Division of Nuclear Medicine, University Hospitals Leuven & Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Neuroimage. 2013 Oct 1;79:304-12. doi: 10.1016/j.neuroimage.2013.04.052. Epub 2013 Apr 25.
Increasing animal genetic, post-mortem and pharmacological evidence supports a role for the cerebral type 1 cannabinoid (CB1) receptor in the pathogenesis of schizophrenia (SCZ) and/or neural circuit dysfunctions responsible for its symptomatology. Moreover, since important interspecies differences are present in CB1 receptor expression, in vivo human data are of direct interest. We investigated an in vivo CB1 receptor expression in SCZ patients compared to healthy controls (CON), and in relation with psychopathological symptom severity using positron emission tomography (PET) and the selective high-affinity radioligand [(18)F]MK-9470. A total of sixty-seven patients with SCZ, with (SCZ-T, n=51) and without (SCZ-F, n=16) antipsychotic treatment, and 12 age and gender-matched CON were investigated with [(18)F]MK-9470 PET. Parametric modified standardized uptake value (mSUV) images, reflecting CB1 receptor binding, were compared and related to psychopathological symptoms. Compared to CON, there was a significant increase of CB1 receptor binding in SCZ patients in the nucleus accumbens, insula, cingulate cortex, inferior frontal cortex, parietal and mediotemporal lobe. Furthermore, in the SCZ-F group only, CB1 receptor binding was negatively correlated to negative symptoms and to depression scores, especially in the nucleus accumbens. Present findings strongly support that CB1 receptor binding is altered in the mesocorticolimbic circuitry of both SCZ-T and SCZ-F patients, especially in the nucleus accumbens. In SCZ-F patients, it is associated with negative symptoms and depression scores.
越来越多的动物遗传学、死后和药理学证据支持大脑 1 型大麻素 (CB1) 受体在精神分裂症 (SCZ) 的发病机制和/或负责其症状的神经回路功能障碍中发挥作用。此外，由于 CB1 受体表达存在重要的种间差异，因此直接关注人类体内数据。我们使用正电子发射断层扫描 (PET) 和选择性高亲和力放射性配体 [(18)F]MK-9470 研究了 SCZ 患者与健康对照 (CON) 之间的体内 CB1 受体表达情况，并与精神病理学症状严重程度相关。共有 67 名 SCZ 患者（包括有抗精神病药物治疗的 SCZ-T 患者，n=51；无抗精神病药物治疗的 SCZ-F 患者，n=16）和 12 名年龄和性别匹配的 CON 患者接受了 [(18)F]MK-9470 PET 检查。比较并关联了反映 CB1 受体结合的参数化标准化摄取值比值 (mSUV) 图像与精神病理学症状。与 CON 相比，SCZ 患者的伏隔核、岛叶、扣带回皮质、额下回皮质、顶叶和中颞叶的 CB1 受体结合显著增加。此外，仅在 SCZ-F 组中，CB1 受体结合与阴性症状和抑郁评分呈负相关，尤其是在伏隔核中。目前的研究结果强烈支持 CB1 受体结合在 SCZ-T 和 SCZ-F 患者的中边缘皮质回路中发生改变，尤其是在伏隔核中。在 SCZ-F 患者中，它与阴性症状和抑郁评分相关。
