Insular cortex abnormalities in schizophrenia: Relationship to symptoms and typical neuroleptic exposure

Biol Psychiatry. 2005 Feb 15;57(4):394-8. doi: 10.1016/j.biopsych.2004.11.010.


Background: The insular cortex is a limbic integration region engaged in emotional and cognitive functions. Previously, we found that neuroleptic-naive subjects had abnormally small insular volumes compared with control subjects, with volume directly related to severity of psychotic symptoms.

Methods: To further investigate insular cortex abnormalities and their functional correlates, we measured insular gray matter volume and cortical surface size, using magnetic resonance images among 30 patients with schizophrenia and a matched control group. The sample was designed to represent a variety of phenomenologic profiles to provide sufficient variance in multiple measures, including severity of illness and exposure to neuroleptics (typical only).

Results: There were no significant differences in morphology between patients and control subjects; however, among patients, psychotic symptoms were inversely correlated with insular volume, replicating our previous finding in neuroleptic-naive subjects. Neuroleptic exposure had a specific effect on insular morphology: increasing drug exposure (measured in dose-years) correlated with larger insular volume.

Conclusions: This effect of neuroleptic exposure might account for the lack of difference in structural measures in this more chronic sample, whereas the initial study on neuroleptic-naive subjects showed group differences. Further research is needed to investigate the potential relationship between changes in insula volume from neuroleptic exposure and clinical outcome.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Brain Mapping
  • Case-Control Studies
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology*
  • Cerebral Cortex / physiopathology
  • Female
  • Functional Laterality
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods
  • Male
  • Psychiatric Status Rating Scales
  • Reproducibility of Results
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*


  • Antipsychotic Agents