title: Pathophysiology of delirium.
abstract: 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.
authors.affiliation: Psychiatric Hospital Amsterdam, The Netherlands.
authors.forename: R C
authors.initials: RC
authors.lastname: van der Mast
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003693:Delirium / Q000378:metabolism / Q000503:physiopathology*; D005067:Euthyroid Sick Syndromes / Q000150:complications / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism; D012307:Risk Factors
chemical_list: D016207:Cytokines; D018377:Neurotransmitter Agents