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
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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. / Sigvard, Anne Korning; Nielsen, Mette Ødegaard; Gjedde, Albert; Bojesen, Kirsten Borup; Fuglø, Dan; Tangmose, Karen; Kumakura, Yoshitaka; Heltø, Kim; Ebdrup, Bjørn H.; Jensen, Lars Thorbjørn; Rostrup, Egill; Glenthøj, Birte Yding.
In: Biological Psychiatry, Vol. 91, No. 2, 2022, p. 236-245.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Dopaminergic Activity in Antipsychotic-Naïve Patients Assessed With Positron Emission Tomography Before and After Partial Dopamine D2 Receptor Agonist Treatment
T2 - Association With Psychotic Symptoms and Treatment Response
AU - Sigvard, Anne Korning
AU - Nielsen, Mette Ødegaard
AU - Gjedde, Albert
AU - Bojesen, Kirsten Borup
AU - Fuglø, Dan
AU - Tangmose, Karen
AU - Kumakura, Yoshitaka
AU - Heltø, Kim
AU - Ebdrup, Bjørn H.
AU - Jensen, Lars Thorbjørn
AU - Rostrup, Egill
AU - Glenthøj, Birte Yding
N1 - Publisher Copyright: © 2021 Society of Biological Psychiatry
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Antipsychotic-naïve schizophrenia
KW - Aripiprazole
KW - Dopa decarboxylase
KW - dopamine
KW - Dopamine
KW - F-DOPA
KW - Partial agonist
KW - Positron emission tomography
KW - Psychosis
KW - Striatum
KW - Treatment outcome
U2 - 10.1016/j.biopsych.2021.08.023
DO - 10.1016/j.biopsych.2021.08.023
M3 - Journal article
C2 - 34743917
AN - SCOPUS:85118566303
VL - 91
SP - 236
EP - 245
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 2
ER -
ID: 285244864