Whilst there is robust evidence of elevated dopamine synthesis capacity once a psychotic disorder has developed, little is known about whether it is altered prior to the first episode of frank illness. We addressed this issue by measuring dopamine synthesis capacity in subjects at ultra high risk of psychosis, and then following them to determine their clinical outcome.
This prospective study included thirty subjects who met standard criteria for being at ultra high risk of psychosis and twenty-nine healthy volunteers. Subjects were scanned using [18F]-DOPA positron emission tomography. The ultra high risk subjects were scanned at presentation and followed-up for at least three years to determine their clinical outcome. Six subjects had co-morbid schizotypal personality disorder and were excluded from the analysis (data are provided for comparison). Of the remaining subjects, nine developed a psychotic disorder subsequent to scanning (psychotic transition group), and 15 did not (non-transition group).
There was a significant effect of group on striatal dopamine synthesis capacity (p=0.006). The psychotic transition group had greater dopamine synthesis capacity in the striatum (p=0.004, effect size=1.18) and its associative subdivision (p=0.015, effect size=1.24) than controls, and showed a positive correlation between dopamine synthesis capacity and symptom severity. Dopamine synthesis capacity was also significantly greater in the psychotic transition than the non-transition group (p=0.036).
These findings provide evidence that the onset of frank psychosis is preceded by presynaptic dopaminergic dysfunction. Further work is required to determine the specificity of elevated dopamine synthesis capacity to particular psychotic disorders.