Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia

Am J Psychiatry. 2003 Jan;160(1):142-8. doi: 10.1176/appi.ajp.160.1.142.


Objective: Studies of patients experiencing their first episode of psychosis have demonstrated that they typically remain undiagnosed and untreated for 1-2 years. It has been postulated that prolonged untreated psychosis may have serious effects: poor response to neuroleptic medications, poor clinical outcomes, and direct neurotoxicity. This study investigated the relationships between duration of untreated initial psychosis and neurocognitive functioning and high-resolution imaging brain measurements.

Method: A total of 156 subjects with DSM-IV schizophrenia, schizophreniform disorder, or schizoaffective disorder were evaluated during their first episode of psychosis. Measurements included nine domains of neurocognitive functioning, volumetric measures of total brain tissue, gray and white matter, and CSF, and measures of brain surface anatomy.

Results: The mean duration of untreated initial psychosis was 74.3 weeks. Correlations between neurocognitive functioning, brain volumetric measurements, and surface anatomy measurements with duration of untreated initial psychosis were weak; none reached statistical significance. When the group was divided on the basis of median duration of untreated initial psychosis, there were again no significant differences between the groups with long and short duration of untreated initial psychosis except on two measures (verbal memory and cortical sulcal depth).

Conclusions: The absence of strong correlations suggests that untreated initial psychosis has no direct toxic neural effects. These results suggest that large-scale initiatives designed to prevent neural injury through early intervention in the prepsychotic or early psychosis phase may be based on incorrect assumptions that neurotoxicity or cognitive deterioration may be avoided. Nevertheless, early treatment is justified because it reduces suffering.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Cerebral Cortex / pathology*
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / psychology
  • Drug Administration Schedule
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging*
  • Male
  • Neuropsychological Tests*
  • Prognosis
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / diagnosis*
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / psychology
  • Schizophrenia / diagnosis*
  • Schizophrenia / drug therapy
  • Schizophrenic Psychology*
  • Sex Factors


  • Antipsychotic Agents