Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

Abstract

Drugs that increase dopamine levels in the brain can cause psychotic symptoms in healthy individuals and worsen them in schizophrenic patients. Psychological stress also increases dopamine release and is thought to play a role in susceptibility to psychotic illness. We hypothesized that healthy individuals at elevated risk of developing psychosis would show greater striatal dopamine release than controls in response to stress. Using positron emission tomography and [ 11 C]raclopride, we measured changes in synaptic dopamine concentrations in 10 controls and 16 psychometric schizotypes; 9 with perceptual aberrations (PerAb, ie positive schizotypy) and 7 with physical anhedonia (PhysAn, ie negative schizotypy). [ 11 C]Raclopride binding potential was measured during a psychological stress task and a sensory-motor control. All three groups showed significant increases in self-reported stress and cortisol levels between the stress and control conditions. However, only the PhysAn group showed significant stress-induced dopamine release. Dopamine release in the entire sample was significantly negatively correlated with smooth pursuit gain, an endophenotype linked to frontal lobe function. Our findings suggest the presence of abnormalities in the dopamine response to stress in negative symptom schizotypy, and provide indirect evidence of a link to frontal function.

The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities

“…In contrast, a study using a mental arithmetic task during a positron-emission tomography (PET) scan, found a decrease in salivary cortisol during the task in controls and no change in CHR youth (Mizrahi et al, 2012). In an earlier study using this stress paradigm during a PET scan, both youth with schizotypal traits and healthy controls showed a significant cortisol response, with no significant difference between the groups (Soliman et al, 2008). The cortisol response in these latter studies might have been confounded by the potentially stress-inducing environment of a PET scan.…”

Increased resting perfusion of the hippocampus in high positive schizotypy: A pseudocontinuous arterial spin labeling study

“…Although there is some evidence of an association between altered dopaminergic neurotransmission and psychometrically identified schizotypy (Woodward et al, 2011), findings are less consistent than in frank psychosis, possibly due to high heterogeneity in the experimental designs and methods used (Mohr & Ettinger, 2014). Moreover, elevated stress‐induced dopamine release as measured with [ 11 C]raclopride PET (Soliman et al, 2008) and increased functional activation as measured with functional MRI (Soliman et al, 2011) in striatal regions in schizotypy has only been observed in relation to negative schizotypal features (reflecting the interpersonal dimension of schizotypy, thought to mirror negative symptoms in schizophrenia), but not in relation to positive schizotypy (reflecting the cognitive‐perception dimension of schizotypy, thought to mirror positive symptoms in schizophrenia). Further research examining the relative contributions of hyperperfusion at different nodes of a hippocampal–striatal–midbrain circuit along a psychosis continuum (psychosis, CHR, and HS), combined with measurements of the different neurotransmitter systems involved (i.e., GABA, glutamate, and dopamine), may provide substantial insights into the neurobiology of risk and resilience for psychiatric disorders (Pantelis & Bartholomeusz, 2014).…”

Abnormal Striatal Dopamine Transmission in Schizophrenia

“…This result has been replicated in subjects at risk to psychosis using other D2 radioligands. An abnormal supra striatal DA response has been found after a metabolic stress challenge with no direct DA impact in unaffected siblings of patients with schizophrenia [66], after psychosocial stress [67,68] and also after amphetamine challenge in psychometric schizotypal subjects [69]. Interestingly, according to the relationship between DA transmission and stress (for a comprehensive review see [70]), it has been shown that the over-DA response evoked by psychosocial stress was correlated with salivary cortisol response to stress [68].…”