkers, this work aims to confirm the targets and mechanisms of LT and CBT-SAD to maximize the impact of future dissemination efforts.

冬季季节性情感障碍（SAD）是一种反复发作的抑郁症亚型，涉及主要疾病 秋季和/或冬季的抑郁发作，每年春季缓解。中央 管理季节性抑郁症的公共卫生挑战是预防冬季抑郁症 复发。此应用程序重点关注两种 SAD 治疗方法，每种治疗方法均适用于某些患者： 光疗法 (LT) 和 SAD 定制的团体认知行为疗法 (CBT-SAD)。 LT 是 急性SAD治疗有最实质性的证据支持其疗效。更正 昼夜节律阶段是LT既定的目标和机制。在我们最近完成的 R01 级 疗效试验显示，CBT-SAD 和 LT 的治疗后结果非常相似，但 CBT-SAD 与 LT 相比，2 年随访中抑郁症复发率较低（CBT 中为 27.3%） SAD 对比 LT 中的 45.6%）。 CBT-SAD 参与并改变了特定的行动机制，季节性 与 LT 相比，CBT-SAD 期间信念的改善速度是 LT 的两倍， CBT-SAD 后的改善与较低的复发风险相关。这 验证性疗效 R01 将应用实验治疗方法来确定如何 每种治疗方法只有在有效时才有效，并确定每种治疗方法的最佳候选者。我们将 确定是否从理论上得出每种治疗目标的候选生物标志物和 效果是该治疗相对于其他治疗的更好结果的规定。 LT 的生物标志物 目标和效果包括昼夜节律相位角差 (PAD) 和照明后瞳孔 响应（PIPR）。 CBT-SAD 目标和效果的生物标志物包括瞳孔扩张和 伽玛波段脑电图对季节性词语的持续反应，假设反映 CBT-SAD 后减少对季节性刺激的参与，并与既定的事实相证实 季节性信念的目标。除了确定变革机制外，我们还将测试 复发时“转换”决策规则的有效性，可为临床决策提供信息 实践。我们将在第 1 个冬季将 160 名患有 SAD 的成年人随机分为 6 周的 CBT-SAD 或 LT； 关注第二个冬季的科目；并且，如果抑郁症复发，请将它们交叉到 替代治疗（即从 LT→CBT-SAD 或 CBT-SAD→LT 切换）。所有科目都将 随后是第 3 个冬季。生物标志物评估将在第 1 个冬季的治疗前和治疗后进行， 在第 2 个冬季随访（以及交叉患者的治疗后）和第 3 个冬季 后续行动。与 NIMH 展示目标参与水平的优先事项一致 RDoC相关生物标志物，本工作旨在确认LT和RDoC的靶点和机制 CBT-SAD 最大限度地发挥未来传播工作的影响。