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Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia

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Li, Tao, Wang, Qiang, Zhang, Jie, Rolls, Edmund T., Yang, Wei, Palaniyappan, Lena, Zhang, Lu, Cheng, Wei, Yao, Ye, Liu, Zhaowen et al.
(2017) Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia. Schizophrenia Bulletin, 43 (2). pp. 436-448. doi:10.1093/schbul/sbw099

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Official URL: http://dx.doi.org/10.1093/schbul/sbw099

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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.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Science > Computer Science
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Schizophrenia -- Physiological aspects
Journal or Publication Title: Schizophrenia Bulletin
Publisher: Oxford University Press
ISSN: 0586-7614
Official Date: 1 March 2017
Dates:
DateEvent
1 March 2017Published
21 July 2016Available
23 July 2016Accepted
Volume: 43
Number: 2
Page Range: pp. 436-448
DOI: 10.1093/schbul/sbw099
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Guo jia zi ran ke xue ji jin wei yuan hui (China) [National Natural Science Foundation of China] (NSFC), China. GuoAC jia ke xue ji shu bu [Ministry of Science and Technology] (CMST), Royal Society (Great Britain). Wolfson Research Merit Award (RSWRMA), Guójiā gāo jìshù yánjiū fāzhǎn jìhuà (China) [National High Technology Research Development Program] (NHTRDP), Shanghai Science & Technology Innovation Plan, Zhongguo ke xue yuan [Chinese Academy of Sciences] (CAS), Wellcome Trust (London, England), Shanghai Shi ke xue ji shu wei yuan hui [Shanghai Science and Technology Commission], Key Laboratory of Psychotic Disorders
Grant number: 61104143 (NSFC), 61573107 (NSFC), 2015CB856003 (NBRPC), 2015AA020507 (NHTRDP), 91230201 (NSFC), 11101429 (NSFC), 11471081 (NSFC), 81271485 (NSFC), 81471362 (NSFC), 13z2260500, 15JC1400101
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDGuo jia zi ran ke xue ji jin wei yuan hui (China)[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
UNSPECIFIEDChina. GuoAC jia ke xue ji shu bu [Ministry of Science and Technology] (CMST)UNSPECIFIED
UNSPECIFIEDRoyal Society (Great Britain). Wolfson Research Merit Award (RSWRMA)UNSPECIFIED
UNSPECIFIEDGuójiā gāo jìshù yánjiū fāzhǎn jìhuà (China) [National High Technology Research Development Program] (NHTRDP)UNSPECIFIED
UNSPECIFIEDShanghai Science & Technology Innovation PlanUNSPECIFIED
UNSPECIFIEDZhongguo ke xue yuan [Chinese Academy of Sciences] (CAS)UNSPECIFIED
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100010269
UNSPECIFIEDShanghai Shi ke xue ji shu wei yuan hui [Shanghai Science and Technology Commission]UNSPECIFIED
UNSPECIFIEDKey Laboratory of Psychotic DisordersUNSPECIFIED

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