Dopaminergic Activity in Antipsychotic-Naïve Patients Assessed With Positron Emission Tomography Before and After Partial Dopamine D2 Receptor Agonist Treatment: Association With Psychotic Symptoms and Treatment Response

Anne Korning Sigvard,Mette Ødegaard Nielsen,Albert Gjedde,Kirsten Borup Bojesen,Dan Fuglø,Karen Tangmose,Yoshitaka Kumakura,Kim Heltø,Bjørn H Ebdrup,Lars Thorbjørn Jensen,Egill Rostrup,Birte Yding Glenthøj

doi:10.1016/j.biopsych.2021.08.023

Abstract

BackgroundDopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of 18F-DOPA to 18F-dopamine (k3) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D2 receptor agonist (aripiprazole) on k3 and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method. MethodsSixty-two individuals (31 patients and 31 control subjects) underwent 18F-DOPA positron emission tomography at baseline, and 15 patients were re-examined after 6 weeks. Clinical re-examinations were completed after 6 weeks (n = 28) and 6 months (n = 15). Symptoms were evaluated with the Positive and Negative Syndrome Scale. ResultsHigh baseline decarboxylation rates (k3) were associated with more positive symptoms at baseline (p < .001) and with symptom improvement after 6 weeks (p = .006). Subregion analyses showed that baseline k3 for the putamen (p = .003) and nucleus accumbens (p = .013) and DSC values for the nucleus accumbens (p = .003) were associated with psychotic symptoms. The tissue reference method yielded no associations between DSC and symptoms or symptom improvement. Neither method revealed any effects of group or treatment on average magnitudes of k3 or DSC, whereas changes in dopamine synthesis were correlated with higher baseline values, implying a potential effect of treatment. ConclusionsStriatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k3 and treatment effect potentially implicate on new treatment strategies.

Highlights

Dopamine activity has been associated with the response to antipsychotic treatment
The patients re-examined with positron emission tomography (PET) had lower baseline Positive and Negative Syndrome Scale (PANSS) total and PANSS general scores than patients who were not re-examined with this method (p, .03) (n = 19)
The association was significant for the putamen (b = 23.1, p = .003) and nucleus accumbens (NAcc) (b = 12.0, p = .013)

Summary

Introduction

Our study used a four-parameter model to test the association between the striatal decarboxylation rate of 18F-DOPA to 18Fdopamine (k3) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with firstepisode psychosis. RESULTS: High baseline decarboxylation rates (k3) were associated with more positive symptoms at baseline (p , .001) and with symptom improvement after 6 weeks (p = .006). The tissue reference method yielded no associations between DSC and symptoms or symptom improvement. Neither method revealed any effects of group or treatment on average magnitudes of k3 or DSC, whereas changes in dopamine synthesis were correlated with higher baseline values, implying a potential effect of treatment. CONCLUSIONS: Striatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k3 and treatment effect potentially implicate on new treatment strategies

Results

Discussion

Conclusion