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 ].…”

Strong associations of telomere length and mitochondrial copy number with suicidality and abuse history in adolescent depressed individuals

“…Major depressive disorder (MDD) is the most common psychiatric disorder in adolescents and is significantly associated with increased morbidity [ 1 – 3 ]. In the United States, MDD is also significantly associated with increased mortality [ 4 ], and is the most significant biological and psychological risk factor for suicide in adolescents [ 3 , 5 – 7 ]. In 2017 the suicide rate in the United States was 11.8 per 100,000 in adolescents and had increased by 57% between 2007 to 2018 [ 8 , 9 ].…”