title: Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.
abstract: Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, PR China.|West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, PR China.|West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, PR China.|Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Oxford Centre for Computational Neuroscience, Oxford, UK.|Department of Computer Science, University of Warwick, Coventry, UK.
authors.forename: Edmund T
authors.initials: ET
authors.lastname: Rolls
authors.affiliation: Shanghai Center for Mathematical Sciences, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Division of Psychiatry and Applied Psychology, University of Nottingham, Centre for Translational Neuroimaging, Institute of Mental Health, Nottingham, UK.|Institute of Mental Health, Nottingham, UK and Penticton Regional Hospital, Penticton, British Columbia, Canada.
authors.forename: Lena
authors.initials: L
authors.lastname: Palaniyappan
authors.affiliation: Shanghai Center for Mathematical Sciences, Shanghai, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, PR China.|School of Computer Science and Technology, Xidian University, Xi'an, Shannxi, PR China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of life science department, Fudan University, Shanghai, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Gong
authors.affiliation: Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, PR China.|School of life science department, Fudan University, Shanghai, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Psychiatry department, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: SANE POWIC, University Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Crow
authors.affiliation: Department of Psychiatry, Medical Science Division, University of Oxford, Oxford, UK.|Oxford Health NHS Foundation Trust, Oxford, UK.|Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Broome
authors.affiliation: Psychiatry department, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Mental Health Center, Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Zhening
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
authors.affiliation: Psychiatry department, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, PR China.|Department of Computer Science, University of Warwick, Coventry, UK.|Shanghai Center for Mathematical Sciences, Shanghai, PR China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002908:Chronic Disease; D063132:Connectome / Q000379:methods*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D062706:Prodromal Symptoms; D012306:Risk; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055815:Young Adult
keywords: Broca’s area; clinical staging model; resting-state fMRI; thalamus; whole brain functional-connectivity analysis