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: 10552379
• 负责人: KELLY J. ROHAN
• 金额: $ 2.62万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10552379
• 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）是复发性抑郁症的一种亚型， 每年春季缓解的秋季和/或冬季的抑郁发作。中央 SAD管理中的公共卫生挑战是预防冬季抑郁症 复发。该应用程序侧重于两种SAD治疗，每种治疗对某些患者有效： 光疗法（LT）和SAD定制的群体认知行为疗法（CBT-SAD）。LT是 急性SAD治疗，有最实质性的证据支持其疗效。校正 昼夜节律是LT的既定目标和机制。在我们最近完成的R 01级 在疗效试验中，CBT-SAD和LT的治疗后结局非常相似，但CBT-SAD 与LT相比，CBT在2年随访中的抑郁复发率更低（CBT中为27.3%， SAD与LT中的45.6%）。CBT-SAD参与并改变了一种特定的作用机制， 与LT相比，CBT-SAD期间的改善率是LT的两倍， 改善与CBT-SAD后复发风险降低相关。这 确证性疗效R 01将采用实验治疗方法来确定 每种治疗方法在有效时都有效，并确定每种治疗方法的最佳候选者。我们将 确定每种治疗靶点的理论上衍生的候选生物标志物， 效果是治疗中与其他相比更好结果的规定性。LT的生物标志物 目标和效果包括昼夜相位角差（PAD）和照射后瞳孔 响应（PIPR）。CBT-SAD的靶点和作用的生物标志物包括瞳孔扩张和 持续的伽马波段脑电图反应季节性的话，这是假设，以反映 在CBT-SAD之后，对季节性刺激的参与较少，并与既定的 季节信仰的目标。除了确定变更机制外，我们还将测试 复发时“转换”决策规则告知临床决策的有效性 实践我们将160名SAD成年患者随机分为6周CBT-SAD或LT组（冬季1）; 在冬季2中跟踪受试者;并且，如果抑郁症复发，将他们交叉到 交替处理（即，从LT转换为CBT-SAD或CBT-SAD转换为LT）。所有受试者将 在冬季3。生物标志物评估将在冬季1的治疗前和治疗后进行， 在冬季2随访时（对于交叉患者，在治疗后再次随访）和冬季3时 跟进。与NIMH在以下层面展示目标参与度的优先事项一致 RDoC相关的生物标志物，这项工作旨在确认LT的靶点和机制， * 建设性的撒哈拉以南非洲国家训练营，以最大限度地扩大今后传播工作的影响。

项目成果

Elucidating treatment targets and mediators within a confirmatory efficacy trial: study protocol for a randomized controlled trial of cognitive-behavioral therapy vs. light therapy for winter depression.

• DOI: 10.1186/s13063-022-06330-9
• 发表时间: 2022-05-12
• 期刊: TRIALS
• 影响因子: 2.5
• 作者: Rohan, Kelly J.;Franzen, Peter L.;Roeckelin, Kathryn A.;Siegle, Greg J.;Kolko, David J.;Postolache, Teodor T.;Vacek, Pamela M.
• 通讯作者: Vacek, Pamela M.