Preprint In severe first episode major depressive disorder, psychosomatic, CFS and FM symptoms are driven by immune activation..., 2023, Maes et al.

[Sly Saint]

Aug 2023
Michael Maes et al

Abstract
Background: Major depressive disorder (MDD) is accompanied by activated neuro-immune pathways, increased physiosomatic and chronic fatigue-fibromyalgia (FF) symptoms. The most severe MDD phenotype, namely major dysmood disorder (MDMD), is associated with adverse childhood experiences (ACEs) and negative life events (NLEs) which induce cytokines/chemokines/growth factors.

Aims: To delineate the impact of ACE+NLEs on physiosomatic and FF symptoms in first episode (FE)-MDMD, and examine whether these effects are mediated by immune profiles.

Methods: ACEs, NLEs, physiosomatic and FF symptoms, and 48 cytokines/chemokines/growth factors were measured in 64 FE-MDMD patients and 32 normal controls.

Results: Physiosomatic, FF and gastro-intestinal symptoms belong to the same factor as depression, anxiety, melancholia, and insomnia. The first factor extracted from these seven domains is labeled the physio-affective phenome of depression. A part (59.0%) of the variance in physiosomatic symptoms is explained by the independent effects of interleukin (IL)-16 and IL-8 (positively), CCL3 and IL-1 receptor antagonist (inversely correlated). A part (46.5%) of the variance in physiosomatic (59.0%) symptoms is explained by the independent effects of interleukin (IL)-16, TNF-related apoptosis-inducing ligand (TRAIL) (positively) and combined activities of negative immunoregulatory cytokines (inversely associated). Partial Least Squares analysis shows that ACE+NLEs exert a substantial influence on the physio-affective phenome which are partly mediated by an immune network composed of interleukin-16, CCL27, TRAIL, macrophage-colony stimulating factor, and stem cell growth factor.

Conclusions: The physiosomatic and FF symptoms of FE-MDMD are partly caused by immune-associated neurotoxicity due to Th-1 polarization, T helper-1, and M1 macrophage activation and relative lowered compensatory immunoregulatory protection.

full paper available
(PDF) In severe first episode major depressive disorder, psychosomatic, chronic fatigue syndrome, and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity. (researchgate.net)

Ethical approval and consent to participate.
The College of Medical Technology at The Islamic University of Najaf, Iraq (18/2021)
approved the research project. Our IRB follows the International Guideline for Human Research
Safety, as well as the World Medical Association Declaration of Helsinki, The Belmont Report,
the CIOMS Guideline, and the International Conference on Harmonization of Good Clinical
Practice, and our study was conducted in accordance with all applicable Iraqi and international
ethics and privacy laws. (ICH-GCP).

Informed Consent Statement
All participants and their parents or legal guardians signed a written consent form.

Declaration of interest
The authors declare no conflicts of interest.

Funding
The C2F program at Chulalongkorn University in Thailand, grant number 64.310/436/2565
to AFA, the Thailand Science Research, and Innovation Fund at Chulalongkorn University
(HEA663000016), and a Sompoch Endowment Fund (Faculty of Medicine) MDCU (RA66/016)
to MM all provided funding for the project

Authors contributions

AFA and PS quantified the biomarkers in the blood serum. MM conducted the study's
statistical analysis. The work is written and edited by MM, AA, BZ, AAA and PS. All authors
have read and approved the final manuscript.

Availability of data
The corresponding author (MM) will make the SPSS file used in the current study available
upon receipt of an appropriate request and once the author has fully exploited the data.

 

[RedFox]

On one hand, conflating severe fatigue with ME is severely misinformed. On the other, research into the biochemical and immunological aspects of depression is sorely needed and potentially valuable. If certain physical symptoms are reasonably correlated with immune markers, it's more sensible to describe them as immunological than "physiosomatic."