Children under three most vulnerable to effects of adversity, with lifelong consequences

A study by the Massachusetts General Hospital (MGH) has found evidence that children under three year of age are the most vulnerable to the effects of adversity – experiences including poverty, family and financial instability, and abuse – based on their epigenetic profiles, also known as chemical tags that alter gene expression and may have consequences for future mental health.

The report, which is to be shared in the 15 May issue of Biological Psychiatry finds that the timing of adverse experiences has more powerful effects than the number of experiences, or whether they took place recently.

Erin Dunn, one of the researchers involved in producing the report, said that the research sought to answer “one of the major unanswered questions in child psychiatry”, namely ‘how do the stressors children experience in the world make them more vulnerable to mental health problems in the future?’

The findings of the report suggest that the first three years of life may be an especially important period for shaping biological processes that ultimately give rise to mental health conditions. “If these results are replicated,” Ms Dunn said, “they imply that prioritising policies and interventions to children who experience adversity during those years may help reduce the long-term risk for problems like depression.”

Previous studies in this domain, conducted on both humans and animals, have found that adverse experiences – such as poverty, food insecurity, family instability and the like – early in life can have lasting effects on epigenetics.

Epigenetics is the process by which chemical ‘tags’ are added to a DNA sequence. Genes can be affected by positive experiences – such as supportive relationships and opportunities for learning – or negative experiences – such as environmental toxins, stressful life circumstances or high levels of stress.

The results of these tags being added – and how many tags, to which genes, and when – creates a unique gene signature. Signatures can be temporary or permanent, and both types affect how easily the genes are switched on or off.

The current study was created to test the idea that there are sensitive periods during which adversity is associated with even greater changes in DNA and ‘tag’ creation. The researchers also compared the ‘sensitive periods’ idea with a previously held assumption, which said that the effects of adversity increase with the number of events, and the idea that effects of adversity are stronger when the adverse event was more recent.

Data was gathered from participants in the Avon Longitudinal Study of Parents and Children, a UK-based study that has been following a group of families since the early 1990s. Participating parents report regularly on many aspects of the health and life experiences of their children, who were enrolled in the study before they were born.

The current investigation analysed data from a subgroup of more than 1,000 randomly selected mother/child pairs from which DNA profiles had been run for the children at birth and at age seven.

The children’s exposure to adversity before the age of seven was based on whether parents reported their child’s repeated experience of seven stressors:

• Abuse by a parent or other caregiver
• Abuse by anyone
• A mother’s mental illness
• Living in a single-adult household
• Family instability
• Family financial stress
• Neighbourhood disadvantage or poverty.

The investigators recorded the number of exposures to each adversity, whether or not they were experienced at specific developmental stages and how close they occurred to the age at which blood samples were taken for the second methylation profile.

In the analysis, researchers identified 38 occasions where adverse experiences were associated with changes in DNA, most of which were associated with the stressful experience that had taken place.

Adversity before the age of three had a significantly greater impact on DNA than did adversity at ages three to five or five to seven. Exposure to adversity was typically associated with an increase in the number of ‘tags’ being added, which would reduce the expression of specific genes.

Neighbourhood disadvantage appeared to have the greatest impact, followed by family financial stress, sexual or physical abuse, and single-adult households.

Although early-childhood experiences had the greatest effects, adversity at older ages was not without an impact. And while the results provide the strongest evidence for the sensitive or ‘vulnerable’ period model, they do not totally rule out any effect related to the accumulation or recency hypotheses.

“These additive effects may work together with the timing of exposure, so it would be interesting to examine more complex mechanisms in future studies with larger groups of participants,” Ms Dunn said, adding that the results need to be replicated by other investigators.

There was also a need for future research to determine whether these changes in DNA are associated with subsequent mental health problems. Only then, researchers said, will they be able to really understand the links between childhood adversity, DNA and the risk of mental health problems; an understanding that could guide them to better ways of preventing those problems from developing.

The study Do Sensitive Periods Exist for Exposure to Adversity? has been published online, and will be available in the print edition of Biological Psychiatry on 15 May 2019.