Brain volume changes in first-episode schizophrenia: a 1-year follow-up study

Arch Gen Psychiatry. 2002 Nov;59(11):1002-10. doi: 10.1001/archpsyc.59.11.1002.


Background: Imaging studies of patients with schizophrenia have demonstrated that brain abnormalities are largely confined to decreases in gray matter volume and enlargement of the lateral and third ventricles. Global gray matter volume has been reported to progressively decrease in childhood-onset and chronic schizophrenia. Global gray matter volumes have not been examined longitudinally in patients with first-episode schizophrenia. One would expect global gray matter to decrease progressively, particularly in first-episode patients, because clinical deterioration is greatest in the early stages of the disease.

Methods: Patients with first-episode schizophrenia who had taken antipsychotic medication for 0 to 16 weeks (n = 34) and matched healthy comparison subjects (n = 36) were included in the study. For all subjects, magnetic resonance imaging scans of the whole brain were obtained at inclusion and after 1 year (mean [SD], 12.7 [1.1] months). Outcome was measured 2 years after inclusion. To compare morphological changes over time between patients and healthy comparison subjects, multiple repeated-measures analyses of variance were conducted with intracranial volume as a covariate. Outcome and cumulative antipsychotic medication were related to changes in patients' brain volumes.

Results: Total brain volume (-1.2%) and gray matter volume of the cerebrum (-2.9%) significantly decreased and lateral ventricle volume significantly increased (7.7%) in patients. The decrease in global gray matter volume significantly correlated with outcome and, independently of that, with higher cumulative dosage of antipsychotic medication.

Conclusions: The loss of global gray matter in schizophrenia is progressive, occurs at an early stage of the illness, and is related to the disease process and antipsychotic medication.

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Brain / pathology*
  • Dominance, Cerebral / physiology
  • Echo-Planar Imaging
  • Female
  • Follow-Up Studies
  • Fourier Analysis
  • Humans
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Magnetic Resonance Imaging*
  • Male
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Reference Values
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology*
  • Schizophrenic Psychology*


  • Antipsychotic Agents