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The Journal of Neuroscience, May 1, 2002, 22(9):3708-3719
Prefrontal Dopamine D1 Receptors and Working Memory in Schizophrenia
Anissa Abi-Dargham1, 2, Osama Mawlawi1, 2, Ilise Lombardo1, Roberto Gil1, Diana Martinez1, Yiyun Huang1, Dah-Ren Hwang1, 2, John Keilp1, Lisa Kochan1, Ronald Van Heertum2, Jack M. Gorman1, 2, and Marc Laruelle1, 2 Departments of 1 Psychiatry and 2 Radiology, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, New York 10032
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.
Key words: dopamine; D1 receptors; schizophrenia; prefrontal cortex; working memory; positron emission tomography
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293708-12$05.00/0
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