van der Mast R C
Psychiatric Hospital Amsterdam, The Netherlands.
J Geriatr Psychiatry Neurol. 1998 Fall;11(3):138-45; discussion 157-8. doi: 10.1177/089198879801100304.
Hypotheses about the pathophysiology of delirium are speculative and largely based on animal research. According to the neurotransmitter hypothesis, decreased oxidative metabolism in the brain causes cerebral dysfunction due to abnormalities of various neurotransmitter systems. Reduced cholinergic function, excess release of dopamine, norepinephrine, and glutamate, and both decreased and increased serotonergic and gamma-aminobutyric acid activity may underlie the different symptoms and clinical presentations of delirium. According to the inflammatory hypothesis, increased cerebral secretion of cytokines due to a wide range of physically stressful events plays an important role in the occurrence of delirium. Since cytokines can influence the activity of various neurotransmitter systems, these mechanisms may interact. Also, more fundamental processes like intraneuronal signal transduction, second messenger systems that at the same time use neurotransmitters as first messengers and play an important role in their synthesis and release, may be disturbed. Furthermore, severe illness and physiologic stress may give rise to modification of blood-brain barrier permeability, the sick euthyroid syndrome with abnormalities of thyroid hormone concentrations, and increased activity of the hypothalamic-pituitary-adrenal axis. These circumstances possibly also contribute to changes in neurotransmitter synthesis and release of cytokines in the brain, and consequently to the occurrence of delirium. Elderly patients are more at risk for developing delirium,very likely due to age-related cerebral changes in stress-regulating neurotransmitter and intracellular signal transduction systems. This paper will expand upon these current theories and discuss their applicability to research and clinical work with elderly patients suffering from delirium.
关于谵妄病理生理学的假说多为推测性的，且很大程度上基于动物研究。根据神经递质假说，大脑中氧化代谢降低会因各种神经递质系统异常而导致脑功能障碍。胆碱能功能减退、多巴胺、去甲肾上腺素和谷氨酸释放过多，以及血清素能和γ-氨基丁酸活性的降低和增加，可能是谵妄不同症状和临床表现的基础。根据炎症假说，由于多种身体应激事件导致大脑中细胞因子分泌增加，在谵妄的发生中起重要作用。由于细胞因子可影响各种神经递质系统的活性，这些机制可能相互作用。此外，更基本的过程如神经元内信号转导、同时将神经递质用作第一信使并在其合成和释放中起重要作用的第二信使系统，可能会受到干扰。此外，严重疾病和生理应激可能导致血脑屏障通透性改变、甲状腺激素浓度异常的病态甲状腺综合征以及下丘脑-垂体-肾上腺轴活性增加。这些情况也可能导致大脑中神经递质合成和细胞因子释放的变化，进而导致谵妄的发生。老年患者发生谵妄的风险更高，很可能是由于与年龄相关的应激调节神经递质和细胞内信号转导系统的大脑变化。本文将详细阐述这些当前理论，并讨论它们在患有谵妄的老年患者研究和临床工作中的适用性。
