Work

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

Year: 2026

Type: article

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.

Source: CNS Spectrums

DOI: 10.1017/s1092852926100960

Authors: Walaa Abdulhussein Al-Azzawi, Hamid Yaghooti, Hussein Al-Hakeim, Michael Maes