MRI Anatomy of Schizophrenia

精神分裂症的 MRI 解剖

• 批准号: 8195955
• 负责人: Robert W McCarley
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8195955
• 关键词: Accounting; Adolescent; Affect; Age; Anatomy; Antipsychotic Agents; Area; Auditory; Award; Brain; Brain Diseases; Brain Pathology; Brain region; Budgets; Caring; Cell Nucleus; Cerebrospinal Fluid; Chronic; Chronic Schizophrenia; Clinical; Communities; Complement; Data; Defect; Development; Diagnostic; Disease; Dose; Evaluation; Event-Related Potentials; Female; Gender; General Population; Generations; Gold; Grant; Handedness; Health; Health Care Costs; Hospitalization; Hospitals; Intervention Trial; Investigation; Knowledge; Language; Lead; Link; Liquid substance; Literature; Lithium; Lobe; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Manuals; Measures; Methods; Modeling; Mood stabilizers; Morbidity - disease rate; N-Methylaspartate; Neurobiology; Onset of illness; Outcome; Parental Ages; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Physicians; Predictive Value; Process; Protocols documentation; Psychiatrist; Publications; Recruitment Activity; Recurrence; Reporting; Research; Research Methodology; Research Personnel; Role; Sampling; Scanning; Schizophrenia; Signs and Symptoms; Socioeconomic Status; Source; Subgroup; Superior temporal gyrus; Symptoms; Techniques; Temporal Lobe; Testing; Therapeutic; Time; Valproic Acid; Ventricular; Veterans; Work; age group; base; cingulate gyrus; compliance behavior; design; dosage; first episode schizophrenia; follow-up; frontal lobe; gamma-Aminobutyric Acid; gray matter; indexing; interest; lateral ventricle; male; neocortical; neural circuit; neurophysiology; neuropsychological; neurotransmission; non-compliance; prospective; protective effect; psychosocial; public health relevance; research clinical testing; severe mental illness; white matter; white matter change

DESCRIPTION (provided by applicant): Background: For many years the serious mental illness of schizophrenia was thought of as the consequence of abnormalities in development which emerged in the course of adolescent brain development, but whose brain abnormalities did not change after onset. Now, however a new paradigm of post-onset progression of loss of brain gray matter and concomitant increase of brain fluid spaces (CSF) visible on structural MRI scans has become a hot topic in schizophrenia research. As well as other studies, our current Merit award-sponsored longitudinal MRI study and its 68 publications provide strong preliminary evidence of progression. Still, many questions remain. Not all investigators agree on progression of gray matter loss as a part of schizophrenia, and the role of treatment medication in progressive brain changes is controversial. Research Methods: To answer key questions about progression, we propose a 5 year longitudinal naturalistic study in two groups, first episode schizophrenia (FESZ) and chronic schizophrenia (CSZ), both compared with equal numbers of healthy controls (HC) matched on age, gender and parental socio- economic status who will have the same longitudinal protocol; all subjects will have 3T MRI scans. FESZ will have MRIs and clinical/diagnostic evaluations: at 1) onset, objectively defined as first hospitalization (N=110 total over 5 years); 2) 6 months after initial scan (N=63 total); 3) 12 months after initial scan (N=40 total); and 4) 30 months after initial scan (N=20 total). The FESZ subject numbers at each time point reflect both our documented follow-up return rate and the duration constraints of a 5 year study and are based on 22 new FESZ entering each year of the study. We will use the gold standard of manual Region of Interest analysis of MRI scans together with clinical symptom/sign measures to provide answers to key questions. To facilitate comparison FESZ and CSZ will receive the same initial and follow-up clinical and neuropsychological evaluations. Medication status will be tracked monthly by the treating physician and compliance, dosage and load will be tracked for association with MRI/clinical changes. An important feature of this naturalistic study is that power calculations based on preliminary data indicate the FESZ sample N will be large enough to permit subgrouping on the basis of medication, gender and other variables. We will use three measures of onset, the schizophrenia onset scale, medication onset and first hospitalization and will determine which provides the best measure of onset, based on predictive value for MRI changes. Hypotheses: We hypothesize, based on preliminary data, that post-onset progression is most rapid in FESZ in the first 6 months after onset, compared with 28 CSZ at initial and at 30 month follow-up. In FESZ we expect gray matter progressive loss in widespread neocortical areas, most intense in frontal and temporal lobe, and, within these lobes, most intense and rapid in particular brain regions linked to SZ functional abnormalities, such as, for example, in superior temporal gyrus language and auditory processing regions, where it will be associated with progression of clinical symptoms of disorganization and thought disorder. We expect antipsychotic medication to slow progression of both gray matter loss & clinical symptoms while mood stabilizers will slow gray matter progression but will have lesser effect on clinical symptoms. PUBLIC HEALTH RELEVANCE: Significance: Our preliminary findings of a rapid post-onset progression of MRI changes in FESZ, if confirmed by the proposed study, would alter our conceptualization of the disorder, and suggest the need for intensive pharmacologic and psychosocial intervention trials at disease onset. Moreover, our study will help define which pharmacological treatments protect against progression. In addition to this potential reformulation of our understanding of progressive brain pathology in schizophrenia, the work proposed will increase our knowledge about what areas of the brain are affected in schizophrenia, an important contribution in its own right. Relevance to Veterans Health: Schizophrenia affects 1% of the general population and is one of the major sources of suffering, morbidity and expense in the VA. In fact, the 100,000 patients treated with schizophrenia each year account for nearly 12% of VA healthcare costs. Increase in knowledge about the brain areas underlying schizophrenia will lead to improvement in treatment and care for afflicted veterans.

描述（由申请人提供）： 背景：多年来，精神分裂症这种严重的精神疾病被认为是青少年大脑发育过程中出现的发育异常的结果，但其大脑异常在发病后并没有改变。然而现在，结构 MRI 扫描中可见的脑灰质丧失的发病后进展以及随之而来的脑液空间 (CSF) 增加的新范例已成为精神分裂症研究的热门话题。与其他研究一样，我们当前的优异奖赞助的纵向 MRI 研究及其 68 篇出版物提供了强有力的进展初步证据。尽管如此，仍然存在许多问题。并非所有研究人员都同意灰质丧失的进展是精神分裂症的一部分，并且治疗药物在进行性大脑变化中的作用存在争议。 研究方法：为了回答有关进展的关键问题，我们提出了一项为期 5 年的纵向自然主义研究，分为两组：首发精神分裂症 (FESZ) 和慢性精神分裂症 (CSZ)，两组均与同等数量的年龄匹配的健康对照 (HC) 进行比较。具有相同纵向协议的性别和父母社会经济地位；所有受试者都将接受 3T MRI 扫描。 FESZ 将进行 MRI 和临床/诊断评估： 1) 发病时，客观定义为首次住院（5 年内总计 N=110）； 2) 初次扫描后 6 个月（总共 N=63）； 3) 初次扫描后 12 个月（总共 N=40）； 4) 初次扫描后 30 个月（总共 N=20）。每个时间点的 FESZ 受试者数量反映了我们记录的随访回报率和 5 年研究的持续时间限制，并且基于每年进入研究的 22 个新 FESZ。我们将使用 MRI 扫描手动感兴趣区域分析的黄金标准以及临床症状/体征测量来提供关键问题的答案。为了便于比较，FESZ 和 CSZ 将接受相同的初始和后续临床和神经心理学评估。主治医生将每月跟踪药物状态，并跟踪依从性、剂量和负荷与 MRI/临床变化的关联。这项自然主义研究的一个重要特征是，基于初步数据的功效计算表明 FESZ 样本 N 将足够大，可以根据药物、性别和其他变量进行分组。我们将使用三种发病指标，即精神分裂症发病量表、药物发作和首次住院治疗，并将根据 MRI 变化的预测值确定哪一种提供最佳的发病指标。 假设：根据初步数据，我们假设，发病后前 6 个月内，FESZ 的发病后进展最快，而初始和 30 个月随访时的 CSZ 为 28 个。在FESZ中，我们预计灰质会在广泛的新皮质区域中逐渐丧失，在额叶和颞叶中最为强烈，并且在这些叶中，在与SZ功能异常相关的特定大脑区域中最为强烈和快速，例如在上颞叶中脑回语言和听觉处理区域，在那里它将与紊乱和思维障碍的临床症状的进展相关。我们预计抗精神病药物可以减缓灰质损失和临床症状的进展，而情绪稳定剂可以减缓灰质的进展，但对临床症状的影响较小。 公共卫生相关性： 意义：我们对 FESZ 发病后 MRI 变化快速进展的初步发现，如果被拟议的研究证实，将改变我们对该疾病的概念，并表明需要在疾病发作时进行深入的药理学和心理社会干预试验。此外，我们的研究将有助于确定哪些药物治疗可以防止病情进展。除了可能重新阐述我们对精神分裂症进行性脑病理学的理解之外，所提出的工作还将增加我们对精神分裂症影响的大脑区域的了解，这本身就是一个重要的贡献。与退伍军人健康的相关性：精神分裂症影响总人口的 1%，是退伍军人管理局痛苦、发病和费用的主要来源之一。事实上，每年治疗 10 万名精神分裂症患者的费用占 VA 医疗费用的近 12%。增加对精神分裂症大脑区域的了解将改善对患有精神分裂症的退伍军人的治疗和护理。