Dopamine synthesis capacity before onset of psychosis: a prospective [18F]-DOPA PET imaging study

Abstract

Objective: While 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. The authors addressed this issue by measuring dopamine synthesis capacity in individuals at ultra-high risk of psychosis and then following them to determine their clinical outcome.

Method: This prospective study included 30 patients who met standard criteria for being at ultra-high risk of psychosis and 29 healthy volunteers. Participants were scanned using [(18)F]6-fluoro-L-dopa positron emission tomography. The ultra-high-risk patients were scanned at presentation and followed up for at least 3 years to determine their clinical outcome. Six patients had comorbid schizotypal personality disorder and were excluded from the analysis (data are provided for comparison). Of the remaining patients, nine developed a psychotic disorder (psychotic transition group) and 15 did not (nontransition group).

Results: There was a significant effect of group on striatal dopamine synthesis capacity. The psychotic transition group had greater dopamine synthesis capacity in the striatum (effect size=1.18) and its associative subdivision (effect size=1.24) than did the healthy comparison subjects and showed a positive correlation between dopamine synthesis capacity and symptom severity. Dopamine synthesis capacity was also significantly greater in the psychotic transition group than in the nontransition group.

Conclusions: These findings provide evidence that the onset of frank psychosis is preceded by presynaptic dopaminergic dysfunction. Further research is needed to determine the specificity of elevated dopamine synthesis capacity to particular psychotic disorders.

Figure 1

Showing mean (error bars=SD) dopamine synthesis capacity (k_i^cer values) for the whole striatum in psychotic transition (N=9), non-transition (N=15) and control (N=29) groups. There were significant differences between psychotic transition and control groups (**p=0.004 corrected) and between the psychotic transition and non-transition groups (*p=0.015 corrected).

Figure 2

Increased dopamine synthesis capacity, relative to controls (N=29), in subjects who were scanned when they presented with prodromal symptoms and subsequently developed a psychotic disorder (psychotic transition group, N=9). The most significant increase was in the head of the left caudate nucleus (p=0.007 family wise error rate corrected).

Figure 3

Increased dopamine synthesis capacity in subjects who were scanned when they presented with prodromal symptoms and subsequently developed a psychotic disorder (psychotic transition group, N=9) relative to subjects who presented with similar symptoms but did not develop a psychotic disorder (non-transition group, N=15). The most significant increase was in the left caudate (p=0.036 family wise error rate corrected).

Figure 4

Showing greater severity of prodromal symptoms (total CAARMS score) is associated with greater dopamine synthesis capacity in the whole striatum (k_i^cer value/min) at presentation in subjects who subsequently developed psychosis (N=9, r=0.67, p=0.049).