Jonathan Flint: Psychiatric Genetics

Q: Can you tell us about the genetic basis of psychiatric disorders?

JF: Every psychiatric disorder that is studied, to some extent, has a genetic contribution. We know this from twin studies and family studies. The contribution varies according to the disorder: schizophrenia and autism have a relatively high contribution, about 80% of variation is due to variation at a genetic level, whereas the conditions I work on, anxiety and depression, are less genetically determined with heritability of about 40%. To put that into perspective, it's about the same as many other common illnesses, type 2 diabetes would be an example.

Q: Why does your research focus on anxiety and depression?

JF: We work on anxiety and depression because those are the commonest psychiatric conditions. There have been a large number of epidemiological studies across the world and they all come to more or less the same conclusion: that depression has a prevalence of between 9 to 16%, and it varies according to gender. I would expect, on average, that one in 5 to 6 women would have one episode of major depression in their lifetime.

Q: Can your research lead to the development of better therapies?

JF: At the moment we're not very good at treating depression. I'd expect that if I see a patient coming into the clinic, I would have a 50% chance of getting them better within say 2 to 3 years. It's not a very successful approach. We have indications that there are some biological problems, psychology as well, and we know from the genetics that there has to be some genetic predisposition. If we were to understand which genetic variants were contributing to this disorder, the idea is, it might put us on the path to helping our patients better, through the development of new therapies.

Q: What are the most important lines of research that have developed in the past 5 or 10 years?

JF: The most important has been the ability to interrogate entire genomes, to see associations between genetic variance and disease. This has been pioneered for other conditions: asthma, diabetes, hypertension, and recently it has been successful in schizophrenia and autism. These approaches have only just become possible with depression and anxiety, largely because we need well-characterised, very large sample sizes, which are very hard to collect.

Q: Why does your line of research matter, why should we put money into it?

JF: Our research, we hope, will lead to our ability to make better diagnoses, and potentially to develop new therapies for this very common and very disabling condition. If you think of this on a global scale, the impact of depression comes second only to ischaemic heart disease, in terms of its effect on people's lives. That's not to say that the mortality is similar, but the morbidity - the extent to which it affects your ability to get on with your life - is tremendous. It's also relatively underfunded. While cancer and heart disease receive large amounts of money, there is relatively little research funding that goes into depression, and one reason for this is because there have been few leads, few really substantial ways into this. Fortunately this is changing, which is why genetics is important, because it gives us a real lead for the first time.

Q: How does your research fit into Translational Medicine within the Department?

JF: Our research is a paradigm of this. We've moved from working with patients, to very careful phenotypic characterisation, through to the genetic analysis, and once we have that we'll be in a position to understand what the molecular basis is. This will enable us to understand the mechanisms that give rise to the condition, and with that information we will then be able to go back into the clinic and improve care for our patients.