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Accepted manuscript

The immune checkpoint pathophysiology of depression and chronic fatigue syndrome due to preeclampsia: focus on sCD80 and sCTLA-4

Published online by Cambridge University Press:  25 March 2025

Jangir Sami Omar ,
Niaz Albarzinji ,
Mengqi Niu ,
Naz Hawree Taher ,
Bayar Aram ,
Mohammed Salam Sulaiman ,
Shatha Rouf Moustafa ,
Hussein Kadhem Al-Hakeim Open the ORCID record for Hussein Kadhem Al-Hakeim [Opens in a new window]  and
Michael Maes Open the ORCID record for Michael Maes [Opens in a new window]
Jangir Sami Omar
Affiliation:
College of Medicine, Hawler Medical University, Erbil, Iraq.
Niaz Albarzinji
Affiliation:
Erbil Center KHCMS, College of Medicine, Hawler Medical University, Erbil, 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
Naz Hawree Taher
Affiliation:
College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Bayar Aram
Affiliation:
Baharka Hospital, Erbil, Iraq.
Mohammed Salam Sulaiman
Affiliation:
Hawler Medical University, College of Pharmacy, Erbil, Iraq.
Shatha Rouf Moustafa
Affiliation:
Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Havalan City, Erbil, Iraq.
Hussein Kadhem Al-Hakeim
Affiliation:
Department of Chemistry, College of Science, University of Kufa, Iraq.
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, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria. Kyung Hee University, Seoul, Dongdaemun-gu, South Korea.
*
*Correspondence Author: Prof. Dr. Michael Maes, M.D., Ph.D. 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. Email: michaelmaes@uestc.edu.cn
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Abstract

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Background

Neuropsychiatric disorders in preeclampsia (PE) women are prevalent and worsen PE outcome. Immune-related biomarkers including soluble sCD80 and cytotoxic T-lymphocyte antigen-4 (sCTLA-4) are not well studied in relation to depression, anxiety, and chronic fatigue due to PE.

Methods

The aim is to study serum immune-inflammatory biomarkers of PE and delineate their associations with the Hamilton Depression (HAMD), Anxiety (HAMA), and Fibro-Fatigue (FF) rating Scale scores. sCD80, sCTLA-4, vitamin D, granulocyte-macrophage colony-stimulating factor, zinc, copper, magnesium, and calcium were measured in 90 PE compared with 60 non-PE pregnant women.

Results

PE women show higher depression, anxiety and FF rating scale scores as compared with control women. sCTLA-4, sCD80, and copper were significantly higher and zinc, magnesium, and calcium significantly lower in PE women than in controls. Multiple regression analysis showed that around 55.8%-58.0% of the variance in the HAMD, HAMA and FF scores was explained by the regression on biomarkers; the top 3 most important biomarkers were sCTLA-4, sCD80, and vitamin D. The sCTLA-4/sCD80 ratio was significantly and inversely associated with the HAMD/HAMA/FF scores. We found that around 70% of the variance in systolic blood pressure could be explained by sCTLA-4, vitamin D, calcium, and copper.

Conclusions

The findings underscore that PE and depression, anxiety, and chronic fatigue symptoms due to PE are accompanied by activation of the immune-inflammatory response system. More specifically, disbalances among soluble checkpoint molecules seem to be involved in the pathophysiology of hypertension and neuropsychiatric symptoms due to PE.

Keywords

Neuroimmuneinflammationchronic fatigue syndromeaffective disordersbiomarkers
Type
Original Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 38
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