Maclullich Alasdair M J, Ferguson Karen J, Miller Thomas, de Rooij Sophia E J A, Cunningham Colm
Geriatric Medicine/MRC Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland, UK.
J Psychosom Res. 2008 Sep;65(3):229-38. doi: 10.1016/j.jpsychores.2008.05.019.
Delirium is a common and serious acute neuropsychiatric syndrome with core features of inattention and cognitive impairment, and associated features including changes in arousal, altered sleep-wake cycle, and other changes in mental status. The main risk factors are old age, cognitive impairment, and other comorbidities. Though delirium has consistent core clinical features, it has a very wide range of precipitating factors, including acute illness, surgery, trauma, and drugs. The molecular mechanisms by which these precipitating factors lead to delirium are largely obscure. In this article, we attempt to narrow down some specific causal pathways. We propose a basic classification for the etiological factors: (a) direct brain insults and (b) aberrant stress responses. Direct brain insults are largely indiscriminate and include general and regional energy deprivation (e.g., hypoxia, hypoglycaemia, stroke), metabolic abnormalities (e.g., hyponatraemia, hypercalcaemia), and the effects of drugs. Aberrant stress responses are conceptually and mechanistically distinct in that they constitute adverse effects of stress-response pathways, which, in health, are adaptive. Ageing and central nervous system disease, two major predisposing factors for delirium, are associated with alterations in the magnitude or duration of stress and sickness behavior responses and increased vulnerability to the effects of these responses. We discuss in detail two stress response systems that are likely to be involved in the pathophysiology of delirium: inflammation and the sickness behavior response, and activity of the limbic-hypothalamic-pituitary-adrenal axis. We conclude by discussing the implications for future research and the development of new therapies for delirium.
谵妄是一种常见且严重的急性神经精神综合征，其核心特征为注意力不集中和认知障碍，相关特征包括觉醒改变、睡眠 - 觉醒周期紊乱以及其他精神状态变化。主要危险因素为老年、认知障碍和其他合并症。尽管谵妄具有一致的核心临床特征，但其诱发因素范围非常广泛，包括急性疾病、手术、创伤和药物。这些诱发因素导致谵妄的分子机制在很大程度上尚不清楚。在本文中，我们试图缩小一些特定的因果途径。我们提出了病因因素的基本分类：(a) 直接脑损伤和 (b) 异常应激反应。直接脑损伤在很大程度上是无差别性的，包括全身性和局部性能量剥夺（如缺氧、低血糖、中风）、代谢异常（如低钠血症、高钙血症）以及药物的影响。异常应激反应在概念和机制上有所不同，因为它们构成了应激反应途径的不良反应，而在健康状态下，这些途径是适应性的。衰老和中枢神经系统疾病是谵妄的两个主要易感因素，与应激和疾病行为反应的强度或持续时间改变以及对这些反应影响的易感性增加有关。我们详细讨论了两个可能参与谵妄病理生理学的应激反应系统：炎症和疾病行为反应，以及边缘 - 下丘脑 - 垂体 - 肾上腺轴的活动。我们通过讨论对未来研究的意义以及谵妄新疗法的开发来得出结论。
