Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences. ASD is more commonly diagnosed in males at a ratio of 4:1, indicating a potential oversight in female-specific ASD research and a risk of underdiagnosis in females. We consider how ASD manifests differently across sexes by exploring differential gene expression in female and male brains and consider how variations in steroid hormones influence ASD characteristics. Synaptic function, including excitation/inhibition ratio imbalance, is influenced by gene mutations and this is explored as a key factor in the cognitive and behavioural manifestations of ASD. We also discuss the role of micro RNAs (miRNAs) and highlight a novel mutation in miRNA-873, which affects a suite of key synaptic genes, neurexin, neuroligin, SHANK and post-synaptic density proteins, implicated in the pathology of ASD. Our review suggests that genetic predisposition, sex differences in brain gene expression, and hormonal factors significantly contribute to the presentation, identification and severity of ASD, necessitating sex-specific considerations in diagnosis and treatments. These findings advocate for personalized interventions to improve the outcomes for individuals with ASD.

中文翻译：

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理解自闭症谱系障碍的性别差异

自闭症谱系障碍 (ASD) 是一种神经发育疾病，其特征是社交缺陷、重复行为和缺乏同理心。其显着的遗传性和潜在的合并症常常导致诊断和治疗方面的挑战。这篇综述探讨了自闭症谱系障碍的生物学基础，重点关注基因表达和激素影响的性别差异。自闭症谱系障碍 (ASD) 更常见于男性，比例为 4:1，这表明女性特有的自闭症谱系障碍 (ASD) 研究可能存在疏忽，并且存在女性漏诊的风险。我们通过探索女性和男性大脑中的差异基因表达来考虑自闭症谱系障碍在不同性别中的不同表现，并考虑类固醇激素的变化如何影响自闭症谱系障碍的特征。突触功能，包括兴奋/抑制比失衡，受到基因突变的影响，这被认为是自闭症谱系障碍认知和行为表现的关键因素。我们还讨论了微小 RNA (miRNA) 的作用，并重点介绍了 miRNA-873 中的一个新突变，该突变影响一系列与 ASD 病理学有关的关键突触基因、neurexin、neuroligin、SHANK 和突触后密度蛋白。我们的综述表明，遗传倾向、大脑基因表达的性别差异和激素因素对自闭症谱系障碍的表现、识别和严重程度有显着影响，因此在诊断和治疗时需要考虑性别特异性。这些发现主张采取个性化干预措施来改善自闭症谱系障碍患者的治疗结果。