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

Abstract

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.