Neurodevelopmental variation of intrinsic functional connectivity and its relationship to psychosis risk and gene expression

内在功能连接的神经发育变异及其与精神病风险和基因表达的关系

• 批准号: 10600405
• 负责人: MARIA JALBRZIKOWSKI
• 金额: $ 4.58万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-17 至 2022-07-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600405
• 关键词: Adolescence; Adolescent Development; Affect; Age; Agreement; Archives; Brain; Brain region; Childhood; Clinical; Cognition; Cognitive; Computing Methodologies; Data; Data Set; Delusions; Development; Developmental Course; Disease; Early Diagnosis; Early Intervention; Early identification; Functional Magnetic Resonance Imaging; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genetic Variation; Genomics; Goals; Hallucinations; Intervention; Knowledge; Laboratories; Link; Longitudinal Studies; Measures; Mental disorders; Modeling; Molecular; Neurocognitive; Neurocognitive Deficit; Neurons; Neurosciences; Outcome; Pattern; Philadelphia; Process; Psychoses; Publishing; Reporting; Rest; Risk; Risk Factors; Sampling; Schizophrenia; Symptoms; Syndrome; Time; Training; Variant; Work; Youth; age related; brain pathway; cohort; follow up assessment; gene discovery; genetic information; genome wide association study; genomic data; graph theory; gray matter; help-seeking behavior; high risk; improved; information processing; multidimensional data; neural circuit; neurodevelopment; neuroimaging; novel; population based; psychosis risk; psychosocial; psychotic symptoms; relating to nervous system; risk variant; schizophrenia risk; symptomatology; tool; transcription factor

Project Summary/Abstract Gaining a better understanding of how psychosis emerges during childhood and adolescence will help us identify causes of the illness and treatment targets to facilitate early detection and intervention. The main goals of this K01 are to 1) identify age-associated variation in resting-state functional connectivity in youth, and how that variation relates to psychosis spectrum symptoms, 2) determine to what extent these psychosis- related features are present in help-seeking youth at clinical high risk (CHR) for developing psychosis and 3) identify genetic factors that contribute to typical and atypical neurodevelopment of resting-state intrinsic functional connectivity. Aim 1 will combine archival resting-state functional magnetic resonance imaging (rsfMRI) data from the Philadelphia Neurodevelopmental Cohort (PNC, N=907) and a highly compatible longitudinal study of normative development (Luna cohort, N=223). Graph theory measures will be calculated from the rsfMRI data and be used to determine the extent to which psychosis spectrum youth deviate from typical development. For Aim 2, I will collect rsfMRI data on CHR youth (N=40) and typically developing controls (N=50), longitudinally, with a goal to determine to what extent age-associated alterations in between- and within- network connectivity are present in CHR youth. Positive symptoms of psychosis, psychosocial functioning, and neurocognitive measures will be collected at the baseline assessment and follow-up assessments. I will explore how intrinsic functional connectivity predicts increases in psychotic symptoms, functioning and/or cognition in this cohort. In Aim 3, genetic information from the PNC and Luna cohort will used to determine how expected gene expression profiles of schizophrenia risk and neurodevelopmental genes are associated with development of between- and within- functional connectivity. My training plan will focus on 1) integrating genomic and neuroimaging data to understand the development of psychiatric disorders, 2) conducting analyses of high dimensional data sets to identify mechanisms of and potential risk factors for psychosis, and 3) acquiring expertise in developmental neuroscience and apply this knowledge to neurodevelopmental models of psychosis. Results from this study will help us identify mechanistic processes of brain development and function and identify to what extent age-associated changes in network-connectivity are intact or already present prior to the onset of psychosis. Through the training plan, I will become an expert in modeling high dimensional data and identifying changes in the brain during adolescence, which I will use to improve the prediction of psychosis and identify critical time periods for intervention.

项目摘要/摘要 对儿童期和青春期期间的精神病的出现有了更好的了解将有助于 美国确定疾病的原因和治疗目标，以促进早期发现和干预。主 该K01的目标是1）确定年轻人的静止状态连通性差异，以及 这种变异与精神病谱系症状有关，2）确定这些精神病在多大程度上 - 在临床高风险（CHR）的寻求帮助的年轻人中，有相关特征的患者患有精神病和3） 确定有助于静止状态的典型和非典型神经发育的遗传因素 功能连接。 AIM 1将结合档案静止状态功能磁共振成像 （RSFMRI）来自费城神经发育队列（PNC，n = 907）和高度兼容的数据 规范发展的纵向研究（Luna队列，n = 223）。图理论将计算 从RSFMRI数据中，用于确定精神病谱系偏离的程度 典型的发展。对于AIM 2，我将收集有关CHR青年的RSFMRI数据（n = 40），通常是开发 纵向对照（n = 50），其目标是确定与年龄相关的变化 CHR青年中存在网络内连接性。精神病的积极症状，社会心理 在基线评估和随访时，将收集功能和神经认知措施 评估。我将探讨内在功能连通性如何预测精神病症状的增加， 该队列中的功能和/或认知。在AIM 3中，来自PNC和Luna队列的遗传信息将 用于确定精神分裂症风险和神经发育的预期基因表达谱 基因与功能性之间和内部连通性之间的发展有关。我的培训计划将 关注1）整合基因组和神经影像学数据以了解精神病的发展 疾病，2）进行高维数据集的分析以识别机制和潜在风险 精神病因素，以及3）获得发育神经科学方面的专业知识，并将这些知识应用于 精神病的神经发育模型。这项研究的结果将有助于我们确定机械过程 大脑发育和功能，并确定与年龄相关的网络连通性变化的程度 在精神病发作之前是完整的或已经存在的。通过培训计划，我将成为专家 在建模高维数据并确定青春期大脑的变化时，我将使用 改善精神病的预测并确定干预的关键时间段。

项目成果

Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder.

• DOI: 10.1038/s41537-023-00411-7
• 发表时间: 2023-12-11
• 期刊: SCHIZOPHRENIA
• 作者: Lewis, Lydia;Corcoran, Mary;Cho, Kang Ik K.;Kwak, YooBin;Hayes, Rebecca A.;Larsen, Bart;Jalbrzikowski, Maria
• 通讯作者: Jalbrzikowski, Maria

Neuroimaging Phenotypes Associated With Risk and Resilience for Psychosis and Autism Spectrum Disorders in 22q11.2 Microdeletion Syndrome.

• DOI: 10.1016/j.bpsc.2020.08.015
• 发表时间: 2021-02
• 期刊: BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
• 影响因子: 5.9
• 作者: Jalbrzikowski, Maria

Elevated emotion reactivity and emotion regulation in individuals at clinical high risk for developing psychosis and those diagnosed with a psychotic disorder.

• DOI: 10.1111/eip.13212
• 发表时间: 2022-07
• 期刊: EARLY INTERVENTION IN PSYCHIATRY
• 影响因子: 2
• 作者: Vines, Leah;Bridgwater, Miranda;Bachman, Peter;Hayes, Rebecca;Catalano, Sabrina;Jalbrzikowski, Maria
• 通讯作者: Jalbrzikowski, Maria