A new Dalhousie University research study suggests that a genetic test could be used alongside a person’s family history to identify youth at risk of developing mental illness. 

The study, published Wednesday in the American Journal of Psychiatry, examined whether an individual’s polygenic scores (the total number of genetic variants they have to assess inherited risk of developing a disease) could help identify youth at higher risk. This in turn could help inform early interventions.

“We have known for a long time that illnesses run in families, mental illnesses in particular,” Dalhousie University professor Dr. Rudolf Uher said in an interview.

“For a long time the best way of knowing how high the risk is for a young person was to know the most about their parents and their aunts and uncles, etc.”

Uher was one of the study’s authors and holds the Canada Research Chair in Early Interventions in Psychiatry at Dalhousie University.

“In previous generations when it was common to have 10 children in a family, there was just much more information then there is now when we have one or two.”

In addition, Uher said, children don’t always grow up with their biological family.

A smiling man in a suit and glasses stands in front of a brightly lit university walkway beside a smiling blond women also in glasses and wearing a bright yellow dress.
Dr. Rudolf Uher and Dr. Alyson Zwicker. Credit: Contributed

‘Yes and yes’

The research involved examining blood and saliva samples from 1,884 young people in eight international studies. In total, 1,339 of those youth had parents with mood or psychotic disorders. 

The study found youth with a greater genetic predisposition to neuroticism — a personality trait linked to anxiety and mood problems — were more likely to develop major mental illness by the time they reached adulthood.  

They also discovered youth with a greater genetic predisposition to well-being were less likely to develop major mental illness.

“We asked two questions. One was in cases where we do not know the family history, can the genetic test at least partially replace it,” Uher said. 

‘The second question was, even in cases where we know the family history, can the genetic test add to it to actually improve the prediction? And for neuroticism, it was yes and yes.”

‘This surprised not just me’

Researchers were looking for genetic variants associated with the mood or psychotic disorders they wanted to predict. But Uher said they also looked at general well-being and neuroticism.

“These are the milder end of things, so that may look less medically significant. But surprisingly, it was this polygene for neuroticism that actually contributed the most to predicting severe mental illness,” Uher said. 

“And I think this surprised not just me, but most of my colleagues.”

Uher described the research as a “big advance.” He said while they knew mental illness runs in families partly because of genetics and partly due to environment, finding genetic associations was challenging.

“We were frustrated because every gene we found to be associated was either false, a red herring, or it was very weak. And that’s the nature of it,” Uher said. 

“The genetic associations with mental illness are individually weak. You need to sum up together all these variants, thousands of them, actually, to get a stronger signal. When we pulled these polygenes together, they predicted about two-thirds as well as family history does.”

‘Over and above family history’

Uher said the neuroticism polygenic score played a unique role because of how it predicted “over and above” the family history. This could prove helpful in the future.

“So now if we want to predict who’s likely to become unwell, who’s likely to remain strong or resilient, then we know that by pulling together family history and the polygenic scores, we get the best prediction, the best estimate,” he said.

The study’s results suggest polygenic scores may be used in combination with information like family history to help identify youth who could benefit from early interventions.

‘Prediction for prevention’

“It’s not necessarily a good thing to know that you are at risk unless you know what to do with it. This is not a prediction for prediction, but it’s a prediction for prevention,” Uher said. 

He stressed that the tests must be used as part of a package with early, preventive interventions aimed at protecting mental health and stopping the development of mental illness.

“We know that if we use these interventions in a targeted way, targeted to the young people who actually need them, they are more relevant and more efficient,” Uher said. “That’s the reason we’re doing this.”

He said they’re now developing and testing early interventions and will select the most promising. They intend to use polygenic scores to determine which early interventions work best.

“At this point, we are doing it based on assessments, based on answers to questionnaires and interviews… One person is more likely to share or more likely to complain, whereas another one may hold back much more,” Uher said. 

“So we need objective measures, and I believe the genetic tests will be one of several objective measures that will help us to personalize the early interventions to strengthen mental health.”

He said another benefit of a genetic test is it can be done at any point and remain valid for a person’s entire life.

‘Will have worldwide impact’

The authors of the study state that to the best of their knowledge, this marks the first time an interaction between a family history and a polygenic score “has been reported in a prospective study of risk for mental disorders.” 

The study’s research team was led by Dr. Alyson Zwicker from Dalhousie University’s Medical School and included global contributors.

“We had been working on early detection of risk and early intervention here in Halifax for the past 10 years and so have people in other countries,” Uher said. 

About four years ago Uher realized that if they waited to have enough participants to undertake the research here, they’d be waiting decades. He reached out to 10 groups around the world collecting similar data and eight immediately said yes.

“These people from the UK, Australia, Netherlands, Spain, the US, and Canada have come together to do this. They all share data with us because they all believe this is super important,” he said.

“Each one of these researchers knew they can’t go it on their own because you don’t get conclusive results from your sample of 200 or 300.”

Uher said the research was undertaken in Halifax because funding was provided by Genome Atlantic and the lead author (Zwicker) is a Dalhousie University medical student.

“I think this is also a good example of Genome Atlantic and Dalhousie coming together, enabling something that will have worldwide impact,” Uher said. 

“A third year medical student leading an international effort like this, I think it’s also a great opportunity for her to grow to be a leader.”

Yvette d’Entremont is a bilingual (English/French) journalist and editor who enjoys covering health, science, research, and education.

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  1. I have just finished reading the “Myth of Normal” by Gabor Mate. One of the big takeaways from that book is just how pernicious this focus on genetics can be, especially for people with mental illness or the topic of mental illness in general. In his book, he makes a very convincing case that genetics is a non-factor in predicting mental illness when compared with trauma, the social environment a child grows up in and government policies. Poverty is a much better predictor of mental illness than genetics. The pernicious part of this type of focus on the sexy science of genetics is that it individualises the problem, which is awesome for those making policies that maintain the status quo. We don’t really need to ensure that children grow up in homes where parents are stressed about paying rent or affording food, we don’t need to ensure that child welfare systems don’t remove black and indigenous children from their homes at disproportionately higher rates than for white children instead of supporting those families (and all families) to be able to survive with dignity. We don’t need to do any of these because these children are “genetically predisposed” to these illnesses and “you can’t change genetics.” Instead what we’ll do is come up with interventions aimed at individual children (provided no doubt by private for profit practitioners) and these will in no way address any of the underlying and real issue affecting children and their mental health outcomes. This stuff is infuriating and just because it’s papered over with the veneer of scientific inquiry doesn’t make the ideology of individual blame any less obvious.