Department of Psychiatry, Vanderbilt University, Nashville, Tennessee, USA.
Dev Neurobiol. 2012 Oct;72(10):1277-87. doi: 10.1002/dneu.22044. Epub 2012 Sep 1.
Gene*environment interactions play critical roles in the emergence of autism and schizophrenia pathophysiology. In both disorders, recent genetic association studies have provided evidence for disease-linked variation in immune system genes and postmortem gene expression studies have shown extensive chronic immune abnormalities in brains of diseased subjects. Furthermore, peripheral biomarker studies revealed that both innate and adaptive immune systems are dysregulated. In both disorders symptoms of the disease correlate with the immune system dysfunction; yet, in autism this process appears to be chronic and sustained, while in schizophrenia it is exacerbated during acute episodes. Furthermore, since immune abnormalities endure into adulthood and anti-inflammatory agents appear to be beneficial, it is likely that these immune changes actively contribute to disease symptoms. Modeling these changes in animals provided further evidence that prenatal maternal immune activation alters neurodevelopment and leads to behavioral changes that are relevant for autism and schizophrenia. The converging evidence strongly argues that neurodevelopmental immune insults and genetic background critically interact and result in increased risk for either autism or schizophrenia. Further research in these areas may improve prenatal health screening in genetically at-risk families and may also lead to new preventive and/or therapeutic strategies.
基因-环境相互作用在自闭症和精神分裂症的发病机制中起着关键作用。在这两种疾病中，最近的遗传关联研究为免疫系统基因与疾病相关的变异提供了证据，而死后基因表达研究表明，患病受试者的大脑存在广泛的慢性免疫异常。此外，外周生物标志物研究显示，固有和适应性免疫系统都失调了。在这两种疾病中，疾病的症状与免疫系统功能障碍相关；然而，在自闭症中，这个过程似乎是慢性和持续的，而在精神分裂症中，它在急性发作时加剧。此外，由于免疫异常持续到成年期，并且抗炎药物似乎有益，因此这些免疫变化很可能会主动导致疾病症状。在动物模型中模拟这些变化提供了进一步的证据，表明产前母体免疫激活会改变神经发育，并导致与自闭症和精神分裂症相关的行为变化。这些汇聚的证据强烈表明，神经发育免疫损伤和遗传背景相互作用，导致自闭症或精神分裂症的风险增加。这些领域的进一步研究可能会改善遗传风险家庭的产前健康筛查，也可能导致新的预防和/或治疗策略。
