Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress

Abstract

Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.

Reduced Quality of Life in Patients with Non-Alcoholic Fatty Liver Disease May Be Associated with Depression and Fatigue

“…Currently, increasing evidence suggests a strong association between NAFLD/NASH and psychological disorders, such as depression [ 30 , 31 ]. We found out that patients with NAFLD had significantly higher scores on HADS-D, compared with the controls (4 [2–6] vs. 2 [0–4], respectively).…”

Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder

“…One study showed negative correlation of DNAm of cg03341655 in the subcutaneous adipose tissue in response to high saturated fatty acids diet [ 39 ]. In fact, both, PD and MDD, as well as chronic stress are related to higher risk of metabolic syndromes and cardiovascular morbidity as has been shown in multiple studies [ 40 – 42 ]. Further EWAS have reported DNAm changes at different CpG-sites in GFOD2 in relation to childhood abuse [ 43 ], maternal alcohol consumption and offspring cord blood methylation [ 44 ] and all-cause mortality in monozygotic twins [ 45 ].…”

Obesity in adolescents may be associated with limitations in daily activities and an increased level of anxiety in patients and their parents – preliminary results of a pilot study

“…Some researchers have suggested the influence of chronic stress on the development of liver damage in people with obesity. According to this theory, as in type 2 diabetes and cardiovascular disease, stress involves both behavioral and biological responses, which activate the hypothalamic -pituitaryadrenal axis, resulting in elevated levels of cortisol and pro-inflammatory biomarkers that could be involved in the development of MAFLD (24,25). Also, pro-inflammatory pathways, immune dysregulation, and systemic or multi-organ inflammation are considered to mediate pathophysiological interaction between certain mental health disorders (25,26).…”

“…According to this theory, as in type 2 diabetes and cardiovascular disease, stress involves both behavioral and biological responses, which activate the hypothalamic -pituitaryadrenal axis, resulting in elevated levels of cortisol and pro-inflammatory biomarkers that could be involved in the development of MAFLD (24,25). Also, pro-inflammatory pathways, immune dysregulation, and systemic or multi-organ inflammation are considered to mediate pathophysiological interaction between certain mental health disorders (25,26). Finally, there are also established relationships between obesity and mental health that may be connected to changes in gut microbiota, resulting in such comorbidity.…”