Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study

Am J Psychiatry. 2013 Jun;170(6):609-15. doi: 10.1176/appi.ajp.2013.12050674.


Objective: Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question.

Methods: The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years.

Results: Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity.

Conclusions: Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Brain / drug effects
  • Brain / pathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuroimaging
  • Prospective Studies
  • Recurrence
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology*
  • Time Factors
  • Young Adult


  • Antipsychotic Agents