首发精神分裂症额叶髓鞘发育异常的磁共振研究

Schizophrenia is a debilitating mental illness with a high worldwide lifetime risk. The neuropathological basis of schizophrenia remains elusive despite centuries of scientific investigation and it may affect diagnose, as well as intervention for this disease. Previous studies indicated that the development and differentiation of oligodendrocytes have a close relationship with schizophrenia. It is also proved that myelination abnormality in schizophrenia is highly genetic related. Moreover, frontal lobe myelination interruption in schizophrenia and the late adolescence are timely overlapping. These all indicated that myelination, especially the frontal lobe myelination is one key factor in schizophrenia. However, for those white matter magnetic resonance imaging studies in first-episode schizophrenia patients, there is a lack of consensus about the localization and extent of the brain areas. The reason may be related to the different size of the samples, the width of age range and the strictness of the age stratification. Systematic study of neuroimaging and clinical features under schizophrenia age grouping for this hypothesis is still lacking. Our current project aims to clarify the frontal lobe myelination abnormality as one great characteristic for schizophrenic diagnose with the multi-modality brain imaging strategy, including diffusion kurtosis imaging and quantitative susceptibility mapping. We will observe the relationship between myelination abnormality and structure, as well as functional network in schizophrenia. The possible correlation between microstructural white matter differences and clinical performances will also be investigated. This project could offer better understanding for the pathogenesis mechanism of schizophrenia, and set neuroimaging indicator as new criteria for diagnosing the disease.

精神分裂症（SCZ）严重危害人类健康，但该病的病理机制不明。以往的尸检及动物实验发现SCZ患者额叶存在髓鞘异常，近期研究发现少突胶质细胞发育、分化异常与SCZ有重要关系，同时，SCZ的髓鞘异常具有一定的遗传背景，且SCZ发病高峰期与髓鞘发育晚期重叠，因此我们推测青春后期及成年早期的额叶髓鞘发育异常是SCZ的重要病理机制。目前借助磁共振技术探讨SCZ脑白质的研究众多，然而多数未充分考虑髓鞘发育这一关键因素，未对SCZ年龄进行系统分层研究，致使到目前为止，额叶髓鞘发育异常在SCZ发病中的机制尚不清楚。本研究拟采用扩散峰度成像、定量磁化率成像等磁共振技术，以首发SCZ为研究对象，从白质分析出发，探索额叶-边缘系统结构网络及主要功能连接模式的变化及关系，并进一步研究白质异常与临床症状的相关性，以期通过上述研究深入理解髓鞘发育在SCZ发病中的作用及相关机制，为SCZ的早期诊断及优化治疗提供客观依据。

精神分裂症（SCZ）严重危害人类健康，但该病的病理机制不明。以往的尸检及动物实验发现SCZ患者额叶存在髓鞘异常，近期研究发现少突胶质细胞发育、分化异常与SCZ有重要关系，同时，SCZ的髓鞘异常具有一定的遗传背景，且SCZ发病高峰期与髓鞘发育晚期重叠，因此我们推测青春后期及成年早期的额叶髓鞘发育异常是SCZ的重要病理机制。目前借助磁共振技术探讨SCZ脑白质的研究众多，然而多数未充分考虑髓鞘发育这一关键因素，未对SCZ年龄进行系统分层研究，致使到目前为止，额叶髓鞘发育异常在SCZ发病中的机制尚不清楚。本研究拟采用扩散峰度成像、定量磁化率成像等磁共振技术，以首发SCZ为研究对象，从白质分析出发，探索额叶-边缘系统结构网络及主要功能连接模式的变化及关系，并进一步研究白质异常与临床症状的相关性，我们运用TBSS方法比较首发精分患者和健康对照DTI参数的差异，并与临床症状进行相关分析，结果发现SCZ患者右侧矢状层、丘脑后辐射、双侧大脑脚、右侧内外囊、胼胝体、右上纵束、右上放射冠等，穹窿 MD 值与一般精神病理学评分呈正相关（r=0. 36，P=0. 02）；胼胝体干 RD 值与一般精神病理学评分、PANSS 总分呈正相关（r=0. 34，P=0. 03；r=0. 56，P<0. 001）；胼胝体压部 RD 值与 PANSS 总分呈正相关（r=0. 30，P=0. 04）。提示首发 SCZ 患者可能存在更为广泛的脑白质髓鞘异常和（或）轴突损伤。我们进一步发现不同年龄的SCZ患者DTI参数亦有不同。通过上述研究我们深入理解了髓鞘发育在SCZ发病中的作用及相关机制，为SCZ的早期诊断及优化治疗提供客观依据。同时由于目前对精神分裂症（SCZ）患者的大脑灰质体积变化测量结果存在差异，故本项目还研究了SCZ与正常健康对照在使用不同软件（FSL，SPM）分析处理灰质结果时的差异，发现对灰质组织分割、图像配准和统计策略的算法可能会导致这些不同的结果，为大脑灰质体积变化的研究结果的差异提供了证据。SCZ会导致大脑灰质体积减少，而抗精神病药物治疗对SCZ的大脑灰质体积也有影响，本项目还通过探讨抗精神病药物治疗对灰质体积的影响，发现某些大脑区域在经过治疗后出现体积减少，为将灰质体积作为评估SCZ对药物治疗是否有反应的生物标记物提供了证据。