Magnetic Resonance Spectroscopy in the Psychosis Risk Syndrome

磁共振波谱检查在精神病风险综合征中的应用

基本信息

批准号：
8703803
负责人：
Stephan F Taylor
金额：
$ 19.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-19 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8703803
关键词：
Accounting Address Affect Age Antipsychotic Agents Behavior Benzodiazepines Biological Assay Brain Brain region Chronic Clinical Data Disease Distress Dorsal Early Diagnosis Emotions Exhibits Foundations Functional Imaging Functional Magnetic Resonance Imaging Funding General Population Glutamates Glutamine Goals Image Individual International Interneurons Intervention Knowledge Link Longitudinal Studies Magnetic Resonance Spectroscopy Measurement Measures Medial Mediator of activation protein N-Methyl-D-Aspartate Receptors Neurobiology Neurotransmitters Occipital lobe Outcome Paranoia Patients Persons Pharmaceutical Preparations Phenotype Prefrontal Cortex Preventive Intervention Process Psychotic Disorders Publishing Recruitment Activity Relative (related person)Reporting Research Role Schizophrenia Signal Transduction Site Speech Syndrome System Testing Therapeutic Therapeutic Intervention Wood material Work Youth attenuated psychosis syndrome blood oxygen level dependent blood oxygenation level dependent response clinical infrastructure design experience falls first episode psychosis gamma-Aminobutyric Acid help-seeking behavior high risk in vivo prevent programs psychotic symptoms public health relevance theories therapy design trait young adult

项目摘要

DESCRIPTION (provided by applicant): The concept of psychosis has shifted in recent decades, as evidenced by an intensive international effort aimed at identifying and treating youth at high risk of psychosis and emerging data that subclinical psychotic symptoms appear in the general population. Individuals with an 'attenuated psychosis syndrome' (APS) present with low levels of reality distortion (unusual thought content, perceptual aberrations, suspiciousness/paranoia), in addition to disorganized speech/behavior, subjective distress and clinical help- seeking. The syndrome is phenotypically continuous with schizophrenia and a critical opportunity in which to study pathophysiological mechanisms that may be common to both APS and schizophrenia. One important potential mechanism may be found in inhibitory GABAergic and excitatory glutamatergic systems. Magnetic resonance spectroscopy (MRS) has enabled the regional measurement of GABA and glutamate/glutamine concentrations, permitting the in vivo assay of these neurotransmitters. Unmedicated patients with schizophrenia have shown elevations of Glx (glutamate/glutamine concentration) and GABA levels in the medial prefrontal cortex (mPFC), a region of the brain implicated in functional and structural imaging studies in schizophrenia and APS. We found the mPFC to exhibit greater sensitivity to benzodiazepine challenge in chronic psychotic patients, suggesting that GABAergic abnormalities. A critical question is whether these abnormalities may be detected in the APS state, which this exploratory R21 proposal will address by measuring cortical GABA and Glx in young persons with APS, compared to matched healthy control subjects and first episode psychosis (FEP) patients. In Aim 1, we will examine GABA and Glx levels in APS individuals in the mPFC and occipital cortex, testing the prediction that GABA and Glx levels will be elevated in APS subjects in the mPFC, relative to healthy controls and medicated FEP patients. In contrast, GABA and Glx are predicted to be reduced in the occipital cortex of both APS and FEP subjects. In Aim 2, we will assess mPFC function in APS individuals and test correlations with GABAergic and Glx signal from this same region. We predict that GABAergic and Glx signals will be inversely correlated with mPFC BOLD signal in the APS patients (but not medicated FEP patients). The anticipated impact of this R21 is three-fold: 1) An essential first step required before an R01-level proposal can examine baseline GABA and Glx as predictors of outcome (conversion to psychosis as well as clinical improvement), 2) An essential first step for a longitudinal study that will examine change in GABA and Glu and associations with outcome; and 3) A mechanistic rationale for designing therapeutic interventions that target GABA/Glx systems in APS.

描述（由申请人提供）：近几十年来，精神病的概念发生了变化，旨在识别和治疗精神病高危青少年的国际努力以及新出现的数据表明普通人群中出现亚临床精神病症状就证明了这一点。患有“弱化精神病综合征”（APS）的个体除了言语/行为混乱、主观痛苦和寻求临床帮助外，还表现出低水平的现实扭曲（不寻常的思想内容、知觉失常、多疑/偏执）。该综合征在表型上与精神分裂症连续，并且是研究 APS 和精神分裂症可能共有的病理生理机制的关键机会。一种重要的潜在机制可能存在于抑制性 GABA 能和兴奋性谷氨酸能系统中。磁共振波谱 (MRS) 能够对 GABA 和谷氨酸/谷氨酰胺浓度进行区域测量，从而可以对这些神经递质进行体内测定。未接受药物治疗的精神分裂症患者的内侧前额皮质 (mPFC) 中的 Glx（谷氨酸/谷氨酰胺浓度）和 GABA 水平升高，该区域是与精神分裂症和 APS 的功能和结构成像研究有关的大脑区域。我们发现慢性精神病患者的 mPFC 对苯二氮卓类药物表现出更高的敏感性，表明 GABA 能异常。一个关键问题是这些异常是否可以在 APS 状态下检测到，这一探索性 R21 提案将通过测量患有 APS 的年轻人的皮质 GABA 和 Glx 来解决这个问题，并与匹配的健康对照受试者和首发精神病 (FEP) 患者进行比较。在目标 1 中，我们将检查 APS 个体 mPFC 和枕叶皮层的 GABA 和 Glx 水平，测试 APS 受试者 mPFC 中 GABA 和 Glx 水平相对于健康对照和药物 FEP 患者升高的预测。相比之下，APS 和 FEP 受试者的枕叶皮质中的 GABA 和 Glx 预计都会减少。在目标 2 中，我们将评估 APS 个体的 mPFC 功能，并测试与来自同一区域的 GABAergic 和 Glx 信号的相关性。我们预测 APS 患者（但不是接受药物治疗的 FEP 患者）中 GABAergic 和 Glx 信号将与 mPFC BOLD 信号呈负相关。该 R21 的预期影响有三重：1) 在 R01 级提案可以检查基线 GABA 和 Glx 作为结果预测因子（转变为精神病以及临床改善）之前所需的必要的第一步，2) 必要的第一步纵向研究的步骤将检查 GABA 和 Glu 的变化以及与结果的关联； 3) 设计针对 APS 中 GABA/Glx 系统的治疗干预措施的机制原理。