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Increased Stress-Induced Dopamine Release in Psychosis

Published:December 02, 2011DOI:https://doi.org/10.1016/j.biopsych.2011.10.009

      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 [11C]-(+)-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 [11C]-(+)-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.

      Key Words

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