Epigenetic alterations related to early-life stressful events

Abstract

LM. Epigenetic alterations related to early-life stressful events.Objective: Early stress events severely impact brain and behaviour. From a neurobiological point of view early stress influences neuroanatomical structures and is associated with a dysregulation of the hypothalamic-pituitary-adrenal axis. The objective of this article is to review the epigenetic alterations implicated in brain adaptation to early stress events. Method: A review of empirical research of epigenetic alterations associated to early stress events was performed. Results: Neuroanatomic and epigenetic alterations have been observed after early stress events. Epigenetics alterations include DNA methylation, histones modifications and microRNA (miRNA) expression. The most studied is largely the former, affecting genes involved in neuroendocrine, neurotransmission and neuroplasticity regulation after early stress exposition. It includes glucocorticoid receptor, FK506-binding protein 5, arginine vasopressin, oestrogen receptor alpha, 5-hydroxy-tryptamine transporter and brain-derived neurotrophic factor. Conclusion: Epigenetic regulation is critical in the interplay between nature and nurture. Alterations in the DNA methylation as well as histones modifications and miRNA expression patterns could explain abnormal behaviours secondary to early stress events. Summations• The exposure to stressful situations early in life is associated with an increased susceptibility to develop both physical and mental illnesses. • Early stress has been consistently related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. • Epigenetic alterations after early stress exposition include DNA methylation, histone modifications and miRNA expression changes. • Alterations in methylation and expression levels of genes involved in the neuroendocrine system, serotonergic neurotransmission and neuroplasticity have been found secondary to early stress exposure. Considerations• To date, few studies relating epigenetic alterations after early stress exposition have been carried out in humans. Results from animal studies cannot be extrapolated to humans. • It is possible that a larger number of genes modulates behaviour through epigenetic mechanisms.

Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study

“…CRHR1 has been related to BDNF expression in the hippocampus. In animal models, the increase in corticoids induced by stress leads to reduction of the apical dendrites of pyramidal neurons of the CA3 region of the hippocampus, an effect related to reduction of BDNF expression (reviewed by Ventura-Juncá [65]). Interestingly, the hippocampal volume reduction could be reversed by antidepressants [66].…”

“…Also, there might be ethnic differences in allele frequencies and/or different linkage groups with other functional polymorphisms in the Chilean population compared to those included in the publications reporting association. In turn, the treatment response might be also influenced by other factors such as epigenetic alterations in genes important to HPA functioning [65,67]. Additionally, the disorder evaluated in this study is moderate to severe depression.…”

Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression

“…The fact that such behaviours occur in the adopted (and not only biological) offspring indicates a significant share of environmental factors in the acquisition of these behaviours [58]. In studies based on animal models, it is pointed out that the abovementioned behaviours are associated with changes in the methylation of genes encoding the glucocorticoid receptor observed in the hippocampal region of the examined animals [20].…”

“…Early childhood experiences associated with severe stressors (considered a risk factor for depression in adult life) are linked with modifications in gene expression [14,15]. Changes in the scope of gene expression affect genes involved in response to stress (hypothalamic-pituitaryadrenal axis, HPA), related to autonomic nervous system hyperactivity and cortical and subcortical processes of neuroplasticity and neurodegeneration [3], including among other genes encoding the glucocorticoid receptor, FK506binding protein 5 (FKBP5) [16], arginine vasopressin and oestrogen receptor alpha, 5-hydroxytryptamine transporter gene (SLC6A4) [17], and brain-derived neurotrophic factors [18][19][20].…”

Xenomelia: A Social Neuroscience View of Altered Bodily Self-Consciousness

“…While interest in brain plasticity was originally triggered from observing behavioral consequences of cortical reorganization after deafferentation, the focus has now shifted toward “experience-dependent neuroplasticity.” Such plasticity extends far beyond the juvenile period (Lillard and Erisir, 2011), and comprises sensorimotor training (Bezzola et al, 2012) and musical experience (Parbery-Clark et al, 2012) in the aging. Together with evidence for epigenetic alterations in both mind and neural matter (Ventura-Junca and Herrera, 2012), and yet other socio-cultural factors (see below), such communication between nature and nurture should not be hastily interpreted as a primacy of either brain or mind. Thus, the correlation between structural cortex alterations and the strength of an individual’s amputation desire (Hilti et al, 2013) could indicate that xenomelia is the consequence of early, perhaps even prenatal neural development (Hilti and Brugger, 2010).…”