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）：用于预测精神病的标记物的识别对于精神分裂症早期干预和预防策略的制定至关重要。尚未尝试针对精神病前期和前驱期的一级或二级预防策略，因为在出​​现轻度精神病症状之前的青春期之前（即出现症状之前）缺乏生物标志物或对病理生理学的扎实了解。假定的“前驱症状”）。因为有一致的证据表明，后来患上精神分裂症的人从童年早期就开始出现显着的神经心理和社会缺陷，因此有充分的理由相信，大脑异常在青春期前就存在，但目前还没有证据表明这种异常发生在青少年时期。时期。本提案旨在开始填补这一关键的知识空白。事实上，精神分裂症的一些最早的症状，如自我意识障碍，以及反映元认知受损的症状，如自我-他人界限受损，经常出现在我们打算研究的年龄范围内有精神分裂症 (ARS) 风险的人群中。学习。我们假设“病前早期”时期的神经生物学特征是大脑发育不良，反映在皮质厚度改变、海马体和内侧前额皮质体积减少、信息处理异常和连接功能障碍。这项初步研究主要针对 8 至 11 岁有精神分裂症风险的儿童，旨在以横断面设计检验有关大脑功能、结构和认知的假设，这将为后续研究纵向进化的资助奠定基础。青春期前 ARS 儿童的大脑结构和功能。该项目将重点关注一个新颖但极具前景的新研究领域；通过评估（使用功能性 MRI）来了解处于危险中的儿童的内部体验的神经基质：1）。大脑功能的“默认模式”； 2）。 “自我反思”（对自己或他人的反思）的神经网络。此外，我们将把我们之前在青少年中所做的工作延伸到儿童时期； 3）。工作记忆期间大脑功能发生改变；4)。结构异常。关于在幼儿中进行这些影像学研究的可行性，研究目标与强调新颖性和创新性的 R21 指南一致。此外，该研究与 2008 年 NIMH 战略计划一致，其中预测和预防精神分裂症和有患病风险的人的残疾是 NIH 的主要优先事项。

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