Experiencing trauma or having certain genetic variants can both put you at risk of depression. But nature and nurture can also interact: traumatic events appear to amplify the effect of genetic risk factors, according to research involving 73,000 people.
People who have depression tend to have a similar level of genetic risk for the condition, regardless of their environment or experiences. But traumatic experiences appear to somehow amplify the impact of these genes, says Gerome Breen at King’s College London, who led the study.
Historically, people have debated whether depression results from genetic factors or experiences. More recently, we have come to understand that both nature and nurture contribute to the condition. “What we didn’t really know was how much genes and environment interacted,” says Breen.
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His team’s findings suggest that genes and environment “interact greater than the sum of their parts”, says Breen. “They seem to have an interaction that is multiplicative between them.”
These results change the way we understand depression, says Heather Whalley at the University of Edinburgh. “We are starting to understand that there might be different paths to depression that might respond to different interventions and treatments,” she says.
Breen and his colleagues analysed data from just over 73,000 people in the UK that have had their genomes sequenced and who have responded to detailed questionnaires about their mental health and exposure to traumatic events and experiences. These included sexual or physical violence, being in an accident and interpersonal traumas, such as feeling unloved as a child.
The researchers used the survey responses to categorise volunteers in terms of whether they had depression or not, and whether they had experienced trauma or not. Separately, they worked out the volunteers’ genetic risk of developing depression using a previously published polygenic risk score – a measure that summarises the predicted total impact of all a person’s genetic variants linked to depression.
The group then studied the relationships between these three factors. “We find that the genetics and environment interact together to increase the risk of depression,” says Breen. People who experience trauma are more likely to develop depression if they are genetically predisposed to the condition.
More surprising is the finding that trauma appears to amplify the effect of these genetic variants. In people who have experienced trauma, depression-linked genetic variants seem more likely to lead to depression, above and beyond what you would expect from simply taking these variants and their life experiences into account. “The genetic variants aren’t different, but the genetic contribution is somehow higher,” says Whalley.
The finding supports the idea that “the environment is activating the genetic effect, as it were”, says Breen. Stress can trigger the release of hormones that influence whether genes are switched on or off, for example. “The genetic variants that someone has affects the extent to which that gene expression is activated in a bad way or a good way,” says Breen.
The findings might help shape future depression treatments. The genetic variants that are most affected by trauma might also be influenced by positive environmental factors, like cognitive behavioural therapy, says Breen. “Maybe the same sort of analysis could identify polygenic risk scores to predict people that might respond better to psychological therapies,” he says.
