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Accepted manuscript

Monomeric CRP and negative acute phase proteins, but not pentameric CRP, as biomarkers of major depression and MDMD

Published online by Cambridge University Press:  18 November 2025

Abbas F. Almulla Open the ORCID record for Abbas F. Almulla [Opens in a new window] ,
Mengqi Niu ,
Drozdstoy Stoyanov Open the ORCID record for Drozdstoy Stoyanov [Opens in a new window] ,
Yingqian Zhang  and
Michael Maes Open the ORCID record for Michael Maes [Opens in a new window]
Abbas F. Almulla
Affiliation:
Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China, Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, 31001, Iraq.
Mengqi Niu
Affiliation:
Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China,
Drozdstoy Stoyanov
Affiliation:
Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria, Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria, Research and Innovation Program for the Development of MU - PLOVDIV (SRIPD-MUP), Creation of a network of research higher schools, National Plan for Recovery and Sustainability, European Union – NextGenerationEU, Medical University of Plovdiv, Plovdiv, Bulgaria, Europe.
Yingqian Zhang*
Affiliation:
Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China,
Michael Maes*
Affiliation:
Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China, Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria, Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria, Research and Innovation Program for the Development of MU - PLOVDIV (SRIPD-MUP), Creation of a network of research higher schools, National Plan for Recovery and Sustainability, European Union – NextGenerationEU, Medical University of Plovdiv, Plovdiv, Bulgaria, Europe. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, South Korea.
*
Corresponding Authors: Prof. Dr. Michael Maes and Yingqian Zhang. Sichuan Provincial Center for Mental Health Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Corresponding Authors: Prof. Dr. Michael Maes and Yingqian Zhang. Sichuan Provincial Center for Mental Health Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
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Abstract

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Background:

Contrary to the negative acute-phase protein (APP) response, there is no consistent correlation between serum pentameric C-reactive protein (pCRP) and major depression (MDD). Monomeric CRP (mCRP), a dissociation product of pCRP under immune-inflammatory conditions, exhibits pro-inflammatory effects; however, it has not been investigated in MDD or its subtypes, major dysmood disorder (MDMD) and simple dysmood disorder (SDMD).

Objective:

To examine serum mCRP, albumin, transferrin, M1 macrophage and Thelper-17 immune profiles, and adverse childhood experiences (ACEs) in MDD, MDMD and SDMD.

Methods:

Seventy-nine MDMD patients, 30 SDMD patients, and 40 controls were included. Serum mCRP was measured by ELISA; albumin, transferrin, and pCRP by biochemical assays; and cytokines using Luminex technology.

Results:

MDMD patients showed significantly higher mCRP compared with SDMD and controls, while both patient groups exhibited reduced albumin and transferrin. Combining mCRP with albumin and transferrin showed an adequate accuracy for MDD (area under the ROC Curve = 0.793). Adding IL-17A and ACEs improved accuracy (ROC=0.855). Serum mCRP levels are additionally associated with pCRP, M1 macrophage profile, body mass index, and ACEs. Up to 36.6% of the variance in overall severity of depression was explained by mCRP, T-helper-17 profile, ACEs (all positively), albumin and transferrin (both inversely).

Conclusion:

Future research in MDD should employ mCRP rather than pCRP as a biomarker of depression/MDMD. Combining mCRP with biomarkers of the negative acute-phase response identified 63.7% of MDD patients with a smoldering acute-phase response, with a specificity of 82.1%. We recommend to assess mCRP rather than pCRP in MDD studies.

Keywords

Monomeric CRPMajor depressionnegative acute phase proteinsinflammationbiomarkersneuroimmunomodulation

Information

Type
Original Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 30
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

Footnotes

*

Co-joint first authors

**

co-corresponding authors.