Abstract:
Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET-MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.
摘要:
自闭症谱系障碍(ASD)患病率的性别差异有据可查,男女比例约为4:1。ASD核心症状的临床表现也可能因性别而异。以前,正电子发射断层扫描(PET)研究已经确定了体内转运蛋白(TSPO)-线粒体蛋白-在主要或仅男性成人患有ASD,我们组报告男性ASD患者的TSPO相对于全脑平均值较低。然而,ASD女性体内TSPO水平是否改变,具体来说,是未知的。这是首次使用[11C]PBR28PET-磁共振成像(MRI)测量ASD成年女性体内TSPO的初步研究。十二名具有ASD和10个年龄和TSPO基因型匹配的对照(CON)的成年女性完成了一次或两次[11C]PBR28PET-MRI扫描。与CON相比,患有ASD的雌性在中扣带皮质和call体的脾中表现出升高的[11C]PBR28标准化摄取值比率(SUVR)。与CON相比,在患有ASD的女性中没有大脑区域显示更低的[11C]PBR28SUVR。几个月的测试重测显示两组在整个时间内稳定的[11C]PBR28SUVR。ASD女性的区域[11C]PBR28SUVR升高,与我们先前对ASD男性的较低区域[11C]PBR28SUVR的发现形成鲜明对比。ASD女性中线粒体蛋白TSPO相对于全脑平均值区域升高的初步证据可能反映了ASD女性特有的神经免疫代谢改变。