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Imaging Hippocampal Function in Psychosis

精神病中海马功能的成像

基本信息

批准号：
10294146
负责人：
STEPHAN HECKERS
金额：
$ 78.35万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/10294146
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 experience experimental study improved network dysfunction preclinical study prevent public health relevance recruit relational memory restoration social deficits translational neuroscience

项目摘要

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（项目总结）