Brain Function and Structure in Young Children at Familial Risk for Schizophrenia

有精神分裂症家族风险的幼儿的脑功能和结构

• 批准号: 8424970
• 负责人: JOHN GABRIELI
• 金额: $ 20.57万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424970
• 关键词: Adolescence; Adolescent; Adult; Age; Area; Back; Basal Ganglia; Behavioral; Biological; Biological Markers; Biological Neural Networks; Brain; Brain region; Characteristics; Child; Childhood; Clinical; Clinical assessments; Cognition; Cognitive; Conceptions; Cross-Sectional Studies; Data; Development; Diffusion Magnetic Resonance Imaging; Early Intervention; Evolution; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Grant; Guidelines; Hippocampus (Brain); Image; Intervention; Judgment; Knowledge; Lateral; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Mothers; National Institute of Mental Health; Neurobiology; Neurocognitive; Neuropsychology; Parietal; Phase; Prefrontal Cortex; Prevention; Prevention strategy; Primary Prevention; Process; Psychotic Disorders; Recruitment Activity; Reporting; Research; Rest; Risk; Scanning; Schizophrenia; Secondary Prevention; Semantics; Short-Term Memory; Solid; Strategic Planning; Structure; Structure of superior temporal sulcus; Surface; Symptoms; Teenagers; Temporal Lobe; Testing; Thick; Thinking; United States National Institutes of Health; Work; base; boys; cognitive neuroscience; design; disability; early childhood; experience; family genetics; high risk; information gathering; information processing; innovation; neuroimaging; neuropsychological; novel; offspring; preadolescence; prepuberty; prevent; public health relevance; relating to nervous system; research study; social; white matter

DESCRIPTION (provided by applicant): The identification of markers for the prediction of psychosis is central to the development of early intervention and prevention strategies for schizophrenia. Primary or secondary prevention strategies oriented to the pre-psychosis and pre-prodromal periods have not been attempted because of an absence of biomarkers or solid knowledge of pathophysiology in the period before adolescence prior to the emergence of mild psychotic symptoms (i.e., prior to the putative "prodrome"). Because there is consistent evidence of significant neuropsychological and social deficits beginning in early childhood of people who later develop schizophrenia, there is strong reason to believe that brain abnormalities are present in the preteen years, but there is no evidence as yet about such abnormalities in that period. The present proposal aims to begin to fill that critical gap of knowledge. Indeed, some of the earliest symptoms of schizophrenia such as disturbances in the sense of self, and those that reflect impaired metacognition such as impaired self-other boundaries are frequently present in those at risk for schizophrenia (ARS) in the age range we intend to study. We hypothesize that the neurobiology of the "early premorbid" period, is characterized by brain dysmaturation, reflected in altered cortical thickness, volume reduction in hippocampus and medial prefrontal cortex, abnormal information processing and dysfunctional connectivity. This preliminary study, focused on children at risk for schizophrenia, ages 8- 11, is designed to test hypotheses about brain function, structure, and cognition in a cross-sectional design that will lay a foundation for subsequent grants designed to study the longitudinal evolution of brain structure and function in prepubertal ARS children. This project will focus on a novel, but highly promising area of new research; the neural substrates of the inner experience of the child at risk, by evaluating (using functional MRI): 1). the "default mode" of brain function and; 2). the neural network underlying 'self reflection' (reflection about oneself or others). Moreover, we will extend to childhood our previous work in adolescents demonstrating; 3). altered brain function during working memory and 4). structural abnormalities. The study goals are consistent with the R21 guidelines emphasizing novelty and innovation, in regard to the feasibility of conducting these imaging studies in young children. Moreover, the study is consistent with the 2008 NIMH Strategic Plan in which prediction and prevention of schizophrenia and disability in those at risk for the illness are key NIH priorities.

描述（由申请人提供）：鉴定精神病预测的标记物对于发展精神分裂症的早期干预和预防策略至关重要。由于在青春期出现之前的青春期（即假定的“ Prodrome''之前，在青春期出现之前，尚未尝试针对精神病和前期时期的初级或二级预防策略，并没有尝试过生物标志物或牢固的病理生理学知识。由于有一致的证据表明，后来发展精神分裂症的人们的幼儿始于幼儿，因此有充分的理由相信，在青春期中，大脑异常存在，但在此期间尚无证据。目前的提案旨在开始填补这一关键的知识差距。的确，精神分裂症的一些最早症状，例如自我意义上的障碍，以及反映元认知受损的症状，例如自我其他界​​限受损，在我们打算研究的年龄范围内有精神分裂症（ARS）风险的人中经常存在。我们假设“早期病前”时期的神经生物学的特征是脑部性障碍，反映在皮质厚度改变，海马体积减少和内侧前额叶皮质，异常信息处理和功能障碍连接性。这项以精神分裂症风险的儿童为8-11岁的初步研究旨在测试有关横断面设计中关于大脑功能，结构和认知的假设，该假设将为后来的赠款奠定基础，以研究旨在研究青春期前ARS ARS儿童脑结构和功能的纵向演变。该项目将重点放在一个新研究的小说但有希望的领域。通过评估（使用功能性MRI）：1），通过评估儿童的内在经历的神经底物。大脑功能的“默认模式”和； 2）。 “自我反思”（关于自己或他人的反思）的神经网络。此外，我们将扩展到童年时期我们先前在青少年展示的工作； 3）。工作记忆期间的大脑功能改变了4）。结构异常。研究目标与强调新颖性和创新的R21指南是一致的，该指南对于在幼儿进行这些成像研究的可行性。此外，这项研究与2008年NIMH战略计划一致，该计划在疾病风险中的精神分裂症和残疾预测和残疾是关键的NIH优先事项。

项目成果

New Targets for Prevention of Schizophrenia: Is It Time for Interventions in the Premorbid Phase?

预防精神分裂症的新目标：现在是在病前阶段进行干预的时候了吗？

• DOI: 10.1093/schbul/sbv050
• 发表时间: 2015
• 期刊: Schizophrenia bulletin
• 影响因子: 6.6
• 作者: Seidman,LarryJ;Nordentoft,Merete
• 通讯作者: Nordentoft,Merete

Hyperactivation of Posterior Default Mode Network During Self-Referential Processing in Children at Familial High-Risk for Psychosis.

• DOI: 10.3389/fpsyt.2021.613142
• 发表时间: 2021
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Collin G;Bauer CCC;Anteraper SA;Gabrieli JDE;Molokotos E;Mesholam-Gately R;Thermenos HW;Seidman LJ;Keshavan MS;Shenton ME;Whitfield-Gabrieli S
• 通讯作者: Whitfield-Gabrieli S