Andrade Chittaranjan
Department of Psychiatry, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India.
Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Clin Psychiatry. 2025 Apr 14;86(2):25f15878. doi: 10.4088/JCP.25f15878.
The global prevalence of autism spectrum disorder (ASD) has quadrupled during the past 3 decades; the reasons for this are many and include broadening of the diagnostic concept, increased awareness of the disorder, increased screening (including of adults and of girl children), and, possibly, increased exposure to environmental risk factors. This article examines genetic and especially environmental risk factors for ASD. Unsurprisingly, hundreds of potential genes have been identified, many of which overlap between ASD, schizophrenia, depression, and cardiometabolic disorders. Likewise, over a hundred environmental exposures have been associated with ASD risk. These include exposure to parental and family characteristics, exposure to maternal disorders arising during pregnancy, exposure to chronic maternal disorders present during pregnancy, exposure to fetal and other pregnancy-related problems/events, exposure to neonatal problems/events, exposure to maternal nutritional deficiencies during pregnancy, maternal exposure to substances during pregnancy, maternal exposure to pharmacological agents during pregnancy, in utero exposure to toxic substances, and early life exposure to toxic substances. Some of the risk factors identified may be causal, some may be markers of intermediary mechanisms, and some may be unrelated markers. About 40 of these risk factors have been confirmed in meta-analysis for association with ASD. Nearly 70 maternal diagnoses have also been associated with ASD, but, after correcting for false discovery error and shared risk, only 30 remain; and, of these 30, almost all may be explained by genetic and environmental risk factors shared between mother and child, judging from findings in discordant sibling pair and paternal negative control analyses. Caveats and nuances in the interpretation of risks are briefly discussed.
在过去30年里，全球自闭症谱系障碍（ASD）的患病率翻了两番；原因众多，包括诊断概念的拓宽、对该疾病认识的提高、筛查范围的扩大（包括对成年人和女童的筛查），以及可能增加的环境危险因素暴露。本文探讨了ASD的遗传因素，尤其是环境危险因素。不出所料，已确定了数百种潜在基因，其中许多在ASD、精神分裂症、抑郁症和心脏代谢疾病之间存在重叠。同样，超过一百种环境暴露与ASD风险相关。这些包括接触父母和家庭特征、孕期母亲出现的疾病、孕期存在的慢性母亲疾病、胎儿及其他与妊娠相关的问题/事件、新生儿问题/事件、孕期母亲营养缺乏、孕期母亲接触物质、孕期母亲接触药物、子宫内接触有毒物质以及生命早期接触有毒物质。所确定的一些危险因素可能是因果关系，一些可能是中间机制的标志物，还有一些可能是无关的标志物。其中约40种危险因素已在荟萃分析中得到证实与ASD相关。近70种母亲诊断也与ASD有关，但在纠正错误发现误差和共同风险后，仅剩下30种；而且，从不一致的同胞对和父亲阴性对照分析的结果来看，这30种中的几乎所有情况都可能由母婴之间共享的遗传和环境危险因素来解释。文中简要讨论了风险解读中的注意事项和细微差别。
