Murphy Felim, Nasa Anurag, Cullinane Dearbhla, Raajakesary Kesidha, Gazzaz Areej, Sooknarine Vitallia, Haines Madeline, Roman Elena, Kelly Linda, O'Neill Aisling, Cannon Mary, Roddy Darren William
Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
Department of Psychiatry, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, Ireland.
Front Psychiatry. 2022 May 6;13:748372. doi: 10.3389/fpsyt.2022.748372. eCollection 2022.
Studies of early life stress (ELS) demonstrate the long-lasting effects of acute and chronic stress on developmental trajectories. Such experiences can become biologically consolidated, creating individual vulnerability to psychological and psychiatric issues later in life. The hippocampus, amygdala, and the medial prefrontal cortex are all important limbic structures involved in the processes that undermine mental health. Hyperarousal of the sympathetic nervous system with sustained allostatic load along the Hypothalamic Pituitary Adrenal (HPA) axis and its connections has been theorized as the basis for adult psychopathology following early childhood trauma. In this review we synthesize current understandings and hypotheses concerning the neurobiological link between childhood trauma, the HPA axis, and adult psychiatric illness. We examine the mechanisms at play in the brain of the developing child and discuss how adverse environmental stimuli may become biologically incorporated into the structure and function of the adult brain a discussion of the neurosequential model of development, sensitive periods and plasticity. The HPA connections and brain areas implicated in ELS and psychopathology are also explored. In a targeted review of HPA activation in mood and psychotic disorders, cortisol is generally elevated across mood and psychotic disorders. However, in bipolar disorder and psychosis patients with previous early life stress, blunted cortisol responses are found to awakening, psychological stressors and physiological manipulation compared to patients without previous early life stress. These attenuated responses occur in bipolar and psychosis patients on a background of increased cortisol turnover. Although cortisol measures are generally raised in depression, the evidence for a different HPA activation profile in those with early life stress is inconclusive. Further research is needed to explore the stress responses commonalities between bipolar disorder and psychosis in those patients with early life stress.
早期生活应激（ELS）的研究表明，急性和慢性应激对发育轨迹具有长期影响。此类经历可在生物学上得以巩固，使人在日后生活中易患心理和精神疾病。海马体、杏仁核和内侧前额叶皮质都是重要的边缘系统结构，参与破坏心理健康的过程。沿着下丘脑 - 垂体 - 肾上腺（HPA）轴及其连接的持续应变负荷导致交感神经系统过度兴奋，这被认为是儿童早期创伤后成人精神病理学的基础。在本综述中，我们综合了有关儿童期创伤、HPA轴和成人精神疾病之间神经生物学联系的当前认识和假设。我们研究了发育中儿童大脑中起作用的机制，并讨论了不良环境刺激如何在生物学上融入成人大脑的结构和功能——这涉及发育的神经序列模型、敏感期和可塑性的讨论。我们还探讨了与ELS和精神病理学相关的HPA连接和脑区。在对情绪和精神障碍中HPA激活的针对性综述中，皮质醇在情绪和精神障碍中通常会升高。然而，与没有早期生活应激史的患者相比，有早期生活应激史的双相情感障碍和精神病患者在觉醒、心理应激源和生理操作时皮质醇反应迟钝。这些减弱的反应发生在皮质醇周转增加背景下的双相情感障碍和精神病患者中。尽管抑郁症患者的皮质醇测量值通常会升高，但早期生活应激者中不同HPA激活模式的证据尚无定论。需要进一步研究来探索有早期生活应激史的患者中双相情感障碍和精神病之间的应激反应共性。
