Brain Kynurenine and BH4 Pathways: Relevance to the Pathophysiology and Treatment of Inflammation-Driven Depressive Symptoms.
Front. Neurosci.. 2018-07-24; 12:
DOI: 10.3389/fnins.2018.00499
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1. Front Neurosci. 2018 Jul 24;12:499. doi: 10.3389/fnins.2018.00499. eCollection
2018.
Brain Kynurenine and BH4 Pathways: Relevance to the Pathophysiology and Treatment
of Inflammation-Driven Depressive Symptoms.
Vancassel S(1)(2), Capuron L(1)(2), Castanon N(1)(2).
Author information:
(1)UMR 1286, Laboratory of Nutrition and Integrative Neurobiology (NutriNeuro),
INRA, Bordeaux, France.
(2)UMR 1286, Laboratory of Nutrition and Integrative Neurobiology (NutriNeuro),
Bordeaux University, Bordeaux, France.
The prevalence of depressive disorders is growing worldwide, notably due to
stagnation in the development of drugs with greater antidepressant efficacy, the
continuous large proportion of patients who do not respond to conventional
antidepressants, and the increasing rate of chronic medical conditions associated
with an increased vulnerability to depressive comorbidities. Accordingly, better
knowledge on the pathophysiology of depression and mechanisms underlying
depressive comorbidities in chronic medical conditions appears urgently needed,
in order to help in the development of targeted therapeutic strategies. In this
review, we present evidence pointing to inflammatory processes as key players in
the pathophysiology and treatment of depressive symptoms. In particular, we
report preclinical and clinical findings showing that inflammation-driven
alterations in specific metabolic pathways, namely kynurenine and
tetrahydrobiopterin (BH4) pathways, leads to substantial alterations in the
metabolism of serotonin, glutamate and dopamine that are likely to contribute to
the development of key depressive symptom dimensions. Accordingly,
anti-inflammatory interventions targeting kynurenine and BH4 pathways may be
effective as novel treatment or as adjuvants of conventional medications rather
directed to monoamines, notably when depressive symptomatology and inflammation
are comorbid in treated patients. This notion is discussed in the light of recent
findings illustrating the tight interactions between known antidepressant drugs
and inflammatory processes, as well as their therapeutic implications.
Altogether, this review provides valuable findings for moving toward more adapted
and personalized therapeutic strategies to treat inflammation-related depressive
symptoms.
DOI: 10.3389/fnins.2018.00499
PMCID: PMC6095005
PMID: 30140200