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Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia

Molecular Psychiatry volume 25, pages 3220–3230 (2020)Cite this article

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A Correction to this article was published on 22 October 2019

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Abstract

Disturbance of glucose metabolism may be implicated in cognitive deficits of schizophrenia in its early phases. Many studies have reported the important role of widespread disruption of white matter (WM) connectivity in pathogenesis, cognitive deficit and psychopathology of schizophrenia. However, no study has investigated their inter-relationships in drug-naive first episode (DNFE) patients with schizophrenia. Glucose metabolism parameters including fasting glucose, insulin and homeostasis model of assessment-insulin resistance (HOMA-IR) index, cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB) and the voxel-wised WM fractional anisotropy (FA) values were examined using DTI in 39 DNFE schizophrenia and 31 control subjects. The Positive and Negative Syndrome Scale was utilized for clinical symptoms. The patients showed significantly greater fasting plasma levels of glucose and insulin and HOMA-IR, and poorer cognitive scores, together with widespread reduced FA values in five brain areas, including left and right corpus callosum, superior longitudinal fasciculus, posterior thalamic radiation, and corona radiata (all p < 0.05). Association analysis showed that glucose level was positively associated with Digital Sequence Test and Continuous Performance Test, but negatively with FA values in posterior thalamic radiation and left corpus callosum in patients (all p < 0.05). Furthermore, multiple regression analysis revealed that the interactions of glucose × FA in left corpus callosum, longitudinal fasciculus and corona radiata were independent contributors to the Brief Visuospatial Memory Test (BVMT) of MCCB, while the interaction of glucose × FA in left corpus callosum, or in longitudinal fasciculus was associated with MCCB mazes and Trail Making A Test, respectively. Therefore, abnormal glucose metabolism, cognitive impairment and widespread disruption of WM structure occur in an early course of schizophrenia onset. An interaction between glucose metabolism abnormality and the WM dysconnectivity may lead to cognitive impairment.

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Article 12 November 2020

Jo Ellen Wilson, Matthew F. Mart, … E. Wesley Ely

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  • 22 October 2019

    A correction to this paper has been published and can be accessed via a link at the top of the paper.

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Funding

Funding for this study was provided by the CAS Pioneer Hundred Talents Program, the National Natural Science Foundation of China (81371477, 61533006, U1808204, 61806042), the project of the Science and Technology Department in Sichuan province (2017JY0094).

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  1. These authors contributed equally: Xiangyang Zhang, Mi Yang

Authors and Affiliations

  1. CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China

    Xiangyang Zhang & Li Wang

  2. Department of Psychology, University of Chinese Academy of Sciences, Beijing, China

    Xiangyang Zhang

  3. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China

    Xiangyang Zhang, Yuping Ning, Xingbing Huang & Fengchun Wu

  4. Department of Stomatology, the Fourth People’s Hospital of Chengdu, Chengdu, China

    Mi Yang

  5. Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China

    Mi Yang, Wei Liao & Huafu Chen

  6. Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China

    Xiangdong Du & Qiufang Jia

  7. Psychiatry Research Center, Beijing HuiLongGuan Hospital, Peking University, Beijing, China

    Dachun Chen, Fengmei Fan & Meihong Xiu

  8. Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, USA

    Jair C. Soares & Bo Cao

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Zhang, X., Yang, M., Du, X. et al. Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia. Mol Psychiatry 25, 3220–3230 (2020). https://doi.org/10.1038/s41380-019-0478-1

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