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

虽然认知行为疗法(CBT)是一种有效的一线干预方法，但对情感性精神障碍患者来说 在精神障碍方面，无应答者的比率仍然很高。重复的消极思维(RNT；即心理仪式、忧虑、 抑郁的沉思)预示着治疗结果不佳，是CBT后常见的残留症状。 因此，迫切需要确定RNT潜在的机械性靶点以优化治疗 应对并减轻情感性精神障碍患者的精神负担和医疗费用。vt.给出 RNT的一个显著特征是难以控制和脱离持之以恒的思维，最近 理论模型认为，注意力和认知控制的缺陷是RNT的基础 生物行为目标。然而，缺乏对这些目标进行验证的研究。这个五年的导师以病人为本 研究职业发展奖将满足这一需求。具体地说，这个项目将检验这一假设 在简化和适应RNT的跨诊断干预中提高注意力调节技能- 情绪调节疗法-注意调节(ERT-AR)-将显著改善拟议的目标 与支持性心理治疗(SPT)对照组的注意/认知控制相关的多项测量 方法目标指数：(A)行为(即，在情绪存在的情况下脱离接触和持续注意 通过眼睛跟踪注视和反应时间测量的刺激)，(B)电生理(即，主动和 提示冲突监视任务中的反应提示锁定和目标锁定的N_2、N_450和P_300事件相关电位)， 以及(C)自我报告(即感知到的转移注意力和集中注意力的能力)。我们还将研究早期迹象 治疗效果，预测ERT-AR将改善RNT和精神功能结果(症状 严重程度、功能损害)相对于SPT，以及目标确认(即，注意力/认知的改变 控制将与RNT和相关症状的变化相关)。研究目标对应于特定的 候选人(瑞安·雅各比博士)在四个关键领域的培训目标，这将使她成为一名独立人士 翻译临床科学家：(1)情感神经科学和生物行为指标测量，(2)临床 试验和实验治疗方法学，(4)高级纵向统计，和(5)职业 发展。培训目标将在Sabine Wilhelm博士(初级)的专家指导下实施 Mentor)，共同导师Diego Pizzagalli博士和Douglas Mennin博士，顾问Dan Dillon博士，Rudi de Raedt博士， 还有大卫·舍恩菲尔德。在基线上，我们将评估临床症状并实施经过充分验证的注意 和认知控制范式。RNT患者将接受8次ERT-AR或SPT治疗，并 将在第4周和第8周重新进行评估。我们将检查目标指数在 治疗，以及治疗期间和3个月随访结果的变化。如果我们的假设是 在支持下，我们将确定一个可用于优化治疗反应的交叉目标 RNT升高的个体，增强了我们的研究结果的概括性，以最大限度地影响公共卫生。

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.