title: Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task.
abstract: BACKGROUND
  The dopamine (DA) D2 receptors exist in 2 states: a high-affinity state (D2 high) that is linked to second messenger systems, responsible for functional effects, exhibits high affinity for agonists (e.g., DA), and a low-affinity state that is functionally inert exhibits lower affinity for agonists. The DA D3 receptor subtype exhibits high agonist affinity, whereas the existence of the multiple affinity states is controversial. Preclinical studies in animal models of psychosis have shown a selective increase of D2 high as the common factor in psychosis, and the D3 receptor has been suggested to be involved in the pathophysiology of schizophrenia.
  
  
  METHODS
  We studied D2 high and D3 in people at clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients with schizophrenia using the novel positron emission tomography radiotracer, [11C]-(+)-PHNO. The binding potential nondisplaceable (BP(ND)) was examined in the regions of interest (ROI; caudate, putamen, ventral striatum, globus pallidus, substantia nigra and thalamus) using an ROI and a voxel-wise approach while participants performed a cognitive task.
  
  
  RESULTS
  We recruited 12 CHR individuals and 13 antipsychotic-naive patients with schizophrenia-spectrum disorder, whom we compared with 12 age- and sex-matched healthy controls. The BP(ND) between patients and controls did not differ in any of the ROIs, consistent with the voxel-wise analysis. Correlations between the BP(ND) in D3-rich regions and psychopathology warrant further investigation.
  
  
  CONCLUSIONS
  In the absence of resting-state (baseline) BP(ND) data, or following a depletion paradigm (i.e., α-methyl partyrosine), it is not possible to ascertain whether the lack of difference among the groups is owing to different levels of baseline DA or to release during the cognitive task.
  
  
  CONCLUSIONS
  To our knowledge, the present study represents the first effort to measure the D2 and D3 receptors under a cognitive challenge in individuals putative/prodromal for schizophrenia using [11C]-(+)-PHNO.
authors.affiliation: PET Centre, Centre for Addiction and Mental Health, Toronto, Ont.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Suridjan
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D018491:Dopamine Agonists; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000378:metabolism; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide