Kynurenine pathway metabolites are increased in inflammatory depression and decrease with omega-3 treatment
Lindahl, Jesper LU ; Söderberg Veibäck, Gustav LU ; Suneson, Klara LU ; Blanking, Wilma ; Tjernberg, Johanna LU ; Ståhl, Darya LU
; Wiman, Åsa
; Ventorp, Filip
LU
; Erhardt, Sophie
and Lindqvist, Daniel
LU
(2026)
In Brain, Behavior, and Immunity - Health
53.
- Abstract
Activation of the kynurenine pathway (KP) with resulting accumulation of neuroactive metabolites may be a downstream pathophysiological mechanism of inflammatory depression. The aims of this study were to investigate KP metabolites in inflammatory depression compared to non-inflammatory depression and healthy controls, and whether these metabolites change with nutraceutical interventions with potential KP-modulating effects. We combined data from two antidepressant clinical trials: one with omega-3 polyunsaturated fatty acids (n-3 PUFAs) and one with a Limosilactobacillus reuteri probiotic supplement as the active intervention. Patients with Major Depressive Disorder (MDD) (n = 170) were stratified at baseline according to... (More)
Activation of the kynurenine pathway (KP) with resulting accumulation of neuroactive metabolites may be a downstream pathophysiological mechanism of inflammatory depression. The aims of this study were to investigate KP metabolites in inflammatory depression compared to non-inflammatory depression and healthy controls, and whether these metabolites change with nutraceutical interventions with potential KP-modulating effects. We combined data from two antidepressant clinical trials: one with omega-3 polyunsaturated fatty acids (n-3 PUFAs) and one with a Limosilactobacillus reuteri probiotic supplement as the active intervention. Patients with Major Depressive Disorder (MDD) (n = 170) were stratified at baseline according to high-sensitivity C-reactive protein (hs-CRP) levels into an inflammatory (hs-CRP ≥1 mg/L, n = 127) and a non-inflammatory (hs-CRP <1 mg/L, n = 43) group. We also included 80 non-depressed healthy controls (HC). We investigated between-group differences in KP metabolites at baseline, treatment-associated changes in these biomarkers and how they relate to clinical response. At baseline, the inflammatory depression group had significantly elevated levels of quinolinic acid (QUIN) (p < 0.01), 3-hydroxykynurenine (3-HK) (p < 0.05), and kynurenine (p < 0.05) levels compared to both non-inflammatory depression and HCs. N-3 PUFAs, but not probiotics or placebo, significantly decreased QUIN (p < 0.05) and 3-HK (p < 0.05). Higher baseline levels and a larger treatment-associated decrease of several KP metabolites were associated with a better clinical response to n-3 PUFAs (p < 0.05). In contrast, probiotic supplementation was not associated with significant changes in KP metabolites, and biomarker associations with treatment response were limited in this cohort. We found evidence of KP activation in MDD, but only in an inflammatory subgroup, suggesting that these biological alterations may be specific to a subset of patients with low-grade inflammation. These findings encourage further investigations into whether, and how, biomarkers of KP activation may predict antidepressant response.
(Less)
- author
- Lindahl, Jesper
LU
; Söderberg Veibäck, Gustav
LU
; Suneson, Klara
LU
; Blanking, Wilma
; Tjernberg, Johanna
LU
; Ståhl, Darya
LU
; Wiman, Åsa
; Ventorp, Filip
LU
; Erhardt, Sophie
and Lindqvist, Daniel
LU
- organization
- publishing date
- 2026-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Kynurenine pathway, Major depressive disorder, N-3 PUFAs, Nutraceuticals, Probiotics, Tryptophan
- in
- Brain, Behavior, and Immunity - Health
- volume
- 53
- article number
- 101221
- publisher
- Elsevier
- external identifiers
-
- pmid:41969822
- scopus:105034899059
- ISSN
- 2666-3546
- DOI
- 10.1016/j.bbih.2026.101221
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/
- id
- 8a95d970-9f3d-42d4-9d66-b1d6e9e35e73
- date added to LUP
- 2026-06-18 10:48:42
- date last changed
- 2026-06-19 03:00:06
@article{8a95d970-9f3d-42d4-9d66-b1d6e9e35e73,
abstract = {{<p>Activation of the kynurenine pathway (KP) with resulting accumulation of neuroactive metabolites may be a downstream pathophysiological mechanism of inflammatory depression. The aims of this study were to investigate KP metabolites in inflammatory depression compared to non-inflammatory depression and healthy controls, and whether these metabolites change with nutraceutical interventions with potential KP-modulating effects. We combined data from two antidepressant clinical trials: one with omega-3 polyunsaturated fatty acids (n-3 PUFAs) and one with a Limosilactobacillus reuteri probiotic supplement as the active intervention. Patients with Major Depressive Disorder (MDD) (n = 170) were stratified at baseline according to high-sensitivity C-reactive protein (hs-CRP) levels into an inflammatory (hs-CRP ≥1 mg/L, n = 127) and a non-inflammatory (hs-CRP <1 mg/L, n = 43) group. We also included 80 non-depressed healthy controls (HC). We investigated between-group differences in KP metabolites at baseline, treatment-associated changes in these biomarkers and how they relate to clinical response. At baseline, the inflammatory depression group had significantly elevated levels of quinolinic acid (QUIN) (p < 0.01), 3-hydroxykynurenine (3-HK) (p < 0.05), and kynurenine (p < 0.05) levels compared to both non-inflammatory depression and HCs. N-3 PUFAs, but not probiotics or placebo, significantly decreased QUIN (p < 0.05) and 3-HK (p < 0.05). Higher baseline levels and a larger treatment-associated decrease of several KP metabolites were associated with a better clinical response to n-3 PUFAs (p < 0.05). In contrast, probiotic supplementation was not associated with significant changes in KP metabolites, and biomarker associations with treatment response were limited in this cohort. We found evidence of KP activation in MDD, but only in an inflammatory subgroup, suggesting that these biological alterations may be specific to a subset of patients with low-grade inflammation. These findings encourage further investigations into whether, and how, biomarkers of KP activation may predict antidepressant response.</p>}},
author = {{Lindahl, Jesper and Söderberg Veibäck, Gustav and Suneson, Klara and Blanking, Wilma and Tjernberg, Johanna and Ståhl, Darya and Wiman, Åsa and Ventorp, Filip and Erhardt, Sophie and Lindqvist, Daniel}},
issn = {{2666-3546}},
keywords = {{Kynurenine pathway; Major depressive disorder; N-3 PUFAs; Nutraceuticals; Probiotics; Tryptophan}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Brain, Behavior, and Immunity - Health}},
title = {{Kynurenine pathway metabolites are increased in inflammatory depression and decrease with omega-3 treatment}},
url = {{http://dx.doi.org/10.1016/j.bbih.2026.101221}},
doi = {{10.1016/j.bbih.2026.101221}},
volume = {{53}},
year = {{2026}},
}