Imaging Hippocampal Function in Psychosis

精神病中海马功能的成像

• 批准号: 10406173
• 负责人: STEPHAN HECKERS
• 金额: $ 81.84万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-07 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406173
• 关键词: Acute; Affect; Animal Model; Anterior; Antiepileptic Agents; Blood flow; Brain; Chronic; Chronic Schizophrenia; Clinical Research; DSM-V; Data; Delusions; Diagnosis; Dimensions; Disease; Disease Pathway; Dissection; Dose; Early Diagnosis; Equilibrium; Evolution; Family; Frequencies; Functional Imaging; Functional disorder; Goals; Heterogeneity; Hippocampus (Brain); Hyperactivity; Image; Individual; Intervention; Levetiracetam; Link; Longitudinal Studies; Maps; Memory; Memory impairment; Modeling; Outcome; Pathway interactions; Patients; Performance; Persons; Pharmacology; Population; Prevention; Prevention strategy; Protocols documentation; Psychoses; Psychotic Disorders; Research; Resolution; Rest; Sampling; Schizophrenia; Schizophreniform Disorder; Severities; Societies; Staging; Structure; Study models; Symptoms; Testing; Time; base; brain abnormalities; clinical heterogeneity; cohort; density; early psychosis; experience; experimental study; improved; network dysfunction; preclinical study; prevent; public health relevance; recruit; relational memory; restoration; social deficits; translational neuroscience

Abstract (Project Summary) We propose to parse the clinical heterogeneity of psychotic disorders by studying the evolution of hippocampal dysfunction in the early stage of psychosis (ESOP). Smaller hippocampal volume is one of the most significant brain abnormalities in chronic schizophrenia, but is less pronounced in prodromal and early stages of psychosis. In contrast, hyperactivity of the anterior hippocampus has been observed in both early and chronic stages of psychosis. Clinical and preclinical studies have identified excitation/inhibition imbalance as a plausible mechanism for hippocampal hyperactivity in psychosis. Clarifying the timing and mechanism of hippocampal dysfunction will improve our ability to intervene and prevent the progression from early psychosis to schizophrenia. We propose to study 2 ESOP cohorts. ESOP-1 will be a new cohort of acutely ill psychotic patients who meet DSM-5 criteria A for schizophrenia for at least one month, but not more than 2 years (i.e., schizophreniform disorder or early schizophrenia). We expect that, at the end of the study, 2/3 of the ESOP-1 cohort will have progressed to schizophrenia, while the remaining 1/3 will be diagnosed with schizophreniform disorder. ESOP- 2 is a well-characterized sample of schizophrenia patients, who have participated in repeated assessments during the first two years of their illness. From ESOP-1 we will recruit 30 patients and 30 healthy control subjects for the restoration of hippocampal excitation/inhibition balance. We predict that the hippocampus is hyperactive in the ESOP-1 cohort, resulting in perturbations of relational, hippocampal-based memory. We expect to find structural changes of the anterior hippocampus only in those ESOP persons who will progress to schizophrenia. In the ESOP-2 cohort, we predict progressive hippocampal volume loss, advancing from the anterior to the posterior region, resulting in more significant memory deficits. We predict that restoring normal excitation/inhibition balance will improve hippocampal function in ESOP persons. To test our hypotheses, we will collect high-density, multi-dimensional assessments of psychosis. We will use high-resolution parcellation protocols of the hippocampus and functional imaging of resting-state and task-based activation. We will use single dose administration of levetiracetam, an anti-epileptic drug, to modulate excitation/inhibition balance. The proposed combination of longitudinal and pharmacological imaging will allow us to study the timing and mechanism of hippocampal dysfunction in psychotic disorders. The integration of these approaches aims to establish a staging model of psychotic disorders, with the ultimate goal to aid early detection, prevention and treatment.

摘要（项目摘要） 我们建议通过研究海马的进化来解析精神障碍的临床异质性 精神病早期阶段的功能障碍（ESOP）。 海马体积变小是慢性精神分裂症最显着的大脑异常之一，但 在精神病的前驱期和早期阶段不太明显。相反，前部过度活跃 在精神病的早期和慢性阶段都观察到了海马体的存在。临床和临床前研究 已经确定兴奋/抑制失衡是海马过度活跃的一个合理机制 精神病。阐明海马功能障碍发生的时间和机制将提高我们的干预能力 并防止从早期精神病进展为精神分裂症。 我们建议研究 2 个 ESOP 队列。 ESOP-1 将是一组新的急性精神病患者，他们满足 DSM-5 标准 A 表示精神分裂症至少一个月，但不超过 2 年（即精神分裂症 障碍或早期精神分裂症）。我们预计，在研究结束时，2/3 的 ESOP-1 队列将拥有 进展为精神分裂症，而剩下的1/3将被诊断为精神分裂样障碍。员工持股计划- 2 是一个特征明确的精神分裂症患者样本，他们参与了重复评估 在他们患病的头两年。从 ESOP-1 中，我们将招募 30 名患者和 30 名健康对照受试者 用于恢复海马兴奋/抑制平衡。 我们预测 ESOP-1 队列中的海马体过度活跃，导致相关的扰动， 基于海马体的记忆。我们期望仅在那些区域中发现前海马体的结构变化 即将发展为精神分裂症的 ESOP 人士。在 ESOP-2 队列中，我们预测进行性海马 容量损失，从前部区域推进到后部区域，导致更严重的记忆缺陷。 我们预测恢复正常的兴奋/抑制平衡将改善 ESOP 中的海马功能 人。 为了检验我们的假设，我们将收集高密度、多维度的精神病评估。我们将使用 海马体的高分辨率分割协议以及静息态和基于任务的功能成像 激活。我们将使用单剂量施用左乙拉西坦（一种抗癫痫药物）来调节 激发/抑制平衡。 所提议的纵向和药理学成像的结合将使我们能够研究时间和 精神病性海马功能障碍的机制。这些方法的整合旨在 建立精神障碍的分期模型，最终目标是帮助早期发现、预防和治疗 治疗。