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.

Aims 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.

Methods 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.

The authors have declared no competing interest.

There is no specific funding for the present research.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Under Document No. 103/2022, the University of Hawler's approval committee in Erbil, Iraq, granted ethical approval for the research endeavor. The authorization verifies that the undertaking conforms to the criteria specified in the “International Guideline for Human Research,” in accordance with the stipulations of the Declaration of Helsinki.

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Highly cited author: 2003-2023 (ISI, Clarivate)

ScholarGPS: Worldwide #1 in molecular neuroscience; #1/4 in pathophysiology Expert worldwide medical expertise ranking, Expertscape (December 2022), worldwide: #1 in CFS, #1 in oxidative stress, #1 in encephalomyelitis, #1 in nitrosative stress, #1 in nitrosation, #1 in tryptophan, #1 in aromatic amino acids, #1 in stress (physiological), #1 in neuroimmune; #2 in bacterial translocation; #3 in inflammation, #4-5: in depression, fatigue and psychiatry.

The database created during this investigation will be provided by the corresponding author (MM) upon a reasonable request once the authors have thoroughly used the data set.