Striatal Connectivity and Clinical Outcome in Psychosis

纹状体连接性和精神病的临床结果

• 批准号: 9920775
• 负责人: Anil K Malhotra
• 金额: $ 50.43万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920775
• 关键词: Age; Anterior; Antipsychotic Agents; Biological Assay; Biological Markers; Brain imaging; Categories; Clinical; Corpus striatum structure; Data; Delusions; Development; Diagnosis; Disease; Dorsal; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hallucinations; Hippocampus (Brain); Individual; Insula of Reil; Lead; Learning; Linear Models; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mental disorders; Modeling; Outcome; Parietal Lobe; Patients; Pharmaceutical Preparations; Pharmacotherapy; Population Heterogeneity; Positive Valence; Prefrontal Cortex; Prognostic Marker; Prospective cohort; Psychotic Disorders; Reporting; Research; Research Domain Criteria; Rest; Rewards; Scanning; Sensitivity and Specificity; Standardization; Symptoms; System; Testing; Time; Treatment Efficacy; Ventral Striatum; base; brain circuitry; cingulate cortex; clinical predictors; cohort; design; effective therapy; first episode psychosis; first episode schizophrenia; follow-up; imaging study; indexing; individual patient; individualized medicine; neural circuit; neuroimaging; next generation; novel; novel marker; patient population; precision medicine; predicting response; psychotic symptoms; recruit; response; sex; symptomatology; tool; treatment response

ABSTRACT Converging lines of evidence suggest a key role for striatal dysconnectivity in the pathophysiology of psychosis. In the proposed study, we will utilize resting state functional magnetic resonance imaging (rs-fMRI), as well as fMRI tasks derived from the Research Domain Criteria (RDoC) framework, to: 1) develop and validate a prognostic biomarker to predict antipsychotic treatment response; and 2) to model the underlying neural circuitry changes associated with state changes in psychotic symptomatology. As a prognostic biomarker, a neuroimaging assay of striatal connectivity can potentially provide a clinically useful tool to advance the goal of precision medicine. As a longitudinal index of symptom change, our model can serve as an objective index against which to measure potential efficacy of newly developed antipsychotic treatments. A large (n=120), well-characterized cohort of patients presenting with a first episode active psychosis (regardless of DSM diagnosis) will be recruited, along with matched controls (n=50). We will utilize two well- validated fMRI tasks capturing two portions of the positive valence system: probabilistic category learning and reward responsiveness; these tasks are designed to interrogate dorsal and ventral corticostriatal circuits, respectively. Our design will be longitudinal, with two scanning sessions performed for each patient: at baseline, and after 12 weeks of treatment. Treatment will be standardized across all patients to reduce potential confounds, and healthy controls will also be scanned at baseline and 12 weeks in order to control for effects of time and practice. Level of psychotic symptomatology (hallucinations, delusions, and thought disorder) will be measured at regular intervals using a comprehensive battery of rating scales. We will utilize Kaplan-Meier estimators and hierarchical linear modeling to examine the association of baseline striatal connectivity, and changes in connectivity over time, with clinical response of psychotic symptoms to antipsychotic treatment. Deliverables will include both baseline and longitudinal biomarkers that can subsequently be tested in broader, more heterogeneous populations of patients with psychosis.

抽象的 融合的证据线表明，纹状体异常连接性在病理生理学中的关键作用 精神病。在拟议的研究中，我们将利用静止状态功能磁共振成像（RS-FMRI）， 以及从研究领域标准（RDOC）框架中得出的fMRI任务，至：1）开发和 验证预后生物标志物以预测抗精神病药物治疗反应； 2）建模基础 神经回路的变化与精神病症状的状态变化有关。作为预后 生物标志物是一种纹状体连接性的神经影像学测定，可能会为临床上有用的工具提供 促进精密医学的目标。作为症状变化的纵向指标，我们的模型可以作为 一个客观指数，以衡量新开发的抗精神病药物的潜在疗效。 大型（n = 120），表征良好的患者，出现了第一集活动精神病 （无论DSM诊断如何）以及匹配的对照（n = 50）。我们将利用两个 已验证的fMRI任务捕获了正价系统的两个部分：概率类别学习和 奖励响应能力；这些任务旨在询问背侧和腹侧皮质纹状体电路， 分别。我们的设计将是纵向的，每个患者进行了两次扫描课程：在 基线，经过12周的治疗。治疗将在所有患者中进行标准化，以减少 潜在的混淆和健康控制也将在基线和12周进行扫描，以控制 时间和实践的影响。精神病症状学水平（幻觉，妄想和思想 疾病）将使用全面的评级量表定期测量。我们将利用 Kaplan-Meier估计器和分层线性建模，以检查基线纹状体的关联 连通性以及随着时间的连​​接性的变化，精神病症状的临床反应对 抗精神病药物。可交付成果将包括基线和纵向生物标志物可以 随后在精神病患者的更广泛，更异质的人群中进行测试。