Prof Mike Owen - Schizophrenia genes

Kat -   We'll be returning to the hunt for depression-related genes later but now we're switching to a different mental health condition - schizophrenia. Affecting around one in a hundred people in the UK, schizophrenia can be extremely debilitating, as well as distressing for the family and friends of sufferers and a wider social issue too.  Professor Mike Owen heads up the MRC Centre for Psychiatric Genetics and Genomics in Cardiff, and I asked him what we know so far about the genetic links to the disease.

Mike -   So, we know that for example that if you have a first degree relative, a close relative with the disorder, say, a parent or a sibling, then your risk of getting the disorder is about 10 times increased.  So, it's about one per cent generally in the population - a risk of getting schizophrenia.  If you have a close relative, it's about 10 per cent.  And we know that that could be shared genes, but it could be shared environments as well.  It could be people living in the same sort of settings have similar experiences.  So, you can do twin studies, adoption studies that show that that clustering in families, if you like, is largely due to shared genes.  But there's a lot of evidence from those sorts of studies.  More recently, now, there's many of us have been doing molecular genetics - looking at the DNA of people to try and identify the specific genes involved.

Kat -   From your talk, one of the key problems was that schizophrenia isn't just one condition.  It seems to be a wide range of conditions.  How are some of the genetic studies starting to shed light on this complexity?

Mike -   Well, the problem I guess is that what we call schizophrenia is a syndrome.  It's a set of symptoms that occur together and it's a bit like trying to do genetics of shortness of breath, I guess, or of chest pain.  Chest pain could be due to a heart attack or it could be due to stomach problems or muscular problems, and so forth.  So yes, probably, it is heterogeneous.  It contains various conditions.  The other problem we have is that it's not nicely circumscribed.  There are related disorders - bipolar disorder for example, which we hear a lot about in the press - kind of merges into it symptomatically.  There's no kind of clear blue water between the two. 

So, what the genetics is telling us is that genes for psychiatric disorders are not specific.  The ones we've discovered so far are not generally speaking specific to one disorder.  They're predisposed to multiple disorders, suggesting that these diagnostic categories that we use don't carve nature at the joints, if you like.  There are reasonable sort of surface description of more complicated things going on lower down.

Kat -   So, in terms of the genes that have come out on some of these studies, perhaps your top suspects, what do they tell us about some of the underlying biology of what's going on?

Mike -   Well, the striking thing has been the degree of convergence onto sets of genes. Genes code for proteins, they contain the instructions for proteins.  And so, what we can do is we can look at the proteins - the genes we found are coding for and see whether they cluster in particular functional groups.  One of our most striking finding today is that there is a clustering of proteins that are involved in synapses. 

Synapses are the sort of structures that allow nerve cells to communicate with each other.  They're also the structures that basically confer the brain's ability to code information.  So, the strength of synapses changes with experience and that codes information, if you like, and that plasticity is the basis for learning and memory, and helps the brain develop.  So, we've identified genes that focus down on a small set of proteins that are involved in this synaptic plasticity.

Kat -   And of course, what people with mental health problems, with schizophrenia, and their families will want to know is about, how will this knowledge help to treat the condition better.  Where are we with coming up with more effective treatments.  They don't seem to have been any breakthroughs for decades really.

Mike -   No, there haven't really been any breakthroughs for 40 odd years.  This work is very much aimed at trying to understand what is going wrong in the brains of people with severe psychiatric disorders and in the hope that we can identify new treatment targets.  Now I have to say, this work is going to take a long time.  The next step is to start to understand the function of some of these genes in the brain and we're starting to do that - well, in three ways.

Looking in people, we can look at people who carry specific genetic factors and we can study their brains with brain imaging methods.  We can use animal models.  We can manipulate the genes and model the risk genes in animals and study their brains and behaviour.  A really exciting new technology is to use stem cells.  We can take cells from people, skin cells and convert them into nerve cells and grow them in a dish and study their developments and the way they relate to other neurons, etc. 

When you identify risk genes for disorders like this, the next phase is intensive kind of neuroscience and that's what's going to happen over the next five, 10, 15 years.  I mean, we have to go this way.  It's the only way I think to get effective treatments.  It's very hard to predict how long anything in science will take.  It could be a breakthrough next week, but I don't want to give false hope either, but there's nothing around the corner, but you know, this is solid progress.  There's solid progress and I think we're entering a new phase of the game now.

Kat - That was Professor Mike Owen from the MRC Centre for Psychiatric Genetics and Genomics in Cardiff. And now it's time for a roundup of this month's genetics news.