Gardner Renee M, Brynge Martin, Sjöqvist Hugo, Dalman Christina, Karlsson Håkan
Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Biol Psychiatry. 2025 Jun 15;97(12):1127-1138. doi: 10.1016/j.biopsych.2024.11.009. Epub 2024 Nov 22.
The maternal immune activation hypothesis has gained attention over the past 2 decades as a potential contributor to the etiology of autism. This hypothesis posits that maternal conditions associated with inflammation during pregnancy may increase the risk of autism in offspring. Autism is highly heritable, and causal environmental contributors to autism largely remain elusive. We review studies on maternal conditions during pregnancy, all associated with some degree of systemic inflammation, namely maternal infections, autoimmunity, and high body mass index. We also review studies of inflammatory markers in biological samples collected from mothers during pregnancy or from neonates and their relationship with autism assessed in children later in life. Recent reports indicate familial clustering of autism, autoimmunity, and infections, as well as genetic correlations between autism and aspects of immune function. Given this literature, there is an apparent risk of confounding of the reported associations between inflammatory exposures and autism by familial genetic factors in both clinical and epidemiological cohort studies. We highlight recent studies that have attempted to address potential confounding to assess evidence of causal effects of inflammation during early life in autism.
在过去20年里，母体免疫激活假说作为自闭症病因的一个潜在因素受到了关注。该假说认为，孕期与炎症相关的母体状况可能会增加后代患自闭症的风险。自闭症具有高度遗传性，导致自闭症的环境因素在很大程度上仍然难以捉摸。我们回顾了关于孕期母体状况的研究，所有这些状况都与某种程度的全身炎症有关，即母体感染、自身免疫和高体重指数。我们还回顾了从孕期母亲或新生儿采集的生物样本中的炎症标志物研究，以及这些标志物与儿童后期自闭症评估之间的关系。最近的报告表明自闭症、自身免疫和感染存在家族聚集现象，以及自闭症与免疫功能方面的遗传相关性。鉴于这些文献，在临床和流行病学队列研究中，家族遗传因素显然存在混淆炎症暴露与自闭症之间所报告关联的风险。我们重点介绍了最近试图解决潜在混杂因素以评估早期生命炎症在自闭症中因果效应证据的研究。
