title: Abnormal causal connectivity by structural deficits in first-episode, drug-naive schizophrenia at rest.
abstract: Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, China; guowenbin76@163.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Guo
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, China;
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, China;
authors.forename: Jianrong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, China;
authors.forename: Liuyu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, China;
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, China;
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, China;
authors.forename: Changqing
authors.initials: C
authors.lastname: Xiao
authors.affiliation: School of Mental Health, Jining Medical University, Jining, China;
authors.forename: Jinguo
authors.initials: J
authors.lastname: Zhai
authors.affiliation: Mental Health Institute of the Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D016022:Case-Control Studies; D015984:Causality; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000473:pathology* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000473:pathology* / Q000503:physiopathology; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
keywords: Granger causality analysis; causal effect; first-episode schizophrenia; structural deficits; voxel-based morphometry