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Plasma proteomic profile of inflammatory depressive symptoms

Ängeby, Filip LU ; Ventorp, Filip LU ; Stiernborg, Miranda LU ; Suneson, Klara LU ; Söderberg Veibäck, Gustav LU ; Lindahl, Jesper LU ; Tjernberg, Johanna LU orcid ; Ståhl, Darya LU orcid ; Berge, Jonas LU and Lavebratt, Catharina , et al. (2026) In Brain, Behavior, & Immunity - Health 56.
Abstract

BACKGROUND: Previous studies suggest that specific depressive symptoms such as low energy, fatigue, sleep and appetite disturbances are associated with systemic low-grade inflammation. In this study, we investigated associations between an inflammatory symptom profile of depression and proteomic markers spanning inflammatory and metabolic pathways.

METHODS: We analyzed 158 proteins related to inflammation and metabolism using proximity extension assay in blood samples from 165 patients with Major Depressive Disorder (MDD). Severity of inflammatory depressive symptoms was assessed using a composite score summarizing Patient Health Questionnaire-9 (PHQ-9) items related to fatigue and sleep/appetite disturbances. We used partial... (More)

BACKGROUND: Previous studies suggest that specific depressive symptoms such as low energy, fatigue, sleep and appetite disturbances are associated with systemic low-grade inflammation. In this study, we investigated associations between an inflammatory symptom profile of depression and proteomic markers spanning inflammatory and metabolic pathways.

METHODS: We analyzed 158 proteins related to inflammation and metabolism using proximity extension assay in blood samples from 165 patients with Major Depressive Disorder (MDD). Severity of inflammatory depressive symptoms was assessed using a composite score summarizing Patient Health Questionnaire-9 (PHQ-9) items related to fatigue and sleep/appetite disturbances. We used partial least squares (PLS), PLS discriminant analysis (PLS-DA) and linear regression models to identify proteins related to inflammatory depressive symptom severity.

RESULTS: Out of the 158 proteins, 14 were selected by either PLS or PLS-DA. After false discovery rate correction, proteins identified by PLS or PLS-DA that remained significantly associated with more severe inflammatory depressive symptoms included several immunometabolic biomarkers, namelyinterleukin-6 (IL-6), hepatocyte growth factor, oncostatin M, thrombospondin-4, low affinity immunoglobulin gamma Fc region receptor II-a and intercellular adhesion molecule 1. With the exception of IL-6, none of these markers showed significant associations with the remaining PHQ-9 items that were not classified as inflammatory depressive symptoms.

CONCLUSIONS: These findings support the growing body of evidence linking inflammatory and metabolic protein alterations to specific depressive symptoms.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Brain, Behavior, & Immunity - Health
volume
56
article number
101311
publisher
Elsevier
external identifiers
  • scopus:105045622085
  • pmid:42565167
ISSN
2666-3546
DOI
10.1016/j.bbih.2026.101311
language
English
LU publication?
yes
id
71544b5b-11d3-4008-898d-0d958b68c65f
date added to LUP
2026-09-10 10:00:00
date last changed
2026-09-11 03:26:46
@article{71544b5b-11d3-4008-898d-0d958b68c65f,
  abstract     = {{<p>BACKGROUND: Previous studies suggest that specific depressive symptoms such as low energy, fatigue, sleep and appetite disturbances are associated with systemic low-grade inflammation. In this study, we investigated associations between an inflammatory symptom profile of depression and proteomic markers spanning inflammatory and metabolic pathways.</p><p>METHODS: We analyzed 158 proteins related to inflammation and metabolism using proximity extension assay in blood samples from 165 patients with Major Depressive Disorder (MDD). Severity of inflammatory depressive symptoms was assessed using a composite score summarizing Patient Health Questionnaire-9 (PHQ-9) items related to fatigue and sleep/appetite disturbances. We used partial least squares (PLS), PLS discriminant analysis (PLS-DA) and linear regression models to identify proteins related to inflammatory depressive symptom severity.</p><p>RESULTS: Out of the 158 proteins, 14 were selected by either PLS or PLS-DA. After false discovery rate correction, proteins identified by PLS or PLS-DA that remained significantly associated with more severe inflammatory depressive symptoms included several immunometabolic biomarkers, namelyinterleukin-6 (IL-6), hepatocyte growth factor, oncostatin M, thrombospondin-4, low affinity immunoglobulin gamma Fc region receptor II-a and intercellular adhesion molecule 1. With the exception of IL-6, none of these markers showed significant associations with the remaining PHQ-9 items that were not classified as inflammatory depressive symptoms.</p><p>CONCLUSIONS: These findings support the growing body of evidence linking inflammatory and metabolic protein alterations to specific depressive symptoms.</p>}},
  author       = {{Ängeby, Filip and Ventorp, Filip and Stiernborg, Miranda and Suneson, Klara and Söderberg Veibäck, Gustav and Lindahl, Jesper and Tjernberg, Johanna and Ståhl, Darya and Berge, Jonas and Lavebratt, Catharina and Lindqvist, Daniel}},
  issn         = {{2666-3546}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Brain, Behavior, & Immunity - Health}},
  title        = {{Plasma proteomic profile of inflammatory depressive symptoms}},
  url          = {{http://dx.doi.org/10.1016/j.bbih.2026.101311}},
  doi          = {{10.1016/j.bbih.2026.101311}},
  volume       = {{56}},
  year         = {{2026}},
}