Childhood trauma, the stress response and metabolic syndrome: A focus on DNA methylation.
Jacqueline Samantha WomersleyJani NothlingSylvanus ToikumoStefanie Malan-MüllerLeigh L van den HeuvelNathaniel W McGregorSoraya SeedatSîan M J HemmingsPublished in: The European journal of neuroscience (2021)
Childhood trauma (CT) is well established as a potent risk factor for the development of mental disorders. However, the potential of adverse early experiences to exert chronic and profound effects on physical health, including aberrant metabolic phenotypes, has only been more recently explored. Among these consequences is metabolic syndrome (MetS), which is characterised by at least three of five related cardiometabolic traits: hypertension, insulin resistance/hyperglycaemia, raised triglycerides, low high-density lipoprotein and central obesity. The deleterious effects of CT on health outcomes may be partially attributable to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates the response to stress, and the consequent fostering of a pro-inflammatory environment. Epigenetic tags, such as DNA methylation, which are sensitive to environmental influences provide a means whereby the effects of CT can be biologically embedded and persist into adulthood to affect health and well-being. The methylome regulates the transcription of genes involved in the stress response, metabolism and inflammation. This narrative review examines the evidence for DNA methylation in CT and MetS in order to identify shared neuroendocrine and immune correlates that may mediate the increased risk of MetS following CT exposure. Our review specifically highlights differential methylation of FKBP5, the gene that encodes FK506-binding protein 51 and has pleiotropic effects on stress responding, inflammation and energy metabolism, as a central candidate to understand the molecular aetiology underlying CT-associated MetS risk.
Keyphrases
- skeletal muscle
- insulin resistance
- dna methylation
- metabolic syndrome
- image quality
- dual energy
- genome wide
- computed tomography
- contrast enhanced
- high density
- high fat diet
- high fat diet induced
- gene expression
- mental health
- healthcare
- oxidative stress
- binding protein
- positron emission tomography
- public health
- blood pressure
- copy number
- type diabetes
- emergency department
- transcription factor
- cardiovascular disease
- social media
- autism spectrum disorder
- body mass index
- physical activity
- health information
- health promotion
- pet ct
- anti inflammatory
- early life
- climate change
- weight gain