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Disrupted relationship between blood glucose and brain dopamine D2/3 receptor binding in patients with first-episode schizophrenia
NeuroImage: Clinical ( IF 4.2 ) Pub Date : 2021-09-13 , DOI: 10.1016/j.nicl.2021.102813
U Sauerzopf 1 , A Weidenauer 1 , I Dajic 1 , M Bauer 2 , L Bartova 1 , B Meyer 1 , L Nics 3 , C Philippe 3 , S Pfaff 3 , V Pichler 3 , M Mitterhauser 4 , W Wadsak 5 , M Hacker 3 , S Kasper 6 , R Lanzenberger 1 , L Pezawas 1 , N Praschak-Rieder 1 , M Willeit 1
Affiliation  

An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behavior, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signaling in drug-naïve patients with first-episode psychosis.

We quantified blood glucose levels and binding of the dopamine D2/3 receptor agonist radioligand (+)-[11C]-PHNO in 15 medication-naïve patients and 27 healthy volunteers employing positron emission tomography.

Whole-brain voxel-wise linear model analysis identified two clusters of significant interaction between blood glucose levels and diagnosis on (+)-[11C]-PHNO binding-potential values. We observed positive relationships between blood glucose levels and binding-potential values in healthy volunteers but negative ones in patients with first episode psychosis in a cluster surviving rigorous multiple testing correction located in the in the right ventral tegmental area. Another cluster of homologous behavior, however at a lower level of statistical significance, comprised the ventral striatum and pallidum. Extracellular dopamine levels are a major determinant of (+)-[11C]-PHNO binding in the brain. In line with the concept that increased dopamine signaling occurs when goal-directed behavior is needed for restoring energy supply, our data indicate that in healthy volunteers, extracellular dopamine levels are high when blood glucose levels are low and vice-versa. This relationship is reversed in patients with first-episode psychosis, possibly reflecting an underlying pathogenic alteration that links two seemingly unrelated aspects of the illness: altered dopamine signaling and dysfunctional glucose homeostasis.



中文翻译:

首发精神分裂症患者血糖与脑多巴胺D2/3受体结合的关系被破坏

脑多巴胺的一个基本功能是协调认知和运动资源,以成功利用环境能源。在开始药物治疗之前和之后,精神分裂症患者的多巴胺传递、目标导向行为和葡萄糖稳态都发生了改变。因此,我们研究了初发精神病患者的血糖水平与脑多巴胺信号传导之间的关系。

我们量化了 15 名未用药患者和 27 名使用正电子发射断层扫描的健康志愿者的血糖水平和多巴胺 D 2/3受体激动剂放射性配体 (+)-[ 11 C]-PHNO 的结合。

全脑体素线性模型分析确定了血糖水平与 (+)-[ 11 C]-PHNO 结合电位值的诊断之间的两个显着相互作用集群。我们观察到健康志愿者的血糖水平和结合电位值之间存在正相关关系,但在右侧腹侧被盖区域的严格多重测试校正中幸存下来的首发精神病患者中,我们观察到了负相关关系。另一组同源行为,但在统计显着性水平较低,包括腹侧纹状体和苍白球。细胞外多巴胺水平是 (+)-[ 11的主要决定因素C]-PHNO 在脑中的结合。与当需要目标导向的行为来恢复能量供应时会增加多巴胺信号传导的概念相一致,我们的数据表明,在健康志愿者中,当血糖水平低时,细胞外多巴胺水平高,反之亦然。这种关系在首发精神病患者中被逆转,可能反映了潜在的致病改变,该改变将疾病的两个看似无关的方面联系起来:改变的多巴胺信号传导和功能失调的葡萄糖稳态。

更新日期:2021-09-17
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