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An inflamed subtype of difficult-to-treat depression

Suneson, Klara LU ; Grudet, Cécile LU orcid ; Ventorp, Filip LU ; Malm, Johan LU ; Asp, Marie LU ; Westrin, Åsa LU and Lindqvist, Daniel LU (2023) In Progress in Neuro-Psychopharmacology and Biological Psychiatry 125.
Abstract

BACKGROUND: Chronic low-grade inflammation may play a role in the pathophysiology of depression, at least in a subset of patients. High-sensitivity C-reactive protein (hs-CRP) has been used to define an inflamed subgroup of depression with specific clinical characteristics and symptoms. In this study we investigated biochemical and clinical characteristics in patients with difficult-to-treat depression with and without chronic low-grade inflammation.

METHOD: We assayed plasma levels of interferon-gamma, tumor necrosis factor-alpha, Interleukin (IL)-10, IL-6, IL-8, and vitamin D in a clinically well-characterized sample of patients with difficult-to-treat depression (n = 263) and healthy controls (n = 46). Serum hs-CRP levels were... (More)

BACKGROUND: Chronic low-grade inflammation may play a role in the pathophysiology of depression, at least in a subset of patients. High-sensitivity C-reactive protein (hs-CRP) has been used to define an inflamed subgroup of depression with specific clinical characteristics and symptoms. In this study we investigated biochemical and clinical characteristics in patients with difficult-to-treat depression with and without chronic low-grade inflammation.

METHOD: We assayed plasma levels of interferon-gamma, tumor necrosis factor-alpha, Interleukin (IL)-10, IL-6, IL-8, and vitamin D in a clinically well-characterized sample of patients with difficult-to-treat depression (n = 263) and healthy controls (n = 46). Serum hs-CRP levels were available in the patient group and were used to define "inflamed depression" (hs-CRP > 3 mg/L). Based on previous studies correlating specific depressive symptoms to inflammatory markers, we calculated a composite score of inflammatory depressive symptoms (Infl-Dep score). A principal component analysis (PCA) was performed to identify patterns of variance in cytokines and vitamin D among patients.

RESULTS: Mean levels of IL-6 and IL-8 were significantly higher in depressed patients compared to controls, also after adjusting for sex, smoking, BMI, and age. None of the other inflammatory markers differed significantly between depressed patients and controls. Two components were extracted using PCA; one showed general cytokine elevations and one represented a pattern where IL-6 and IL-8 were inversely related to vitamin D (IL6-IL8-VitD component). The inflamed subgroup (hs-CRP > 3, n = 51) exhibited significantly higher BMI, higher Infl-Dep scores and higher IL6-IL8-VitD component scores than uninflamed patients (hs-CRP ≤ 3, n = 212). There were no significant differences in overall depression severity or suicidality between the inflamed and uninflamed groups.

CONCLUSION: Our results support the hypothesis of an inflamed subgroup of depression as a meaningful construct. This subgroup may have certain biological and clinical characteristics and more studies are needed to determine potential clinical implications.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Progress in Neuro-Psychopharmacology and Biological Psychiatry
volume
125
article number
110763
publisher
Elsevier
external identifiers
  • scopus:85152255667
  • pmid:37037323
ISSN
0278-5846
DOI
10.1016/j.pnpbp.2023.110763
language
English
LU publication?
yes
additional info
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
id
665d6641-d5e7-49bf-84b2-8bfcdd736b84
date added to LUP
2023-05-08 19:27:18
date last changed
2024-06-29 03:56:42
@article{665d6641-d5e7-49bf-84b2-8bfcdd736b84,
  abstract     = {{<p>BACKGROUND: Chronic low-grade inflammation may play a role in the pathophysiology of depression, at least in a subset of patients. High-sensitivity C-reactive protein (hs-CRP) has been used to define an inflamed subgroup of depression with specific clinical characteristics and symptoms. In this study we investigated biochemical and clinical characteristics in patients with difficult-to-treat depression with and without chronic low-grade inflammation.</p><p>METHOD: We assayed plasma levels of interferon-gamma, tumor necrosis factor-alpha, Interleukin (IL)-10, IL-6, IL-8, and vitamin D in a clinically well-characterized sample of patients with difficult-to-treat depression (n = 263) and healthy controls (n = 46). Serum hs-CRP levels were available in the patient group and were used to define "inflamed depression" (hs-CRP &gt; 3 mg/L). Based on previous studies correlating specific depressive symptoms to inflammatory markers, we calculated a composite score of inflammatory depressive symptoms (Infl-Dep score). A principal component analysis (PCA) was performed to identify patterns of variance in cytokines and vitamin D among patients.</p><p>RESULTS: Mean levels of IL-6 and IL-8 were significantly higher in depressed patients compared to controls, also after adjusting for sex, smoking, BMI, and age. None of the other inflammatory markers differed significantly between depressed patients and controls. Two components were extracted using PCA; one showed general cytokine elevations and one represented a pattern where IL-6 and IL-8 were inversely related to vitamin D (IL6-IL8-VitD component). The inflamed subgroup (hs-CRP &gt; 3, n = 51) exhibited significantly higher BMI, higher Infl-Dep scores and higher IL6-IL8-VitD component scores than uninflamed patients (hs-CRP ≤ 3, n = 212). There were no significant differences in overall depression severity or suicidality between the inflamed and uninflamed groups.</p><p>CONCLUSION: Our results support the hypothesis of an inflamed subgroup of depression as a meaningful construct. This subgroup may have certain biological and clinical characteristics and more studies are needed to determine potential clinical implications.</p>}},
  author       = {{Suneson, Klara and Grudet, Cécile and Ventorp, Filip and Malm, Johan and Asp, Marie and Westrin, Åsa and Lindqvist, Daniel}},
  issn         = {{0278-5846}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Elsevier}},
  series       = {{Progress in Neuro-Psychopharmacology and Biological Psychiatry}},
  title        = {{An inflamed subtype of difficult-to-treat depression}},
  url          = {{http://dx.doi.org/10.1016/j.pnpbp.2023.110763}},
  doi          = {{10.1016/j.pnpbp.2023.110763}},
  volume       = {{125}},
  year         = {{2023}},
}