EEG Biomarkers of Psychosis Risk and Adolescent Neurodevelopment

精神病风险和青少年神经发育的脑电图生物标志物

• 批准号: 8635387
• 负责人: Peter Bachman
• 金额: $ 15.41万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-03 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635387
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Age; Appearance; Area; Basic Science; Biological Markers; Biological Neural Networks; Birth; Brain; Characteristics; Childhood; Clinical; Clinical Research; Cognition; Cognitive; Communities; Consultations; Coupling; DSM-IV; Data; Data Analyses; Data Collection; Detection; Development; Distant; Early Diagnosis; Electroencephalography; Electrophysiology (science); Enrollment; Event; Exhibits; Functional disorder; Goals; Image; Imaging technology; Impaired cognition; Impairment; Investigation; Lead; Learning; Linear Regressions; Link; Maps; Measures; Mediating; Memory; Mental disorders; Methods; Modeling; Motor; National Institute of Mental Health; Neurologic; Occupational; Onset of illness; Outcome; Participant; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Performance; Phase; Physiological; Population; Prefrontal Cortex; Psychologist; Psychopathology; Psychotic Disorders; Recruitment Activity; Regression Analysis; Reliance; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Schizophrenia; Sensory; Severities; Short-Term Memory; Signal Transduction; Site; Source; Speed; Staging; Stimulus; Strategic Planning; Structure; Symptoms; Synapses; Syndrome; Task Performances; Testing; Time; Training; Visuospatial; Work; Writing; age related; base; design; effective intervention; first episode schizophrenia; follow-up; functional decline; functional disability; help-seeking behavior; high risk; hippocampal pyramidal neuron; malformation; meetings; millisecond; neural circuit; neurobehavioral; neurodevelopment; patient oriented; psychotic symptoms; relating to nervous system; skills; social; tool

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.

描述（申请人提供）：随着人们越来越认识到，许多以前被认为仅限于成年期的精神疾病实际上在童年时就表现出最初的迹象，并在青春期开始完全出现，NIMH在其战略计划中规定临床研究应该“比较健康发展的轨迹与精神障碍的轨迹，以便更好地了解第一个实例或实例，当发展偏离轨道时。具体而言，这一目标涉及需要“利用成像技术绘制精神障碍的轨迹”，并发现“精神障碍的危险因素的早期发现”。“与这些优先事项一致，目前的申请涉及申请人从成人精神病理学研究人员转变为具有技能和专业知识的发展认知神经科学家的计划，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。该提案是在与一个临床和发展神经科学家团队以及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具有纵向工作专业知识的统计学家协商后撰写的，该提案描述了对三组青少年的认知和神经连接进行为期一年的调查。（年龄12-17岁）：被判定为处于发展精神分裂症的临床高风险（由于存在亚阈值症状）的求助患者、符合精神分裂症首次发作的DSM-IV标准的患者以及匹配的社区比较受试者。 在研究入组时，然后在12个月随访时，所有参与者将进行一组实验性认知测试，同时记录事件相关的EEG数据。EEG能够提供大规模神经回路中同步活动的时间敏感测量。每个认知测试都招募了前额叶-后额叶神经回路的不同子集。这些特殊的神经回路对于连接 前额皮质到更靠后、更早熟的皮质区域（例如，感觉和运动区域），并且是青春期大脑中发生的一些最戏剧性的发展和优化的部位，因为它过渡到稳定的成人功能。因此，这些神经回路在认知挑战下发挥功能的效率应该提供基线功能障碍的证据，并且在长达一年的研究中该效率的变化应该提供异常成熟的证据（如果存在）。事实上，发展精神分裂症的潜在风险被认为是这些功能连接的一个子集失调（例如，通过锥体神经元突触的选择性病理学）;然而，关于坦率的精神病症状的出现和关于典型的青少年发育中的里程碑，这些疾病机制确切地何时出现仍然是未知的。总的来说，这些结果将提供一个敏感的措施的完整性的神经连接，被认为是青少年神经发育和精神分裂症的发病机制提供基板。