Fernando Caravaggio1, Carol Borlido2, Alan Wilson3, Ariel Graff-Guerrero4. 1. Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 2374 Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. 2. Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. 3. Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 2374 Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. 4. Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 2374 Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: ariel.graff@camh.ca.
Abstract
BACKGROUND: Using positron emission tomography (PET) it is possible to estimate endogenous dopamine (DA) occupying D2/3 receptors (D2/3R) in the living human brain. Persons with schizophrenia (SZ) (previously medicated and naïve) have increased endogenous DA occupying D2/3R in the caudate. It is unknown whether currently medicated patients demonstrate increased DA levels at D2/3R. Moreover, DA levels have not been estimated in SZ using agonist radiotracers, which may offer a more sensitive quantification over antagonists. METHODS: Using the agonist radiotracer [(11)C]-(+)-PHNO, DA levels were estimated at D2/3R (ΔBP(ND)) in three patients with SZ (male, mean age=30±16). Patients were currently being treated long-term with Olanzapine (147±88 nmol/L). Results were compared to ten healthy controls (HCs). RESULTS: Medicated persons with SZ had greater ΔBP(ND) in the left caudate (U=2, Z=-2.20, p=.03) and right putamen (U=2, Z=-2.20, p=.03). No differences were observed in the ventral striatum or globus pallidus. CONCLUSIONS: It is possible to estimate endogenous DA at D2/3R in SZ patients currently taking antipsychotics. Despite medication, patients continue to have increased endogenous DA at D2/3R. This lends more biological support to the clinical observation that relapses in symptoms can occur in the face of complete antipsychotic discontinuation. Future studies with larger samples are warranted.
BACKGROUND: Using positron emission tomography (PET) it is possible to estimate endogenous dopamine (DA) occupying D2/3 receptors (D2/3R) in the living human brain. Persons with schizophrenia (SZ) (previously medicated and naïve) have increased endogenous DA occupying D2/3R in the caudate. It is unknown whether currently medicated patients demonstrate increased DA levels at D2/3R. Moreover, DA levels have not been estimated in SZ using agonist radiotracers, which may offer a more sensitive quantification over antagonists. METHODS: Using the agonist radiotracer [(11)C]-(+)-PHNO, DA levels were estimated at D2/3R (ΔBP(ND)) in three patients with SZ (male, mean age=30±16). Patients were currently being treated long-term with Olanzapine (147±88 nmol/L). Results were compared to ten healthy controls (HCs). RESULTS: Medicated persons with SZ had greater ΔBP(ND) in the left caudate (U=2, Z=-2.20, p=.03) and right putamen (U=2, Z=-2.20, p=.03). No differences were observed in the ventral striatum or globus pallidus. CONCLUSIONS: It is possible to estimate endogenous DA at D2/3R in SZ patients currently taking antipsychotics. Despite medication, patients continue to have increased endogenous DA at D2/3R. This lends more biological support to the clinical observation that relapses in symptoms can occur in the face of complete antipsychotic discontinuation. Future studies with larger samples are warranted.
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