Neurochemical Imaging and Mapping of Excitatory and Inhibitory Neurometabolites in Adults with Autism Spectrum Disorder

近年来，成年人对自闭症谱系障碍(ASD)的认识有了戏剧性的增长。新的证据表明，患病率可能高于2%，在接受特殊教育学校的低功能学科中，患病率为0.75%，在接受正规教育的高功能学科中，患病率约为1.89%。根据ICD-10，ASD被归类为神经发育障碍。ASD的确切病因和发病机制尚不清楚。重要的病因学概念侧重于兴奋性和抑制性神经递质(如谷氨酸和GABA)之间的关系的作用，并基于尸检、动物和遗传研究。磁共振波谱是一种独特的工具，非侵入性地评估这些代谢物在活体中的人脑。到目前为止，在ASD中进行的光谱研究很少，特别是在患有高功能ASD的成年人中，也没有研究报告同时检测到兴奋性谷氨酸和抑制性GABA信号。我们项目的总体目标有两个。在第一个子项目中，我们想要研究成人高功能ASD的GABA能和谷氨酸能神经传递，使用新建立和验证的方法，用单体素磁共振波谱(MRS)测定背侧ACC、DLPFC和顶叶皮质的GABA。在第二个子项目中，我们希望进一步改进MRS采集和后处理算法，从单体素MRS成像发展到GABA信号的光谱成像。因此，我们希望开发一种临床上可行的方法来定位ASD患者较大脑区的兴奋性和抑制性递质信号，以确定这些发现对ASD的意义，并确定作为该疾病诊断目的、严重程度评估或治疗反应的生物标志物的可行性。

In recent years there has been a dramatic increase in the awareness of autism spectrum disorders (ASD) in adults. New evidence shows that the prevalence may be higher than 2%, with 0.75% in low functioning subjects attending special educational schools and ~1.89% of high functioning subjects receiving regular schooling. According to ICD-10, ASD is classified as a neurodevelopmental disorder. The precise etiology and pathogenesis of ASD is not clear. Important pathogenetic concepts focus on the role of a relation between excitatory and inhibitory neurotransmitters like glutamate and GABA, and are based on post-mortem, animal and genetic studies. Magnet resonance spectroscopy is a unique tool to non-invasively assess these metabolites in vivo in the human brain. So far, very few spectroscopic studies were performed in ASD, especially in adults with high functioning ASD, and no studies report simultaneous detection of excitatory glutamate and inhibitory GABA signals. The overall aim of our project is twofold. In a first subproject we want to investigate GABA-ergic and glutamatergic neurotransmission in adult high functioning ASD employing the newly established and validated method of GABA-determination with single voxel magnetic resonance spectroscopy (MRS) in dorsal ACC, DLPFC and parietal cortex. In the second subproject we want to further improve the MRS acquisition and post-processing algorithms to proceed from single voxel MRS imaging to spectroscopic imaging of the GABA signal. Consequently, we want to develop a clinically feasible method to map excitatory and inhibitory transmitter signals in larger brain areas of ASD patients, to establish the significance of these findings for ASD, and determine the feasibility as a biomarker for diagnostic purpose, severity assessment or treatment response in this disorder.