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A plasma protein profile of antidepressant response to omega-3 fatty acids

Lindahl, Jesper LU ; Stiernborg, Miranda ; Ventorp, Filip LU ; Suneson, Klara LU ; Söderberg Veibäck, Gustav LU ; Tjernberg, Johanna LU ; Ståhl, Darya LU orcid ; Hjärn, Marie ; Lavebratt, Catharina and Lindqvist, Daniel LU (2025) In Progress in Neuro-Psychopharmacology and Biological Psychiatry 141.
Abstract

Background: Previous studies suggest an antidepressant effect of omega-3 fatty acids (n-3 PUFAs). This effect may be larger in patients with low-grade inflammation, defined as mild elevations of high sensitivity C-reactive protein or other commonly used inflammatory markers. The antidepressant mechanisms of n-3 PUFAs are not fully understood but may involve modulation of immunometabolic processes and neurotrophic effects. Here we investigated inflammatory and cardiometabolic biomarkers in patients with major depressive disorder (MDD) and controls, how these biomarkers change with n-3 PUFA treatment, and their association with antidepressant response. Methods: Ninety-four MDD patients were treated with 2.2 g eicosapentaenoic acid, 400 mg... (More)

Background: Previous studies suggest an antidepressant effect of omega-3 fatty acids (n-3 PUFAs). This effect may be larger in patients with low-grade inflammation, defined as mild elevations of high sensitivity C-reactive protein or other commonly used inflammatory markers. The antidepressant mechanisms of n-3 PUFAs are not fully understood but may involve modulation of immunometabolic processes and neurotrophic effects. Here we investigated inflammatory and cardiometabolic biomarkers in patients with major depressive disorder (MDD) and controls, how these biomarkers change with n-3 PUFA treatment, and their association with antidepressant response. Methods: Ninety-four MDD patients were treated with 2.2 g eicosapentaenoic acid, 400 mg docosahexaenoic acid, and 800 mg other omega-3 fatty acids per day, added to stable antidepressant treatment for 8 weeks. Inflammatory and cardiometabolic plasma markers were assayed in MDD patients, before and after n-3 PUFA treatment, and in healthy controls (n = 76) using proximity extension assay technology. Treatment response was defined as ≥50 % reduction on the 17-item Hamilton Depression Rating Scale. Partial least squares discriminant analysis identified plasma proteins with differential levels between patients, controls, responders, and non-responders. Results: After adjusting for relevant covariates and multiple comparisons, baseline levels of several biomarkers associated with immunometabolic functions and neurotrophic processes differed significantly between MDD patients and controls and between n-3 PUFA responders and non-responders. Some of these biomarkers, related to cell-cell communication and neurotrophy, increased significantly with treatment. Conclusion: These findings provide new insights into the antidepressant mechanisms of n-3 PUFAs. Consistent with previous reports, we found evidence of pre-treatment immune activation in responders compared to non-responders, which could be used to personalize antidepressant n-3 PUFA treatment.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiometabolic biomarkers, Inflammation, Major depressive disorder, N-3 PUFAs
in
Progress in Neuro-Psychopharmacology and Biological Psychiatry
volume
141
article number
111481
publisher
Elsevier
external identifiers
  • scopus:105014650537
  • pmid:40882806
ISSN
0278-5846
DOI
10.1016/j.pnpbp.2025.111481
language
English
LU publication?
yes
id
43cebce0-cd7f-40f8-b800-11acf9a7d6b4
date added to LUP
2025-10-20 12:19:40
date last changed
2025-10-20 12:20:30
@article{43cebce0-cd7f-40f8-b800-11acf9a7d6b4,
  abstract     = {{<p>Background: Previous studies suggest an antidepressant effect of omega-3 fatty acids (n-3 PUFAs). This effect may be larger in patients with low-grade inflammation, defined as mild elevations of high sensitivity C-reactive protein or other commonly used inflammatory markers. The antidepressant mechanisms of n-3 PUFAs are not fully understood but may involve modulation of immunometabolic processes and neurotrophic effects. Here we investigated inflammatory and cardiometabolic biomarkers in patients with major depressive disorder (MDD) and controls, how these biomarkers change with n-3 PUFA treatment, and their association with antidepressant response. Methods: Ninety-four MDD patients were treated with 2.2 g eicosapentaenoic acid, 400 mg docosahexaenoic acid, and 800 mg other omega-3 fatty acids per day, added to stable antidepressant treatment for 8 weeks. Inflammatory and cardiometabolic plasma markers were assayed in MDD patients, before and after n-3 PUFA treatment, and in healthy controls (n = 76) using proximity extension assay technology. Treatment response was defined as ≥50 % reduction on the 17-item Hamilton Depression Rating Scale. Partial least squares discriminant analysis identified plasma proteins with differential levels between patients, controls, responders, and non-responders. Results: After adjusting for relevant covariates and multiple comparisons, baseline levels of several biomarkers associated with immunometabolic functions and neurotrophic processes differed significantly between MDD patients and controls and between n-3 PUFA responders and non-responders. Some of these biomarkers, related to cell-cell communication and neurotrophy, increased significantly with treatment. Conclusion: These findings provide new insights into the antidepressant mechanisms of n-3 PUFAs. Consistent with previous reports, we found evidence of pre-treatment immune activation in responders compared to non-responders, which could be used to personalize antidepressant n-3 PUFA treatment.</p>}},
  author       = {{Lindahl, Jesper and Stiernborg, Miranda and Ventorp, Filip and Suneson, Klara and Söderberg Veibäck, Gustav and Tjernberg, Johanna and Ståhl, Darya and Hjärn, Marie and Lavebratt, Catharina and Lindqvist, Daniel}},
  issn         = {{0278-5846}},
  keywords     = {{Cardiometabolic biomarkers; Inflammation; Major depressive disorder; N-3 PUFAs}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Progress in Neuro-Psychopharmacology and Biological Psychiatry}},
  title        = {{A plasma protein profile of antidepressant response to omega-3 fatty acids}},
  url          = {{http://dx.doi.org/10.1016/j.pnpbp.2025.111481}},
  doi          = {{10.1016/j.pnpbp.2025.111481}},
  volume       = {{141}},
  year         = {{2025}},
}