title: Progressive gray matter changes in first episode schizophrenia: a 4-year longitudinal magnetic resonance study using VBM.
abstract: Schizophrenia is a disabling illness, characterized by a heterogeneous course including clinical deterioration and poor outcome. Accumulating findings in schizophrenia suggest that it might involve two pathophysiologic processes, one early in life (neurodevelopmental), and one after onset of the illness (neurodegenerative). Longitudinal imaging studies after onset of the illness may help to clarify these pathophysiological aspects of schizophrenia, but so far, probably due to methodological differences, there have been no conclusive results. The present study sets out to investigate longitudinal gray matter changes in patients with first-episode schizophrenia relative to healthy subjects over the first 4 years of the illness and the relation of gray matter changes in patients with functional outcome, using an objective automatic method not biased to one particular structure to analyze gray matter changes.
  
  
  METHODS
  We included 28 first-episode neuroleptic-naïve patients with DSM-IV diagnosis of schizophreniform disorder or schizophrenia, and 17 controls. 15 patients and 11 controls completed the longitudinal study and were reevaluated after four years. Gray matter changes over time were measured with voxel-based morphometry (VBM) using SPM5. Functional outcome was measured with the global assessment functioning scale (GAF).
  
  
  RESULTS
  Excessive decrease in gray matter was found in patients as compared to healthy individuals in the left superior temporal gyrus and right orbitofrontal gyrus, and excessive increase in the bilateral lingual gyrus and right cuneus. Additionally, gray matter changes in patients in the left lingual gyrus, right insula and right cerebellum, were inversely related to functional outcome (p<0.001 uncorrected at voxel level, p<0.05 family-wise-error corrected at cluster level).
  
  
  CONCLUSIONS
  There are differing longitudinal gray matter changes in patients with schizophrenia during the first years of the illness as compared to healthy individuals. Some progressive gray matter changes in patients are related to functional outcome.
authors.affiliation: Programa Esquizofrenia Clinic, Department of Psychiatry, Institute of Neuroscience, Hospital Clinic, Barcelona, Spain. manesantacana@yahoo.es
authors.forename: Anna
authors.initials: A
authors.lastname: Mané
authors.forename: Carles
authors.initials: C
authors.lastname: Falcon
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Mateos
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Egea
authors.forename: Guillermo
authors.initials: G
authors.lastname: Horga
authors.forename: Francisco
authors.initials: F
authors.lastname: Lomeña
authors.forename: Nuria
authors.initials: N
authors.lastname: Bargalló
authors.forename: Alberto
authors.initials: A
authors.lastname: Prats-Galino
authors.forename: Miguel
authors.initials: M
authors.lastname: Bernardo
authors.forename: Eduard
authors.initials: E
authors.lastname: Parellada
mesh_terms: D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D018450:Disease Progression; D005192:Family Health; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000473:pathology / Q000503:physiopathology; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology*; D012565:Schizophrenic Psychology