Points of divergence on a bumpy road: early development of brain and immune threat processing systems following postnatal adversity.
Points of divergence on a bumpy road: early development of brain and immune threat processing systems following postnatal adversity.
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DOI：
10.1038/s41380-022-01658-9
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发表时间：
2023-01
影响因子：
11
通讯作者：
Brenhouse, Heather C.
中科院分区：
文献类型：
--
作者：
Brenhouse, Heather C.
终生的适应不良行为或疾病往往源于动态发育时期的早期生理失常。当功能障碍归因于早期生活逆境（ELA）时，当环境本身不适合支持健康行为的发展时，尤其如此。接触 ELA 与对潜在威胁的非典型敏感性和反应密切相关——这种特征可以适应早期逆境使个人为终生危险做好准备的情况，但通常表现为情绪调节和社会关系方面的困难。通过综合动物研究的结果，这篇综述将从相关的皮质边缘大脑回路和免疫机制的角度来考虑威胁敏感性，这两种机制在生命早期都不成熟，可以最大限度地适应环境挑战，以保护个体的福祉。驱动皮质边缘回路差异发育的力量包括照顾刺激、生理和心理压力以及影响发育轨迹的性别。这些力量直接指导免疫系统的发育过程，免疫系统与大脑内的感觉系统和情绪调节回路进行双向通信。炎症信号提供了进一步影响皮质边缘可塑性的时间和性质的力量，同时还调节对未来环境威胁（即损伤或病原体）的敏感性。这些系统程序的早期发展会威胁到青少年时期的敏感性，为整个成年时期的可能功能开辟道路。为了制定预防或管理 ELA 暴露人群适应不良威胁敏感性的策略，有必要充分了解这些早期的分歧点。
Lifelong indices of maladaptive behavior or illness often stem from early physiological aberrations during periods of dynamic development. This is especially true when dysfunction is attributable to early life adversity (ELA), when the environment itself is unsuitable to support development of healthy behavior. Exposure to ELA is strongly associated with atypical sensitivity and responsivity to potential threats—a characteristic that could be adaptive in situations where early adversity prepares individuals for lifelong danger, but which often manifests in difficulties with emotion regulation and social relationships. By synthesizing findings from animal research, this review will consider threat sensitivity through the lenses of associated corticolimbic brain circuitry and immune mechanisms, both of which are immature early in life to maximize adaptation for protection against environmental challenges to an individual’s well-being. The forces that drive differential development of corticolimbic circuits include caretaking stimuli, physiological and psychological stressors, and sex, which influences developmental trajectories. These same forces direct developmental processes of the immune system, which bidirectionally communicates with sensory systems and emotion regulation circuits within the brain. Inflammatory signals offer a further force influencing the timing and nature of corticolimbic plasticity, while also regulating sensitivity to future threats from the environment (i.e., injury or pathogens). The early development of these systems programs threat sensitivity through juvenility and adolescence, carving paths for probable function throughout adulthood. To strategize prevention or management of maladaptive threat sensitivity in ELA-exposed populations, it is necessary to fully understand these early points of divergence.
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