Increased prefrontal cortical D1 receptors in drug naive patients with schizophrenia: a PET study with [11C]NNC112

被引:97
作者
Abi-Dargham, Anissa [1 ,2 ]
Xu, Xiaoyan [1 ]
Thompson, Judy L. [1 ]
Gil, Roberto [1 ]
Kegeles, Lawrence S. [1 ]
Urban, Nina [1 ]
Narendran, Raj [3 ]
Hwang, Dah-Ren [4 ]
Laruelle, Marc [1 ,5 ,6 ]
Slifstein, Mark [1 ]
机构
[1] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA
[2] Columbia Univ, Dept Radiol, Coll Phys & Surg, New York, NY 10032 USA
[3] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA
[4] Amgen Pharmaceut, Thousand Oaks, CA USA
[5] GlaxoSmithKline, London, England
[6] Univ London Imperial Coll Sci Technol & Med, London, England
关键词
Antipsychotics; D-1; receptor; dorsolateral prefrontal cortex; positron emission tomography; schizophrenia; SPATIAL WORKING-MEMORY; MESOLIMBIC DOPAMINE TRANSMISSION; POSITRON-EMISSION-TOMOGRAPHY; FRONTAL-CORTEX; SEROTONIN(2A) RECEPTORS; D1; RECEPTORS; BINDING; CLOZAPINE; RELEASE; 5-HT2A;
D O I
10.1177/0269881111409265
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
D-1 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 D-1 radiotracer, [C-11]NNC112, in drug naive (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 D-1 receptors in schizophrenia is related to the illness itself and may be corrected and normalized by chronic antipsychotic treatment.
引用
收藏
页码:794 / 805
页数:12
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