Effects of negative stressors on DNA methylation in the brain: Implications for mood and anxiety disorders

Abstract

Stress is a major contributor to anxiety and mood disorders. The recent discovery of epigenetic changes in the brain resulting from stress has enhanced our understanding of the mechanism by which stress is able to promote these disorders. Although epigenetics encompasses chemical modifications that occur at both DNA and histones, much attention has been focused on stress-induced DNA methylation changes on behavior. Here, we review the effect of stress-induced DNA methylation changes on physiological mechanisms that govern behavior and cognition, dysregulation of which can be harmful to mental health. A literature review was performed in the areas of DNA methylation, stress, and their impact on the brain and psychiatric illness. Key findings center on genes involved in the hypothalamic-pituitary-adrenal axis, neurotransmission and neuroplasticity. Using animal models of different stress paradigms and clinical studies, we detail how DNA methylation changes to these genes can alter physiological mechanisms that influence behavior. Appropriate levels of gene expression in the brain play an important role in mental health. This dynamic control can be disrupted by stress-induced changes to DNA methylation patterns. Advancement in other areas of epigenetics, such as histone modifications and the discovery of the novel DNA epigenetic mark, 5-hydroxymethylcytosine, could provide additional avenues to consider when determining the epigenetic effects of stress on the brain.

Severity of eating disorder symptoms related to oxytocin receptor polymorphisms in anorexia nervosa

“…Examination of the methylation status of risk genes in psychiatric illness may provide an additional indicator of gene expression (Hing et al, 2014). One study has reported that OXTR is more highly methylated in subjects with anorexia than healthy women (Kim et al, 2014b).…”

Repeated forced swim stress has additive effects in anxiety behavior and in cathecolamine levels of adult rats exposed to deltamethrin

“…Stress is a critical environmental trigger for the development of depression, anxiety, cardiovascular diseases, immunity disorders and others (Goodman et al, 2012;Hing et al, 2014;Kario et al, 2003;Meyer and Hamel, 2014;Sterner and Kalynchuk, 2010). Pyrethroid insecticides release noradrenaline and adrenaline (de Boer et al, 1988) and increase anxiety (De Souza Spinosa et al, 1999;Moniz et al, 1994).…”

Stress and depression: old questions, new approaches

“…Increasingly applied to humans, these studies investigate stress-induced DNA methylation (and other) processes in the brain that alter gene expression. These studies focus largely on genes related to HPA axis functions, neurotransmission, and neuroplasticity [54]. Environmentally (stress) induced DNA methylation has been shown to have both shortterm and long-term effects and in some instances intergenerational effects [55 ].…”