title: Symptom dimensions are associated with progressive brain volume changes in schizophrenia.
abstract: BACKGROUND
  There is considerable variation in progressive brain volume changes in schizophrenia. Whether this is related to the clinical heterogeneity that characterizes the illness remains to be determined. This study examines the relationship between change in brain volume over time and individual variation in psychopathology, as measured by five continuous symptom dimensions (i.e. negative, positive, disorganization, mania and depression).
  
  
  METHODS
  Global brain volume measurements from 105 schizophrenia patients and 100 healthy comparison subjects, obtained at inclusion and 5-year follow-up, were used in this study. Symptom dimension scores were calculated by factor analysis of clinical symptoms. Using linear regression analyses and independent-samples t-tests, the relationship between symptom dimensions and progressive brain volume changes, corrected for age, gender and intracranial volume, was examined. Antipsychotic medication, outcome and IQ were investigated as potential confounders.
  
  
  RESULTS
  In patients, the disorganization dimension was associated with change in total brain (β=-0.295, p=0.003) and cerebellar (β=-0.349, p<0.001) volume. Furthermore, higher levels of disorganization were associated with lower IQ, irrespective of psychiatric status (i.e. patient or control). In healthy comparison subjects, disorganization score was not associated with progressive brain volume changes.
  
  
  CONCLUSIONS
  Heterogeneity in progressive brain volume changes in schizophrenia is particularly associated with variation in disorganization. Schizophrenia patients with high levels of disorganization exhibit more progressive decrease of global brain volumes and have lower total IQ. We propose that these patients form a phenotypically and biologically homogenous subgroup that may be useful for etiological (e.g., genetic) studies.
authors.affiliation: University Medical Center Utrecht, Department of Psychiatry, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Collin
authors.forename: E M
authors.initials: EM
authors.lastname: Derks
authors.forename: N E M
authors.initials: NE
authors.lastname: van Haren
authors.forename: H G
authors.initials: HG
authors.lastname: Schnack
authors.forename: H E
authors.initials: HE
authors.lastname: Hulshoff Pol
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.forename: W
authors.initials: W
authors.lastname: Cahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003863:Depression / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D012559:Schizophrenia / Q000473:pathology*; D012562:Schizophrenia, Disorganized / Q000473:pathology*; D012565:Schizophrenic Psychology