Elsevier

Biological Psychiatry

Volume 70, Issue 2, 15 July 2011, Pages 175-182
Biological Psychiatry

Archival Report
Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms

https://doi.org/10.1016/j.biopsych.2010.12.006Get rights and content

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.

Section snippets

Participants

Participants were recruited from a subsample of the Three-City (3C) study, an epidemiological cohort study that included 9294 persons, 65 years of age and over, not institutionalized, and living in Bordeaux, Dijon, and Montpellier in 1999–2000. The general methodology of the 3C study was published elsewhere (38). Participants in the present study (n = 284) were drawn from the Bordeaux site at 7-year follow up, the only site where concomitant inflammatory assays and detailed neuropsychiatric

Results

Two hundred eighty-four subjects were included. The mean age of participants was 79.9 years (SD = 4.5 years), and the median age was 80 years. One hundred ninety-seven participants (69.4%) were women, and forty (14%) had a lifetime history of major depression. The mean BMI in the study population was 25.4 kg/m2 (SD = 4.0). Data for biological markers and relationships with age, as assessed by multiple regression analyses controlling for gender and BMI, are shown in Table 1. Overall, there was a

Discussion

Results from this study clearly support the notion of inflammaging (11, 12), because they indicate significant relationships between aging and circulating concentrations of immune markers. As expected, older age was associated with increased concentrations of both IL-6 and neopterin, indicative of immune activation in elderly persons. In addition, older age together with inflammation correlated negatively with tryptophan concentrations and positively with kynurenine concentrations and with the

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    Authors SL and DF contributed equally to this work.

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