fMRI study of developing medial prefrontal cortical function in pediatric OCD

描述（由申请人提供）：强迫症（OCD）是一种常见的致残精神疾病，通常难以治疗。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”，在这个窗口期，治疗干预可能会直接阻止进展为慢性疾病。为了探索与儿童强迫症相关的神经行为发育机制，候选人已开始在功能磁共振成像（fMRI）和儿童精神病学方面开展工作。针对额外技能获取的需求，一个5年的职业发展计划将提供1)儿童神经影像学、2)发育神经科学和3)临床研究技能的基本基础。职业发展将由一个研究项目来塑造，该项目旨在通过测试年轻患者CSPT功能和结构的假设成熟异常来扩展CSPT在儿童强迫症中的初步发现。当成人强迫症患者在简单的认知任务中犯错误时，CSPT元素（扣带前部吻侧皮层、后内侧额叶皮层和背外侧前额叶皮层）的过度活跃反应就会发生。此外，在成人强迫症中，CSPT电路中过度的白质连接已经被证明，这可能是由CSPT功能的过度活跃驱动的，比如对错误的反应。在本研究中，将研究青春期前、青春期和青春期发育阶段CSPT回路的错误处理功能和白质一致性，以开始阐明CSPT异常在强迫症早期过程中的出现和发展。出色的部门支持；在功能磁共振成像、儿童强迫症、认知情感发展和临床研究方面的集体专业知识；而且，密歇根大学为未来的转化研究提供了机会，这使得密歇根大学成为颁发该奖项的理想环境。公共卫生相关性：强迫症影响着数百万美国儿童，了解与早期发病疾病相关的大脑成熟异常将有助于提高对这种致残状况的理解、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.