IN VIVO 31P-1H MRSI/MRI OF CHRONIC SCHIZOPHRENIA

精神分裂症通常被认为是一种多样化和异质性的疾病 而且很难建立有意义的亚型， 可以可靠地识别，具有稳定的进程，并具有 明显的神经生物学基础。在以前的工作中，我们和 其他人已经确定了一组严重的精神分裂症患者， 广泛性认知障碍，一个非常糟糕的结果，主要是 阴性或缺陷症状，并有坚持不懈的慢性病史 生病了。这一亚组中的患者被描述为“非常 不良结局“或”Kraepelian“精神分裂症患者。 已确定符合所有诊断标准的患者 精神分裂症，但认知正常或仅有轻微损害 功能。这些患者有一种更良性的疾病，其特征是 一个相对较好的结果，以及间歇性发作的历史 复发包括阳性症状的重新出现，夹杂着 在社区中稳定生活的时间长短不一。我们和其他人也有 发现与膜相关的明显的分子异常 从未用药的磷脂和高能磷酸盐代谢， 首发精神分裂症患者被认为反映了夸大的突触 修剪。我们最近的发现表明，这些分子变化比 在有认知障碍的受试者中突出。拟议的研究 将评估精神分裂症可能被分开这一普遍假设 分成两个临床状态、病程、 神经生物学和分子相关。我们打算利用 31P-1H相关的临床和神经认知评估 磁共振波谱成像(31P-1HMRSI)和磁共振 磁共振成像(MRI)来评估这一一般理论。我们的假设 有认知缺陷的精神分裂症患者将接受磁共振成像和核磁共振检查 研究结果与突触修剪和突触修剪的显著夸大一致 没有或轻度认知障碍的精神分裂症患者将没有或仅有轻微的认知障碍 核磁共振检查结果。

Schizophrenia is generally regarded as a diverse and heterogeneous disorder and it has been difficult to establish meaningful subtypes that can be reliably identified, that have a stable course, and have demonstrable neurobiological underpinnings. In previous work, we and others have identified a subgroup of schizophrenic patients with severe, generalized cognitive impairment, a very poor outcome, predominance of negative, or deficit, symptoms, and a history of unremitting, chronic illness. Patients in this subgroup have been characterized as "Very Poor Outcome" or "Kraepelinian" schizophrenics. Another subgroup of patients has been identified that meet all diagnostic criteria for schizophrenia but have normal or only mildly impaired cognitive function. These patients have a more benign disorder characterized by a relatively good outcome, and a history of intermittent episodes of relapse involving re-emergence of positive symptoms, intermixed with varying lengths of stable life in the community. We and others also have identified distinct molecular abnormalities related to membrane phospholipid and high-energy phosphate metabolism in never-medicated, first-episode schizophrenics thought to reflect exaggerated synaptic pruning. Our recent findings indicate these molecular changes are more prominent in subjects with cognitive impairment. The proposed research will evaluate the general hypothesis that schizophrenia may be divided into two major syndromes differing in clinical status, course, neurobiological and molecular correlates. We propose to utilize clinical and neurocognitive assessment in association with 31P-1H magnetic resonance spectroscopy imaging (31P-1H MRSI) and magnetic resonance imaging (MRI) to evaluate this general theory. Our hypothesis is that schizophrenics with cognitive deficit will have MRSI and MRI findings consistent with a marked exaggeration of synaptic pruning and schizophrenics with no or mild cognitive deficit will have no or minimal MRSI findings.