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Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy

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Abstract

Intermediate phenotype could be used to investigate genetic susceptibility. However, genetic and environmental heterogeneity may interfere with identification of intermediate phenotypes. In this study, we minimized these interferences by using a novel group strategy. A total of 22 drug-naive and first-episode schizophrenia (FES) patients, along with 22 of their kin healthy siblings (HS), 22 non-kin healthy siblings (nHS) of other schizophrenia patients and 22 healthy controls (HC), were recruited. Brain imaging was acquired from the participants. Voxel-based analysis was used to investigate differences in white matter integrity derived from diffusion tensor imaging among the four groups. Two cognitive tests related to our findings were selected to confirm the related phenotypic changes. All of the FES, HS, and nHS groups showed decreased fractional anisotropy (FA) values in the left inferior frontal gyrus (IFG) compared with the HC group (p < 0.05, FDR corrected). The scores of Hopkins Verbal learning Test-Revised and Animal Naming in FES patients were significantly lower than in participants belonging to the other three groups (p < 0.05). Significant correlation between Animal Naming scores and FA values in the left IFG was found in FES patients (r = 0.53, p = 0.01). Moreover, FES patients also showed decreased FA values in the left medial frontal gyrus, left inferior temporal gyrus, left parahippocampal gyrus, left posterior cingulate, and right middle temporal gyrus compared with HC (p < 0.05, FDR corrected). Decreased FA values in the left IFG is a possible intermediate phenotype of schizophrenia, and this finding supports the hypothesis that disrupted connectivity of white matter may be the key substrate of schizophrenia.

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Acknowledgements

This research was supported by National R&D Special Fund for Health Profession by the Ministry of Health of the Peoples’ Republic of China (Grant No. 201002003), National Natural Science Foundation of China (81071093, 81270019, 81260210, 81361120396, 81360211, 81471363 and 30900483), and the Natural Science Foundations of Guangxi (2013GXNSFAA019107).

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    Authors and Affiliations

    1. Mental Health Institute of the Second Xiangya Hospital, National Clinical Research Center on Mental Disorders, National Technology Institute on Mental Disorders, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, 410011, Hunan, China

      Jianjun Ou, Hailong Lyu, Maorong Hu, Wenbin Guo, Xiaofeng Guo, Lihua Li, Qinling Wei, Juan Wang, Fang Liu, Renrong Wu, Jindong Chen, Lehua Li & Jingping Zhao

    2. Mental Hospital of Nanchang University and Mental Health Center of Jiangxi Province, Nanchang, 330029, People’s Republic of China

      Maorong Hu & Bin Hu

    3. Key Laboratory for Neuro Information of the Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, People’s Republic of China

      Jun Li, Junjie Zheng, Feng Liu & Huafu Chen

    4. Mental Health Center, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530007, Guangxi, People’s Republic of China

      Wenbin Guo

    5. Medical Center at the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, People’s Republic of China

      Lihua Li

    6. Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China

      Qinling Wei

    7. Department of Radiology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

      Zhong He

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    1. Jianjun Ou
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    Jianjun Ou, Hailong Lyu, and Maorong Hu have contributed equally to this work.

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    Ou, J., Lyu, H., Hu, M. et al. Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy. Eur Arch Psychiatry Clin Neurosci 268, 89–98 (2018). https://doi.org/10.1007/s00406-016-0752-z

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