Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex
Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex
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DOI：
10.1038/npp.2011.43
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发表时间：
2011-07-01
影响因子：
7.6
通讯作者：
Zavitsanou, Katerina
中科院分区：
文献类型：
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作者：
Dalton, Victoria S.;Long, Leonora E.;Zavitsanou, Katerina
许多研究表明，精神分裂症（SCZ）的内源性大麻素系统失调。在本研究中，我们研究了大麻素CB 1受体（CB 1 R）结合和mRNA表达的背外侧前额叶皮层（DLPFC）（布罗德曼区46）的SCZ患者和对照组，死后。受体密度进行了研究，使用放射自显影与CB 1 R配体[H-3] CP 55 940和CB 1 R mRNA表达进行了测定，使用定量RT-PCR在一个队列的16例偏执型SCZ，21例非偏执型SCZ和37名对照组的年龄，死后间隔和pH值匹配。所有的情况下，从悉尼大学组织资源中心。使用单因素方差分析（ANOVA）和事后Bonferroni检验以及协方差分析（ANCOVA）对结果进行分析，以控制可能影响CB 1 R表达的人口统计学因素。诊断对DLPFC所有层的定量[H-3] CP 55 940结合有主要影响（F（2，71）= 3.740，p = 0.029）。事后检验表明，这种主要效应是由于偏执型SCZ患者的CB 1 R结合水平比对照组高22%。当采用ANCOVA时，这种效应被加强（F（2，67）= 6.048，p = 0.004），偏执型SCZ患者与对照组（p = 0.004）和非偏执型组（p = 0.016）显著不同。相反，不同疾病亚型和对照组之间的mRNA表达没有显著差异。我们的研究结果证实了SCZ中存在CB 1 R失调，并强调需要进一步研究该受体的作用，特别是在诊断为偏执型SCZ的患者中。Neuropsychopharmacology（2011）36，1620-1630; doi：10.1038/npp.2011.43; 2011年4月6日在线发表
A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB1 receptor (CB1R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB1R ligand [H-3] CP 55 940 and CB1R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB1R expression. There was a main effect of diagnosis on [H-3] CP 55 940 binding quantified across all layers of the DLPFC (F(2,71) = 3.740, p = 0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB1R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67) = 6.048, p = 0.004) with paranoid SCZ patients differing significantly from the control (p = 0.004) and from the non-paranoid group (p = 0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB1R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ. Neuropsychopharmacology (2011) 36, 1620-1630; doi:10.1038/npp.2011.43; published online 6 April 2011