title: The tryptophan depletion theory in delirium: not confirmed in elderly hip fracture patients.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To compare plasma tryptophan and kynurenine levels, and IDO activity in hospitalized patients with and without delirium.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dept. of Internal Medicine, Geriatrics section, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.dejonghe@amc.uva.nl
authors.forename: Annemarieke
authors.initials: A
authors.lastname: de Jonghe
authors.forename: Barbara C
authors.initials: BC
authors.lastname: van Munster
authors.forename: Durk
authors.initials: D
authors.lastname: Fekkes
authors.forename: Hannah E
authors.initials: HE
authors.lastname: van Oosten
authors.forename: Sophia E
authors.initials: SE
authors.lastname: de Rooij
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D003693:Delirium / Q000097:blood / Q000378:metabolism*; D005260:Female; D006620:Hip Fractures / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000502:physiology*; D007737:Kynurenine / Q000097:blood / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D011184:Postoperative Period; D011446:Prospective Studies; D012701:Serotonin / Q000096:biosynthesis; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012701:Serotonin; D007737:Kynurenine; D014364:Tryptophan