Neurocircuit mechanisms of OCD across the lifespan

描述（由申请人提供）：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。心理学理论表明，强迫症症状是由于对表现错误的过度焦虑而难以从简单的任务（例如洗手，锁门）中解脱出来。认知行为疗法（CBT）是治疗强迫症的金标准，在任务执行过程中反复将患者暴露于与强迫症相关的“错误”线索，直到这种焦虑习惯化。虽然CBT在儿童样本中比成人样本更有效，但这两个年龄组的患者通常都会留下残留症状，这突出了对更好治疗的需求，并提高了发育敏感性治疗可能优化个体患者结局的可能性。大脑刺激和/或认知训练有可能 增强CBT，但在这些策略可以适当针对之前，需要了解CBT的神经机制。先前在青少年和成人强迫症的神经影像学工作显示，即使强迫症症状没有直接引起，错误处理的神经基质也有共同和不同的改变。具体而言，青少年和成人表现出夸大的前额叶皮层（aIns）活动，而青少年表现出与较低症状严重程度相关的后内侧额叶皮层（pMFC）活动过度，成人表现出非典型的aIns-vmPFC连接，通过CBT恢复正常。这些研究结果指出，在aIns，pMFC和vmPFC的错误处理，可能需要有针对性地提高恢复，并可能需要有针对性地在不同的发展阶段的发展敏感的变化。基于这些初步数据，CBT可以通过增加青年人的pMFC活性，或通过恢复成年人aIns和vmPFC之间的正常关系来发挥作用。与之前的神经影像学研究不同，CBT将在青少年和成人患者中进行研究，并与活跃的非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）患者，均患有儿童期发作的OCD，将随机接受最先进的CBT治疗OCD或压力管理训练（SMT），这是一种对OCD症状影响最小的积极控制疗法。使用经过验证的激励性表现监测任务（激励性侧翼任务，IFT）和静息状态功能性MRI，将解决以下目标：目标1）证明与CBT治疗相关的神经变化，目标2）评价发育对CBT机制的影响。这些知识将阐明发育特异性的神经靶点，在这些靶点上，通过经颅磁刺激和/或认知训练来指导脑刺激治疗，以增强强迫症的CBT。

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.