Epigenetic Mechanism of Early Life Stress-Induced Depression: Focus on the Neurotransmitter Systems

Abstract

Depression has an alarmingly high prevalence worldwide. A growing body of evidence indicates that environmental factors significantly affect the neural development and function of the central nervous system and then induce psychiatric disorders. Early life stress (ELS) affects brain development and has been identified as a major cause of depression. It could promote susceptibility to stress in adulthood. Recent studies have found that ELS induces epigenetic changes that subsequently affect transcriptional rates of differentially expressed genes. The epigenetic modifications involved in ELS include histone modifications, DNA methylation, and non-coding RNA. Understanding of these genetic modifications may identify mechanisms that may lead to new interventions for the treatment of depression. Many reports indicate that different types of ELS induce epigenetic modifications of genes involved in the neurotransmitter systems, such as the dopaminergic system, the serotonergic system, the gamma-aminobutyric acid (GABA)-ergic system, and the glutamatergic system, which further regulate gene expression and ultimately induce depression-like behaviors. In this article, we review the effects of epigenetic modifications on the neurotransmitter systems in depression-like outcomes produced by different types of ELS in recent years, aiming to provide new therapeutic targets for patients who suffer from depression.

Obtaining novel data-driven hypotheses from teaching activities: an example assessing the role of the FKBP5 gene in major depression

“…Early life stress (ELS) plays a causal role in many psychiatric disorders, including major depressive disorder (MDD; Cheng et al, 2022). ELS is relevant to one of the most robust hypotheses of MDD mechanism: impairment of the hypothalamus-pituitary-adrenal (HPA) axis.…”

Remembering through the genome: the role of chromatin states in brain functions and diseases

“…Early life conditions such as stress before or after birth can have effects on physiology, behavior and cognition that can last until adulthood [78]. These effects have been associated with transcriptional and epigenetic changes in components of the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter signaling and neuroimmune pathways in neuronal and glial cells in the brain [79][80][81][82][83]. For instance, chronic stress between postnatal day (PND) 10 and 17 in mice globally alters the level of H3K79me1/2 in nucleus accumbens (NAc) in the adult brain, a region involved in motivation and reward [12].…”

Epigenetic processes associated with neonatal spinal transection

“…To date, most of the literature on adult spinal cord plasticity has focused on injury outcomes (Wang, Li, et al., 2016;), pain (Jiang et al., 2017; Zhao et al., 2017), or disease (Martin & Wong, 2013; Miranpuri et al., 2017), with limited data providing a developmental profile of epigenetic mechanisms associated with neurobehavioral plasticity in the spinal cord. Understanding these mechanisms may shed insight on why the spinal cord is most responsive to environmental input during early development, as epigenomics is a known moderator of environmental input and future behavioral states, including increased disease states (e.g., Cheng et al., 2022; McGowan et al., 2009; Roth et al., 2009; Szyf, 2009; Weaver et al., 2004).…”