前额叶-丘脑-小脑环路功能连接增强对精神病超高危人群发病的预判研究

Increasing evidence and our study suggest that functional connectivity (FC) of the prefrontal-thalamic-cerebellar circuit increases in first-episode schizophrenia and decreases in chronic schizophrenia. Therefore, we deduced that individuals with ultra-high risk for psychosis (UHR) would exhibit increased FC in the prefrontal-thalamic-cerebellar circuit for the reason that brain anatomical and functional alterations occurred before the development of schizophrenia. However, it is widely recognized as a challenge for the clinicians to the lack of an indictor to identify individuals with UHR who will develop schizophrenia later. The present study is devoted to explore such an indictor. The resting-state functional magnetic resonance imaging (MRI) data are analyzed by using the network homogeneity method to explore the FC of the prefrontal-thalamic-cerebellar circuit in individuals with UHR. Then a Cox’s regression model is established by computing the mean FC values of the clusters with abnormal FC in the prefrontal-thalamic-cerebellar circuit. The fit goodness of the Cox’s regression model is examined in tracing of the mean FC values of the clusters with abnormal FC in the prefrontal-thalamic-cerebellar circuit in another UHR group. The success of the present study will help clinicians to discriminate individuals with UHR who will develop schizophrenia later, and to suggest the effective intervention in order to prevent the development of schizophrenia. Hence, it will minimize the functional impairment and mortality of schizophrenia, and decrease the economic and social burden caused by schizophrenia. It will also be helpful in elucidating the pathophysiology of schizophrenia.

文献报道与我们的研究已经发现首发精神分裂症前额叶-丘脑-小脑环路功能连接增强，而慢性精神分裂症该环路功能连接降低。因为大脑结构与功能的改变早于精神分裂症发病，因此我们推测精神病超高危人群发病前有前额叶-丘脑-小脑环路功能连接增强。临床上迄今对超高危人群发病的预判缺乏敏感有效的客观指标。本项目致力寻找这样一种客观指标，拟对超高危人群和正常对照两组被试进行静息态功能磁共振扫描，用网络一致性的分析方法来统计超高危人群发病组前额叶-丘脑-小脑环路功能连接增强的脑区平均功能连接值的大小，建立Cox回归模型并拟合Cox曲线，并在另一组超高危人群中对Cox回归模型进行拟合优度考察。研究地顺利进行，不仅能将超高危人群发病个体预判出来，选择恰当的干预措施，从而降低或有效延缓精神分裂症的发生，减轻精神分裂症造成的经济和社会负担，而且对阐明精神分裂症的脑机制亦具有指导价值。

临床上缺乏对精神病的“超高危人群”（UHR）前额叶-丘脑-小脑环路改变的系统研究。本项目拟从脑影像学角度来探讨精神分裂症超高危人群前额叶-丘脑-小脑环路的功能连接异常，用基于种子点功能连接分析和网络一致性分析两种分析方法来分析超高危人群前额叶-丘脑-小脑环路的功能连接异常，并对之进行1年的随访研究。结果发现：UHR病例转化为精神分裂症等重性精神障碍的1年转化率为25.61%；UHR病例的前额叶灰质体积增加（右侧额下回和右侧直回）、前额叶-枕叶功能连接异常（左侧额中回和左侧距状回功能）、左侧丘脑的PAS (parameter of asymmetry)值可以将UHR病例从正常对照中区分出来；并且UHR病例和精神分裂症患者共享的小脑-默认网络功能连接增强。这些研究成果为阐述精神分裂症尤其是精神分裂症发病早期的发病机制提供了有力的证据。