Stress-induced dopamine release in humans at risk of psychosis: a [11C]raclopride PET study.
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.
Soliman
Alexandra
A
McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada.
O'Driscoll
Gillian A
GA
Pruessner
Jens
J
Holahan
Anne-Lise V
AL
Boileau
Isabelle
I
Gagnon
Danny
D
Dagher
Alain
A
D000328:Adult; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D006728:Hormones / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D008425:Maternal Behavior; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D011698:Pursuit, Smooth / Q000187:drug effects; D020891:Raclopride; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012306:Risk; D012569:Schizotypal Personality Disorder / Q000000981:diagnostic imaging / Q000378:metabolism; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000378:metabolism*
D018492:Dopamine Antagonists; D006728:Hormones; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D020891:Raclopride; D004298:Dopamine