title: Prefrontal dopamine D1 receptors and working memory in schizophrenia.
abstract: Studies in nonhuman primates documented that appropriate stimulation of dopamine (DA) D1 receptors in the dorsolateral prefrontal cortex (DLPFC) is critical for working memory processing. The defective ability of patients with schizophrenia at working memory tasks is a core feature of this illness. It has been postulated that this impairment relates to a deficiency in mesocortical DA function. In this study, D1 receptor availability was measured with positron emission tomography and the selective D1 receptor antagonist [11C]NNC 112 in 16 patients with schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched healthy controls. [11C]NNC 112 binding potential (BP) was significantly elevated in the DLPFC of patients with schizophrenia (1.63 +/- 0.39 ml/gm) compared with control subjects (1.27 +/- 0.44 ml/gm; p = 0.02). In patients with schizophrenia, increased DLPFC [11C]NNC 112 BP was a strong predictor of poor performance at the n-back task, a test of working memory. These findings confirm that alteration of DLPFC D1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia. Increased D1 receptor availability observed in patients with schizophrenia might represent a compensatory (but ineffective) upregulation secondary to sustained deficiency in mesocortical DA function.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, New York 10032, USA. aa324@columbia.edu
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: Osama
authors.initials: O
authors.lastname: Mawlawi
authors.forename: Ilise
authors.initials: I
authors.lastname: Lombardo
authors.forename: Roberto
authors.initials: R
authors.lastname: Gil
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.forename: Dah-Ren
authors.initials: DR
authors.lastname: Hwang
authors.forename: John
authors.initials: J
authors.lastname: Keilp
authors.forename: Lisa
authors.initials: L
authors.lastname: Kochan
authors.forename: Ronald
authors.initials: R
authors.lastname: Van Heertum
authors.forename: Jack M
authors.initials: JM
authors.lastname: Gorman
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
mesh_terms: D000328:Adult; D000367:Age Factors; D001552:Benzazepines / Q000493:pharmacokinetics; D001572:Benzofurans / Q000493:pharmacokinetics; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D008570:Memory, Short-Term; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D025341:Principal Component Analysis; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014055:Tomography, Emission-Computed
chemical_list: D001552:Benzazepines; D001572:Benzofurans; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C077123:NNC 112