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Psychosomatics. 2012 May-Jun;53(3):236-43. doi: 10.1016/j.psym.2011.09.009. Epub 2012 Mar 27.

The tryptophan depletion theory in delirium: not confirmed in elderly hip fracture patients.

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Dept. of Internal Medicine, Geriatrics section, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.



The tryptophan depletion theory assumes that low tryptophan levels are present in delirium. These lower levels may be regarded as a biochemical marker for cellular immune activation, which may lead to increased catabolism of tryptophan into kynurenine via stimulation of the enzyme indoleamine 2,3-dioxygenase (IDO) by interferon-γ.


To compare plasma tryptophan and kynurenine levels, and IDO activity in hospitalized patients with and without delirium.


Repeated plasma samples were prospectively collected in hip fracture patients, aged 65 years and older. The presence of delirium was assessed daily. The associations of a delirious state and tryptophan, kynurenine, and the kynurenine/tryptophan ratio measured in samples taken 'before', 'during delirium', and 'after delirium' were analyzed with linear mixed models.


A total of 469 samples from 140 patients were collected. Adjusted for the days on which they were drawn, there was no difference for all three measured factors in patients with and without delirium, except for an association between a higher kynurenine/tryptophan ratio and delirium in a subgroup analysis in preoperative samples.


The results do not confirm the previously found lower tryptophan levels in delirium on which the tryptophan depletion theory is based. However, a preoperative higher kynurenine/tryptophan ratio could be indicative of delirium.

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