title: Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study.
abstract: BACKGROUND
  We sought to determine whether the brain dysmorphology previously observed cross-sectionally in people with schizophrenia progresses over time and whether such progression is related to the severity of the illness course.
  
  
  METHODS
  Men with chronic schizophrenia (n = 24) and control men (n = 25) received 2 brain magnetic resonance imaging scans, on average 4 years apart. Changes in brain volume were adjusted for head-repositioning error and expressed as slopes (cubic centimeters per year). Clinical course severity for the schizophrenic patients was assessed using the mean of time 1 and time 2 Brief Psychiatric Rating Scale (BPRS) scores and the percentage of time the patient was hospitalized during the interscan interval.
  
  
  RESULTS
  Schizophrenic patients exhibited faster volume decline than control subjects in right frontal gray matter and bilateral posterior superior temporal gray matter, as well as faster cerebrospinal fluid volume expansion in right frontal sulci, left lateral ventricle, and bilateral prefrontal and posterior superior temporal sulci. Faster rates of frontal sulcal expansion were related to greater BPRS total and positive symptom scores and longer time hospitalized. Prefrontal gray matter decline and sulcal expansion were associated with greater BPRS negative symptom scores and longer time hospitalized. Temporal lobe gray matter decline was associated with greater BPRS total and negative symptom scores.
  
  
  CONCLUSIONS
  This controlled study revealed that patients with chronic schizophrenia exhibited accelerated frontotemporal cortical gray matter decline and cortical sulcal and lateral ventricular expansion. Further, greater clinical severity was associated with faster rates of frontotemporal brain volume changes. These observations are consistent with a progressive pathophysiological process but need to be replicated in a larger sample.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. daniel.mathalon@yale.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Mathalon
authors.forename: E V
authors.initials: EV
authors.lastname: Sullivan
authors.forename: K O
authors.initials: KO
authors.lastname: Lim
authors.forename: A
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology*; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D002552:Cerebral Ventricles / Q000033:anatomy & histology; D002555:Cerebrospinal Fluid / Q000502:physiology; D002908:Chronic Disease; D007839:Functional Laterality; D006760:Hospitalization; D006801:Humans; D007902:Length of Stay; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000175:diagnosis*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D012737:Sex Factors