Targeting Attentional and Cognitive Control to Enhance the Transdiagnostic Treatment of Repetitive Negative Thinking

虽然认知行为疗法（CBT）是一种有效的第一线干预的个人情感， 疾病，无应答率仍然很高。重复性消极思维（RNT），心理仪式，忧虑， 抑郁性反刍）预示着不良的治疗结果，是CBT后常见的残留症状。 因此，迫切需要确定RNT的机制靶点以优化治疗 这将有助于缓解和减轻情感性精神障碍患者的精神负担和医疗费用。给定 RNT的一个标志性特征是难以控制和脱离持续性思维， 理论模型提出，注意力和认知控制的缺陷是RNT的基础， 生物行为目标然而，缺乏验证这些目标的研究。这五年的指导病人导向 研究职业发展奖将满足这一需求。具体来说，这个项目将测试假设 在跨诊断干预中提高注意力调节技能， 情绪调节疗法-注意力调节（ERT-AR）-将显着改善建议的目标， 与支持性心理治疗（SPT）对照组相比， 方法目标指数：（a）行为（即，脱离接触和持续的注意力在情绪的存在 通过眼睛跟踪注视和反应时间测量的刺激），（B）电生理学（即，积极主动和 在线索冲突监控任务中的反应性线索和目标锁定的N2、N450和P300事件相关电位）， 以及（c）自我报告（即，转移和集中注意力的能力）。我们还将检查早期迹象， 治疗效果，预测ERT-AR将改善RNT和精神功能结局（症状 严重程度，功能障碍），以及目标验证（即，注意力/认知的变化 控制将与RNT和相关症状的变化相关）。研究目的与具体 培训目标的候选人（博士瑞安·比）在四个关键领域，将推出她作为一个独立的 转化临床科学家：（1）情感神经科学和生物行为目标的测量，（2）临床 试验和实验治疗方法学，（4）高级纵向统计学，（5）职业生涯 发展培训目标将在Sabine Wilhelm博士（初级）的专家指导下实施 导师），共同导师博士迭戈Pizzagalli和道格拉斯Mennin，和顾问博士丹狄龙，鲁迪德Raedt， 和大卫·舍恩菲尔德。在基线时，我们将评估临床症状，并给予有效的注意力 和认知控制模式。然后将为RNT患者提供8次ERT-AR或SPT治疗， 将在第4周和第8周重新进行评估。我们将研究我们的目标指数在 治疗，以及治疗和3个月随访结果的变化。如果我们的假设 支持，我们将确定一个交叉目标，可以参与优化治疗反应， RNT升高的个体，增强了我们研究结果的普遍性，以最大限度地提高公共卫生影响。

Although cognitive behavioral therapy (CBT) is an efficacious first-line intervention for individuals with affective disorders, non-responder rates remain high. Repetitive negative thinking (RNT; i.e., mental rituals, worries, depressive ruminations) predicts poor treatment outcome and is a common residual symptom following CBT. Thus, there is an urgent unmet need to identify the mechanistic targets underlying RNT to optimize treatment response and reduce the psychiatric burden and healthcare costs for patients with affective disorders. Given that a hallmark feature of RNT is the difficulty controlling and disengaging from perseverative thought, recent theoretical models propose that deficits in attentional and cognitive control underlie RNT as fundamental biobehavioral targets. Yet studies validating these targets are lacking. This five-year Mentored Patient-Oriented Research Career Development Award will address this need. Specifically, this project will test the hypothesis that enhancing attention regulation skills in a transdiagnostic intervention streamlined and adapted for RNT – Emotion Regulation Therapy-Attention Regulation (ERT-AR) – will significantly improve the proposed target of attentional/cognitive control relative to a supportive psychotherapy (SPT) control group as measured by multi- method target indices: (a) behavioral (i.e., disengagement and sustained attention in the presence of emotional stimuli measured by eye tracking fixations and reaction time), (b) electrophysiological (i.e., proactive and reactive cue- and target-locked N2, N450, and P300 event related potentials in a cued conflict monitoring task), and (c) self-report (i.e., perceived ability to shift and focus attention). We also will examine early signs of treatment efficacy, predicting that ERT-AR will improve RNT and psychiatric functioning outcomes (symptom severity, functional impairment) relative to SPT, and target validation (i.e., changes in attentional/cognitive control will correlate with changes in RNT and associated symptoms). Study aims correspond to specific training goals for the candidate (Dr. Ryan Jacoby) in four key areas that will launch her as an independent translational clinical scientist: (1) affective neuroscience and measurement of biobehavioral targets, (2) clinical trials and experimental therapeutics methodology, (4) advanced longitudinal statistics, and (5) career development. Training goals will be implemented with the expert guidance of Dr. Sabine Wilhelm (primary mentor), co-mentors Drs. Diego Pizzagalli and Douglas Mennin, and advisors Drs. Dan Dillon, Rudi De Raedt, and David Schoenfeld. At baseline, we will assess clinical symptoms and administer well-validated attentional and cognitive control paradigms. Patients with RNT will then be provided 8 sessions of ERT-AR or SPT and will be re-administered assessments at weeks 4 and 8. We will examine changes in our target indices during treatment, as well as changes in outcomes over treatment and 3-month follow-up. If our hypotheses are supported, we will identify a cross-cutting target that can be engaged to optimize treatment response for individuals with elevated RNT, enhancing the generalizability of our findings for maximum public health impact.