Abstract
Background: Dopamine 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. Methods: Sixty-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. 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). 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. 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Biological Psychiatry |
| Vol/bind | 91 |
| Udgave nummer | 2 |
| Sider (fra-til) | 236-245 |
| Antal sider | 10 |
| ISSN | 0006-3223 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:BYG is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. BHE received lecture fees and/or is part of the advisory board at Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia AB, Takeda Pharmaceutical Company, Boehringer Ingelheim, and Lundbeck Pharma A/S. All other authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This study was funded by Ph.D. grants and a postdoc grant from the Mental Health Services in the Capital Region of Denmark (to AKS, KT, and M?N), a Ph.D. grant from the Faculty of Health and Medical Sciences, University of Copenhagen (to KBB), an independent grant from the Lundbeck Foundation to the Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (Grant No. R155-2013-16337 [to BYG]), grants from the W?rzner Foundation (to AKS) and Gerhard Lind Foundation (to AKS), and support from the Mental Health Services, Capital Region of Denmark (to BYG). The funding sources played no role in the design or conduction of the study design, nor in the collection, analysis, and interpretation of data, nor in the writing, review approval, and submission of the manuscript for publication. We wish to thank the staff at the Center for Neuropsychiatric Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, especially Gitte Saltoft, Helle Sch?bel, Kasper Jessen, and Mikkel Erlang, at the PET center, University Hospital Herlev, especially Tri Hien Viet Huynh, Nina Tietgen, and Sofie Pilgaard, without whom the PET procedures could not have been carried out. In addition, we thank Functional Imaging Unit?Rigshospitalet. Claus Svarer and Lars Pindborg from Neurobiology Research Unit?Rigshospitalet for fruitful discussion on methods. BYG is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. BHE received lecture fees and/or is part of the advisory board at Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia AB, Takeda Pharmaceutical Company, Boehringer Ingelheim, and Lundbeck Pharma A/S. All other authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: The Pan European Collaboration on Antipsychotic Na?ve Schizophrenia II (PECANSII); https://www.clinicaltrials.gov/ct2/show/NCT02339844?term=Glenth%C3%B8j&cond=Schizophrenia&rank=7; NCT02339844.
Funding Information:
This study was funded by Ph.D. grants and a postdoc grant from the Mental Health Services in the Capital Region of Denmark (to AKS, KT, and MØN), a Ph.D. grant from the Faculty of Health and Medical Sciences , University of Copenhagen (to KBB), an independent grant from the Lundbeck Foundation to the Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (Grant No. R155-2013-16337 [to BYG]), grants from the Wørzner Foundation (to AKS) and Gerhard Lind Foundation (to AKS), and support from the Mental Health Services, Capital Region of Denmark (to BYG).
Publisher Copyright:
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