Genetic tests could create better depression treatment  

Published:

1 December 2024

World’s largest DNA analysis of people with depression reveals hundreds of inherited genetic differences, which could eventually help to match people with an antidepressant that works for them.  

DNA analysis of more than 5 million people, including 370,000 UK Biobank participants, has revealed almost 700 genetic differences in people with depression. It’s the largest ever study to understand the genetic underpinning of major depression, which affects around 300 million people worldwide. 

The genetics of depression have been difficult to unpick. “There are probably hundreds or 1000s of different genetic contributors,” explains the study’s co-leader Cathryn Lewis from King’s College London, UK. “None individually are causal, but cumulatively, they can put someone at increased risk of depression.” 

Largest study of depression genetics

There are probably hundreds or 1000s of different genetic contributors … cumulatively, they can put someone at increased risk of depression.” 

Professor Cathryn Lewis, King’s College London, UK

Lewis, her University of Edinburgh colleague Andrew McIntosh and a team of more than 300 researchers looked at genetic data of almost 700,000 people with depression and more than 4.3 million without depression from 29 countries. About a quarter of the people were from non-European backgrounds, making this the largest genetic study of depression in people from all ancestries as well as the largest study on the topic overall. One hundred of the genetic differences the team identified were thanks to the inclusion of people from diverse ancestries. 

Some of the genetic differences seem to affect the amygdala, a part of the brain that plays a key role in processing emotions including our ‘fight or flight’ response, and the hippocampus, an area of the brain responsible for memory and learning. 

The team now wants to uncover how people’s genetic background influences what type of antidepressant works for them. “Currently it’s done by trial and error,” Lewis says. “People are prescribed one particular antidepressant, and after a few weeks, if that doesn’t work, they might move to another one. It can take quite a long time to get the right drug.” 

“How did this work for you?”

Lewis and her colleagues looked at GP records of 230,000 UK Biobank participants as well as more than 170,000 participants’ replies to a detailed UK Biobank online mental health questionnaire. In the questionnaire, three quarters of people with depression said that medication helped their symptoms. This shows that it’s “really important to ask people with depression ‘How did this work for you?’ and not just rely on clinical sources”, Lewis says. Clinical studies tend to only note if a drug eliminates symptoms entirely and nuanced effects of medication can be missed. 

Currently it’s done by trial and error. People are prescribed one particular antidepressant, and after a few weeks, if that doesn’t work, they might move to another one. It can take quite a long time to get the right drug. 

Professor Cathryn Lewis, King’s College London, UK

While there seems to be a definite genetic component to the way different people respond to different antidepressants, “it is very much research in progress”, Lewis points out. “We need to do much larger studies across bigger data sets.” 

No more trial and error

Eventually, genetic testing could help doctors to match their patients with the right antidepressant. “In my dream world, our genetic information would be part of our clinical record,” Lewis says. “It would be stored for everyone and could be interrogated when it was needed.” 

Her hope is that genetic testing could increase the number of people who respond to an antidepressant. Given how common depression is and how widely antidepressants are prescribed, this would mean “a lot of people getting better more quickly”, she says.