Transposable elements make up a much larger portion of the genome than protein-coding genes, yet we know relatively little about their function in the human genome. However, we are beginning to more fully understand their role in brain development, neuroinflammation, and adaptation to environmental insults such as stress. For instance, glucocorticoid receptor activation regulates transposable elements in the brain following acute stress. Early life is a period of substantial brain development during which transposable elements play a role. Environmental exposures and experiences during early life that promote abnormal regulation of transposable elements may lead to a cascade of events that ultimately increase susceptibility to disorders later in life. Recent attention to transposable elements in psychiatric illness has begun to clarify associations indicative of dysregulation of different classes of transposable elements in stress-related and neurodevelopmental illness. Though individual susceptibility or resiliency to psychiatric illness has not been explained by traditional genetic studies, the wide inter-individual variability in transposable element composition in the human genome make TEs attractive candidates to elucidate this differential susceptibility. In this review, we discuss evidence that regulation of transposable elements in the brain are stage-specific, sensitive to environmental factors, and may be impacted by early life perturbations. We further present evidence of associations with stress-related and neurodevelopmental psychiatric illness from a developmental perspective.

与蛋白质编码基因相比，转座因子在基因组中所占的比例要大得多，但是我们对它们在人类基因组中的功能知之甚少。但是，我们开始更充分地了解它们在大脑发育，神经炎症和适应压力等环境损害中的作用。例如，糖皮质激素受体激活在急性应激后调节大脑中的转座因子。早期生命是大脑大量发育的时期，在此期间可转座因子发挥作用。生命早期的环境暴露和经验会促进转座因子的异常调控，可能导致一系列事件，最终增加生命后期对疾病的易感性。最近对精神疾病中转座因子的关注已开始阐明与应激相关和神经发育疾病中不同类别的转座因子失调有关的关联。尽管传统遗传研究尚未解释个体对精神疾病的易感性或适应性，但人类基因组中转座因子组成的广泛个体间差异使TEs成为阐明这种易感性的诱人候选人。在这篇综述中，我们讨论了证据，即大脑中转座因子的调节是阶段特定的，对环境因素敏感，并且可能会受到早期生活扰动的影响。我们从发展的角度进一步提出与压力相关和神经发育性精神疾病相关的证据。