Neuro-immune and metabolic disorders in association with depression, anxiety, and chronic fatigue-fibromyalgia symptoms due to nonalcoholic fatty liver disease
8 affiliations
- 1Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University Faculty of Medical Sciences, Islamic Republic of Iran
- 2Department of Chemistry, Faculty of Science, University of Kufa, Iraq
- 3Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
- 4Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China
- 5Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- 6Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria
- 7Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria
- 8Kyung Hee University, Seoul, Dongdaemun-gu, South Korea
Abstract
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. This study aims to determine the relationships between the severity of NAFLD, the severity of the above neuropsychiatric symptoms and neuro-immune, metabolic, and TRYCAT pathway biomarkers.
Methods: This case–control study included 56 patients with Grade 1 NAFLD, 52 with Grade 2 NAFLD, 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, HOMA2 insulin resistance index (HOMA2IR), and atherogenic indices.
Results: The severity of depression, anxiety, and fibro-fatigue symptoms was significantly higher in NAFLD than in controls and in grade 2 as compared with grade 1 NAFLD. The atherogenic and HOMA2IR indices increased significantly from controls to grade 1 and then 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 fibro-fatigue 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.
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BibTeX
@article{alazzawi2026neuroimmune,
title = {{Neuro-immune and metabolic disorders in association with depression, anxiety, and chronic fatigue-fibromyalgia symptoms due to nonalcoholic fatty liver disease}},
author = {Walaa Abdulhussein Al-Azzawi and Hamid Yaghooti and Hussein Al-Hakeim and Michael Maes},
journal = {CNS Spectrums},
year = {2026},
month = may,
doi = {10.1017/s1092852926100960},
url = {https://doi.org/10.1017/s1092852926100960},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neuro-immune and metabolic disorders in association with depression, anxiety, and chronic fatigue-fibromyalgia symptoms due to nonalcoholic fatty liver disease
AU - Walaa Abdulhussein Al-Azzawi
AU - Hamid Yaghooti
AU - Hussein Al-Hakeim
AU - Michael Maes
PY - 2026
DA - 2026/05/26
JO - CNS Spectrums
DO - 10.1017/s1092852926100960
UR - https://doi.org/10.1017/s1092852926100960
AB - 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. This study aims to determine the relationships between the severity of NAFLD, the severity of the above neuropsychiatric symptoms and neuro-immune, metabolic, and TRYCAT pathway biomarkers. Methods: This case–control study included 56 patients with Grade 1 NAFLD, 52 with Grade 2 NAFLD, 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, HOMA2 insulin resistance index (HOMA2IR), and atherogenic indices. Results: The severity of depression, anxiety, and fibro-fatigue symptoms was significantly higher in NAFLD than in controls and in grade 2 as compared with grade 1 NAFLD. The atherogenic and HOMA2IR indices increased significantly from controls to grade 1 and then 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 fibro-fatigue 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.
SN - 1092-8529
SN - 2165-6509
ER -