Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
J Psychopharmacol. 2012 Jun;26(6):794-805. doi: 10.1177/0269881111409265. Epub 2011 Jul 18.
D₁ 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 D1 radiotracer, [¹¹C]NNC112, in drug naïve (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 D1 receptors in schizophrenia is related to the illness itself and may be corrected and normalized by chronic antipsychotic treatment.
D₁ 受体是皮质中多巴胺传递的主要介质，参与受精神分裂症影响的认知功能。先前的影像学研究表明，这些受体在精神分裂症中的表达存在异常，但尚未得出明确的结论。造成这种差异的一个原因可能是先前的抗精神病药物暴露。我们使用正电子发射断层扫描（PET）和 D₁ 示踪剂 [¹¹C]NNC112，对未经药物治疗（DN，n = 12）和停药（DF，n = 13）的精神分裂症患者以及 40 名健康对照者（HC，n = 40 名，每组 24 名）进行了研究。我们测量了结合潜能 BPP，并对部分容积效应进行了校正。该结果是在核心 MRI 上勾画的皮质和纹状体亚区中获得的。与对照组相比，DN 患者的皮质区 BPP 校正后明显升高。在 DF 与对照组的比较中，未发现这种增加。此外，在 DF 组中，DF 间隔与皮质 BPP 呈正相关。我们的结论是，精神分裂症中 D₁ 受体的上调与疾病本身有关，并且可能通过慢性抗精神病药物治疗得到纠正和正常化。
