fMRI study of developing medial prefrontal cortical function in pediatric OCD

描述（由申请人提供）：强迫症（OCD）是一种常见的致残性精神疾病，通常难以接受现有的治疗。强迫症在儿童和青少年时期的发病表明，非典型的大脑成熟可能是这种疾病的基础，并要求对儿科患者进行研究，以确定一个“发育窗口”，在这个窗口中，治疗干预可能会被引导到中止慢性疾病的进展。为了探索与儿童强迫症相关的神经行为发育机制，候选人开始了功能性磁共振成像（fMRI）和儿童精神病学的工作。为了满足额外技能获取的需求，5年职业发展计划将为1）儿科神经影像学，2）发育神经科学和3）临床研究技能提供必要的基础。职业发展将通过一个研究项目来塑造，该研究项目旨在通过测试年轻患者中CSPT功能和结构的假设成熟异常来扩展皮质-纹状体-苍白球丘脑（CSPT）参与儿童强迫症的初步发现。当患者在简单的认知任务上犯错误时，CSPT元素-喙前扣带皮层、后内侧额叶皮层和背外侧前额叶皮层-的过度活跃反应发生在成人强迫症中。此外，在成人强迫症中已经证明了CSPT回路内的过度白色连接，并且可能由CSPT功能的过度活跃（例如对错误的反应）驱动。在拟议的研究中，错误处理功能和CSPT电路的白色物质的一致性将在青春期前，青春期和青春期的发展阶段进行研究，开始，以阐明如何CSPT异常出现和发展过程中的早期强迫症。出色的部门支持;在功能磁共振成像，儿科强迫症，认知情感发展和临床研究的集体专业知识;和，未来的转化研究的机会，使密歇根大学为这个奖项的理想环境。 公共卫生相关性：强迫症影响着数百万美国儿童，了解与早发性疾病相关的大脑成熟异常将有助于促进对这种致残性疾病的理解、治疗和最终预防。

DESCRIPTION (provided by applicant): Obsessive compulsive disorder (OCD) is a common and disabling psychiatric illness that is often refractory to available treatments. The onset of OCD during childhood and adolescence suggests that atypical brain maturation may underlie the disorder, and mandates the study of pediatric patients to define a "developmental window" at which therapeutic interventions may be directed to abort progression to chronic illness. To probe the mechanisms of neurobehavioral development relevant to pediatric OCD, the Candidate has begun work in functional magnetic resonance imaging (fMRI) and child psychiatry. Addressing the need for additional skill acquisition, a 5-year career development plan will provide an essential grounding in 1) pediatric neuroimaging, 2) developmental neuroscience, and 3) clinical research skills. Career development will be shaped by a research project designed to extend preliminary findings of cortico-striatal-pallidalthalamic (CSPT) involvement in pediatric OCD by testing for hypothesized maturational abnormalities of CSPT function and structure in young patients. Hyperactive response of CSPT elements - the rostral anterior cingulate cortex, posterior medial frontal cortex, and dorsolateral prefrontal cortex - occurs in adult OCD when patients commit errors on simple cognitive tasks. In addition, excessive white matter connectivity within CSPT circuitry has been demonstrated in adult OCD, and could be driven by hyperactivity of CSPT functions, such as the response to errors. In the proposed study, error-processing function and white matter coherence of CSPT circuitry will be studied across prepubertal, pubertal and adolescent stages of development to begin to elucidate how CSPT abnormalities emerge and progress during the early course of OCD. Outstanding departmental support; collective expertise in fMRI, pediatric OCD, cognitive-emotional development, and clinical research; and, opportunities for future translational research make the University of Michigan an ideal environment for this award. PUBLIC HEALTH RELEVANCE: OCD affects millions of American children, and understanding the abnormalities of brain maturation associated with early onset illness will help to foster improved understanding, treatment, and eventually, prevention of this disabling condition.