Research in focus: ‘Our Future Health is a goldmine for studies on depression’

Spotlight – 28 January 2025
There’s a lot we need to discover about the genetics of depression, says Professor Cathryn Lewis, and Our Future Health is the programme that can lead to those crucial breakthroughs
Cathryn Lewis, Professor of Genetic Epidemiology & Statistics at King’s College London

“Depression is currently one of the biggest problems in society, particularly for young people,” says Professor Cathryn Lewis, Professor of Genetic Epidemiology & Statistics at King’s College London. “The economic and personal burden of mental health disorders is massive. My team aims to use genetics to understand why depression happens – and how we can treat it effectively.”

Cathryn is a statistician by training and now leads a team researching the role of genetics in mental health disorders, with a focus on depression. The team has applied to study our volunteers’ data, to find out more about how the disease begins and progresses. Cathryn also recently became a Research Ambassador for Our Future Health, which means she’s using her research expertise to help us shape our programme.

Learning more about the causes of – and treatment for – depression is important work. “Everyone has low mood at some point in their life, and for about one in six people, that is severe enough to be clinically diagnosed as depression.“ says Cathryn.

“Our research looks at how genetics affects our risk of developing depression – and how it may control our response to treatment.

“Our Future Health is exciting because the programme is expanding the amount of data available for studies into depression. It’s a uniquely powerful resource that will enable us to get a better handle on the genetic component of depression.”

How genetics affects depression

“Mental health disorders are complex. Over the last 10 years, we’ve started to identify some of the genetic determinants of depression. We know it’s not a single gene disorder but a polygenic one. That means there are hundreds, probably thousands, of inherited genetic variants across the genome that can increase or decrease people’s risk.

“We’ll be using Our Future Health data for two different studies,” Cathryn says. “The first is to expand on previous studies identifying the genetic aspect of depression. We can look at volunteers’ questionnaire answers and identify two groups of people – those who say they’ve been diagnosed with depression, and those who have not. We can then compare the genetic information of the two sets. We think this will enable us to identify new genetic variants associated with depression.

“However, genes aren’t the only contributing factor,” she says. “Lifestyle and life factors are important too. For example, stressful life events increase people’s risk of developing depression.

“Both sources of risk seem to contribute to depression independently and cumulatively. So, it’s possible that those with low genetic vulnerability to depression might be able to deal with more stressful life events before becoming depressed.” 

Cathryn says we need an approach that looks at all the factors that lead to depression. This is where Our Future Health is valuable. “The breadth and depth of the different types of de-identified data that volunteers share is going to be key.

“There’s the sign-up questionnaire in which people report mental health problems and if they have a diagnosis. There’s the genetic data. And there’s health records too. That’s important because depression is usually diagnosed and treated by GPs. Researchers like my team will be able to see when a person is diagnosed, and what happens afterwards.

“Our Future Health is a goldmine for furthering our studies – but we have a lot of mining to do to find the nuggets that will improve our understanding of depression.”

Using genetics in the long term

Depression is an episodic disorder, which means it can come back, sometimes again and again. “Currently, when someone is diagnosed, we don’t know what will happen next,” says Cathryn. “Some people will have a single episode of depression, recover, and never suffer again. Some will have two episodes. Other people will have recurrent episodes throughout their life.

“Our Future Health’s data has real power, because we’ll follow people across their lifespan. We’ll know if someone has a single episode or multiple episodes and how serious those episodes are.

“We’ll also be able to look for patterns that can be used in the future to predict how the condition will affect others. And we’ll be able to look at genetics too, to see if there’s a link between different genetic variants and whether depression returns.”

Genetics and antidepressants

The second study that Cathryn’s team is doing with Our Future Health will use genetic analysis to learn how to prescribe antidepressants more effectively.

“Antidepressants are one of the most widely prescribed types of drugs,” she says. “For many people, they do help with recovery.

“However, for some people, it’s difficult to find the right antidepressant that will help them recover from an episode. It’s very common for people to need to try several different antidepressants before they get relief from symptoms.”

Currently, doctors must take a trial-and-error approach to prescribing the right antidepressant. A patient is given a particular drug for several weeks. If they don’t respond, the doctor will try a different drug. And so on.

 “We know that genetics is part of the reason that people don’t respond to an antidepressant,” Cathryn says. “This research, to identify the genetic component of people’s response to antidepressants, is very much work in progress. But we now have the genetic technology. And we have the statistical tools. What we haven’t had, up until now, is large studies with good data.

“Our Future Health will be transformational. Our study will look at volunteer’s de-identified GP records to find out their history of antidepressant use. If someone has stayed on a single antidepressant, it suggests the treatment is helping them. If someone has switched antidepressants after a few weeks, it suggests that it’s not working for them. We can then search for genetic variants that may have controlled this response to a particular drug.

“This work is very much at the discovery stage,” says Cathryn. A lot of analysis and studies will need to be done before conclusions can be drawn, but it’s an exciting start. “Eventually our work could lead to personalised prescribing, so the first prescription would be more likely to work according to your genetic profile.

“For a lot of people, that could cut out those difficult weeks of being on a drug that’s not working. It would help a lot of people get better, more quickly.”

Let’s prevent disease together

By volunteering for Our Future Health, you can help health researchers discover new ways to prevent, detect and treat common conditions such as diabetes, cancer, heart disease, stroke and Alzheimer’s.