Dopamine Synthesis Capacity Before Onset of Psychosis: A Prospective [18F]-DOPA PET Imaging Study
- 1 December 2011
- journal article
- research article
- Published by American Psychiatric Association Publishing in American Journal of Psychiatry
- Vol. 168 (12), 1311-1317
- https://doi.org/10.1176/appi.ajp.2011.11010160
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 [18F]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.Keywords
This publication has 39 references indexed in Scilit:
- Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal gangliaNeurology, 2007
- Multi-resolution Bayesian regression in PET dynamic studies using waveletsNeuroImage, 2006
- Cannabis-Induced Psychosis-Like Experiences Are Associated with High SchizotypyPsychopathology, 2006
- Mapping the Onset of Psychosis: The Comprehensive Assessment of At-Risk Mental StatesAustralian & New Zealand Journal of Psychiatry, 2005
- Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [18F]dopa-PET studyBrain, 1999
- CSF homovanillic acid in schizotypal personality disorderAmerican Journal of Psychiatry, 1993
- Dopamine in schizophrenia: a review and reconceptualizationAmerican Journal of Psychiatry, 1991
- Plasma homovanillic acid in schizotypal personality disorderAmerican Journal of Psychiatry, 1991
- Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake DataJournal of Cerebral Blood Flow & Metabolism, 1983
- Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in ratsNature, 1980