Targeting adolescent depression symptoms using network-based real-time fMRI neurofeedback and mindfulness meditation

项目摘要 青少年重度抑郁症（MDD）是一种常见且令人衰弱的疾病。目前，黄金标准治疗 仅对大约一半的患者有效，强调需要开发新的干预措施， 特别是针对核心潜在机制，更有效地治疗这种复发性疾病。 沉思，对抑郁症状持续的倾向，有助于MDD的发作， 预测治疗无反应和复发。在神经水平上，反刍的特征是 默认模式网络（DMN）内的功能连接，之前的研究也一直 在MDD中展示了DMN超连接模式。有趣的是，正念冥想， 将注意力集中到当下，减少固执的思考，沉思的倾向和抑郁 症状此外，我们的研究和其他研究表明，青少年可以将正念练习应用于 减少感知的压力，增加持续的注意力，并抑制DMN活动。尽管正念具有 深刻的心理健康益处，对一些人来说，单靠正念可能不足以减轻沉思 抑郁症发作期间的倾向。也就是说，MDD症状，包括动机减少，注意力不集中， 缺乏自我效能，可能会阻碍患者成功获得和利用正念的进展 改变人们对环境和关系的看法所需的策略。直接解决这个问题 挑战，我们建议使用实时功能磁共振成像神经反馈，以提高收购和利用， 正念技能，以更好地针对DMN超连接，反刍和抑郁症状。 我们开发了一种新颖的、15分钟的基于正念的实时神经反馈（mbNF）范式 人们通过观察大脑活动的视觉显示，并练习正念， DMN激活。在R61阶段，90名被诊断患有MDD的青少年（年龄13-18岁）将完成45分钟的 扫描仪外的正念训练测试目标参与减少DMN超连接， 最佳剂量，然后将青少年随机接受15分钟或30分钟的mbNF疗程 （n=45/剂量组）。如果我们满足我们的Go标准（即，显著降低DMN超连接性），然后我们将 进行到R33阶段，以调查使用mbNF的正念是否优于仅使用正念。因此，在本发明中， 一个新的样本120抑郁症青少年（13-18岁）将参加一个双盲随机临床 尝试并接受最佳mbNF剂量的正念（即，根据R61）或仅正念（n=60/组）。 我们将测试-使用临床医生管理的仪器，自我报告，和生态瞬时评估- 无论是与仅正念相比，正念与mbNF都有助于更大程度地减少临床医生 评估抑郁症状（主要结局）以及减少反刍（次要结局） 在治疗后、1个月和3个月评估中。作为一个整体，mbNF直接符合 精准医疗倡议，如果成功，可能会彻底改变抑郁症青少年的临床护理。

PROJECT SUMMARY Adolescent major depressive disorder (MDD) is common and debilitating. Presently, gold-standard treatments are only effective for approximately half of patients, underscoring the need to develop novel interventions, particularly to target core underlying mechanisms and more effectively treat this recurrent disorder. Rumination, the tendency to perseverate about depressive symptoms, contributes to MDD onset and predicts treatment non-response and relapse. At the neural level, rumination is characterized by elevated functional connectivity within the default mode network (DMN), and prior research also has consistently demonstrated patterns of DMN hyperconnectivity in MDD. Interestingly, mindfulness meditation, which trains attentional focus to the present moment, reduces perseverative thinking, ruminative tendencies, and depression symptoms. Further, our research and others have shown that adolescents can apply mindfulness practices to decrease perceived stress, increase sustained attention, and suppress DMN activity. Although mindfulness has profound mental health benefits, for some, mindfulness alone may not be sufficient to mitigate ruminative tendencies during a depressive episode. That is, MDD symptoms, including reduced motivation, inattention, and lack of self-efficacy, may impede a patient’s progress in successfully acquiring and utilizing mindfulness strategies necessary to change perceptions about one’s environment and relationships. To directly address this challenge, we propose using real-time fMRI neurofeedback to enhance the acquisition and utilization of mindfulness skills to better target DMN hyperconnectivity, rumination, and depressive symptoms. We developed a novel, 15-minute mindfulness-based, real-time neurofeedback (mbNF) paradigm whereby people observe a visual display of their brain activity and practice mindfulness to volitionally reduce DMN activation. In the R61 phase, 90 adolescents (ages 13-18) diagnosed with MDD will complete a 45-minute mindfulness training outside the scanner. To test target engagement of reducing DMN hyperconnectivity and optimal dosing, adolescents will then be randomized to receive either a 15- or a 30-minute mbNF session (n=45/dose group). If we meet our Go criterion (i.e., significantly reducing DMN hyperconnectivity), we will then proceed to the R33 phase to investigate whether mindfulness with mbNF outperforms mindfulness only. Thus, a new sample of 120 depressed adolescents (ages 13-18) will participate in a double-blind randomized clinical trial and receive mindfulness with the optimal mbNF dose (i.e., per the R61) or mindfulness only (n=60/group). We will test–using clinician-administered instruments, self-reports, and ecological momentary assessment– whether compared to mindfulness only, mindfulness with mbNF contributes to a greater reduction in clinician assessed depression symptoms (primary outcome) as well as decreased rumination (secondary outcome) across the post-treatment, 1-month, and 3-month assessments. As a whole, mbNF is directly in line with precision medicine initiatives, and if successful, could revolutionize clinical care for depressed adolescents.