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病的临床异质性 精神病早期（ESOP）的功能障碍。 海马体积较小是慢性精神分裂症中最重要的脑异常之一，但是 精神病的前驱和早期阶段不太明显。相反，前部的多动症 在精神病的早期和慢性阶段都观察到海马。临床和临床前研究 已经确定激发/抑制失衡是海马多动症的合理机制 精神病。澄清海马功能障碍的时间和机制将提高我们干预的能力 并防止早期精神病发展到精神分裂症。 我们建议研究2个ESOP队列。 ESOP-1将是遇到急性疾病的精神病患者的新队列 精神分裂症的DSM-5标准至少一个月，但不超过2年（即精神分裂症 疾病或早期精神分裂症）。我们希望，在研究结束时，ESOP-1队列的2/3将有 发展为精神分裂症，而其余的1/3将被诊断为精神分裂症。埃斯 2是一个精神分裂症患者的良好表征样本，他们参加了重复评估 在他们病的头两年中。从ESOP-1中，我们将招募30名患者和30名健康对照组 为了恢复海马激发/抑制平衡。 我们预测海马在ESOP-1队列中是多动的，导致关系扰动， 基于海马的内存。我们希望仅在其中发现前海马的结构变化 ESOP的人会发展为精神分裂症。在ESOP-2队列中，我们预测进行性海马 体积损失，从前部向后区域前进，导致更明显的记忆缺陷。 我们预测，恢复正常的激发/抑制平衡将改善ESOP中的海马功能 人。 为了检验我们的假设，我们将收集精神病的高密度，多维评估。我们将使用 海马的高分辨率拟合方案以及静止状态和基于任务的功能成像 激活。我们将使用抗癫痫药的Levetiracetam的单剂量给药来调节 激发/抑制平衡。 纵向和药理学成像的拟议组合将使我们能够研究时间和 心理疾病中海马功能障碍的机制。这些方法的整合旨在 建立一个精神疾病的分期模型，其最终目标是帮助早期发现，预防和 治疗。