title: Increased prefrontal cortical D₁ receptors in drug naive patients with schizophrenia: a PET study with [¹¹C]NNC112.
abstract: D₁ receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these receptors in schizophrenia, but no conclusive picture has emerged yet. One source of discrepancy may have been prior antipsychotic exposure. We used positron emission tomography (PET) and a D1 radiotracer, [¹¹C]NNC112, in drug naïve (DN, n = 12) and drug free (DF, n = 13) patients with schizophrenia and 40 healthy control subjects (HC, n = 40 total, n = 24 per comparison group) matched for age, gender, ethnicity, parental socioeconomic status and cigarette smoking. We measured the binding potential BPP, corrected for partial volume effects. The outcome measure was obtained in cortical and striatal subregions outlined on coregistered individual MRIs. Partial volume effect corrected BPP measures were significantly higher in DN vs controls in cortical regions. No such increases were found in the DF versus controls comparison. Furthermore, in the DF group, DF interval correlated positively with cortical BPP. We conclude that upregulation of D1 receptors in schizophrenia is related to the illness itself and may be corrected and normalized by chronic antipsychotic treatment.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. aa324@columbia.edu
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Judy L
authors.initials: JL
authors.lastname: Thompson
authors.forename: Roberto
authors.initials: R
authors.lastname: Gil
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Nina
authors.initials: N
authors.lastname: Urban
authors.forename: Raj
authors.initials: R
authors.lastname: Narendran
authors.forename: Dah-Ren
authors.initials: DR
authors.lastname: Hwang
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001552:Benzazepines; D001572:Benzofurans; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D019275:Radiopharmaceuticals; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; D001572:Benzofurans; D019275:Radiopharmaceuticals; D017447:Receptors, Dopamine D1; C077123:NNC 112; D004298:Dopamine