Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression

Abstract

The genome (genes), epigenome, and environment work together from the earliest stages of human life to produce a phenotype of human health or disease. Epigenetic modifications, including among other things: DNA methylation, modifications of histones and chromatin structure, as well as functions of noncoding RNA, are coresponsible for specific patterns of gene expression. This refers also to mental disorders, including depressive disorders. Early childhood experiences accompanied by severe stressors (considered a risk factor for depression in adult life) are linked with changes in gene expression. They include genes involved in a response to stress (hypothalamic-pituitary-adrenal axis, HPA), associated with autonomic nervous system hyperactivity and with cortical, and subcortical processes of neuroplasticity and neurodegeneration. These are, among others: gene encoding glucocorticoid receptor, FK506 binding protein 5 gene (FKBP5), gene encoding arginine vasopressin and oestrogen receptor alpha, 5-hydroxy-tryptamine transporter gene (SLC6A4), and gene encoding brain-derived neurotrophic factor. How about personality? Can the experiences unique to every human being, the history of his or her development and gene-environment interactions, through epigenetic mechanisms, shape the features of our personality? Can we pass on these features to future generations? Hence, is the risk of depression inherent in our biological nature? Can we change our destiny?

Figure 1

Health and disease (depression)—determinants.

Figure 2

Intergenerational factors affecting the development of depression. HPA: hypothalamic–pituitary–adrenal axis.