title: Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis.
abstract: Altered striatal dopaminergic neurotransmission is thought to be fundamental to schizophrenia. Increased presynaptic dopaminergic activity ([18F]-DOPA PET) may predate the onset of psychotic symptoms and correlates to clinical symptoms in subjects at Ultra High Risk (UHR) for developing psychosis. Postsynaptic dopaminergic neurotransmission has not been investigated yet in UHR patients. We hypothesized that synaptic dopamine concentration would be increased in UHR patients, and that synaptic dopamine concentration would be related to symptom severity. 14 UHR patients and 15 age and IQ matched controls completed an [123I]-IBZM SPECT scan at baseline and again after dopamine depletion with alpha-methyl-para-tyrosine (AMPT). We measured changes in radiotracer binding potential, compared these between UHR patients and controls, and correlated these to symptom severity. The UHR group as a whole did not differ significantly from controls. AMPT significantly reduced symptom severity in the UHR group (p=0.014). Higher synaptic dopamine concentration predicted larger reduction of positive symptoms following depletion in the UHR group (p=0.01). In UHR patients, positive symptoms responded to dopamine depletion, comparable to observations in schizophrenia, suggesting a similar mechanism. Higher synaptic dopamine concentration was associated with more severe positive symptoms and a greater reduction of these symptoms following depletion.
authors.affiliation: Academic Medical Centre, Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Oswald J N
authors.initials: OJ
authors.lastname: Bloemen
authors.forename: Mariken B
authors.initials: MB
authors.lastname: de Koning
authors.forename: Tobias
authors.initials: T
authors.lastname: Gleich
authors.forename: Julia
authors.initials: J
authors.lastname: Meijer
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.forename: Don H
authors.initials: DH
authors.lastname: Linszen
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.forename: Thérèse A M J
authors.initials: TA
authors.lastname: van Amelsvoort
mesh_terms: D000328:Adult; D001549:Benzamides; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000652:urine; D018492:Dopamine Antagonists; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D005260:Female; D059907:Functional Neuroimaging / Q000523:psychology*; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood; D011618:Psychotic Disorders / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000652:urine; D011759:Pyrrolidines; D011869:Radioligand Assay / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology
chemical_list: D001549:Benzamides; C581293:DRD2 protein, human; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019805:alpha-Methyltyrosine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid