title: Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia.
abstract: BACKGROUND
  Schizophrenia has a characteristic onset during adolescence or young adulthood but also tends to persist throughout life. Structural magnetic resonance studies indicate that brain abnormalities are present at onset, but longitudinal studies to assess neuroprogression have been limited by small samples and short or infrequent follow-up intervals.
  
  
  METHODS
  The Iowa Longitudinal Study is a prospective study of 542 first-episode patients who have been followed up to 18 years. In this report, we focus on those patients (n = 202) and control subjects (n = 125) for whom we have adequate structural magnetic resonance data (n = 952 scans) to provide a relatively definitive determination of whether progressive brain change occurs over a time interval of up to 15 years after intake.
  
  
  RESULTS
  A repeated-measures analysis showed significant age-by-group interaction main effects that represent a significant decrease in multiple gray matter regions (total cerebral, frontal, thalamus), multiple white matter regions (total cerebral, frontal, temporal, parietal), and a corresponding increase in cerebrospinal fluid (lateral ventricles and frontal, temporal, and parietal sulci). These changes were most severe during the early years after onset. They occur at severe levels only in a subset of patients. They are correlated with cognitive impairment but only weakly with other clinical measures.
  
  
  CONCLUSIONS
  Progressive brain change occurs in schizophrenia, affects both gray matter and white matter, is most severe during the early stages of the illness, and occurs only in a subset of patients. Measuring severity of progressive brain change offers a promising new avenue for phenotype definition in genetic studies of schizophrenia.
authors.affiliation: Psychiatric Iowa Neuroimaging Consortium, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. luanngodlove@uiowa.edu
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Andreasen
authors.forename: Peg
authors.initials: P
authors.lastname: Nopoulos
authors.forename: Vincent
authors.initials: V
authors.lastname: Magnotta
authors.forename: Ronald
authors.initials: R
authors.lastname: Pierson
authors.forename: Steven
authors.initials: S
authors.lastname: Ziebell
authors.forename: Beng-Choon
authors.initials: BC
authors.lastname: Ho
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000706:statistics & numerical data*; D008297:Male; D059906:Neuroimaging / Q000379:methods / Q000706:statistics & numerical data*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011446:Prospective Studies; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D012565:Schizophrenic Psychology