The pathophysiology of schizophrenia disorders: perspectives from the spectrum

Am J Psychiatry. 2004 Mar;161(3):398-413. doi: 10.1176/appi.ajp.161.3.398.


Objective: This overview focuses on neurobiological abnormalities found in subjects with schizotypal personality disorder, the prototype of the schizophrenia spectrum disorders, and chronic schizophrenia in the context of common vulnerabilities shared by schizotypal personality disorder and schizophrenia, as well as the factors that protect against the severe cognitive/social deficits and frank psychosis of chronic schizophrenia. A pathophysiological model of the relationship between schizotypal personality disorder and schizophrenia was developed based on this data.

Method: The authors provide a selective review of major findings regarding the pathophysiology of schizotypal personality disorder and integrate these results in conjunction with preclinical studies into a model of the pathophysiology of the spectrum.

Results: People with schizotypal personality disorder share phenomenological, genetic, and cognitive abnormalities with people with chronic schizophrenia. While temporal volume reductions appear to be common to both groups, there may be preservation of frontal lobe volume in schizotypal personality disorder compared to schizophrenia. Findings to date regarding striatal volume, metabolic rate, and dopamine release in subjects with schizotypal personality disorder compared to subjects with chronic schizophrenia are consistent with hypotheses of reduced striatal dopaminergic activity in schizotypal personality disorder compared to schizophrenia.

Conclusions: Genetic or environmental factors that promote greater frontal capacity and reduced striatal dopaminergic reactivity might contribute to sparing people with schizotypal personality disorder from the psychosis and severe social and cognitive deterioration of chronic schizophrenia. Further research is required to test these hypotheses more definitively.

Publication types

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

MeSH terms

  • Atrophy
  • Brain / pathology
  • Brain / physiopathology*
  • Chronic Disease
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Dopamine / metabolism
  • Frontal Lobe / pathology
  • Frontal Lobe / physiopathology
  • Humans
  • Neuropsychological Tests
  • Risk Factors
  • Schizophrenia / diagnosis
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology*
  • Schizophrenic Psychology*
  • Schizotypal Personality Disorder / diagnosis
  • Schizotypal Personality Disorder / genetics
  • Schizotypal Personality Disorder / physiopathology*


  • Dopamine