What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia

Hilleke E. Hulshoff Pol, René S. Kahn

Research output: Contribution to journalReview articlepeer-review

305 Scopus citations


Numerous imaging studies have revealed structural brain changes in schizophrenia. Decreases in brain tissue are accompanied by increases in ventricle volumes and cerebrospinal fluid. Whether or not these brain changes are progressive beyond the first episode is subject to debate. To assess if progressive brain changes occur in chronically ill patients, 11 longitudinal magnetic resonance imaging and computed tomography studies were reviewed. Patients were ill for on average 10 years at their initial scan. Follow-up intervals varied between 1 and 10 years. Overall, the findings suggest continuous progressive brain tissue decreases and lateral ventricle volume increases in chronically ill patients, up to at least 20 years after their first symptoms. The extent of progressive brain tissue decrease in patients (-0.5% per year) is twice that of healthy controls (-0.2% per year). These findings are consistent with the extent of postmortem brain tissue loss in schizophrenia. Progressive volume loss seems most pronounced in the frontal and temporal (gray matter) areas. Progressive lateral ventricle volume increases are also found. More pronounced progressive brain changes in patients is associated with poor outcome, more negative symptoms, and a decline in neuropsychological performance in one or some of the studies, but not consistently so. Higher daily cumulative dose of antipsychotic medication intake is either not associated with brain volume changes or with less prominent brain volume changes. The progressive brain changes present in chronic schizophrenia may represent a continuous pathophysiological process taking place in the brains of these patients that warrants further study.

Original languageEnglish
Pages (from-to)354-366
Number of pages13
JournalSchizophrenia Bulletin
Issue number2
StatePublished - Mar 2008
Externally publishedYes


  • Brain
  • CT
  • Longitudinal
  • MRI
  • Outcome
  • Progressive
  • Schizophrenia
  • Structural


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