Psychosis patients show increased stress-induced dopamine release
MedWire News: Patients with schizophrenia and those at clinical high risk (CHR) for psychosis exhibit increased levels of dopamine in response to stress compared with mentally healthy individuals, Canadian research shows.
"A pathologic response to common life stressors, in which a hyper-responsive dopaminergic system is thought to play a key role, is a potential etiologic factor in the triggering and relapse of psychosis," explain Romina Mizrahi (University of Toronto, Ontario) and team.
"However, there is no direct evidence that brain dopaminergic response to stress is exaggerated in psychosis," they add.
To investigate, the researchers studied 10 antipsychotic-naïve schizophrenia patients, 12 patients at CHR for psychosis who met diagnostic criteria for a prodromal syndrome, and 12 mentally healthy individuals (controls). The three groups were comparable in terms of demographic characteristics.
All participants underwent positron emission tomography (PET) scans of the brain before and while performing a psychosocial stress task (the Montreal Imaging Stress Task). This involves performing mental arithmetic on a computer screen that also displays information about the total number of errors, expected average number of errors, time spent on the current problem, and performance feedback for each problem.
The team used the ability of endogenous dopamine to compete with PET radiotracer [11C]-(+)-PHNO binding to the D2/3 receptors to assess stress-induced dopamine release, as concentrations of the neurochemical cannot be measured directly in the living human brain.
Stress-induced dopamine release was estimated as the percentage of change in binding potential between the first and second scans in the limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST).
The researchers found that there was a significant difference between both of the patient groups and controls regarding dopamine release in the AST and SMST, with CHR and schizophrenia patients showing greater [11C]-(+)-PHNO displacement in response to the stress task than controls. There were no significant between-group differences regarding dopamine release in the LST.
Bonferroni-corrected comparisons confirmed that [11C]-(+)-PHNO displacement in the AST among controls (-2.86%) was significantly different from that in CHR (6.97%) and schizophrenia patients (11.44%) in response to stress. The difference in displacement between the two patients groups was not significant.
Mizrahi and team conclude in Biological Psychiatry: "This work highlights the role of dopamine dysregulation in psychosis and its possible link to stress.
"Our findings encourage future research into strategies focusing on the modulation of stress-induced dopamine release for the purpose of relapse prevention in schizophrenia and even the possibility of averting or delaying conversion to psychosis in at-risk individuals."
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By Mark Cowen