Dissecting early life stress-induced adolescent depression through epigenomic approach

Abstract

Early life stress (ELS), such as abuse and neglect during childhood, can lead to psychiatric disorders in later life. Previous studies have suggested that ELS can cause profound changes in gene expression through epigenetic mechanisms, which can lead to psychiatric disorders in adulthood; however, studies on epigenetic modifications associated with ELS and psychiatric disorders in adolescents are limited. Moreover, how these epigenetic modifications can lead to psychiatric disorders in adolescents is not fully understood. Commonly, DNA methylation, histone modification, and the regulation of noncoding RNAs have been attributed to the reprogramming of epigenetic profiling associated with ELS. Although only a few studies have attempted to examine epigenetic modifications in adolescents with ELS, existing evidence suggests that there are commonalities and differences in epigenetic profiling between adolescents and adults. In addition, epigenetic modifications are sex-dependent and are influenced by the type of ELS. In this review, we have critically evaluated the current evidence on epigenetic modifications in adolescents with ELS, particularly DNA methylation and the expression of microRNAs in both preclinical models and humans. We have also clarified the impact of ELS on psychiatric disorders in adolescents to predict the development of neuropsychiatric disorders and to prevent and recover these disorders through personalized medicine.

Genome–Environment Interactions and Psychiatric Disorders

“…It has been demonstrated that miRNAs form highly correlated networks in the brains of patients with MDD that differ from healthy controls, indicating that miRNA networks can cause specific behavioral phenotypes. In rats it has been demonstrated that rats which show learned helplessness, a clinical phenotype indicative of suicide risk, have a diminished miRNA response in the frontal cortex to acute stress compared to controls, indicating that anomalous expression of miRNAs results in defects in the stress coping response [ 52 ].…”

The role of ncRNAs in depression

“…Specifically, they serve as biomarkers for diagnosing depression and anxiety and tracking therapeutic responses to these conditions [ 10 ]. A lot of recent research has proved the relationship between ncRNAs and depression [ 11 , 12 ]. For instance, siRNA can be an effective experimental tool to study depression [ 13 ].…”

Differential Chromatin Architecture and Risk Variants in Deep Layer Excitatory Neurons and Grey Matter Microglia Contribute to Major Depressive Disorder

“…Genome-wide associations studies (GWAS) have identified over 200 MDD risk loci 11–13 ; however, similarly to other psychiatric phenotypes, characterizing the functional impact of such variants has remained challenging as they mostly map outside protein-coding regions. In addition to genetic variation, the adverse effects of environmental factors, such as early-life stress, on increasing the risk for depression 14,15 , are mediated by regulatory changes 16 . Single-cell atlases of open chromatin cis-regulatory elements (cCREs) holds promise to uncover mechanisms whereby disease-associated risk-variants may impact cell-specific gene-regulatory targets 17,18 .…”