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: 8465914
• 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 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8465914
• 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; 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（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期的精神疾病实际上在儿童时期就出现了最初的症状，并在青春期开始完全显现，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时的第一个或多个实例。”具体来说，这一目标涉及需要“利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危险因素”。与这些优先事项一致，当前的申请涉及申请人从成人精神病理学研究员转变为发育认知神经科学家的计划，该科学家具有研究青春期作为精神疾病（例如精神分裂症）发展的敏感时期的技能和专业知识。该提案是在与临床和发展神经科学家团队以及进行基础研究的发展心理学家和临床心理学家以及具有纵向工作专业知识的统计学家协商后撰写的，描述了对三组青少年（12-17岁）的认知和神经连接进行为期一年的调查：被判断为发展为精神分裂症临床高风险的寻求帮助的患者（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。 在研究登记时以及在 12 个月的随访时，所有参与者都将进行一组实验性认知测试，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中同步活动的时间敏感测量。所提出的认知测试均招募了前额-后神经回路的各个子集。这些特殊的神经回路对于连接 前额皮质到更靠后、较早成熟的皮质区域（例如感觉和运动区域），并且是青春期大脑中发生的一些最显着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作用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效率的变化应该提供异常成熟（如果存在）的证据。事实上，人们认为，罹患精神分裂症的潜在风险是这些功能连接的一部分失调（例如，通过锥体神经元突触的选择性病理学）；然而，这些疾病机制究竟何时出现、出现明显的精神病症状以及典型青少年发展的里程碑仍然未知。总的来说，这些结果将为神经连接的完整性提供灵敏的测量，这些神经连接被认为为青少年神经发育和精神分裂症发病机制提供了基础。