Brain-wide functional inter-hemispheric disconnection is a potential biomarker for schizophrenia and distinguishes it from depression☆ (2024)

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Brain-wide functional inter-hemispheric disconnection is a potential biomarker for schizophrenia and distinguishes it from depression☆ (1)

Author(s):

Shuixia Guo a , 1 ,

Keith M. Kendrick b , c , 1 ,

Jie Zhang d ,

Matthew Broome e ,

Rongjun Yu f ,

Zhening Liu g ,

Jianfeng Feng d , h , *

Publication date (Electronic): 23 June 2013

Journal: NeuroImage : Clinical

Publisher: Elsevier

Keywords: Functional connectivity, Inter-hemispheric, Intra-hemispheric, Schizophrenia, SVM

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      Abstract

      Schizophrenia is associated with disconnectivity in the brain although it is still unclear whether changes within or between hemispheres are of greatest importance. In this paper, an analysis of 152 schizophrenia patients compared with 122 healthy controls was carried out. Comparisons were also made with 39 depression patients and 37 controls to examine whether brain-wide changes in inter- or intra-hemispheric functional connectivity are most associated with the disorder and can distinguish it from depression. The authors developed new techniques (first and second order symmetry) to investigate brain-wide changes in patients (45 regions per hemisphere) and their association with illness duration and symptom severity. Functional connectivity between the same regions in left- and right-hemispheres (first order symmetry) was significantly reduced as was that between the same pairs of regions in the left- and right-hemispheres (second order symmetry) or using all possible inter-hemispheric connections in schizophrenia patients. By contrast, no significant changes were found for brain-wide intra-hemispheric links. First order symmetry changes correlated significantly with positive and negative symptom severity for functional connections linked via the anterior commissure and negative symptoms for those linked via the corpus callosum. Support vector machine analysis revealed that inter-hemispheric symmetry changes had 73–81% accuracy in discriminating schizophrenia patients and either healthy controls or depressed patients. In conclusion, reduced brain-wide inter-hemispheric functional connectivity occurs in schizophrenia, is associated with symptom severity, and can discriminate schizophrenia patients from depressed ones or healthy controls. Brain-wide changes in inter-hemispheric connections may therefore provide a useful potential biomarker for schizophrenia.

      Highlights

      • Define a novel measure: first and second symmetry to show dysfunctional links

      • We find that inter-hemispheric disconnection is a biomarker for schizophrenia.

      • Changes are found for links via the anterior commissure, but not corpus callosum.

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      Most cited references41

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      Rethinking schizophrenia.

      Thomas Insel (2010)

      How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This 'rethinking' of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.

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        Resting-state functional connectivity in neuropsychiatric disorders.

        Michael D. Greicius (2008)

        This review considers recent advances in the application of resting-state functional magnetic resonance imaging to the study of neuropsychiatric disorders. Resting-state functional magnetic resonance imaging is a relatively novel technique that has several potential advantages over task-activation functional magnetic resonance imaging in terms of its clinical applicability. A number of research groups have begun to investigate the use of resting-state functional magnetic resonance imaging in a variety of neuropsychiatric disorders including Alzheimer's disease, depression, and schizophrenia. Although preliminary results have been fairly consistent in some disorders (for example, Alzheimer's disease) they have been less reproducible in others (schizophrenia). Resting-state connectivity has been shown to correlate with behavioral performance and emotional measures. It's potential as a biomarker of disease and an early objective marker of treatment response is genuine but still to be realized. Resting-state functional magnetic resonance imaging has made some strides in the clinical realm but significant advances are required before it can be used in a meaningful way at the single-patient level.

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          Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity.

          Lynn Paul, Warren S Brown, Ralph Adolphs (2007)

          Agenesis of the corpus callosum (AgCC), a failure to develop the large bundle of fibres that connect the cerebral hemispheres, occurs in 1:4000 individuals. Genetics, animal models and detailed structural neuroimaging are now providing insights into the developmental and molecular bases of AgCC. Studies using neuropsychological, electroencephalogram and functional MRI approaches are examining the resulting impairments in emotional and social functioning, and have begun to explore the functional neuroanatomy underlying impaired higher-order cognition. The study of AgCC could provide insight into the integrated cerebral functioning of healthy brains, and may offer a model for understanding certain psychiatric illnesses, such as schizophrenia and autism.

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            Author and article information

            Contributors

            Jianfeng Feng

            Journal

            Journal ID (nlm-ta): Neuroimage (Amst)

            Journal ID (iso-abbrev): Neuroimage (Amst)

            Title: NeuroImage : Clinical

            Publisher: Elsevier

            ISSN (Electronic): 2213-1582

            Publication date PMC-release: 23 June 2013

            Publication date (Electronic): 23 June 2013

            Publication date Collection: 2013

            Volume: 2

            Pages: 818-826

            Affiliations

            [a ]College of Mathematics and Computer Science, Key Laboratory of High Performance Computing and Stochastic Information Processing (Ministry of Education of China), Hunan Normal University, Changsha, Hunan 410081, PR China

            [b ]Key Laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, PR China

            [c ]Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, PR China

            [d ]Centre for Computational Systems Biology, School of Mathematical Sciences, Fudan University, Shanghai 200433, PR China

            [e ]Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK

            [f ]School of Psychology and Center for Studies of Psychological Application, South China Normal University, Guangzhou, PR China

            [g ]Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha 410011, PR China

            [h ]Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK

            Author notes

            [* ]Corresponding author at: Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK. Tel.: +44 7799572480; fax: +44 2476523193. jianfeng64@ 123456gmail.com

            [1]

            Contributed equally to this work (joint first authors).

            Article

            Publisher ID: S2213-1582(13)00076-4

            DOI: 10.1016/j.nicl.2013.06.008

            PMC ID: 3777798

            PubMed ID: 24179833

            SO-VID: db8171b8-3775-44c4-ac73-55c2c151dbdf

            Copyright © © 2013 The Authors

            License:

            This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

            History

            Date received : 19 March 2013

            Date revision received : 24 May 2013

            Date accepted : 16 June 2013

            Categories

            Subject: Article


            Keywords: functional connectivity,inter-hemispheric,intra-hemispheric,schizophrenia,svm

            Data availability:

            Keywords: functional connectivity, inter-hemispheric, intra-hemispheric, schizophrenia, svm

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            Brain-wide functional inter-hemispheric disconnection is a potential biomarker for schizophrenia and distinguishes it from depression☆ (2024)

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