Neurocircuit mechanisms of OCD across the lifespan

强迫症整个生命周期的神经回路机制

基本信息

批准号：
9116013
负责人：
Kate Dimond Fitzgerald
金额：
$ 62.09万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-25 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9116013
关键词：
Address Adolescent Adult Affect Age Anterior Anxiety Behavioral Biological Neural Networks Brain Brain region Characteristics Childhood Cognitive Therapy Cues Data Development Evaluation Exhibits Exposure to Fright Functional Magnetic Resonance Imaging Goals Gold Handwashing Health Hyperactive behavior Incentives Insula of Reil Intervention Knowledge Lead Left Life Longevity Medial Mediator of activation protein Mental disorders Methods Modeling Monitor Obsession Obsessive-Compulsive Disorder Onset of illness Outcome Patients Performance Prefrontal Cortex Process Psychological Theory Psychotherapy Randomized Recovery Research Residual state Rest Ritual compulsion Sample Size Sampling Scanning Severities Signal Transduction Staging Symptoms Task Performances Testing Therapeutic Trials Thinking Training Training Technics Transcranial magnetic stimulation Work Youth active control adolescent patient age group base cognitive training disability effective therapy excessive anxiety frontal lobe improved improved outcome individual patient individualized medicine neuroimaging neuromechanism relating to nervous system response standard care stress management symptomatic improvement trial design

项目摘要

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.

描述（由申请人提供）：强迫症（OCD）是一种常见的精神病，通常在儿童时期出现，并在50％的患者中造成终身残疾。心理理论表明，由于对性能错误的过度焦虑，强迫症症状是由于难以脱离简单任务的难度（例如洗手手，锁定门）的驱动。强迫症的金标准治疗认知行为疗法（CBT）在任务执行过程中反复暴露于与OC相关的“错误”线索，直到这种焦虑习惯为止。尽管CBT比成人样本更有效，但两个年龄段的患者通常都有残留症状，强调需要更好地治疗，并提高了发育敏感的治疗方法可以优化个别患者的结果。大脑刺激和/或认知训练有可能增强CBT，但是需要对这些策略进行适当针对的CBT神经机制的了解。即使没有直接引起OCD症状，在青少年和成人强迫症中的神经影像学工作也会显示出具有错误处理的神经基质的常见和不同变化。具体而言，青少年和成年人表现出夸张的前岛（AINS）活性，而青少年则显示后内侧额叶皮层（PMFC）多动，与症状较低的严重程度相关，成年人显示非典型AINS -VMPFC连接，与CBT融为一体。这些发现表明，在AINS，PMFC和VMPFC中，可能需要将误差处理的发展敏感变化，以增强恢复，并且可能需要在开发的不同阶段以不同的方式针对目标。基于这些试验数据，CBT可以通过增加青年的PMFC活动或恢复成人AINS和VMPFC之间的正常关系来起作用。与先前的神经成像研究区别，将在青少年和成年患者中研究CBT，并与主动的非CBT疾病相比，以控制心理治疗的非特异性作用。 60名青少年（13-17岁）和60名成人（25-45岁）患者，均患有儿童期OCD，将其随机分为OCD的最先进的CBT或压力管理培训（SMT），这是一种对OCD症状影响最小的主动控制治疗。使用经过验证的，激励性的性能监控任务（激励侧翼任务，IFT）和静止状态功能性MRI，将解决以下目的：目标1）证明与CBT治疗相关的神经变化，目标2）评估开发对CBT机制的影响。这些知识将阐明特定于发育的神经靶标，以通过经颅磁刺激和/或认知训练来指导脑刺激治疗，以增强OCD的CBT。