Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

T Li, Q Wang, J Zhang, ET Rolls, W Yang, L Palaniyappan, L Zhang, W Cheng, Y Yao, Z Liu, X Gong, Q Luo, Y Tang, TJ Crow, MR Broome, K Xu, C Li, J Wang, Z Liu, G LuF Wang, J Feng

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89 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)436-448
Number of pages13
JournalSchizophrenia bulletin
Issue number2
Early online date21 Jul 2016
Publication statusPublished - 1 Mar 2017


  • whole brain functional-connectivity analysis
  • thalamus
  • resting-state fMRI
  • clinical staging model
  • Broca’s area


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