Chronic fatigue syndrome, depression, and anxiety symptoms due to relapsing-remitting multiple sclerosis are associated with... 2025 Maes et al

Full title: Chronic fatigue syndrome, depression, and anxiety symptoms due to relapsing-remitting multiple sclerosis are associated with reactivation of Epstein-Barr virus and Human Herpesvirus 6

Abstract

Background: Relapsing-remitting multiple sclerosis (RRMS) is defined by elevated IgG/IgA/IgM responses targeting Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA) and deoxyuridine-triphosphatases (dUTPases) of Human herpsesvirus-6 (HHV-6) and EBV. These responses suggest that the viruses are being replicated and reactivated. An increased prevalence of chronic fatigue syndrome, depression, and anxiety is associated with signs of immune activation in RRMS. Nevertheless, there is a lack of data regarding the association between viral reactivation and neuropsychiatric symptoms of RRMS.

Methods: This study investigated the IgG/IgA/IgM responses to EBNA, and EBV and HHV-6-dUTPases, in 58 remitted RRMS patients and 63 normal controls. The McDonald criteria were employed to establish the diagnosis of MS. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score were employed to evaluate disabilities caused by RRMS. We evaluated the scores of the Hamilton Depression (HAMD) and Anxiety (HAMA) Rating Scales, and Fibro-Fatigue (FF) scale. One latent construct was extracted from the EDSS, MSSS, FF, HAMD, and HAMA scores.

Results: We discovered that the combined effects of IgG and IgM-HHV-6-dUTPAses accounted for 63.7% of the variance in this construct. Furthermore, the total FF, HAMA, and HAMD scores were substantially associated with the IgG and IgM-HHV-6-dUTPAses, accounting for approximately 38.7% to 51.0% of the variance. The three neuropsychiatric rating scale scores were also significantly correlated with IgA reactivity directed to both dUTPases and IgG/IgA/IgM to EBNA.

Conclusion: The reactivation and replication of HHV-6 and EBV significantly contributes to chronic fatigue syndrome, as well as symptoms of depression and anxiety due to RRMS.

PubMed abstract only

Previous pre-print version

 

I've put this in the ME/CFS research sub-forum due to the use of "chronic fatigue syndrome" in the title but I think this study confirms that the many publications by Maes et al that talk about chronic fatigue syndrome are actually about chronic fatigue, as measured by his Fibro-Fatigue (FF) scale.

From the preprint (my bold),
"The study systematically excluded patients and controls who exhibited medical conditions, such as thyroid disorders, renal or liver diseases, diabetes mellitus type 1, cardiovascular diseases, (auto)immune disorders such as cancer, inflammatory bowel disease, rheumatoid arthritis, chronic obstructive pulmonary disease, psoriasis, and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)."

 

So they think that CFS is not the same as CFS/ME or ME/CFS?

 

Really, who knows, as I don't. If it helps anybody figuring it out, our discussion thread on the FibroFatigue scale that they use is here, A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale), 2002, Zachrisson et al