Developing rumination-focused treatment to reduce risk for depression recurrence (RDR) in adolescence

新出现的证据表明，复发形式的重性抑郁症（MDD）往往会恶化， 随着人们进入成年期，发作的时间会更长，更严重。然而，我们仍然有很长的路要走， 治疗可以降低抑郁症复发（RDR）的短期和长期风险。了解具体 迫切需要RDR机制来促进复发预防（并可能对 治疗）。目前的建议使用了一种治疗方法，有证据表明可以改变沉思的习惯， 倾向于以重复的，被动的和抽象的方式接近困难和相关的负面情绪 心理模式（习惯）。相反，我们教青少年利用适应性，具体和具体的心理 图案（例如，解决问题、情绪处理）。反刍集中CBT（RFCBT）的开发， 具体针对并减少或改变反刍习惯。在成人中的初步工作和我们的试点数据 提示RFCBT可以有效减少青少年的反刍。此外，我们的工作 小组和其他一些小型研究表明，沉思的习惯可以在神经水平上测量， 默认模式网络（DMN，增加了网络连接）中大脑节点的连接 如DMN和认知控制网络（CCN）之间的连接模式。因此，我们建议 使用RFBCT改变160名MDD缓解期青少年（14-18岁）的沉思习惯（通过KSAD-PL） 和提高反刍（高于50的T），目标是实现反刍的显著临床变化， 并观察与DMN下降相关的关键DMN和CCN节点之间的连接变化， 沉思的习惯后一种知识可以提供关于如何使用替代疗法的信息（例如， 神经调节），以有效地改变反刍习惯和相关的神经网络通路， 将使治疗目标更加精确。将RFCBT组（N=30）与 R61的仅评估（AO）组（N=30），以及R61的主动治疗，放松治疗（RelaxT） R33（每组N = 50），分享一些积极的变革策略。对于R61，我们预计 (Aim 1）RF-CBT将导致（a）反刍的显著降低和（B）来自LPPC的连接性降低 到RIFG，这两个“Go”标准都是为了继续到R33阶段。对于（目标2），我们期望作业的程度 参与将涉及（a）反刍习惯，（B）LPCC-RIFG rs-fMRI连接性，和 在探索性反刍诱导任务期间增加的激活程度。RRS变化的稳定性也将 在12个月时进行评估。该R61/R33具有相同的RRS变化Go标准（效应量为.5）， LPCC - RIFG连接性变化（0.5效应量）。此外，R33增加了MDD复发的预测 (Aims 3a（维度）和Aim 3b（分类）），以进入RO 1多位点阶段。我们的初步数据 我建议，即使我们的Go标准没有得到满足，我们也会在获得更好的理解方面取得迭代收益 神经网络的目标，无论是在维护或补偿反刍的习惯，以及RDR。

Emerging evidence suggests that the recurrent form of Major Depressive Disorder (MDD) tends to worsen, with more severe and longer episodes as people move into adulthood. Yet, we are still a very long way from treatments that can reduce short- and long-term Risk for Depressive Relapse (RDR). Understanding specific mechanisms of RDR is urgently needed to promote relapse prevention (and may have long-term benefits for treatment). The present proposal uses a treatment that has evidence for modifying the ruminative habit, a tendency to approach difficulties and associated negative emotions with a repetitive, passive and abstract mental pattern (habit). In contrast, we teach adolescents to utilize adaptive, concrete and specific mental patterns (e.g., problem-solving, emotion processing). Rumination focused CBT (RFCBT) was developed to specifically target and reduce or modify the ruminative habit. Initial work among adults and our pilot data among adolescents suggests that rumination can be effectively reduced with RFCBT. In addition, work by our group and a few other small studies suggests that the ruminative habit can be measured at the neural level in connectivity of brain nodes in the Default Mode Network (DMN, increased within network connectivity) as well as in patterns of connectivity between the DMN and Cognitive Control Network (CCN). As such, we proposed to use RFBCT to modify the ruminative habit in 160 adolescents (age 14-18) with remitted MDD (via KSAD-PL) and elevated rumination (above T of 50), with the goal of achieving significant clinical change in rumination, and to observe changes in connectivity between key DMN and CCN nodes associated with decline in the ruminative habit. The latter knowledge may provide information on how to use alternative therapies (e.g., neuromodulation) to effectively modify the ruminative habit and the associated neural network pathways, which would lead to greater precision in the targeting of treatment. The RFCBT arm (N=30) is compared to an assessment only (AO) arm (N=30) for the R61, and to an active therapy, Relaxation Therapy (RelaxT) for the R33 (N = 50 in each group), that shares some of the active strategies for change.. For R61, we expect that (Aim 1) RF-CBT will result in (a) significant decreases in rumination and (b) decreased connectivity from LPPC to RIFG, both "Go" criteria for continuation to the R33 phase. For (Aim 2), we expect that degree of homework engagement will relate to degree of change in (a) ruminative habit, (b) in LPCC-RIFG rs-fMRI connectivity, and degree of increased activation during exploratory rumination induction task. Stability of RRS changes will also be evaluated at 12 months. This R61/R33 has the same Go criteria of RRS change (effect size of .5) and LPCC - RIFG connectivity changes (.5 effect size). In addition, the R33 adds prediction of MDD recurrence (Aims 3a (dimensional) and Aim 3b(categorical)) to proceed to the RO1 multisite phase. Our preliminary data suggest that even if our Go criteria are not met, we will make iterative gains in gaining a better understanding neural network targets, both in maintenance of or compensation for the ruminative habit, as well as for RDR.