title: Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy.
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.
authors.affiliation: 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.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ou
authors.affiliation: 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.
authors.forename: Hailong
authors.initials: H
authors.lastname: Lyu
authors.affiliation: 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.|Mental Hospital of Nanchang University and Mental Health Center of Jiangxi Province, Nanchang, 330029, People's Republic of China.
authors.forename: Maorong
authors.initials: M
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.|Mental Health Center, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530007, Guangxi, People's Republic of China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: 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.|Medical Center at the Second Affiliated Hospital, Nanchang University, Nanchang, 330006, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: 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.|Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China.
authors.forename: Qinling
authors.initials: Q
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Radiology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: He
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Renrong
authors.initials: R
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Jindong
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Lehua
authors.initials: L
authors.lastname: Li
authors.affiliation: Mental Hospital of Nanchang University and Mental Health Center of Jiangxi Province, Nanchang, 330029, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: 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. chenhf@uestc.edu.cn.
authors.forename: Huafu
authors.initials: H
authors.lastname: Chen
authors.affiliation: 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. zhaojingpingcsu@163.com.
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D010641:Phenotype; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D055815:Young Adult
keywords: Diffusion tensor imaging; First-episode schizophrenia; Fractional anisotropy; Intermediate phenotype; Siblings; White matter