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

精神分裂症通常被认为是一种多样性和异质性的 疾病，很难建立有意义的亚型， 可以可靠地识别，有一个稳定的过程，并有 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个精神分裂症患者亚组， 广泛性认知障碍，结局极差， 阴性，或缺陷，症状，以及持续的，慢性的 病 该亚组中的患者被表征为“非常 结果不佳”或“克雷佩利式”精神分裂症患者。 的另一个亚组 已确定符合所有诊断标准的患者， 精神分裂症，但具有正常或仅轻度受损的认知功能 功能 这些患者有一种更良性的疾病，其特征是 结果相对较好，有间歇性发作史 复发涉及阳性症状的重新出现， 在社区中稳定生活的时间长短各不相同。我们和其他人 确定了与膜相关的不同分子异常 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过度的突触 修剪我们最近的发现表明这些分子变化 在认知障碍的受试者中尤为突出。 拟议研究 将评估精神分裂症可能分为 分为两个主要的综合征，在临床状态，过程， 神经生物学和分子相关性。 我们建议利用 与31 P-1H相关的临床和神经认知评估 磁共振波谱成像（31 P-1H MRSI）和磁共振成像（MRI） 核磁共振成像（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会有MRSI和MRI 结果与突触修剪的显著夸大一致， 没有或轻度认知缺陷的精神分裂症患者， MRSI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.