Epigenetic processes in depressive and anxiety disorders

Depressive and anxiety disorders are the most common mental health problems, affecting millions of people worldwide, often leading to negative outcomes in all aspects of life, including work, family, and participation in community activities. These mental health problems exhibit considerable sex- and gender-based variations, with both depressive and anxiety disorders affecting women approximately twice as often as men. The complex etiology of depressive and anxiety disorders highlights the importance of genetic susceptibility and increased sensitivity to early social environment and to later-life stressful events. This chapter focuses on epigenetic mechanisms of mood and anxiety disorders. We review the literature on how DNA methylation and histone modifications may translate environmental effects at the molecular level, with potentially long-lasting effects on gene expression. Studies have shown that depressive and anxiety disorders are associated with alterations in DNA methylation of hypothesis-driven candidate gene regions, such as the glucocorticoid receptor promoter. Effects, however, are small, especially when assessed in peripheral samples, such as blood or saliva. Similarly, epigenome-wide association studies using blood samples revealed small-to-modest alterations (1%-9% differences in DNA methylation levels) in a subset of genes in individuals with depressive or anxiety symptoms. In addition, studies combining analyses of blood and brain samples pointed to the involvement of neuronal differentiation, axon guidance, and inhibitory neurotransmitter systems. By the end of the chapter, epigenetic aspects of pharmacologic and behavioral therapies for depressive and anxiety disorders are discussed.