Traumatic stress and the circadian system: neurobiology, timing and treatment of posttraumatic chronodisruption

Background: Humans have an evolutionary need for a well-preserved internal ‘clock’, adjusted to the 24-hour rotation period of our planet. This intrinsic circadian timing system enables the temporal organization of numerous physiologic processes, from gene expression to behaviour. The human circadian system is tightly and bidirectionally interconnected to the human stress system, as both systems regulate each other’s activity along the anticipated diurnal challenges. The understanding of the temporal relationship between stressors and stress responses is critical in the molecular pathophysiology of stress-and trauma-related diseases, such as posttraumatic stress disorder (PTSD). Objectives/Methods: In this narrative review, we present the functional components of the stress and circadian system and their multilevel interactions and discuss how traumatic stress can affect the harmonious interplay between the two systems. Results: Circadian dysregulation after trauma exposure (posttraumatic chronodisruption) may represent a core feature of trauma-related disorders mediating enduring neurobiological correlates of traumatic stress through a loss of the temporal order at different organizational levels. Posttraumatic chronodisruption may, thus, affect fundamental properties of neuroendocrine, immune and autonomic systems, leading to a breakdown of biobehavioral adaptive mechanisms with increased stress sensitivity and vulnerability. Given that many traumatic events occur in the late evening or night hours, we also describe how the time of day of trauma exposure can differentially affect the stress system and, finally, discuss potential chronotherapeutic interventions. Conclusion: Understanding the stress-related mechanisms susceptible to chronodisruption and their role in PTSD could deliver new insights into stress pathophysiology, provide better psychochronobiological treatment alternatives and enhance preventive strategies in stress-exposed populations. • The human circadian and stress system are both essential for biobehavioural regulation with numerous reciprocal interaction. • Posttraumatic chronodisruption (i.e., circadian dysregulation after trauma) represents a core feature of PTSD, mediating neurobiological correlates of trauma through multilevel temporal order loss.

背景：人类在进化进程中需要一套维持完好的内在生物钟，以适配地球24小时的自转周期。这套固有昼夜节律计时系统可实现众多生理过程的时序组织，从基因表达直至行为活动。人体昼夜节律系统与应激系统存在紧密的双向互联关系，二者可通过协同调控以应对预期的日间生理挑战。阐明应激源与应激反应之间的时序关联，对于应激相关及创伤相关疾病（如创伤后应激障碍（posttraumatic stress disorder, PTSD））的分子病理生理学研究至关重要。
目的/方法：在本篇叙事性综述中，我们将阐述应激系统与昼夜节律系统的功能组成及其多层面交互机制，并探讨创伤性应激如何破坏二者的协同互作。
结果：创伤暴露后出现的昼夜节律紊乱（posttraumatic chronodisruption，创伤后节律紊乱）可能是创伤相关障碍的核心特征，该紊乱可通过破坏不同组织层级的时序秩序，介导创伤性应激的持续性神经生物学关联。因此，创伤后节律紊乱可影响神经内分泌、免疫及自主神经系统的基础功能，进而导致生物行为适应机制崩溃，提升机体的应激敏感性与易感性。鉴于多数创伤事件发生于傍晚或夜间时段，我们还将阐明创伤暴露的当日时刻如何对应激系统产生差异化影响，并最终探讨潜在的时辰治疗干预手段。
结论：阐明易受节律紊乱影响的应激相关机制及其在创伤后应激障碍中的作用，可为应激病理生理学研究提供全新视角，为临床提供更优质的心理时辰生物学治疗方案，并强化应激暴露人群的预防策略。
• 人体昼夜节律系统与应激系统均为生物行为调控的核心组分，二者存在大量双向交互作用。
• 创伤后节律紊乱（posttraumatic chronodisruption，即创伤后发生的昼夜节律紊乱）是创伤后应激障碍的核心特征，可通过多层面时序秩序丧失介导创伤的神经生物学关联。