Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia
Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia
复制标题
DOI：
10.1016/j.neuroimage.2013.04.052
复制
发表时间：
2013-10-01
期刊：
影响因子：
5.7
通讯作者：
Van Laere, Koen
中科院分区：
文献类型：
--
作者：
Ceccarini, Jenny;De Hert, Marc;Van Laere, Koen
越来越多的动物遗传、尸检和药理学证据支持脑1型大麻素（CB1）受体在精神分裂症（SCZ）发病机制和/或导致其症状的神经回路功能障碍中的作用。此外，由于CB1受体表达存在重要的物种间差异，因此体内人类数据具有直接意义。我们使用正电子发射断层扫描（PET）和选择性高亲和力放射配体[F-18]MK-9470研究了SCZ患者体内CB1受体表达与健康对照（CON）的关系，以及与精神病理症状严重程度的关系。采用[F-18]MK-9470 PET对67例SCZ患者进行了调查，其中有（SCZ- t, n = 51）和（SCZ- f, n = 16）抗精神病药物治疗，12例年龄和性别匹配的CON患者。参数修改的标准化摄取值（mSUV）图像，反映CB1受体结合，比较和相关的精神病理症状。与CON相比，SCZ患者在伏隔核、脑岛、扣带皮层、额下皮层、顶叶和中颞叶的CB1受体结合明显增加。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，特别是在伏隔核。目前的研究结果有力地支持了CB1受体结合在SCZ-T和SCZ-F患者的中皮质边缘回路中发生改变，特别是在伏隔核中。在SCZ-F患者中，它与阴性症状和抑郁评分相关。(C) 2013爱思唯尔公司版权所有。
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 [F-18]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 [F-18]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. (C) 2013 Elsevier Inc. All rights reserved.