Preprint Neuro-immune and metabolic disorders in association with depression, anxiety, and chronic fatigue-fibromyalgia [...] due to [NAFLD], 2025, Al-Azzawi+

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Neuro-immune and metabolic disorders in association with depression, anxiety, and chronic fatigue-fibromyalgia symptoms due to non-alcoholic fatty liver disease

Walaa Abdulhussein Al-Azzawi, Hamid Yaghooti, Hussein Kadhem A-Hakeim, Michael Maes

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Background
Nonalcoholic fatty liver disease (NAFLD) is frequently associated with depression, anxiety, and chronic fatigue syndrome (CFS). Major depression and NAFLD are accompanied by low-grade inflammation, increased atherogenicity and insulin resistance.

There is a paucity of data on serum tryptophan and tryptophan catabolites (TRYCATs) in relation to these symptoms in patients with NAFLD. The aim of this study is to determine the relationships between the severity of NAFLD, severity of the above neuropsychiatric symptoms and neuro-immune, metabolic and TRYCAT pathway biomarkers.

Methods
This case-control study included fifty-six Grade 1 NAFLD patients, fifty-two Grade 2 NAFLD patients, and 60 healthy controls. We assessed serum insulin, tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, indoleamine 2, 3-dioxygenase 1 (IDO1), Interleukin (IL)-6, IL-10, the HOMA2 insulin resistance (HOMA2IR), and atherogenity indices.

Results
The severity of depression, anxiety, and CFS was significantly higher in NAFLD than in controls, and in grade 2 as compared with grade 1 NAFLD. The atherogenic and HOMA2IR indices significantly increased from controls to grade 1 to grade 2.

Serum tryptophan, kynurenine, kynurenic acid, and 3-OH-kynurenine were significantly lower in NAFLD and especially in Grade 2 than in controls, while IL-6 and IL-10 were higher in grade 2 NAFLD than in controls. The rating scale scores were significantly and positively correlated with liver tests, atherogenicity and HOMA2 indices, and inversely with tryptophan and TRYCATs.

Conclusions
Affective and CFS symptoms due to NAFLD might be mediated by the cumulative neurotoxic effects of lipids, IR, and lowered anti-inflammatory and antioxidant effects of the TRYCAT pathway.

Link | PDF (Preprint: ResearchGate) [Open Access]
 
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The study is both about "CFS" and excluded people with "CFS".

The severity of depression, anxiety, and CFS was significantly higher in NAFLD than in controls
The severity of CFS and fibromyalgia was assessed by a senior psychiatrist using the Fibro-Fatigue scale (45).
The present study excluded patients and controls who had diabetes type 1, systemic (auto)immune diseases like inflammatory bowel disease, rheumatoid arthritis, renal disease, as well as neurodegenerative and neuroinflammatory disorders, including Parkinson’s and Alzheimer's disease, multiple sclerosis, or stroke. Also, we excluded any subjects with a lifetime or current history of psychiatric axis-1 disorders, such as major affective disorders (major depressive disorder and bipolar disorder, dysthymia, generalized anxiety disorder, panic disorder), schizo-affective disorder, schizophrenia, psycho-organic syndrome, substance-use disorders (except tobacco-use disorder) and CFS.

Similar issue in another paper from Michael Maes:
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)."
 
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