Brain connectivity and the role of myelin in Psychosis

大脑连接和髓磷脂在精神病中的作用

• 批准号: 10133144
• 负责人: SOPHIA FRANGOU
• 金额: $ 62.82万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-10 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10133144
• 关键词: Address; Adolescence; Algorithmic Analysis; Anterior; Area; Autopsy; Axon; Behavior; Bilateral; Brain; Brain imaging; Brain region; Clinical; Cognition; Cognitive deficits; Complement; Complex; Coupled; Data; Dimensions; Early Diagnosis; Functional disorder; Gene Expression; Genes; Histologic; Human; Individual; Insula of Reil; Intervention; Interview; Investigation; Knowledge; Lateral; Link; Magnetic Resonance Imaging; Measurable; Measures; Middle frontal gyrus structure; Modeling; Morphology; Myelin; Neurobiology; Neurons; Oligodendroglia; Onset of illness; Participant; Pathology; Patients; Pharmaceutical Preparations; Phenotype; Physiological; Primary Prevention; Property; Psychopathology; Psychoses; Psychotic Disorders; Reporting; Reproducibility; Research Domain Criteria; Resolution; Role; Sampling; Scanning; Schizophrenia; Series; Severities; Severity of illness; Siblings; Speed; Structure; Superior temporal gyrus; Symptoms; System; Testing; Therapeutic Agents; Time; base; burden of illness; case control; cognitive function; cognitive testing; connectome; density; diffusion weighted; disability; disability burden; disorder risk; dysmyelination; emerging adult; experience; experimental study; follow-up; graph theory; healthy volunteer; imaging study; improved outcome; indexing; insight; magnetic field; myelination; neural network; neurodevelopment; neuroimaging; neurophysiology; novel; novel therapeutic intervention; novel therapeutics; prevent; processing speed; psychotic symptoms; recruit; relating to nervous system; response; schizophrenia risk; secondary analysis; support network; theories; therapy development

Despite the wealth of magnetic resonance imaging (MRI) studies supporting the dysconnectivity model of schizophrenia, our understanding of the underlying neurophysiological mechanisms remains limited. Abnormalities in myelination are a plausible candidate as myelination is essential for the coordinated activity of neural networks that support cognitive function and behaviour. Moreover, myelin-related pathology has long been postulated in schizophrenia on the basis of post-mortem and gene expression evidence. Dys-myelination is also a key component of neurodevelopment theories of schizophrenia because myelination of cortical association areas in late adolescence and early adulthood coincides with the peak period of risk for disease onset. This application will harness the power of ultra-high-field MRI coupled with advanced analyses algorithms to detect and quantify cortical myelin in a way that has never been possible before and test the relevance of myelination for schizophrenia-related dysconnectivity. We provide initial evidence for intracortical myelin abnormalities in patients with recent onset schizophrenia and demonstrate their impact on connectivity and disease severity. In this application, we propose a series of experiments with three specific aims. First, we aim to demonstrate the reproducibility of our initial findings on schizophrenia-related intracortical myelin changes in an independent sample of patients with recent onset psychosis and relate these changes to the topological properties of the functional and structural connectome; we will also examine the functional correlates of compromised myelin integrity on clinical features and cognition (Aim 1). Second, we plan to test for longitudinal changes in myelination in patients with schizophrenia over a 2-year follow-up period and investigate their relevance to disease severity and course (Aim 2). Third, we will test whether abnormalities in myelination are related to familial risk of schizophrenia by investigating intracortical myelin and its effect on the functional and structural connectome and cognition in unaffected siblings of patients, both cross-sectionally and over a 2-year follow-up period (Aim 3). The inclusion of unaffected siblings will also allow for the investigation of myelin-related abnormalities relevant to schizophrenia without the confounding effect of medication. The results of this study will provide novel evidence for unlocking the mechanistic “black box” in schizophrenia and will open new avenues for treatment using interventions that may target myelin pathology.

尽管有丰富的磁共振成像(MRI)研究支持连接障碍模型 精神分裂症，我们对潜在的神经生理机制的了解仍然有限。 髓鞘形成的异常是一个合理的候选因素，因为髓鞘形成是细胞协调活动的关键。 支持认知功能和行为的神经网络。此外，髓鞘相关的病理由来已久 根据尸检和基因表达证据推测为精神分裂症患者。DYS-髓鞘形成 也是精神分裂症神经发育理论的关键组成部分，因为皮质髓鞘形成 青春期晚期和成年期早期的关联区与疾病风险的高峰期相吻合 开始了。这一应用将利用超高场磁共振结合先进分析的力量 以一种前所未有的方式检测和量化皮质髓鞘的算法，并测试 髓鞘形成与精神分裂症相关的连接障碍的相关性。我们提供了皮质内的初步证据 新发精神分裂症患者的髓鞘异常及其对连接性的影响 以及疾病的严重性。在这一应用中，我们提出了一系列具有三个特定目标的实验。首先，我们 目的证明我们对精神分裂症相关皮质内髓鞘的初步研究结果的重复性。 最近发病的精神病患者的独立样本中的变化，并将这些变化与 功能和结构连接体的拓扑性质；我们还将研究泛函 髓鞘完整性受损与临床特征和认知的相关性(目标1)。第二，我们计划测试 精神分裂症患者2年随访期髓鞘纵向变化的研究 调查它们与疾病严重程度和病程的相关性(目标2)。第三，我们将测试是否存在异常情况 通过研究皮质内髓鞘及其对精神分裂症的影响，髓鞘形成与精神分裂症的家族风险有关 横断面研究患者未受影响同胞的功能和结构连接体与认知 以及两年的随访期(目标3)。包括未受影响的兄弟姐妹也将允许 与精神分裂症相关的髓鞘相关异常的调查 药物治疗。这项研究的结果将为解开黑匣子机制提供新的证据 并将为使用可能针对髓鞘病理的干预措施治疗开辟新的途径。

项目成果

Initial evidence of abnormal brain plasticity in anorexia nervosa: an ultra-high field study.

• DOI: 10.1038/s41598-022-06113-x
• 发表时间: 2022-02-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Pappaianni E;Borsarini B;Doucet GE;Hochman A;Frangou S;Micali N
• 通讯作者: Micali N

Brain age prediction in schizophrenia: Does the choice of machine learning algorithm matter?

• DOI: 10.1016/j.pscychresns.2021.111270
• 发表时间: 2021-04-30
• 期刊: Psychiatry research. Neuroimaging
• 作者: Lee WH;Antoniades M;Schnack HG;Kahn RS;Frangou S
• 通讯作者: Frangou S

The Enduring Allure of Explanatory Reductionism in Schizophrenia.

• DOI: 10.1016/j.biopsych.2020.01.008
• 发表时间: 2020-04-15
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Frangou S

Depth-dependent intracortical myelin organization in the living human brain determined by in vivo ultra-high field magnetic resonance imaging.

• DOI: 10.1016/j.neuroimage.2018.10.023
• 发表时间: 2019-01-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Sprooten E;O'Halloran R;Dinse J;Lee WH;Moser DA;Doucet GE;Goodman M;Krinsky H;Paulino A;Rasgon A;Leibu E;Balchandani P;Inglese M;Frangou S
• 通讯作者: Frangou S