Wang Bonnie M, Mills Zoe, Jones Hannah F, Montgomery Johanna M, Lee Kevin Y
Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
J Neurochem. 2025 May;169(5):e70088. doi: 10.1111/jnc.70088.
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder clinically diagnosed by persistent deficits in three areas of social communication and interaction, plus at least two of four types of restricted repetitive behaviors. ASD has been shown to be caused by genetic predisposition and environmental factors; however, the heterogeneity of ASD complicates its diagnosis and treatment. Early behavioral interventions have shown significant benefits, emphasizing the urgent need for reliable diagnostic biomarkers to enhance long-term outcomes. Here we provide a systematic review that outlines current findings on genetic and neurological biomarkers for presymptomatic ASD diagnoses, assessed prior to the observation of behavioral manifestations. Specifically, we offer insights into the mechanisms of presymptomatic neurological, biological, structural, and functional markers for ASD, compare outcomes across studies, and critically assess their limitations and implications. Recent findings highlight genotype-guided therapeutic strategies in animal models, such as dietary zinc supplementation for reversing ASD-associated behaviors by synaptic deficits. However, the differential efficacy based on underlying genotypes, along with challenges in identifying reliable genomic biomarkers prior to symptom onset, indicates the need for further research. Notably, recent advancements in imaging technologies like magnetic resonance imaging, electroencephalography, and pupillometry have shown promising markers in neonates, and at 3 and 9 months old, respectively. Newer developments in magnetoencephalography hardware can facilitate the much-needed infant ASD studies. It is important to note that many of these biomarker findings are preliminary, and further validation for clinical use is required. Continued research is needed to advance the practicality, reliability, and acceptability of these biomarkers to improve ASD diagnosis and treatment strategies.
自闭症谱系障碍（ASD）是一种常见的神经发育障碍，临床上通过社交沟通与互动的三个领域持续存在缺陷，以及四种限制性重复行为中的至少两种来诊断。已证明ASD是由遗传易感性和环境因素引起的；然而，ASD的异质性使其诊断和治疗变得复杂。早期行为干预已显示出显著益处，这凸显了迫切需要可靠的诊断生物标志物以改善长期预后。在此，我们提供一项系统综述，概述了在观察到行为表现之前评估的用于症状前ASD诊断的遗传和神经学生物标志物的当前研究结果。具体而言，我们深入探讨了ASD症状前神经、生物学、结构和功能标志物的机制，比较了各研究的结果，并批判性地评估了它们的局限性和影响。最近的研究结果突出了动物模型中基于基因型的治疗策略，例如通过补充膳食锌来逆转由突触缺陷引起的ASD相关行为。然而，基于潜在基因型的疗效差异，以及在症状出现前识别可靠基因组生物标志物的挑战，表明需要进一步研究。值得注意的是，磁共振成像、脑电图和瞳孔测量等成像技术的最新进展分别在新生儿、3个月和9个月大的婴儿中显示出有前景的标志物。脑磁图硬件的新发展可以促进急需的婴儿ASD研究。需要注意的是，许多这些生物标志物的研究结果都是初步的，需要进一步验证以用于临床。需要持续研究以提高这些生物标志物的实用性、可靠性和可接受性，从而改善ASD的诊断和治疗策略。
