Associations between dopamine D2 receptor availability and BMI depend on age.
Associations between dopamine D2 receptor availability and BMI depend on age.
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DOI：
10.1016/j.neuroimage.2016.05.044
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发表时间：
2016-09
期刊：
影响因子：
5.7
通讯作者：
Zald DH
中科院分区：
文献类型：
--
作者：
Dang LC;Samanez-Larkin GR;Castrellon JJ;Perkins SF;Cowan RL;Zald DH
多巴胺D2/3受体亚型（DRD2/3）是肥胖研究中研究最广泛的神经递质生物标志物，但迄今为止的结果一直不一致，通常涉及小样本，并且很少考虑受试者的年龄，尽管年龄对DRD2/3水平有很大影响。我们的目的是通过在BMI从体重过轻到极度肥胖的大样本中检查这种关联来澄清DRD2/3可用性与BMI之间的关系。130名年龄在18岁至81岁之间的健康受试者接受了带有[18F]falllypride的PET检查，这是一种高亲和力的DRD2/3配体。正如预期的那样，DRD2/3的可用性随着年龄的增长而下降。关键是，年龄与DRD2/3可用性在预测中脑和纹状体区域（尾状体、壳核和腹侧纹状体）的BMI有显著的相互作用。在30岁以下的受试者中，BMI与DRD2/3可用性无关。相比之下，在30岁以上的受试者中，BMI与中脑、壳核和腹侧纹状体的DRD2/3可用性呈正相关。目前的结果与突出的多巴胺能功能减退假说不一致，该假说提出DRD2/3可用性降低与BMI增加有关，并强调了年龄在评估DRD2/3功能相关因素中的重要性。
The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects’ ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese. 130 healthy subjects between 18 and 81 years old underwent PET with [18F]falllypride, a high affinity DRD2/3 ligand. As expected, DRD2/3 availability declined with age. Critically, age significantly interacted with DRD2/3 availability in predicting BMI in the midbrain and striatal regions (caudate, putamen, and ventral striatum). Among subjects under 30 years old, BMI was not associated with DRD2/3 availability. By contrast, among subjects over 30 years old, BMI was positively associated with DRD2/3 availability in the midbrain, putamen, and ventral striatum. The present results are incompatible with the prominent dopaminergic hypofunction hypothesis that proposes that a reduction in DRD2/3 availability is associated with increased BMI, and highlights the importance of age in assessing correlates of DRD2/3 function.