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: Anissa Abi-Dargham, Osama Mawlawi, Ilise Lombardo, Roberto Gil, Diana Martinez, Yiyun Huang, Dah-Ren Hwang, John Keilp, Lisa Kochan, Ronald Van Heertum, Jack M Gorman, Marc Laruelle
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 22 Issue 9 Pg. 3708-19 (May 01 2002) ISSN: 1529-2401 [Electronic] United States
• PMID: 11978847 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzazepines
• Benzofurans
• Carbon Radioisotopes
• Dopamine Antagonists
• Receptors, Dopamine D1
• NNC 112

Topics

• Adult
• Age Factors
• Benzazepines (pharmacokinetics)
• Benzofurans (pharmacokinetics)
• Binding, Competitive
• Carbon Radioisotopes
• Dopamine Antagonists (pharmacokinetics)
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Memory Disorders (complications, diagnosis, physiopathology)
• Memory, Short-Term
• Neuropsychological Tests
• Predictive Value of Tests
• Prefrontal Cortex (diagnostic imaging, metabolism)
• Principal Component Analysis
• Receptors, Dopamine D1 (antagonists & inhibitors, metabolism)
• Schizophrenia (complications, diagnosis, diagnostic imaging, physiopathology)
• Tomography, Emission-Computed