title: Processing speed impairment in schizophrenia is mediated by white matter integrity.
abstract: BACKGROUND
  Processing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter (WM) integrity in schizophrenia is unclear.
  
  
  METHODS
  Individuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory and executive functioning. Group differences in WM integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished WM integrity was tested.
  
  
  RESULTS
  WM integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed but not in other cognitive domains. Diminished WM integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed.
  
  
  CONCLUSIONS
  Cognitive impairment in schizophrenia was mediated by reduced WM integrity. This relationship was strongest for processing speed because deficits in working memory, verbal learning and executive functioning were not mediated by WM integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve WM integrity or ameliorate WM disruption may enhance processing speed and functional outcome in schizophrenia.
authors: Psychotic Disorders and Psychiatric Neuroimaging Programs, Department of Psychiatry,Vanderbilt University School of Medicine,Nashville, TN,USA.
authors: H
authors: H
authors: Karbasforoushan
authors: Psychotic Disorders and Psychiatric Neuroimaging Programs, Department of Psychiatry,Vanderbilt University School of Medicine,Nashville, TN,USA.
authors: B
authors: B
authors: Duffy
authors: Psychotic Disorders and Psychiatric Neuroimaging Programs, Department of Psychiatry,Vanderbilt University School of Medicine,Nashville, TN,USA.
authors: J U
authors: JU
authors: Blackford
authors: Psychotic Disorders and Psychiatric Neuroimaging Programs, Department of Psychiatry,Vanderbilt University School of Medicine,Nashville, TN,USA.
authors: N D
authors: ND
authors: Woodward
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D003337:Corpus Callosum / Q000000981:diagnostic imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D006778:Hospitals, Psychiatric; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance; D011859:Radiography; D012044:Regression Analysis; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D013714:Tennessee; D066127:White Matter / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents