Altered cerebellar effective connectivity in first-episode schizophrenia and their long-term changes after treatment
Author Block: X. Wei1, H. Cao2, C. Luo1, Q. Zhao1, C. Xia1, Z. Li1, Z. Liu1, Q. Gong1, S. Lui1; 1Chengdu/CN, 2Manhasset, NY/US
Purpose: We aimed to the find the detailed directional connectivity disruption of cerebellar cortex.
Methods or Background: Cerebellar functional dysconnectivity plays a key role in schizophrenia (SZ) pathology. One hundred and eighty drug naïve first-episode patients with SZ (54 were reassessed after one-year treatment) and 166 healthy controls (HCs) were included. Their resting-state functional magnetic resonance images were used to perform Granger causal analysis, in which nine functional systems of the cerebellum were defined as seeds. The observed directional connectivity alterations at baseline were further assessed at follow-up and associated with psychotic symptom changes.
Results or Findings: We observed increased information projections in the first episode SZ from cerebellum to cerebrum (i.e., from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased information projections in the first episode SZ were mainly from cerebrum to cerebellum (i.e., from the right inferior temporal gyrus, the left middle temporal gyrus, the left putamen, and the right angular gyrus to the cerebellar language system) and inside the cerebellum (i.e., from the cerebellar cingulo-opercular system to the right cerebellum Crus II). With symptom remission after one-year antipsychotic treatment, the information projections from cerebrum to cerebellum were partly restored. The normalization extent of the information projection from the left middle temporal gyrus to the cerebellar language system was positively correlated with the change in general psychopathological symptoms.
Conclusion: These findings suggest that the decreased information projections from the cerebrum into the cerebellum during the acute phase of schizophrenia may be a state-dependent alteration that is related to symptoms and medication. While the increased information projections from the cerebellum may reflect a persistent pathologic trait.
Limitations: Not applicable.
Funding for this study: This study was supported by the National Natural Science Foundation of China (Project Nos. 82120108014, 82071908), National Key R&D Program of China (Project Nos.2022YFC2009901,2022YFC2009900/2022YFC209903), China Postdoctoral Science Foundation (Project No. 2022M722270), the Youth Science Fund of the Natural Science Foundation of Sichuan Province, China (Project No. 2022NSFSC1435), CAMS Innovation Fund for Medical Sciences (CIFMS) (Project No. 2021-I2M-C&T-A-022), Chengdu Science and Technology Office, major technology application demonstration project (Project Nos. 2022-YF09-00062-SN, 2022-GH03-00017-HZ), Sichuan Science and Technology Program (Project No. 2021JDTD0002), Sichuan University Postdoctoral Interdisciplinary Innovation Fund (Project No. JCXK2209), the Fund of the Beijing Medical Award Foundation (Project No. YXJL-2022-0665-0189), Dr. Su Lui acknowledges the support from Humboldt Foundation Friedrich Wilhelm Bessel Research Award and Chang Jiang Scholars (Program No. T2019069).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University