DNA methylation mediates the link between childhood adversity and depression, study suggests microbiologystudy

Past psychology research suggests that there is a strong relationship between difficult experiences during childhood and the development of depressive symptoms. In fact, statistics suggest that adverse experiences during childhood can double the risk of being diagnosed with depression later in life.

Researchers at Massachusetts General Hospital, Harvard Medical School and other institutes, led by the Head of the Dunn Lab Erin C. Dunn, recently carried out a study exploring how DNA methylation, an epigenetic modification that entails the addition of a methyl group to the DNA, contributes to the well-documented relationship between childhood adversity and depression.

Their findings, published in Nature Mental Health, suggest that DNA methylation mediates the relationship between adversity and depressive symptoms.

“Exposure to childhood adversity, such as abuse and financial hardship, can more than double the risk of developing depression later in life,” Alexandre A. Lussier, first author of the paper and Head of the Lussier Lab at Massachusetts General Hospital, told Medical Xpress.

“Although this connection might seem obvious, the biological mechanisms that translate early-life adversity into mental health challenges have been difficult to unravel. One potential explanation lies in epigenetics —the study of how environmental factors can influence gene activity without altering the DNA sequence.”

Recent research gathered evidence suggesting that DNA methylation can serve as a “dimmer switch” that turns gene expression up or down. Yet most past studies have focused on its contribution to some types of cancer, neurological disorders and overall mental health, thus its contribution to the link between childhood adversity and depression was rarely explored.

“Our study set out to fill this gap in the literature, by examining whether changes in DNA methylation could serve as the biological pathway linking early-life adversity to depressive symptoms during adolescence,” said Lussier. “By doing so, we aimed to shed light on the mechanisms underlying mental health vulnerability and resilience.”

To explore the contribution of DNA methylation to the link between adversity and depression, Lussier and his colleagues analyzed data collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC is an ongoing, large-scale research effort that has collected data from several children across the U.K. from birth to the age of 11, tracking multiple measures of adversity and depressive symptoms.

“We used a method called longitudinal mediation modeling to examine how genome-wide DNA methylation changes might act as a bridge between early-life adversity and later depressive symptoms,” explained Lussier. “This approach allowed us to trace how adversity could lead to biological changes, which then explain mental health outcomes in early adolescence.”

To unveil the connections between adversity and biological changes associated with mental health challenges, the researchers used a statistical method known as structural equation modeling. This approach allowed them to assess the interaction between different factors, such as adversity, DNA methylation and depression over time.

“Using this method, we identified groups of DNA methylation sites (known as loci) that mediate, or partially explain, the connection between early adversity and depressive symptoms in adolescence,” said Lussier. “These findings offer a clearer and more detailed understanding of the biological mechanisms influencing mental health.”

The analyses carried out by the researchers yielded interesting findings, with changes in blood DNA methylation explaining up to 73% of the relationship between childhood adversity and depressive symptoms experienced by the children in the analyzed data sample at the age of 11. Overall, the team’s findings thus suggest that DNA methylation is a crucial mechanism mediating the influence of early life experiences on mental health outcomes in early adolescence.

“What stands out even more is that over half of the DNA sites we identified had protective effects, meaning they were associated with reduced depressive symptoms,” said Lussier. “This result challenges the traditional view that biological changes stemming from adversity are purely harmful. Instead, our findings suggest DNA methylation may also serve as a mechanism of resilience, helping some individuals better cope with adversity.”

This recent study gathered new valuable insight that improves the present understanding of resilience and the effects of childhood adversity at a biological level. In the future, it could inspire new studies focusing on the contribution of DNA methylation to the development of mental health disorders, while also potentially informing interventions aimed at mitigating adverse effects of challenging childhood experiences.

“Our next steps focus on investigating whether these indicators of biological risk and resilience could be used to predict individuals who may be more vulnerable to developing mental illness,” added Lussier.

“This line of research could pave the way for early interventions tailored to those most at risk. We are also exploring how DNA methylation might change in response to positive life experiences, such as supportive relationships or therapeutic interventions, and whether these changes could enhance resilience.”

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