Inflammation-Related alterations in tyrosine metabolism are associated with anhedonia and reduced motivation in Obesity: Influence of Early-Life adversity.
Brain, Behavior, and Immunity. 2026-03-01; : 106547
DOI: 10.1016/j.bbi.2026.106547
Lire sur PubMed
https://www.bordeaux-neurocampus.fr/12530
1. Brain Behav Immun. 2026 Mar 13:106547. doi: 10.1016/j.bbi.2026.106547. Online
ahead of print.
Inflammation-Related alterations in tyrosine metabolism are associated with
anhedonia and reduced motivation in Obesity: Influence of Early-Life adversity.
Montet J(1), Montalban E(1), Dexpert S(1), Magne E(2), Beau C(3), Forestier
D(2), Ledaguenel P(3), Gostner J(4), Fuchs D(4), Aouizerate B(5), Capuron L(6).
Author information:
(1)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux,
France.
(2)Service de Chirurgie Digestive et Pariétale, Clinique Tivoli, F-33000
Bordeaux, France.
(3)Service de Chirurgie Digestive et Pariétale, Clinique Jean Villar, F-33520
Bruges, France.
(4)Division of Biological Chemistry, Biocenter, Innsbruck Medical University,
A-6020 Innsbruck, Austria.
(5)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux,
France; Centre de Référence Régional des Pathologies Anxieuses et de la
Dépression, Hôpital Charles Perrens, F-33076 Bordeaux, France.
(6)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux,
France. Electronic address: .
Neuropsychiatric symptoms are highly prevalent in obesity, and mounting data
highlight the key role of adiposity-related inflammation in their etiology.
Pro-inflammatory cytokines may disrupt dopamine metabolism and function,
contributing to depressive manifestations such as anhedonia, loss of motivation,
and fatigue, which are poorly alleviated by standard antidepressants. However,
although obesity is characterized by chronic inflammation, not all individuals
with obesity develop depression, underscoring an incomplete understanding of
this association and the likely contribution of additional vulnerability
factors. Our previous findings point to early-life adversity (ELA) as a
potential contributor. Inflammation and ELA may converge on the dopamine system
by impairing the activity of GTP-cyclohydrolase I (GTP-CH1), a key enzyme in the
synthesis of tetrahydrobiopterin, which catalyzes the conversion of
phenylalanine to tyrosine, a dopamine precursor. To test this possibility,
seventy-two adults with obesity were recruited, and the relationships between
systemic inflammation, peripheral markers of GTP-CH1 pathway activity, and
neuropsychiatric symptoms were assessed, along the influence of ELA. Results
showed that higher levels of inflammation were associated with an increased
phenylalanine/tyrosine (PHE/TYR) ratio, consistent with altered tyrosine
metabolism. This metabolic alteration was further linked to greater depressive
symptoms, particularly anhedonia and reduced motivation. ELA did not
significantly interact with inflammation to influence tyrosine metabolism but
contributed additively to symptom severity alongside systemic inflammation.
Overall, these findings suggest that inflammation-related disruptions in
tyrosine metabolism may contribute to hedonic and motivational symptoms in
obesity, while ELA may shape a vulnerability context that amplifies symptom
expression.
Copyright © 2026. Published by Elsevier Inc.
DOI: 10.1016/j.bbi.2026.106547
PMID: 41833755
Conflict of interest statement: Declaration of Competing Interest The authors
declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.