Frontoparietal Network Integrity and Risk for Psychosis

额顶网络完整性和精神病风险

• 批准号: 9085375
• 负责人: JUSTIN T BAKER
• 金额: $ 18.23万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9085375
• 关键词: Adolescence; American; Anterior; Applications Grants; Attention; Benchmarking; Biological; Biological Markers; Biology; Bipolar Disorder; Brain; Caring; Chronic; Clinical; Clinical Research; Clinical Services; Cognitive; Data; Data Set; Development; Diagnostic; Disease; Dissection; Dorsal; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; General Hospitals; Genetic; Genetic Risk; Genetic Variation; Genomics; Goals; Grant; Health; Hospitals; Impaired cognition; Individual; Investigation; Jordan; K-Series Research Career Programs; Laboratory Study; Lateral; Lead; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Massachusetts; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Neurobiology; Newly Diagnosed; Outcome; Parietal Lobe; Pathway interactions; Patients; Pattern; Phase; Pilot Projects; Play; Population; Prefrontal Cortex; Process; Psychiatrist; Psychologist; Psychotic Disorders; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Schizoaffective Disorders; Schizophrenia; Staging; Stratification; Structure; Syndrome; System; Temporal Lobe; Testing; Training; Variant; base; career; case control; cingulate cortex; clinical risk; cognitive control; functional status; genome wide association study; healthy volunteer; high risk; image processing; imaging genetics; improved; medical schools; neuroimaging; novel; patient oriented; predictive modeling; prodromal psychosis; psychogenetics; psychotic symptoms; relating to nervous system; resilience; statistics; targeted biomarker; tool; young adult

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Justin Baker, a psychiatrist and neuroscientist at McLean Hospital and the Harvard Medical School. Dr. Baker is establishing himself as a young investigator in patient- oriented clinical research of schizophrenia and bipolar disorder. This K23 award will provide Dr. Baker with the support necessary to accomplish the following goals: (1) to become expert at patient-oriented clinical research in psychotic disorders; (2) to conduct investigations of neurobiological correlates in patients in early stages of psychotic illness; (3) to implement advanced genetic methods in clinical studies; and (4) to develop an independent clinical research career. To achieve these goals, Dr. Baker has assembled a mentoring team comprised of two primary mentors, Dr. Jordan Smoller, Director of Psychiatric Genetics at Massachusetts General Hospital (MGH), who conducts genetic investigations in schizophrenia and bipolar disorder, and Dr. Dost Ongur, Chief of the McLean Hospital Psychotic Disorders Division who leads a neuroimaging laboratory studying the biology of psychotic illness. Consultants include Dr. Randy Buckner, Director of Psychiatric Neuroimaging at MGH, a neuroscientist who contributes advanced neuroimaging expertise, Larry Seidman, a psychologist with expertise in the early phases of schizophrenia and bipolar disorder, and Dr. Ben Neale, an expert in statistics and statistical genetics, particularly in the field of psychiatric genetics. Psychotic disorders, including schizophrenia (SZ and bipolar disorder with psychosis (BPP) are heritable conditions, and yet little is known about changes to brain structure and function that may arise from genetic variation and in turn confer clinical risk. Dr. Baker's research will focus on the neural system changes that accompany elevated genetic risk for SZ and BPP in a psychiatrically healthy young adult population (Aim 1) and the neural system changes that accompany early stages of SZ and BPP (Aim 2). In Aim 1, Dr. Baker will establish the effects of polygenic risk factors for SZ and BPP, obtained from the Psychiatric Genetics Consortium, on brain structure and function, by leveraging a large existing imaging-genetics sample (>1800) from psychiatrically healthy individuals. In addition, he will create a novel polygenic risk score based on variation in brain function in healthy volunteers and test whether this score informs clinical outcomes in a cross-diagnostic patient sample. In Aim 2, Dr. Baker will analyze two data sets of brain MRI from early stages of psychosis: one from an existing sample of structural and functional MRI scans obtained from patients prodromal for psychosis from the North American Prodrome Longitudinal Study; for the second, Dr. Baker will conduct a cross-sectional pilot study to generate preliminary data on the effects of newly diagnosed psychosis on brain structure and function, leveraging the clinical services of the McLean Psychotic Disorders Division. This research will form the basis for a study of risk prediction modeling in high risk and newly diagnosed schizophrenia and bipolar disorder, to be proposed in an R01 grant application before the end of the K award.

描述（由申请人提供）：这是麦克莱恩医院和哈佛医学院的精神科医生和神经科学家贾斯汀·贝克博士的K23奖。贝克博士正在建立自己是年轻的研究者，从事以患者为导向的临床研究 精神分裂症和躁郁症。该K23奖将为贝克博士提供实现以下目标所需的支持：（1）成为以患者为导向的精神病临床研究专家； （2）对精神病早期患者的神经生物学相关性进行调查； （3）在临床研究中实施先进的遗传方法； （4）发展独立的临床研究职业。为了实现这些目标，贝克博士组建了一支由两名主要导师组成的指导团队，马萨诸塞州综合医院（MGH）精神病遗传学总监乔丹·斯莫勒（Jordan Smoller）博士在精神分裂症和双极疾病中进行了遗传研究，以及麦克莱恩医院医院精神疾病的遗传学调查。顾问包括MGH的精神神经影像学总监Randy Buckner博士，他是一名神经科学家，他贡献了高级神经影像学专业知识，Larry Seidman，Larry Seidman，Larry Seidman是精神分裂症早期阶段和双色体障碍的心理学家，以及Ben Neale博士，以及统计和统计学遗传学专家Ben Neale博士，尤其是精神遗传学的专家。 Psychotic disorders, including schizophrenia (SZ and bipolar disorder with psychosis (BPP) are heritable conditions, and yet little is known about changes to brain structure and function that may arise from genetic variation and in turn confer clinical risk. Dr. Baker's research will focus on the neural system changes that accompany elevated genetic risk for SZ and BPP in a psychiatrically healthy young adult population (Aim 1) and the neural system changes that accompany early stages of SZ和BPP（AIM 2）。在AIM 2中的跨诊断患者样本中，Baker博士将分析精神病早期的两个数据集MRI：一个来自现有的结构和功能性MRI扫描样本，这些样本从北美前驱纵向纵向研究的患者中。第二次，贝克博士将进行一项横断面试验研究，以生成有关新诊断的精神病对脑结构和功能影响的初步数据，利用麦克莱恩精神疾病部门的临床服务。这项研究将构成研究高风险和新诊断的精神分裂症和躁郁症的风险预测建模的基础，这将在k奖结束之前在R01赠款应用中提出。