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Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia
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(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
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 | ||||||||||||||||||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science > Computer Science Faculty of Medicine > Warwick Medical School |
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| 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: |
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| Date of first compliant deposit: | 29 July 2016 | ||||||||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||||||||
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