Volunteers are being invited to sign up to the UK's largest ever study into genetic links to depression and anxiety.
One in three of us will display symptoms of anxiety or depression at some point in our lives, but less than half of us will receive medication or therapy that ‘makes us better’.
Something needs to change. Geneticists and other leading mental health researchers are today imploring us to play our part, by contributing to research efforts. King’s College London and the National Institute for Health Research (NIHR) are aiming to attract 40,000 participants to send a swab of saliva in the post and answer some online questions, with a view to nailing DNA’s influence on mental health and much more besides.
"I would hope that within a generation this kind of work would help us make better informed decisions about what treatments people need and when to intervene with which groups."
The Genetic Links to Anxiety and Depression study is to be known as ‘GLAD’ for short. Will we be happier for taking part? Or is there a danger we might actually end up with less say in our treatment options if our families are ‘biologically loaded’? What is already known about the links between DNA and mental illness? Mental Health Today discusses these issues and more with Professor Thalia Eley, Professor of Developmental Behavioural Genetics, NIHR Maudsley Biomedical Research Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London.
Q: What do we currently know about the extent to which genetics influences mental health?
“We know from the twin literature* that 30 – 40 percent of the risk for anxiety or depression comes from genetics. Then the rest comes from what people experience in their lives. Genetics are not the whole story by any means, so we definitely need to continue to explore and understand how social risk factors and other aspects of people’s individual experiences in their lives are important in development of these conditions.”
Q: Do we know whether it’s genes themselves that are carrying an influence as high as 30-40 percent, or is it possible that children have learned coping behaviours from their parents? Will this study be more definitive?
“Looking at DNA is a different method from the more traditional family based designs such as twin designs. It doesn’t carry the same complexities about it because you are going straight to the DNA. That’s an advantage of this approach that we’re taking in this study, that it’s the DNA itself that we’re looking at to understand the genetic influences.”
Q: Have DNA studies been carried out before to establish whether mental illnesses are genetically inherited?
“There have been some publications and other large studies – particularly in depression, there are some rather large studies in the literature. There was one that came out earlier this summer that was an international collaboration that we are a part of. It identified 44 genetic variations that it found to be important in understanding differences in individuals with depression and without depression. We will be the largest study recruiting from a single population getting detailed information about anxiety and depression so we will be able to drive the field forward significantly.”
Q: Why is it helpful that we have learned that there are 44 genetic variations that are significant in understanding differences in individuals with anxiety or depression?
“It's not terribly helpful at the moment is it? It’s part of the journey of learning what the specific genes are that influence depression – and once we know that we can begin using that information. In time we will be able to have scores that add different genetic influences together and help us understand risk for development of anxiety or depression in the first place. The information will also help us understand likely response to different interventions and treatments. The first 44 identified are just part of an ongoing story and there’s a lot more we still need to learn. We’re not trying to narrow down 44 [‘depression genes’] to one. There will be hundreds of genes identified. We’ve found those 44 and there are many more to find.
Q: Are these same genes contributors to other mental illnesses as well?
"Yes! We know that there’s quite a bit of overlap between depression and anxiety. That’s one of the reasons we’re exploring the two together. There’s far more known about the genetics of depression than there is about the genetics of anxiety at the moment but we do know that there’s a massive overlap between the two condition. That’s one of the reasons we’re why we’re doing the recruitment and the project the way we are, with participants who have experienced either. There’s also quite a bit of overlap, in terms of the genes, between pure depression and bipolar disorder. We’re interested in recruiting anyone who has experienced any kind of depression, including bipolar disorder, into this study."
Q: How long could it be before we know which genes expose people to heightened risk of anxiety or depression and which treatments it would be most effective for individuals to receive?
"What we hope is that this kind of work will feed into a kind of personalised medicine approach. I would have thought that in the next ten-fifteen years we’ll be at the point where, as part of decision making about whether somebody should first try a medication versus a talking treatment, part of the information used to make that decision will be the extent of genetic risk they have for the disorder."
"You could have, say, 100 people experiencing significant difficulty in social adversity, but only a subset of them would respond to that with depression. And the ones who do would likely be the ones who carried a very high number of the genetic variants associated with depression, so they were at a higher biological risk and then when they experienced significant social adversity those greater risks act together."
Q: Should we be placing such emphasis on genetics when it’s only thought to represent up to 40 percent of the influence on developing anxiety or depression?
"It doesn’t really matter in terms of treatment that’s it’s only 30-40 percent of the influences on risk in the first place that are genetic. And it doesn’t matter whether the treatment has anything to do with the genes or not. The point is to figure out for any one individual what the most appropriate treatment is; to figure out whether they are someone with a very high biological loading or whether they are someone with a much lower biological loading. Then the treatment decisions you might make about those individuals might differ. So that’s the way I see it being useful in terms of healthcare. But I also think it’s quite likely that the more we learn about specific genetic influences that are relevant to the development of anxiety and depression, the more likely we are to come up with drugs that tackle disorders in different ways than the ones that have been explored so far. I think there’s a new and growing interest in getting back into exploring new drug development for depression and anxiety because of these huge data sets that are being provided by these big genome wide studies."
Q: Will the biobank bring us closer to a personalised medicine approach?
"First we need to do the discovery science, and then you’d need to do clinical trials testing it, so we must be at least ten years away but I would hope we wouldn’t be any more than twenty years away. I would hope that within a generation this kind of work would help us make better informed decisions about what treatments people need and when to intervene with which groups."
Q: How is participant data going to be secured?
"Everything we’re doing is GDPR compliant, which is something that everyone will have been hearing about recently. All of the data is coded with a private ID number that is nothing to do with their names or contact information like their email address. There’s only a very small number of ethically approved researchers who are able to make the link between ID number and name. So everyone’s data will being kept very secure and it won’t be being passed out to anybody other than other researchers who are ethically approved to work with the data."
"People always worry about that, particularly with DNA and when we’re asking for linkage to medical records, which is another part of this project: we ask people to consent to allow us access to their medical records so that we can fully understand what they’ve experienced and how that might be relevant to their depression and anxiety and their treatment outcomes."
Q: What would you say to people who argue that rather than spending £1m researching genetic influence, we should instead by tackling social or societal influences on mental health?
"As people can sign up to take part in any of the projects that are hosted by the bio-resource, there might be studies around social media usage, there might be studies around family break up, there might be studies around migration, around exam stress. All these different aspects that we know are important in anxiety and depression can be explored by recruiting from this bio-resource of participants who’ve agreed to be contacted. It’s a limitless set of possibilities really in terms of how we can explore it."
"I envisage a considerable amount of work that’s got nothing to do with genetics coming out of this project around aspects of society as it is today and how different aspects of that might be influencing risk for depression and anxiety. The project is much, much bigger than just the genetic questions that we can explore with the initial data that we get."
"I see the NIHG bio-resource as a way to completely transform the landscape of mental health research in this country. There will be people out there with all sorts of questions about the things they think are likely to matter in mental health today. We know that anxiety is on the increase, particularly in our young women. We know that people are very concerned about the mental health of our young people and young people are the real target of this project. We really want people aged 16 to 25 to sign up because they are a very high risk group in that age range at any point in society, but right now they are particularly at increased risk."
"It’s a call to action really. We know that a third of individuals experiences these symptoms across their lifespan, so that’s a huge proportion of the population. And of those that really feel they need some treatment, quite a significant proportion don’t receive any and those that do, only half get better. So you can see that there’s a massive, massive burden of individuals who are experiencing these conditions and either not receiving treatment or not getting better following their treatment and it’s really that that we want to tackle."
*Twin studies compare traits of identical twins who share 100% of their genetic material to those of non-identical twins who share about 50% of the genes on which humans differ.
* You can sign up here to take part in the research.
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