EEG Biomarkers of Psychosis Risk and Adolescent Neurodevelopment

描述（由申请人提供）：随着越来越多的人认识到，许多以前被认为仅限于成年的精神疾病实际上在儿童时期就出现了最初的迹象，并在青春期开始全面出现，NIMH在其战略计划中规定临床研究应该“将健康发展的轨迹与精神障碍的轨迹进行比较，以便更好地了解发展偏离轨道的第一个或多个实例。”具体来说，这一目标涉及到“使用成像技术绘制精神障碍的轨迹”，以及发现“早期发现精神障碍的风险因素”。与这些优先事项相一致，目前的申请涉及到申请人从成人精神病理学研究员转变为具有技能和专业知识的发展认知神经科学家，以研究青春期作为精神分裂症等精神障碍发展的敏感时期。在咨询了一组临床和发展神经科学家、一名从事基础研究的发展心理学家和临床心理学家以及一名从事纵向研究的统计学家后，该提案描述了对三组青少年（12-17岁）为期一年的认知和神经连通性调查：寻求帮助的患者被判定为精神分裂症的临床高危患者（由于存在亚阈值症状），符合DSM-IV精神分裂症首次发作标准的患者，以及匹配的社区比较受试者。在研究登记和12个月的随访中，所有参与者将进行一系列实验性认知测试，同时记录与事件相关的脑电图数据。脑电图能够提供大规模神经回路同步活动的时间敏感测量。所提出的认知测试每一个都需要不同的前额-后脑神经回路子集。这些特殊的神经回路对于连接大脑至关重要

DESCRIPTION (provided by applicant): With growing recognition that a number of psychiatric illnesses previously thought to be restricted to adulthood actually show their initial signs in childhood and begin to emerge fully during adolescence, NIMH mandated in its Strategic Plan that clinical research should, "compare trajectories of healthy development to those of mental disorders in order to better understand the first instance or instances, when development moves off course." Specifically, this objective involves the need to "map the trajectory of mental disorders using imaging technologies," and discovery of "early detection of risk factors for mental disorders." Consistent with these priorities, the current application involves a plan for th applicant to transform from an adult psychopathology researcher to a developmental cognitive neuroscientist with skills and expertise to study adolescence as a sensitive period in the development of psychotic disorders such as schizophrenia. Written in consultation with a team of clinical and developmental neuroscientists, as well as a developmental psychologist and clinical psychologist who both conduct basic research, and a statistician with expertise in longitudinal work, the proposal describes a one year-long investigation of cognition and neural connectivity in three groups of adolescents (ages 12-17 years) : help-seeking patients judged to be at clinical high-risk for developing schizophrenia (due to the presence of sub-threshold symptoms), patients who meet DSM-IV criteria for a first episode of schizophrenia, and matched community comparison subjects. At study enrollment and then again at 12 month follow-up, all participants will perform a set of experimental cognitive tests while event-related EEG data are recorded. EEG is capable of providing temporally-sensitive measures of synchronized activity in large-scale neural circuits. The proposed cognitive tests each recruit various subsets of prefrontal-posterior neural circuits. These particular neural circuits are critical for linking the prefrontal cortex to more posterior, earlier-maturing cortical regions (e.g., sensory and motor areas), and are the site of some of the most dramatic development and optimization that occurs in the brain during adolescence, as it transitions to stable, adult functioning. Therefore, the efficiency with which these neural circuits function under cognitive challenge should provide evidence of baseline dysfunction, and change in that efficiency over the year-long study should provide evidence of aberrant maturation if present. In fact, latent risk for developing schizophrenia is thought to dysregulate a subset of these functional connections (e.g., through selective pathology of pyramidal neurons synapses); however, exactly when these illness mechanisms arise with respect to the appearance of frank psychotic symptoms and with respect to landmarks in typical adolescent development remains unknown. Collectively, these results will provide a sensitive measure of the integrity of the neural connections that are thought to provide the substrate for both adolescent neurodevelopment and schizophrenia pathogenesis.