In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study
In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study
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DOI：
10.1038/s41380-020-0784-7
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发表时间：
2020-05
影响因子：
11
通讯作者：
Masamichi Yokokura;Kiyokazu Takebasashi;Akiyo Takao;Kyoko Nakaizumi;E. Yoshikawa;M. Futatsubashi;
中科院分区：
文献类型：
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作者：
Masamichi Yokokura;Kiyokazu Takebasashi;Akiyo Takao;Kyoko Nakaizumi;E. Yoshikawa;M. Futatsubashi;
皮质多巴胺系统和小胶质细胞活化的改变与注意力缺陷/多动障碍（ADHD）的病理生理学有关，注意力缺陷/多动障碍（ADHD）是一种神经发育障碍，可以用多巴胺增强剂（哌甲酯）常规治疗，尽管不能令人满意。在这里，我们研究了多巴胺D1受体（D1R）和激活的小胶质细胞的贡献和他们的相互作用，ADHD患者的临床严重程度，使用正电子发射断层扫描（PET）。24名精神病初治ADHD患者和24名年龄和性别匹配的典型发育（TD）受试者接受了[11 C] SCH 23390对D1R和[11 C]（R）PK 11195对活化小胶质细胞的PET测量，以及临床症状和认知功能评估。与TD受试者相比，ADHD受试者的前扣带回皮质（ACC）中的D1 R减少，背外侧前额叶皮质（DLPFC）和眶额皮质（OFC）中激活的小胶质细胞增加。ACC中D1R的降低与ADHD参与者的严重多动症相关。小胶质细胞激活的DLPFC与缺陷的处理速度和注意力的能力，并在OFC与较低的处理速度在ADHD的个人。此外，在DLPFC和OFC的D1R和激活的小胶质细胞之间的正相关性被发现是显着特定的ADHD组，而不是TD组。目前的研究结果表明，小胶质细胞活化和D1R减少以及它们的异常相互作用是ADHD神经生理机制的基础，并表明这些生物分子变化是一种新的治疗靶点。
Alterations in the cortical dopamine system and microglial activation have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), one of neurodevelopmental disorders that can be conventionally treated with a dopamine enhancer (methylphenidate) albeit unsatisfactorily. Here, we investigated the contributions of the dopamine D1 receptor (D1R) and activated microglia and their interactions to the clinical severities in ADHD individuals using positron emission tomography (PET). Twenty-four psychotropic-naïve ADHD individuals and 24 age- and sex-matched typically developing (TD) subjects underwent PET measurements with [11C]SCH23390 for the D1R and [11C](R)PK11195 for activated microglia as well as assessments of clinical symptoms and cognitive functions. The ADHD individuals showed decreased D1R in the anterior cingulate cortex (ACC) and increased activated microglia in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared with the TD subjects. The decreased D1R in the ACC was associated with severe hyperactivity in the participants with ADHD. Microglial activation in the DLPFC were associated with deficits in processing speed and attentional ability, and that in the OFC was correlated with lower processing speed in the ADHD individuals. Furthermore, positive correlations between the D1R and activated microglia in both the DLPFC and the OFC were found to be significantly specific to the ADHD group and not to the TD group. The current findings suggest that microglial activation and the D1R reduction as well as their aberrant interactions underpin the neurophysiological mechanism of ADHD and indicate these biomolecular changes as a novel therapeutic target.