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

冬季季节性情感障碍(SAD)是复发性抑郁症的一个亚型，主要累及 在每年春天缓解的秋季和/或冬季期间的抑郁发作。中环 应对SAD的公共卫生挑战是预防冬季抑郁症 反复发作。这个应用程序侧重于两种SAD治疗方法，每种方法都对某些患者有效： 光疗法(LT)和针对SAD量身定制的团体认知行为疗法(CBT-SAD)。这就是 急性SAD治疗有最确凿的证据支持其疗效。更正 昼夜节律是LT的既定目标和机制。在我们最近完成的R01-Level CBT-SAD和LT的疗效试验和治疗后结果非常相似，但CBT-SAD 在两年的随访中，抑郁症的复发比LT少(CBT组27.3% Sad与LT的45.6%)。CBT-SAD参与并改变了一种特定的作用机制，季节性 信念，与LT相比，在CBT-SAD期间的改善速度是LT的两倍 改善与CBT-SAD术后复发风险降低有关。这 确认疗效R01将应用实验治疗学方法来确定如何 每种疗法在有效的时候都有效，并确定每种疗法的最佳候选者。我们会 确定理论上派生的每个治疗目标的候选生物标记物 效果规定了在这种治疗中比在另一种治疗中结果更好。LT的生物标志物 目标和效果包括昼夜相位角差(PAD)和光照后的瞳孔 响应(PIPR)。CBT-SAD靶点和作用的生物标志物包括瞳孔扩张和 对季节性词语的持续伽马频段脑电反应，假设这反映了 CBT-SAD后较少接触季节性刺激，并与已建立的 季节性信仰的目标。除了确定更改机制外，我们还将测试 复发时“切换”决策规则在指导临床决策中的作用 练习一下。我们将160名患有SAD的成年人随机分为CBT-SAD或LT治疗6周，在冬季1； 在第二个冬季跟踪受试者；如果抑郁复发，将他们交叉进入 替代处理(即，从LTCBT-SAD或CBT-SADLT切换)。所有的科目都将是 3冬季紧随其后。生物标志物评估将在1冬季治疗前和治疗后进行， 在冬季2次随访(对于那些转居者，在治疗后再次进行)和在冬季3次 后续行动。与NIMH在以下级别展示目标参与度的优先事项一致 RDoC相关的生物标志物，本工作旨在确定LT和RDoC的靶点和机制。 CBT-SAD，以最大限度地发挥未来传播努力的影响。

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.