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Int J Neural Syst. 2019 Jun;29(5):1850032. doi: 10.1142/S0129065718500326. Epub 2018 Jul 16.

Aberrant Prefrontal-Thalamic-Cerebellar Circuit in Schizophrenia and Depression: Evidence From a Possible Causal Connectivity.

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* The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, Center for Information in Medicine, School of life Science and Technology, University of Electronic Science and Technology of China, Chengdu P. R. China.
† Department of psychiatry, Chengdu Mental Health Center, Chengdu, P. R. China.
‡ Psychological Medicine Center, The First Affiliated Hospital of Xinjiang, Medical University, Urumqi, P. R. China.
§ Biology Department, Emory University, Atlanta, GA, USA.
¶ Department of EEG Source Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.


Neuroimaging studies have suggested the presence of abnormalities in the prefrontal-thalamic-cerebellar circuit in schizophrenia (SCH) and depression (DEP). However, the common and distinct structural and causal connectivity abnormalities in this circuit between the two disorders are still unclear. In the current study, structural and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 20 patients with SCH, 20 depressive patients and 20 healthy controls (HC). Voxel-based morphometry analysis was first used to assess gray matter volume (GMV). Granger causality analysis, seeded at regions with altered GMVs, was subsequently conducted. To discover the differences between the groups, ANCOVA and post hoc tests were performed. Then, the relationships between the structural changes, causal connectivity and clinical variables were investigated. Finally, a leave-one-out resampling method was implemented to test the consistency. Statistical analyses showed the GMV and causal connectivity changes in the prefrontal-thalamic-cerebellar circuit. Compared with HC, both SCH and DEP exhibited decreased GMV in middle frontal gyrus (MFG), and a lower GMV in MFG and medial prefrontal cortex (MPFC) in SCH than DEP. Compared with HC, both patient groups showed increased causal flow from the right cerebellum to the MPFC (common causal connectivity abnormalities). And distinct causal connectivity abnormalities (increased causal connectivity from the left thalamus to the MPFC in SCH than HC and DEP, and increased causal connectivity from the right cerebellum to the left thalamus in DEP than HC and SCH). In addition, the structural deficits in the MPFC and its causal connectivity from the cerebellum were associated with the negative symptom severity in SCH. This study found common/distinct structural deficits and aberrant causal connectivity patterns in the prefrontal-thalamic-cerebellar circuit in SCH and DEP, which may provide a potential direction for understanding the convergent and divergent psychiatric pathological mechanisms between SCH and DEP. Furthermore, concomitant structural and causal connectivity deficits in the MPFC may jointly contribute to the negative symptoms of SCH.


Schizophrenia; causal connectivity; depression; gray matter; resting-state fMRI


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