Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
J Neurosci. 2024 Apr 3;44(14):e1218232024. doi: 10.1523/JNEUROSCI.1218-23.2024.
Alterations in γ-aminobutyric acid (GABA) have been implicated in sensory differences in individuals with autism spectrum disorder (ASD). Visual signals are initially processed in the retina, and in this study, we explored the hypotheses that the GABA-dependent retinal response to light is altered in individuals with ASD. Light-adapted electroretinograms were recorded from 61 adults (38 males and 23 females; = 22 ASD) in response to three stimulus protocols: (1) the standard white flash, (2) the standard 30 Hz flickering protocol, and (3) the photopic negative response protocol. Participants were administered an oral dose of placebo, 15 or 30 mg of arbaclofen (STX209, GABA agonist) in a randomized, double-blind, crossover order before the test. At baseline (placebo), the a-wave amplitudes in response to single white flashes were more prominent in ASD, relative to typically developed (TD) participants. Arbaclofen was associated with a decrease in the a-wave amplitude in ASD, but an increase in TD, eliminating the group difference observed at baseline. The extent of this arbaclofen-elicited shift significantly correlated with the arbaclofen-elicited shift in cortical responses to auditory stimuli as measured by using an electroencephalogram in our prior study and with broader autistic traits measured with the autism quotient across the whole cohort. Hence, GABA-dependent differences in retinal light processing in ASD appear to be an accessible component of a wider autistic difference in the central processing of sensory information, which may be upstream of more complex autistic phenotypes.
γ-氨基丁酸 (GABA) 的改变与自闭症谱系障碍 (ASD) 个体的感觉差异有关。视觉信号最初在视网膜中进行处理，在这项研究中，我们探讨了以下假设，即 GABA 依赖的光对 ASD 个体的视网膜反应发生改变。从 61 名成年人（38 名男性和 23 名女性；=22 名 ASD）中记录了适应光的视网膜电图，以响应三种刺激方案：（1）标准白色闪光，（2）标准 30Hz 闪烁协议，和（3）光暗负反应协议。参与者以随机、双盲、交叉的顺序口服安慰剂、15 或 30mg 阿巴氯芬（STX209，GABA 激动剂），然后进行测试。在基线（安慰剂）时，与典型发育（TD）参与者相比，ASD 个体对单个白色闪光的 a 波幅度更为明显。阿巴氯芬与 ASD 中 a 波幅度的降低有关，但与 TD 中的增加有关，消除了基线观察到的组间差异。这种阿巴氯芬引起的变化与我们之前的研究中使用脑电图测量的听觉刺激引起的皮质反应的阿巴氯芬引起的变化以及整个队列中使用自闭症商数测量的更广泛的自闭症特征显著相关。因此，ASD 中 GABA 依赖性视网膜光处理差异似乎是中枢处理感觉信息的更广泛自闭症差异的一个可及组成部分，这可能是更复杂的自闭症表型的上游。
