Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study
Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study
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DOI：
10.1038/s41380-022-01464-3
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发表时间：
2022-02-18
影响因子：
11
通讯作者：
Yamasue, Hidenori
中科院分区：
文献类型：
--
作者：
Murayama, Chihiro;Iwabuchi, Toshiki;Yamasue, Hidenori
自闭症的社会动机假说提出，自闭症谱系障碍（ASD）的社会沟通症状源于非典型的社会注意力和奖励网络，其中多巴胺充当关键的调解者。然而，尽管有证据表明ASD患者在处理奖励和社会刺激时在纹状体外区域显示非典型激活，但以前的研究没有测量ASD中纹状体外多巴胺D2/3受体（D2/3R）的可用性。在这里，我们研究了纹状体外D2/3R的可用性与ASD的个人和ASD的社会沟通症状，使用正电子发射断层扫描（PET）的关联。此外，我们采用了全脑多变量模式分析的静息态功能磁共振成像（fMRI），以确定区域的功能连接与D2/3R的可用性依赖于ASD诊断的相关性。22名无精神药物的ASD男性和24名年龄和智力匹配的发育正常男性接受了[C-11] FLB 457 PET、fMRI和临床症状评估。ASD参与者在多巴胺能通路的D2/3R丰富的纹状体外区域表现出较低的D2/3R可用性。其中，丘脑后部区域（主要包括枕）显示出较低D2/3R可用性的最大效应量，这与ASD参与者中自闭症诊断观察表-2的社会情感域得分较高相关。此外，较低的D2/3R可用性与丘脑-颞上沟和小脑-内侧枕叶皮质的功能连接性较低相关，特别是在ASD患者中。目前的研究结果为自闭症的社会动机理论提供了新的分子证据，并提供了一个新的治疗靶点。
The social motivation hypothesis of autism proposes that social communication symptoms in autism-spectrum disorder (ASD) stem from atypical social attention and reward networks, where dopamine acts as a crucial mediator. However, despite evidence indicating that individuals with ASD show atypical activation in extrastriatal regions while processing reward and social stimuli, no previous studies have measured extrastriatal dopamine D2/3 receptor (D2/3R) availability in ASD. Here, we investigated extrastriatal D2/3R availability in individuals with ASD and its association with ASD social communication symptoms using positron emission tomography (PET). Moreover, we employed a whole-brain multivariate pattern analysis of resting-state functional magnetic resonance imaging (fMRI) to identify regions where functional connectivity atypically correlates with D2/3R availability depending on ASD diagnosis. Twenty-two psychotropic-free males with ASD and 24 age- and intelligence quotient-matched typically developing males underwent [C-11]FLB457 PET, fMRI, and clinical symptom assessment. Participants with ASD showed lower D2/3R availability throughout the D2/3R-rich extrastriatal regions of the dopaminergic pathways. Among these, the posterior region of the thalamus, which primarily comprises the pulvinar, displayed the largest effect size for the lower D2/3R availability, which correlated with a higher score on the Social Affect domain of the Autism Diagnostic Observation Schedule-2 in participants with ASD. Moreover, lower D2/3R availability was correlated with lower functional connectivity of the thalamus-superior temporal sulcus and cerebellum-medial occipital cortex, specifically in individuals with ASD. The current findings provide novel molecular evidence for the social motivation theory of autism and offer a novel therapeutic target.