Increased stress-induced dopamine release in psychosis

Biol Psychiatry. 2012 Mar 15;71(6):561-7. doi: 10.1016/j.biopsych.2011.10.009. Epub 2011 Nov 30.


Background: A pathologic response to common life stressors, in which a hyperresponsive dopaminergic system is thought to play a key role, is a potential etiologic factor in the triggering and relapse of psychosis. However, there is no direct evidence that brain dopaminergic response to stress is exaggerated in psychosis.

Methods: Using the ability of endogenous dopamine (DA) to compete with [(11)C]-(+)-PHNO binding, as measured with positron emission tomography, we examined stress-induced DA release in response to a validated psychosocial stress task. We studied 12 clinical high-risk (CHR), 10 antipsychotic-naive subjects with schizophrenia (SCZ), and 12 matched healthy volunteers (HV). Stress-induced DA release was estimated as the percent change in binding potential between conditions (stress and control scan) in the striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST).

Results: We found a significant difference between groups in the AST (F = 8.13, df = 2,31, p = .001), and at the SMST (F = 3,64, df = 2,31, p = .03) but not in the LST (F = .43, df = 2,31, p = .40) with CHR and SCZ having larger [(11)C]-(+)-PHNO displacement in response to the stress. Bonferroni-corrected comparisons confirmed that HV displacement (-2.86%) in the AST was significantly different in CHR (6.97%) and SCZ (11.44%) (with no significant difference between CHR and SCZ).

Conclusions: This study reveals a sensitized dopaminergic response to stress in a psychiatric condition and may have important theoretical and clinical implications regarding efforts to abort or delay relapse and/or conversion to psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain Mapping / methods
  • Dopamine / metabolism*
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Image Processing, Computer-Assisted / methods
  • Male
  • Positron-Emission Tomography / methods
  • Psychotic Disorders / complications
  • Psychotic Disorders / diagnostic imaging
  • Psychotic Disorders / metabolism*
  • Saliva / metabolism
  • Schizophrenia / complications
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*
  • Young Adult


  • Dopamine
  • Hydrocortisone