Adversity Before Age Three Has Greatest Effect on Psychiatric Risk
Key findings
- Researchers have identified 38 DNA sites that were differently methylated in 7-year-olds who had been exposed to poverty, abuse or other forms of adversity, compared with unexposed controls
- Twenty-two of the sites were related to adversity that occurred in very early childhood, before three years of age
- Exposure in very early childhood was associated with DNA methylation differences for nearly all adversity types
- Neither accumulation nor recency of adversity explained the considerable variability in DNA methylation
- The findings suggest that adversity during very early childhood might be especially likely to become wired into neural circuitry
It's well established that exposure to childhood adversity, such as poverty and abuse, at least doubles the risk of childhood- and adult-onset psychiatric disorders. Evidence has been increasing of late that childhood adversity actually becomes molecularly programmed into the cells in the body.
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Specifically, early adversity has been linked to DNA methylation (DNAm), in which chemical tags get added to the DNA in specific places. These tags are thought to play a key role in determining if genes are turned on or off.
In the case of childhood adversity, these biological memories are thought to persistently alter genome function, which could be the mechanism of increased susceptibility to psychiatric disorders.
Erin C. Dunn, ScD, MPH, a researcher in the Psychiatric and Neurodevelopmental Genetics Unit at Massachusetts General Hospital, and colleagues expanded this knowledge with a recent report in Biological Psychiatry. The team showed that DNAm differenes are more common if exposure to adversity occurs before age three.
Three Age Groups, Seven Types of Adversity
The researchers analyzed data from the prospective Avon Longitudinal Study of Parents and Children. As part of that study, 1,018 mothers selected at random agreed to have their child provide cord blood samples at birth and another blood sample at age seven.
On at least four occasions between their child's birth and seventh birthday, mothers were asked to report whether the child had been exposed to any of seven adverse or potentially adverse experiences:
- Caregiver physical or emotional abuse
- Sexual or physical abuse (by anyone)
- Maternal psychopathology
- Having only one adult in the household
- Family instability
- Financial stress and/or poverty
- Neighborhood disadvantage and/or poverty
All told, 67% of the children had experienced at least one type of adversity at some point during very early childhood (before three years of age), early childhood (three to five years of age) or middle childhood (six to seven years of age).
DNAm and Exposure to Adversity
Using the blood samples, the researchers measured DNAm at 485,000 sites across the genome where a cytosine nucleotide is followed by a guanine nucleotide (CG sites). They identified 38 CG sites that were hypermethylated or hypomethylated in seven-year-olds who had been exposed to adversity, compared with children not exposed to adversity.
Many of the differentially methylated sites are involved in the regulation of central nervous system growth, axon development and neuron apoptosis.
DNAm and Timing/Type of Adversity
At 35 of the CG sites, differential methylation was related to the timing of exposure to adversity, usually adversity during very early childhood (22 sites).
Neighborhood disadvantage was the type of adversity that predicted the greatest number of differential methylation sites (10 sites). That was followed by financial stress (nine sites), sexual or physical abuse (five sites) and having only one adult in the household (five sites). Exposure in very early childhood was associated with DNAm differences for nearly all types of adversity studied.
Competing Theories
The researchers concluded that there is a sensitive period for the effect of childhood adversity on DNA methylation. They compared this idea to two possibilities that have been advanced by other groups:
- The accumulation theory: holds that the effect of adversity on DNAm increases with the number of occasions exposed, regardless of timing
- The recency theory: holds that the effect of adversity on DNAm is stronger for more recent events
Neither accumulation nor recency of adversity explained the considerable variability in DNAm, the researchers determined.
They note that when adversity occurs in very early childhood, it coincides with the foundational development of brain architecture. During this vulnerable life stage, experiences of childhood adversity might be especially likely to become wired into neural circuitry.
A related fact, the authors add, is that DNAm changes can persist—or weaken—within an individual across the life span. They speculate that very early exposure to adversity might produce particularly stable DNAm patterns that are more likely to persist—and might even be used someday as predictive markers of eventual psychopathology.
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