Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Neuropsychopharmacology. 2022 Jun;47(7):1421-1427. doi: 10.1038/s41386-022-01306-4. Epub 2022 Apr 5.
Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia and, to some extent astroglia during neuropsychiatric diseases with inflammation. This preliminary analysis explored, for the first time, whether TSPO binding was altered in male and female participants with ASD in vivo using full kinetic quantification. Thirteen individuals with ASD (IQ > 70 [n = 12], IQ = 62 [n = 1]), 5 F, 25 ± 5 years) were scanned with [F]FEPPA PET. Data from 13 typically developing control participants with matching age and TSPO rs6971 polymorphism (9 F, age 24 ± 5 years) were chosen from previous studies for comparison. The two tissue compartment model (2TCM) was used to determine the total volume of distribution ([F]FEPPA V) in four previously identified regions of interest (ROI): prefrontal, temporal, cerebellar, and anterior cingulate cortices. We observe no significant difference in [F]FEPPA V relative to controls (F= 1.74, p = 0.20). However, 2 ASD participants with higher V had concurrent major depressive episodes (MDE), which has been consistently reported during MDE. After excluding those 2 ASD participants, in a post-hoc analysis, our results show lower [F]FEPPA V in ASD participants compared to controls (F= 6.62, p = 0.02). This preliminary analysis provides evidence suggesting an atypical neuroimmune state in ASD.
越来越多的证据表明免疫系统在自闭症谱系障碍 (ASD) 中起着重要作用。正电子发射断层扫描 (PET) 可以定量测定转位蛋白 18kDa(TSPO),该标志物在伴有炎症的神经精神疾病中主要在小胶质细胞中表达增加,在一定程度上在星形胶质细胞中表达增加。这项初步分析首次探索了使用全动力学定量是否改变了 ASD 男性和女性参与者体内的 TSPO 结合。13 名 ASD 参与者(智商>70 [n=12],智商=62 [n=1]),5 名女性,25±5 岁)接受了 [F]FEPPA PET 扫描。从以前的研究中选择了 13 名具有匹配年龄和 TSPO rs6971 多态性的发育正常的对照参与者的数据(9 名女性,年龄 24±5 岁)进行比较。使用两组织室模型(2TCM)来确定四个先前确定的感兴趣区域(ROI)中的总分布容积 ([F]FEPPA V):前额叶、颞叶、小脑和前扣带回皮质。我们没有观察到 [F]FEPPA V 与对照组相比存在显著差异(F=1.74,p=0.20)。然而,2 名 ASD 参与者的 V 更高,他们同时患有重度抑郁症发作(MDE),这在 MDE 期间一直有报道。在排除这 2 名 ASD 参与者后,在事后分析中,我们的结果显示 ASD 参与者的 [F]FEPPA V 低于对照组(F=6.62,p=0.02)。这项初步分析提供了证据,表明 ASD 中存在非典型神经免疫状态。