Abstract
Major depressive disorder (MDD), which is highly associated with non-alcoholic fatty liver disease (NAFLD), has complex pathogenic mechanisms. However, a limited number of studies have evaluated the mutual pathomechanisms involved in MDD and NAFLD development. Chronic stress-mediated elevations in glucocorticoid (GC) levels play an important role in the development of MDD-related NAFLD. Elevated GC levels can induce the release of inflammatory factors and changes in gut permeability. Elevated levels of inflammatory factors activate the hypothalamic–pituitary–adrenal (HPA) axis, which further increases the release of GC. At the same time, changes in gut permeability promote the release of inflammatory factors, which results in a vicious circle among the three, causing disease outbreaks. Even though the specific role of the thyroid hormone (TH) in this pathogenesis has not been fully established, it is highly correlated with MDD and NAFLD. Therefore, changing lifestyles and reducing psychological stress levels are necessary measures for preventing MDD-related NAFLD. Among them, GC inhibitors and receptor antagonists may be key in the alleviation of early and mid-term disease progression. However, combination medications may be important in late-stage diseases, but they are associated with various side effects. Traditional Chinese medicines have been shown to be potential therapeutic alternatives for such complex diseases.
Highlights
Major depressive disorder (MDD) is characterized by loss of interest, difficulty in paying attention, decreased appetite, and suicidal ideation, among other abnormal cognitive, behavioral, and social functions, with low mood as the main symptom [1]
Significant correlations between IL-18 and alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), TG, high-sensitivity C-reactive protein, and the degree of liver steatosis have been reported [135]. These findings suggest that inflammatory factors in MDD and non-alcoholic fatty liver disease (NAFLD) have important mediating roles, and they may be important links between the two conditions
There is a significant correlation between MDD and NAFLD, and they mediate and promote each other, gradually forming a vicious circle, which is obvious in patients with MDDassociated NAFLD
Summary
Major depressive disorder (MDD) is characterized by loss of interest, difficulty in paying attention, decreased appetite, and suicidal ideation, among other abnormal cognitive, behavioral, and social functions, with low mood as the main symptom [1]. Excessive release of stress-related corticosteroids can promote peripheral blood leukocyte migration to liver tissues and elevate proinflammatory cytokine levels, such as TNF-α and IL-6 These activated inflammatory cells produce more ROS, thereby exacerbating OS, causing inflammation and liver necrosis [63]. If TRADD, TRAF2, and RIPK are separated from their receptors, they recruit fasrelated death domain protein (FADD) and precaspase-8 (Caspase 8) to form a TNF-α-induced signal complex II (complex II), which in turn binds ROS regulatory factor 1 (Romo1) located in the mitochondria and recruits Bcl-xl protein to reduce the mitochondrial membrane potential and to activate ROS as well as JNK to promote cell apoptosis [147, 159]. GM contributes to the development and progression of NAFLD through several mechanisms: modulation of intestinal permeability by promoting endotoxemia as well as other microbe products that promote systemic and hepatic inflammation; modulation of choline metabolism (required for VLDL synthesis and export of lipids from the liver); generation of endogenous ethanol as well as other toxic products such as toxic compound TMAO; and modulation of BA homeostasis and FXR functions [220]
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