Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
JAMA Psychiatry. 2013 Jan;70(1):49-58. doi: 10.1001/jamapsychiatry.2013.272.
A growing body of evidence suggests that aberrant immunologic systems underlie the pathophysiologic characteristics of autism spectrum disorder (ASD). However, to our knowledge, no information is available on the patterns of distribution of microglial activation in the brain in ASD.
To identify brain regions associated with excessively activated microglia in the whole brain, and to examine similarities in the pattern of distribution of activated microglia in subjects with ASD and control subjects.
Case-control study using positron emission tomography and a radiotracer for microglia--11C-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide) (11C-PK11195).
Subjects recruited from the community.
Twenty men with ASD (age range, 18-31 years; mean [SD] IQ, 95.9 [16.7]) and 20 age- and IQ-matched healthy men as controls. Diagnosis of ASD was made in accordance with the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised.
Regional brain 11C-PK11195 binding potential as a representative measure of microglial activation.
The 11C-PK11195 binding potential values were significantly higher in multiple brain regions in young adults with ASD compared with those of controls (P < .05, corrected). Brain regions with increased binding potentials included the cerebellum, midbrain, pons, fusiform gyri, and the anterior cingulate and orbitofrontal cortices. The most prominent increase was observed in the cerebellum. The pattern of distribution of 11C-PK11195 binding potential values in these brain regions of ASD and control subjects was similar, whereas the magnitude of the 11C-PK11195 binding potential in the ASD group was greater than that of controls in all regions.
Our results indicate excessive microglial activation in multiple brain regions in young adult subjects with ASD. The similar distribution pattern of regional microglial activity in the ASD and control groups may indicate augmented but not altered microglial activation in the brain in the subjects with ASD.
越来越多的证据表明，异常的免疫系统是自闭症谱系障碍（ASD）病理生理特征的基础。然而，据我们所知，目前尚无关于 ASD 患者大脑中小胶质细胞激活分布模式的信息。
确定与全脑过度激活小胶质细胞相关的脑区，并检查 ASD 患者和对照组中小胶质细胞激活分布模式的相似性。
使用正电子发射断层扫描和小胶质细胞放射性示踪剂 [11C]（R）-（1-[2-氯苯基]-N-甲基-N-[1-甲基丙基]-3 异喹啉羧酰胺）（[11C]（R）-PK11195）进行病例对照研究。
从社区招募受试者。
20 名年龄在 18-31 岁（平均[标准差]智商 95.9[16.7]）的 ASD 男性患者（病例组）和 20 名年龄和智商匹配的健康男性作为对照组。ASD 的诊断符合孤独症诊断观察量表和孤独症诊断访谈修订版。
小胶质细胞激活的代表性测量指标-局部脑[11C]（R）-PK11195 结合潜能。
与对照组相比，年轻 ASD 患者的多个脑区[11C]（R）-PK11195 结合潜能值显著升高（P <.05，校正）。结合潜能值增加的脑区包括小脑、中脑、脑桥、梭状回和前扣带回皮质及眶额皮质。小脑的增加最为显著。ASD 和对照组这些脑区[11C]（R）-PK11195 结合潜能值的分布模式相似，而 ASD 组各脑区[11C]（R）-PK11195 结合潜能值均大于对照组。
我们的结果表明，年轻 ASD 患者的多个脑区存在小胶质细胞过度激活。ASD 组和对照组的区域性小胶质细胞活性分布模式相似，这表明 ASD 患者脑内小胶质细胞的激活增强但未改变。
