Table 2 Summarizes the common factors found to have a relevance in the pathogenesis of both NAFLD and psychiatric disorders

Genetic

PNPLA3 (adiponutrin) polymorphisms

- Hydrolase activity on triglycerides and retinyl esters

- In pituitary: regulation of glucose and fatty acid homeostasis, appetite and energy expenditure

Linked to pathogenesis

Bipolar disorder

- Unknown mechanism

- Probably linked to inflammation and oxidative stress

miR-34a

- Hepatic lipogenesis & lipid secretion

- Neurodevelopment & synaptogenesis

NAFLD progression & heritability

Bipolar disorder

- Elevated in diagnosed of BD

- Decreases in response to lithium

Mitochondria, inflammation and oxidative stress

Altered mitochondrial metabolism

- Protection against fatty acid accumulation

- Energy production

Excessive oxidative species are linked to hepatic inflammation, accumulation of fatty tissue and progression of NASH

Linked to:

- Pathogenesis: neuroinflammation, dysregulation of brain energy generation & dysfunction in stress response mechanisms

- Progression & poorer outcomes

In several disorders:

- Bipolar disorder**

- Depression

- PTSD

- Psychosis & schizophrenia

- Autism

Microbiota

Gut dysbiosis

- Digestion of nutrients

- Production of vitamin K & B

- Maintenance of the intestinal mucosa

- Immune barrier effect

- Lipid accumulation in the liver

- Increased absorption of disaccharides

- Accelerated hepatic lipogenesis

- Inflammation and steatosis

ADHD, autism, depression, dementia

- Inflammatory dysregulation mediated by bacterial products

- Probiotics as suggested therapies

Psychological factors, lifestyle, exercise and diet

Personality traits

Enhancing adequate lifestyles

- Weight gain and fatty tissue proliferation

- Dysregulation in immune response

Nonadaptive traits

- High neuroticism

- Low conscientiousness

Exercise

Protective effects against inflammation

Low activity linked to

- Weight gain and fat accumulation in liver

- Impaired glucose metabolism

- Upregulation of immune response, inflammation and fibrosis

Poorer mental health

- Low levels of activity linked to higher risk of depression

Impaired glucose metabolism and DM2

Regulating levels of exertion and fatigue during exercise

- Weigh gain

- Accumulation of fatty tissue in liver

- Increased lipogenesis

- Increased ROS and lipid metabolism by-products

- Upregulation of inflammation

Unhealthy lifestyles

Link to higher risk of depression

Obesity

Normal diet secures energy intake and essential nutrients

NAFLD

- Fatty tissue proliferation

- Inflammation and oxidative stress

- Unhealthy lifestyles

- Medication adverse events

- Higher risk of depression