Centre for Neuroregeneration and Centre for Clinical Brain Sciences, University of Edinburgh Edinburgh, UK.
Department of Human Genetics, Radboud University Medical Center Nijmegen, Netherlands.
Front Neurosci. 2014 Dec 8;8:394. doi: 10.3389/fnins.2014.00394. eCollection 2014.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.
自闭症谱系障碍(ASD)是一种神经发育障碍,其特征是社交互动和沟通受损,以及行为和兴趣受限。有人假设兴奋性和抑制性神经递质的平衡失调是这些疾病的基础。在这里,我们证明了这两条途径的基因都受到 ASD 的影响,并且在成年而非年幼的自闭症个体的大脑皮层中,抑制性和兴奋性基因的表达发生了改变。我们已经开发出一种基于基因表达的测量兴奋性和抑制性差异的方法,并且观察到在 ASD 与对照组相比,在这个测量中抑制相对于兴奋降低。在年轻的自闭症大脑中,这种差异无法检测到。鉴于自闭症的许多精神特征在早期就已经存在,这表明观察到的基因表达失衡是 ASD 的衰老现象,而不是其根本原因。