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，精神分裂症的严重精神疾病被认为是在青春期大脑发育过程中出现的发育异常的结果，但发病后其脑异常并没有改变。现在，然而，在结构性MRI扫描中可见的脑灰质丧失和脑流体空间（CSF）的增长的新范式已成为精神分裂症研究中的热门话题。除其他研究外，我们当前的优异奖颁发的纵向MRI研究及其68个出版物提供了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损失的发展作为精神分裂症的一部分，而治疗药物在进行性脑部变化中的作用是有争议的。 研究方法：为了回答有关进展的关键问题，我们提出了两组5年的纵向自然主义研究，即第一事件精神分裂症（FESZ）和慢性精神分裂症（CSZ），均与年龄，性别和父母社会经济状况相匹配的健康对照组（HC）相比，他们将拥有相同的纵向协议；所有受试者将进行3T MRI扫描。 Fesz将进行MRI和临床/诊断评估：1）发病，客观地定义为第一次住院（n = 110多年来）； 2）初次扫描后6个月（总计n = 63）； 3）初次扫描后12个月（n = 40总计）；和4）初次扫描后30个月（n = 20总计）。每个时间点的FESZ主题编号都反映了我们记录的随访回报率和5年研究的持续时间约束，并且基于每年研究的22个新Fesz。我们将使用MRI扫描的手动区域分析的黄金标准以及临床症状/符号指标，以提供关键问题的答案。为了促进比较，FESZ和CSZ将获得相同的初始和随访临床和神经心理学评估。治疗医师和合规性，剂量和负载将每月跟踪药物状态，以与MRI/临床变化相关。这项自然研究的一个重要特征是，基于初步数据的功率计算表明，Fesz样品N足够大，可以根据药物，性别和其他变量允许亚组进行亚组。我们将使用三种措施，即精神分裂症的发作量表，药物发作和第一次住院，并将基于MRI变化的预测价值确定最佳发作量度。 假设：我们根据初步数据假设，在发作后的头六个月，发出后的进展最快，而初始和30个月的随访中为28 CSZ。在Fesz中，我们期望在广泛的新皮质区域，额叶和颞叶中最强烈，并且在这些叶中，在这些叶中最强烈，在这些裂片中，与SZ功能异常相关的最强烈和迅速的大脑区域，例如，例如，在较高的暂时性的语言和听觉处理区域中，它会与临床症状相关联。我们预计抗精神病药物会减慢灰质损失和临床症状的进展，而情绪稳定剂将减缓灰质进展，但对临床症状的影响较小。 公共卫生相关性： 意义：如果拟议的研究证实，我们对Fesz中MRI变化的快速发生后进展的初步发现将改变我们对疾病的概念，并表明需要在疾病开始时进行强化药理和心理社会干预试验。此外，我们的研究将有助于定义哪种药理治疗可防止进展。除了对我们对精神分裂症进行性脑病理学的理解的潜在重新制定之外，提出的工作还将增加我们对精神分裂症中哪些大脑影响的知识，这本身就是重要的贡献。与退伍军人健康的相关性：精神分裂症会影响1％的普通人群，是VA中苦难，发病率和费用的主要来源之一。实际上，每年接受精神分裂症治疗的100,000例患者占VA医疗保健费用的近12％。关于精神分裂症的大脑区域知识的知识增加将导致对痛苦的退伍军人的治疗和护理的改善。