[Abnormal changes of static and dynamic functional connectivity of dopaminergic midbrain in patients with first-episode schizophrenia and their correlations with clinical symptoms].

Objective: To investigate the abnormal changes of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in the dopaminergic midbrain (ventral dorsal tegmental area and bilateral substantia nigra compacta, VTA/SNc) in patients with first-episode schizophrenia(SCH), and their correlation with the Positive and Negative Symptom Scale (PANSS). Methods: The data of 198 first-episode untreated schizophrenia patients and 199 healthy controls (HC) matched by age, sex and years of education who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2019 to May 2022 were prospectively collected. All subjects underwent high resolution structural MRI and resting state functional magnetic resonance imaging (rs-fMRI) scanning. The dopaminergic midbrain (VTA/SNc) was defined as three regions of interest (ROI). The sFC and dFC analyses with VTA/SNc as seeds were performed to produce a whole-brain diagram initially, which subsequently were compared between schizophrenia group and HC group. Finally, the correlation analysis of sFC and dFC values with the PANSS scores were performed, including the positive scale score, negative scale score, general psychopathology scale score, total score and symptom scores. Results: There were 86 males and 112 females in SCH group, and aged (23±9) years. Meanwhile, there were 95 males and 104 females in HC group, and aged (22±5) years. In the SCH group, the positive (P), the negative (N) and the general psychopathology (G) scale scores and the total score (T) of the PANSS scale was 20±7, 21±7, 41±11 and 82±22, respectively. Compared with the HC group, the VTA showed decreased sFC with four clusters including cerebellar vermis 7/9, left putamen, right thalamus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-4.35, -4.81, -4.35 and -4.65; voxel P<0.005; cluster P<0.05), the right SNc showed decreased sFC with four clusters including left cerebellar hemisphere 4/5/8, right putamen, right medial orbitofrontal gyrus and the left putamen in the schizophrenia group (peak center, t=-4.91, -5.15, -4.77 and -5.21; voxel P<0.005; cluster P<0.05), and the left SNc showed decreased sFC with four clusters including the left putamen, right putamen, right medial orbitofrontal gyrus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-5.82, -4.83 and -4.65; voxel P<0.005; cluster P<0.05). Compared with the HC group, the VTA showed decreased dFC with the right inferior parietal gyrus, right angular gyrus and right superior parietal gyrus in schizophrenia group (t=-4.17). In the schizophrenia group, the sFC value of cluster 2 (left putamen) with VTA as seed and cluster 4 (left putamen) with right SNc as seed were positively correlated with the positive scale scores in PANSS (r=0.141, 0.169, both P<0.05). The sFC and dFC values of significant regions were also correlated with hallucination, delusion, suspicion, hostility, communication disorder, passivity/indifference, lack of communication, stereotyped thinking, depression, non-cooperation, lack of judgment and insight, impulse control disorder, active social avoidance (all P<0.05). Conclusion: The static and dynamic functional connectivity (stability) of VTA/SNc to cerebellum, thalamus, striatum, prefrontal lobe and cingulate gyrus in first-episode schizophrenia patients were decreased, which were closely related to the positive and negative symptoms of schizophrenia.目的： 探讨首发精神分裂症（SCH）患者中脑多巴胺区［腹侧背盖区及双侧黑质致密部（VTA/SNc）］静态功能连接（sFC）及动态功能连接（dFC）的异常改变，及其与阳性与阴性症状量表（PANSS）的相关性。 方法： 前瞻性收集2019年1月至2022年5月郑州大学第一附属医院收治的198例首发未用药SCH患者，以及年龄、性别、受教育年限与之匹配的199名健康对照（HC）组资料。所有被试均行高分辨率结构像MRI及静息态功能MRI（rs-fMRI）扫描。将中脑多巴胺区（VTA/SNc）定义为三个种子点，采用sFC和dFC方法分析SCH组与HC组VTA/SNc功能连接具有统计学差异的脑区，将差异脑区提取的sFC和dFC值与患者的PANSS量表中阳性量表分、阴性量表分、一般精神病理量表分、总分以及各症状分进行相关性分析。 结果： SCH组男86例，女112例，年龄（23±9）岁，HC组男95例，女104例，年龄（22±5）岁。SCH组的PANSS量表中阳性量表分为（20±7）分，阴性量表分为（21±7）分，一般精神病理量表分为（41±11）分，总分为（82±22）分。与HC组相比，SCH组VTA与小脑蚓部7/9区、左侧壳核、右侧丘脑、左侧中扣带回四个脑区团块sFC值降低（峰值中心，t值分别为-4.35、-4.81、-4.35、-4.65，体素P<0.005，团块P<0.05），右侧SNc与左侧小脑半球4/5/8区、右侧壳核、右侧内侧眶额回、左侧壳核四个脑区团块sFC值降低（峰值中心，t值分别为-4.91、-5.15、-4.77、-5.21，体素P<0.005，团块P<0.05），左侧SNc与右侧壳核、右侧内侧眶额回、左侧中扣带回三个脑区团块sFC值降低（峰值中心，t值分别为-5.82、-4.83、-4.65，体素P<0.005，团块P<0.05）；SCH组VTA与右侧顶下回、右侧角回、右侧顶上回dFC变异值降低（t=-4.17）。SCH组以VTA为种子点的脑区团块2（左侧壳核）、以右侧SNc为种子点的脑区团块4（左侧壳核）的sFC值与PANSS量表中的阳性量表分呈正相关（r=0.141、0.169，均P<0.05），差异脑区功能连接值尚与幻觉、妄想、猜疑、敌对、交流障碍、被动/淡漠、交流缺乏、刻板思维、抑郁、不合作、判断和自知力缺乏、冲动控制障碍、主动回避社交这些症状呈现相关性（均P<0.05）。 结论： 首发SCH患者中脑多巴胺区（VTA/SNc）与小脑、丘脑、纹状体、前额叶、扣带回等脑区静态功能连接或动态功能连接（稳定性）降低，并与疾病阳性与阴性症状分数存在相关性。.