Prof Cathryn Lewis - Depression genes

This month I'm reporting back from the Genetics Society Spring meeting, which was held at the beginning of April at the Royal Society in London. Called "Psychiatric Genetics: Pathways and Prospects", the meeting featured talks from leading scientists from around the world, discussing how genetic research is shedding light on mental illness and improving life for sufferers.

To kick off, I spoke to Cathryn Lewis, professor of statistical genetics and epidemiology at Kings College London, who's searching for genes involved in depression. I asked her to explain a bit about the scale of the problem when it comes to psychiatric diseases in the UK.

Cathryn -   Mental health issues in general, and depression in particular, are a major issue in the UK.  So, up to one in five people will suffer from depression at some point in their life and for some people, that will be a major impact on their life. They will have recurrent episodes of depression throughout their life, and never really recover their full life as it was before they became depressed.  And of course, that has an enormous impact on individuals' lives, on their family, it causes problems for employment and security of life, and economically, it has a major effect on the UK economy.

Kat -   When we talk about depression, we're not talking about feeling a bit sad or a bit moopy.  This is what psychiatrists would diagnose as an illness.

Cathryn -   That's right, absolutely.  I mean, everyone has days or even weeks where they feel a bit under the weather, but we have very clear criteria for diagnosing depression that are well applied by GPs and beyond that by psychiatrists.  So, we're really talking about severe episodes of depression that really stop people carrying out their normal life in the way that they would wish it.

Kat -   In terms of where we are with understanding how genetics, how nature or nurture contribute to this?  With the genetics part of it, where are we with trying to get a handle on the genes involved in depression?

Cathryn -   So for depression, we've made less progress in identifying specific genes than many other diseases where research has moved very fast over the last few years.  Now, we know from twin studies and from family studies that if someone has a relative with depression, then they themselves are at increased risk of depression.  Genes have a major contribution to that.  That's really interesting to know, but what we want to be able to do for the next step is identify the specific genes and the variants in those genes that could put people at increased risk of depression.  There are several things that we can do with that.  It may help us identify people that are at particular risk of depression before they suffer with an episode of depression.  It gives us biological insights as to how depression works in the body, it may give us new drug targets and that would be hugely beneficial for the whole field.

Kat -   In one of the talks we saw about the genetics of schizophrenia, they've done a lot of studies looking at lots and lots of people and you can kind of see this particular candidate genes popping out.  That's not really the case with depression, is it?  Why is that?

Cathryn -   So, the schizophrenia studies have moved forward very fast and they now have over 100 different genes that they know play a role in schizophrenia.  In depression, we haven't got that far.  We have no confirmed genes for depression despite many decades of work for many international research groups.  It seems that for depression, the whole disorder is much more heterogeneous.  We know that people suffer from depression in different ways, different symptoms may be important to them, and that's clearly having an impact on how we can carry out genetic studies.

Kat -   Is part of the problem that depression isn't just one thing, in the same way that cancer is now being divided, not just down into bowel cancer and breast cancer, but you have KRAS positive bowel cancer.  Is the problem that we've just been putting everything that's depression into one bucket?

Cathryn -   We suspect that that is true.  We know that there are certain things in depression that make it more genetic, early onset depression, recurrent depression where people have subsequent episodes certainly have stronger family histories.  It feels like depression, although it's very prevalent in the population, it's probably not a disorder with a single genetic pattern and it may be by subdividing different types of depression, looking at the different genes that contribute to subsets of that. And also, how that works with some of the environmental risk factors of things like stressful life events which we know increases risk of depression.  I think we're going to need to model this more completely across all the different symptoms and the different contributions to risk before we can really make progress in identifying specific genetic variants for the disease.

Kat -   And from your perspective, what one thing would you really like to see change in maybe the next couple of years in terms of our understanding of the biological causes of depression?

Cathryn -   I'd like to see that we can identify some genes that really shed some light on the biological causes and what we can do about it.  Just knowing the name of the genes doesn't get us very far.  We need to take that downstream.  We need to use that for developing more drugs for understanding the physiology of the disease.  It's such a common disorder that we really should be making progress in this direction. 

One of the things that we need to do this is we need large studies.  We need people to get involved, to contribute DNA, to get involved in research when they're invited to do so.  And it's really only with this combination between researchers like me, and patients and relatives suffering from the disease that we can hope to make progress.

Kat -   That was Professor Cathryn lewis from Kings College London.