Neurocircuit mechanisms of OCD across the lifespan

描述(申请人提供)：强迫症(OCD)是一种常见的精神疾病，通常出现在儿童时期，并导致超过50%的患者终身残疾。心理学理论认为，强迫症的症状是由于对表现错误的过度焦虑而难以将情感从简单的任务(如洗手、锁门)中分离出来。认知行为疗法(CBT)是治疗强迫症的黄金标准疗法，它会让患者在任务执行过程中反复暴露在与OC相关的“错误”提示下，直到这种焦虑习惯为止。虽然CBT在儿童样本中比成人样本更有效，但两个年龄段的患者通常都会留下残留症状，这突显了更好治疗的必要性，并增加了发育敏感治疗可能会优化个别患者结局的可能性。脑刺激和/或认知训练有可能 增强CBT，但在这些策略可以适当地定向之前，需要了解CBT的神经机制。先前对青少年和成人强迫症的神经成像研究显示，即使强迫症症状不是直接引发的，错误处理的神经底物也会发生共同和明显的变化。具体地说，青少年和成人表现出夸大的前岛(ANS)活动，青少年表现出与较低症状严重程度相关的后内侧额叶皮质(PMFC)活动，成年人表现出与CBT正常化的不典型的ANS-vmPFC连接。这些发现表明，在ANS、pMFC和vmPFC中，错误处理对发育敏感，可能需要针对这些变化来促进恢复，并且可能需要在不同的发育阶段针对不同的目标。根据这些试验数据，CBT可以通过增加年轻人的pMFC活动，或通过恢复成人的ANS和vmPFC之间的正常关系来发挥作用。与以前的神经影像研究不同，CBT将在青少年和成人患者中进行研究，并与积极的、非CBT条件进行比较，以控制心理治疗的非特异性影响。60名青少年(年龄13-17岁)和60名成人(年龄25-45岁)均为儿童期起病的强迫症患者，他们将随机接受最先进的CBT治疗强迫症，或接受压力管理训练(SMT)，这是一种对强迫症症状影响最小的主动控制疗法。使用有效的、受激励的绩效监测任务(激励性侧翼任务，IFT)和静息状态功能磁共振成像，将解决以下目标：目的1)展示与CBT治疗相关的神经变化，以及目的2)评估发展对CBT机制的影响。这一知识将阐明发育的特定神经靶点，以指导经颅磁刺激和/或认知训练以加强强迫症的CBT治疗的脑刺激治疗。

DESCRIPTION (provided by applicant): Obsessive-compulsive disorder (OCD) is a common psychiatric illness that often emerges in childhood and causes life-long disability in over 50% of patients. Psychological theory suggests that OCD symptoms are driven by difficulty disengaging affect from simple tasks (e.g. washing hands, locking a door) due to excessive anxiety about performance errors. Cognitive behavioral therapy (CBT), the gold standard treatment for OCD, repeatedly exposes patients to OC-relevant "error" cues during task performance until this anxiety habituates. While CBT is more effective in pediatric than adult samples, patients from both age groups are usually left with residual symptoms, highlighting the need for better treatments and raising the possibility that developmentally sensitive treatment may optimize outcomes for individual patients. Brain stimulation and/or cognitive training have the potential to augment CBT, but knowledge of the neural mechanisms of CBT is needed before these strategies can be appropriately targeted. Prior neuroimaging work in adolescent and adult OCD show common and distinct alterations of neural substrate for error-processing, even when OCD symptoms are not directly provoked. Specifically, adolescents and adults exhibit exaggerated anterior insula (aIns) activity, while adolescents show posterior medial frontal cortex (pMFC) hyperactivity that associates with lower symptom severity, and adults show atypical aIns - vmPFC connectivity that normalized with CBT. These findings point to developmentally sensitive alterations of error processing in the aIns, pMFC and vmPFC that may need to be targeted to enhance recovery and may need to be targeted differently at different stages of development. Based on these pilot data, CBT could work by increasing pMFC activity in youth, or by restoring the normal relationship between aIns and vmPFC in adults. In distinction to prior neuroimaging research, CBT will be studied in adolescent and adult patients, and in comparison to an active, non-CBT condition to control for non-specific effects of psychotherapy. Sixty adolescent (age 13-17) and 60 adult (age 25 - 45) patients, both with childhood onset OCD, will be randomized to either state-of-the art CBT for OCD, or stress management training (SMT), an active control therapy with minimal effects on OCD symptoms. Using a validated, incentivized performance monitoring task (Incentive Flanker Task, IFT) and resting state functional MRI, the following aims will be addressed: Aim 1) Demonstrate neural changes associated with CBT treatment, and Aim 2) Evaluate the effects of development on mechanisms of CBT. This knowledge will elucidate developmentally specific neural targets at which to direct brain stimulation therapy with transcranial magnetic stimulation and/or cognitive training to augment CBT for OCD.