Abstract
Stress early in life is a known risk factor for the development of affective disorders later in life. Epigenetic mechanisms, such as DNA methylation, may have an important role in mediating that risk. Recent epigenetic research reported on the long-term relationship between traumatic stress in childhood and DNA methylation in adulthood. In this study, we examined the impact of various types of stress (perinatal stress, stressful life events (SLEs) and traumatic youth experiences) on methylation of the glucocorticoid receptor gene (NR3C1) in the blood of a population sample of 468 adolescents (50.4% female, mean age 16.1 years). Second, we determined whether stress at different ages was associated with higher NR3C1 methylation. NR3C1 methylation rates were higher after exposure to SLEs and after exposure to traumatic youth experiences. NR3C1 methylation in adolescence was not higher after exposure to perinatal stress. Experience of SLEs in adolescence was associated with a higher NR3C1 methylation, independently of childhood SLEs. We demonstrate that not only traumatic youth experiences but also (more common) SLEs are associated with higher NR3C1 methylation. In addition, our findings underline the relevance of adolescent stress for epigenetic changes in the NR3C1 gene.
Highlights
Severe maltreatment or neglect in childhood are known risk factors for development of affective disorders and have been associated with altered programming of the hypothalamicpituitary-adrenal (HPA) axis.[1,2,3,4] Epigenetic modifications are thought to link early-life stress to later susceptibility to affective disorders, such as anxiety or depression, through interference with the development and functioning of the HPA axis early in life.[5]
For amplicon 3, repeated exposure to other traumatic youth experiences was associated with lower methylation rates (B = − 0.26, P o 0.01)
Experience of multiple SLEs and exposure to traumatic experiences between birth and adolescence were associated with higher NR3C1 methylation rates in adolescents
Summary
Severe maltreatment or neglect in childhood are known risk factors for development of affective disorders and have been associated with altered programming of the hypothalamicpituitary-adrenal (HPA) axis.[1,2,3,4] Epigenetic modifications are thought to link early-life stress to later susceptibility to affective disorders, such as anxiety or depression, through interference with the development and functioning of the HPA axis early in life.[5] More recently, the notion that stress can have a direct effect on epigenetic modifications across the life span has been proposed, which in turn affects brain plasticity and may lead to anxiety.[6] The epigenetic process of DNA methylation involves the addition of methyl groups on cytosine–guanine dinucleotides (CpGs) in gene promoters and regulatory regions, which regulate gene transcription.[7] The presence of these methyl groups is associated with reduced gene expression by reducing access to the DNA. Methylated regions can repress transcription indirectly by attracting methylated DNAbinding proteins, which can alter the chromatin formation, disabling access to DNA for transcription.[8,9,10,11,12] Whereas much research focuses on the function of epigenetic modifications, less is known about how they are environmentally induced
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