AUTHOR=Fiacco Serena , Gardini Elena Silvia , Mernone Laura , Schick Lea , Ehlert Ulrike 

TITLE=DNA Methylation in Healthy Older Adults With a History of Childhood Adversity—Findings From the Women 40+ Healthy Aging Study

JOURNAL=Frontiers in Psychiatry

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00777

DOI=10.3389/fpsyt.2019.00777

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> Adversity in early development seems to increase the risk of stress-related somatic disorders later in life. Physiologically, functioning of the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes is often discussed as long-term mediators of risk. In particular, DNA methylation in the glucocorticoid receptor gene promoter (<italic>NR3C1</italic>) has been associated with type and strength of early life adversity and subsequent effects on HPA axis signaling in humans. Animal studies, moreover, suggest changes in DNA methylation in the estrogen receptor gene (<italic>ER</italic>α) upon early life adversity. We investigated the association of type and severity of childhood adversity with methylation in <italic>NR3C1</italic> and <italic>ER</italic>α and additionally considered associations between methylation and steroid hormone secretion.</p><p><bold>Methods:</bold> The percentage of methylation within the <italic>NR3C1</italic> promoter and the <italic>ER</italic>α shore was investigated using dried blood spot samples of 103 healthy women aged 40–73 years. Childhood adversity was examined with the Childhood Trauma Questionnaire. Linear regression analyses were performed with methylation as dependent variable and the experience of emotional abuse and neglect, physical abuse and neglect, and sexual abuse (compared to non-experience) as independent variables. All analyses were controlled for age, BMI, annual household income, and smoking status and were adjusted for multiple testing.</p><p><bold>Results:</bold> Overall, over 70% of the sample reported having experienced any kind of abuse or neglect of at least low intensity. There were no significant associations between childhood adversity and methylation in the <italic>NR3C1</italic> promoter (all <italic>p</italic> &gt; .10). Participants reporting emotional abuse showed significantly higher methylation in the <italic>ER</italic>α shore than those who did not (<italic>p</italic> = .001). Additionally, higher levels of adversity were associated with higher levels of <italic>ER</italic>α shore methylation (<italic>p</italic> = .001).</p><p><bold>Conclusion:</bold> In healthy women, early life adversity does not seem to result in NR3C1 promoter hypermethylation in midlife and older age. This is the first study in humans to suggest that childhood adversity might, however, epigenetically modify the ERα shore. Further studies are needed to gain a better understanding of why some individuals remain healthy and others develop psychopathologies in the face of childhood adversity.</p>