Prefrontal dopamine D1 receptors and working memory in schizophrenia

被引:554
作者
Abi-Dargham, A
Mawlawi, O
Lombardo, I
Gil, R
Martinez, D
Huang, YY
Hwang, DR
Keilp, J
Kochan, L
Van Heertum, R
Gorman, JM
Laruelle, M
机构
[1] New York State Psychiat Inst & Hosp, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA
关键词
dopamine; D-1; receptors; schizophrenia; prefrontal cortex; working memory; positron emission tomography;
D O I
10.1523/jneurosci.22-09-03708.2002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Studies in nonhuman primates documented that appropriate stimulation of dopamine (DA) D-1 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, D-1 receptor availability was measured with positron emission tomography and the selective D-1 receptor antagonist [C-11] NNC 112 in 16 patients with schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched healthy controls. [C-11] 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 [C-11] 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 D-1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia. Increased D-1 receptor availability observed in patients with schizophrenia might represent a compensatory (but ineffective) upregulation secondary to sustained deficiency in mesocortical DA function.
引用
收藏
页码:3708 / 3719
页数:12
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