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.

项目概要/摘要 更好地了解童年和青春期精神病如何出现将有所帮助 我们确定疾病的原因和治疗目标，以便于早期发现和干预。主要 K01 的目标是 1) 确定青年人静息状态功能连接中与年龄相关的变化，以及 这种变化如何与精神病谱系症状相关，2）确定这些精神病的程度- 相关特征存在于患有精神病的临床高风险 (CHR) 寻求帮助的青少年中，并且 3) 识别有助于静息态内在神经发育的典型和非典型神经发育的遗传因素 功能连接。目标 1 将结合档案静息态功能磁共振成像 (rsfMRI) 数据来自费城神经发育队列 (PNC, N=907) 和高度兼容的 规范发展的纵向研究（Luna 队列，N=223）。将计算图论度量 来自 rsfMRI 数据并用于确定青少年精神病谱系偏离的程度 典型发展。对于目标 2，我将收集 CHR 青少年 (N=40) 和典型发育中儿童的 rsfMRI 数据 纵向控制（N = 50），目的是确定之间年龄相关的改变程度 - CHR 青少年中存在网络内连通性。精神病、社会心理的阳性症状 将在基线评估和随访时收集功能和神经认知测量 评估。我将探讨内在功能连接如何预测精神病症状的增加， 该群体的功能和/或认知。在目标 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 基因与功能间和功能内连接的发展相关。我的训练计划将 重点关注 1) 整合基因组和神经影像数据以了解精神病学的发展 疾病，2) 对高维数据集进行分析，以确定其机制和潜在风险 精神病的因素，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。这项研究的结果将帮助我们识别机械过程 大脑发育和功能的变化，并确定与年龄相关的网络连接变化程度 完好无损或在精神病发作前就已存在。通过培训计划，我将成为专家 对高维数据进行建模并识别青春期期间大脑的变化，我将用它来 提高对精神病的预测并确定干预的关键时间段。

项目成果

State-Dependent Functional Dysconnectivity in Youth With Psychosis Spectrum Symptoms.

患有精神病谱系症状的青少年中状态依赖性功能脱节。

• 发表时间: 2020
• 影响因子: 6.6
• 作者: Mennigen, Eva;Jolles, Dietsje D;Hegarty, Catherine E;Gupta, Mohan;Jalbrzikowski, Maria;Olde Loohuis, Loes M;Ophoff, Roel A;Karlsgodt, Katherine H;Bearden, Carrie E
• 通讯作者: Bearden, Carrie E

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

临床上患精神病的高风险个体和被诊断患有精神病的个体的情绪反应性和情绪调节能力升高。

• 发表时间: 2022-07
• 作者: Vines, Leah;Bridgwater, Miranda;Bachman, Peter;Hayes, Rebecca;Catalano, Sabrina;Jalbrzikowski, Maria
• 通讯作者: Jalbrzikowski, Maria

Structural Brain Alterations in Youth With Psychosis and Bipolar Spectrum Symptoms.

患有精神病和躁郁症谱系症状的青少年的大脑结构改变。

• 发表时间: 2019
• 影响因子: 13.3
• 作者: Jalbrzikowski, Maria;Freedman, David;Hegarty, Catherine E;Mennigen, Eva;Karlsgodt, Katherine H;Olde Loohuis, Loes M;Ophoff, Roel A;Gur, Raquel E;Bearden, Carrie E
• 通讯作者: Bearden, Carrie E

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

结构磁共振成像测量与临床精神病高风险个体精神病发作的关联：ENIGMA 工作组的大型分析。

• 发表时间: 2021-07-01
• 影响因子: 25.8
• 作者: ENIGMA Clinical High Risk for Psychosis Working Group;Jalbrzikowski, Maria;Hayes, Rebecca A;Wood, Stephen J;Nordholm, Dorte;Zhou, Juan H;Fusar;Uhlhaas, Peter J;Takahashi, Tsutomu;Sugranyes, Gisela;Kwak, Yoo Bin;Mathalon, Daniel H;K
• 通讯作者: K

The association between cortical gyrification and sleep in adolescents and young adults.

青少年和年轻人皮质回旋与睡眠之间的关联。

• 发表时间: 2023-09-16
• 作者: Santos, João Paulo Lima;Hayes, Rebecca;Franzen, Peter L;Goldstein, Tina R;Hasler, Brant P;Buysse, Daniel J;Siegle, Greg J;Dahl, Ronald E;Forbes, Erika E;Ladouceur, Cecile D;McMakin, Dana L;Ryan, Neal D;Silk, Jennifer S;Jalbrzikowski, Maria;S
• 通讯作者: S