Chronic low-grade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism: role in neuropsychiatric symptoms.
Biological Psychiatry. 2011-07-01; 70(2): 175-182
DOI: 10.1016/j.biopsych.2010.12.006
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1. Biol Psychiatry. 2011 Jul 15;70(2):175-82. doi: 10.1016/j.biopsych.2010.12.006.
Epub 2011 Jan 31.
Chronic low-grade inflammation in elderly persons is associated with altered
tryptophan and tyrosine metabolism: role in neuropsychiatric symptoms.
Capuron L(1), Schroecksnadel S, Féart C, Aubert A, Higueret D, Barberger-Gateau
P, Layé S, Fuchs D.
Author information:
(1)Laboratory of Psychoneuroimmunology, Nutrition and Genetics, INRA, Centre
Hospitalier Universitaire of Bordeaux, Bordeaux, France.
Comment in
Biol Psychiatry. 2011 Jul 15;70(2):111-2.
BACKGROUND: Neuropsychiatric symptoms are common complaints of elderly persons.
Recent data suggest that chronic low-grade inflammation, a fundamental
characteristic of aging, plays a role. Effects might rely on the influence of
inflammation on the activity of two enzymatic pathways, the
indoleamine-2,3-dioxygenase (IDO) and the guanosine-triphosphate-cyclohydrolase-1
(GTP-CH1) pathways, which are involved in the biosynthesis of monoamines. The
present study assessed this possibility in 284 healthy elderly subjects drawn
from the Three-City cohort.
METHODS: Assays included the measurement of serum interleukin-6 and
C-reactive-protein, as inflammatory markers; tryptophan, kynurenine, and their
ratio as index of IDO activity; and neopterin, phenylalanine, tyrosine, and
nitrite, as markers of GTP-CH1 activity. In addition, structured assessments of
depressive symptomatology, fatigue, and general behavioral/neurovegetative
symptoms were performed.
RESULTS: As expected, age correlated significantly with concentrations of immune
markers and neuropsychiatric symptoms. Increased inflammation was related to
reduced tryptophan concentrations and increased kynurenine levels, suggestive of
IDO-induced increased tryptophan catabolism. In addition, inflammation was
associated with increases in neopterin and nitrite levels and in phenylalanine
concentrations at the expense of tyrosine. Interestingly, increased tryptophan
catabolism was associated with the depressive symptoms of lassitude, reduced
motivation, anorexia, and pessimism. In contrast, variations in markers of
GTP-CH1 activity correlated more with neurovegetative symptoms, including sleep
disturbance, digestive symptoms, fatigue, sickness, and motor symptoms.
CONCLUSIONS: These findings show that chronic low-grade inflammation in aging is
associated with alterations in enzymatic pathways involved in monoamine
metabolism and suggest that these alterations might participate in the
pathophysiology of neuropsychiatric symptoms in elderly persons.
Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All
rights reserved.
DOI: 10.1016/j.biopsych.2010.12.006
PMID: 21277567 [Indexed for MEDLINE]