title: Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia.
abstract: OBJECTIVE
  The pathophysiology of chronic schizophrenia may reflect long term brain changes related to the disorder. The effect of chronicity on intrinsic functional connectivity patterns in schizophrenia without the potentially confounding effect of antipsychotic medications, however, remains largely unknown.
  
  
  METHODS
  We collected resting-state fMRI data in 21 minimally treated chronic schizophrenia patients and 20 healthy controls. We computed regional functional connectivity strength for each voxel in the brain, and further divided regional functional connectivity strength into short-range regional functional connectivity strength and long-range regional functional connectivity strength. General linear models were used to detect between-group differences in these regional functional connectivity strength metrics and to further systematically investigate the relationship between these differences and clinical/behavioral variables in the patients.
  
  
  RESULTS
  Compared to healthy controls, the minimally treated chronic schizophrenia patients showed an overall reduced regional functional connectivity strength especially in bilateral sensorimotor cortex, right lateral prefrontal cortex, left insula and right lingual gyrus, and these regional functional connectivity strength decreases mainly resulted from disruption of short-range regional functional connectivity strength. The minimally treated chronic schizophrenia patients also showed reduced long-range regional functional connectivity strength in the bilateral posterior cingulate cortex/precuneus, and increased long-range regional functional connectivity strength in the right lateral prefrontal cortex and lingual gyrus. Notably, disrupted short-range regional functional connectivity strength mainly correlated with duration of illness and negative symptoms, whereas disrupted long-range regional functional connectivity strength correlated with neurocognitive performance. All of the results were corrected using Monte-Carlo simulation.
  
  
  CONCLUSIONS
  This exploratory study demonstrates a disruption of intrinsic functional connectivity without long-term exposure to antipsychotic medications in chronic schizophrenia. Furthermore, this disruption was connection-distance dependent, thus raising the possibility for differential neural pathways in neurocognitive impairment and psychiatric symptoms in schizophrenia.
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Xijin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
authors.forename: Mingrui
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Radiology, Peking University People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Yunyao
authors.initials: Y
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Qingjiu
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: The Sixth People's Hospital of Hebei Province, Baoding, Hebei Province 071000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Sixth People's Hospital of Hebei Province, Baoding, Hebei Province 071000, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Li
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Radiology, Peking University People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hong
authors.affiliation: The Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhassett, NY 11030, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Szeszko
authors.affiliation: Ministry of Health Key Laboratory of Mental Health, Institute of Mental Health, Peking University, Beijing 100191, China. Electronic address: yuxin@bjmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China. Electronic address: yong.he@bnu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002908:Chronic Disease; D003198:Computer Simulation; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009010:Monte Carlo Method; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D012146:Rest; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013997:Time Factors
keywords: Connection distance; Neuropsychology; Resting-state fMRI; Schizophrenia