Socioeconomic Deprivation, Adverse Childhood Experiences and Medical Disorders in Adulthood: Mechanisms and Associations

Abstract

Severe socioeconomic deprivation (SED) and adverse childhood experiences (ACE) are significantly associated with the development in adulthood of (i) enhanced inflammatory status and/or hypothalamic–pituitary–adrenal (HPA) axis dysfunction and (ii) neurological, neuroprogressive, inflammatory and autoimmune diseases. The mechanisms by which these associations take place are detailed. The two sets of consequences are themselves strongly associated, with the first set likely contributing to the second. Mechanisms enabling bidirectional communication between the immune system and the brain are described, including complex signalling pathways facilitated by factors at the level of immune cells. Also detailed are mechanisms underpinning the association between SED, ACE and the genesis of peripheral inflammation, including epigenetic changes to immune system-related gene expression. The duration and magnitude of inflammatory responses can be influenced by genetic factors, including single nucleotide polymorphisms, and by epigenetic factors, whereby pro-inflammatory cytokines, reactive oxygen species, reactive nitrogen species and nuclear factor-κB affect gene DNA methylation and histone acetylation and also induce several microRNAs including miR-155, miR-181b-1 and miR-146a. Adult HPA axis activity is regulated by (i) genetic factors, such as glucocorticoid receptor polymorphisms; (ii) epigenetic factors affecting glucocorticoid receptor function or expression, including the methylation status of alternative promoter regions of NR3C1 and the methylation of FKBP5 and HSD11β2 ; (iii) chronic inflammation and chronic nitrosative and oxidative stress. Finally, it is shown how severe psychological stress adversely affects mitochondrial structure and functioning and is associated with changes in brain mitochondrial DNA copy number and transcription; mitochondria can act as couriers of childhood stress into adulthood.

Susceptibility to COVID‐19 in populations with health disparities: Posited involvement of mitochondrial disorder, socioeconomic stress, and pollutants

“…[ 60,61 ] These adverse childhood conditions can influence health as adults including physiological processes affecting mitochondrial functions. [ 62,63 ] Severe socioeconomic deprivation may lead to adverse childhood experiences and separately or together can adversely affect mitochondrial structure, function, mtDNA copy number, and transcription. [ 63 ]…”

Preventing the development of severe COVID-19 by modifying immunothrombosis

“…Dexamethasone exerts its anti-inflammatory effects by upregulating the activity of glucocorticoid receptors ( GR ) and inhibiting the activity of a number of proinflammatory transcription factors including NF-κB reviewed [ 307 ]. This is an important point as the weight of histopathological evidence suggests that non resolving ARDS is associated with increased activity of nuclear NF-κB and decreased activity of nuclear GRs [ 308 , 309 ].…”

Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

“…These findings illustrate the complexity and interdependence of the factors underpinning experiences during childhood and behaviours during childhood and adolescence and future CVD risk and the need for holistic remedial measures. In addition, there is evidence to suggest that the behaviours and psychological distress associated with socioeconomic deprivation may result from limited life choices and are in many cases not related to personality or any underlying psychological abnormalities [460]. It is however interesting to note that the association between socioeconomic deprivation and CVD may stem from perceived rather than objective socioeconomic status [461].…”