Abstract
BackgroundElevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness. The effects of antipsychotic medication on dopamine synthesis capacity are poorly understood, and no prospective studies have examined this question in a solely first-episode psychosis sample. Furthermore, it is unknown whether antipsychotic efficacy is linked to reductions in dopamine synthesis capacity. We conducted a prospective [18F]-dihydroxyphenyl-L-alanine positron emission tomography study in antipsychotic naïve/free people with first-episode psychosis commencing antipsychotic treatment. MethodsDopamine synthesis capacity (indexed as influx rate constant) and clinical symptoms (measured using Positive and Negative Syndrome Scale) were measured before and after at least 5 weeks of antipsychotic treatment in people with first-episode psychosis. Data from a prior study indicated that a sample size of 13 would have >80% power to detect a statistically significant change in dopamine synthesis capacity at alpha = .05 (two tailed). ResultsA total of 20 people took part in the study, 17 of whom were concordant with antipsychotic medication at therapeutic doses. There was no significant effect of treatment on dopamine synthesis capacity in the whole striatum (p = .47), thalamus, or midbrain, nor was there any significant relationship between change in dopamine synthesis capacity and change in positive (ρ = .35, p = .13), negative, or total psychotic symptoms. ConclusionsDopamine synthesis capacity is unaltered by antipsychotic treatment, and therapeutic effects are not mediated by changes in this aspect of dopaminergic function.
Highlights
Elevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness
Our main findings were that there was no significant change in striatal dopamine synthesis capacity with antipsychotic treatment and no significant association between change in dopamine synthesis capacity and change in psychotic symptoms
Our finding of no change in presynaptic striatal dopamine function with prolonged antipsychotic treatment is consistent with acute studies in healthy volunteers, which found no significant overall change in dopamine synthesis capacity after treatment with a number of different antipsychotic drugs [53,54,55]
Summary
Patients were recruited from first-episode psychosis services in London. Inclusion criteria were diagnosis of a psychotic disorder according to ICD-10 criteria [28], fulfilling criteria for having a first episode of psychosis [29], requiring treatment with antipsychotic medication, and being antipsychotic naïve or antipsychotic free for at least 6 weeks [other clinical studies in similar populations require being antipsychotic free for a minimum of 3 weeks [30,31]]. People presenting with first-episode psychosis received one baseline [18F]-DOPA scan prior to initiation of antipsychotic medication. All participants received follow-up [18F]-DOPA scans and clinical measures (PANSS, Global Assessment of Functioning, and CGI-I) after at least 5 weeks of antipsychotic treatment at an adequate dose as defined in the Maudsley Prescribing Guidelines and meeting concordance criteria described above. Because hypothesis 2 related to the relationship between dopamine synthesis capacity and symptom change irrespective of treatment (examining possible state effects), all subjects who took part in the study were included (including those nonconcordant with antipsychotic medication and those receiving inadequate antipsychotic treatment) in the primary analysis. We conducted a further exploratory analysis to determine whether correlations between dopamine synthesis capacity and symptom change were seen in patients who met full adherence criteria to test specificity to antipsychotic treatment. Change in dopamine synthesis capacity (DSC) was calculated as follows: Change in DSC 1⁄4 DSCbaseline DSCfollow-up à 100 DSCbaseline
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