At Risk of Mental Illness?

Could genetic tests help diagnose people who are at risk of developing psychiatric conditions and catch them before they are ill?
20 March 2014

Interview with 

Professor Barbara Sahakian, Cambridge University, Professor Michael Owen, Cardiff University


There's significant stigma surrounding psychiatric conditions. However, one in four of us will experience mental ill heath in our lifetimes. At any time in the UK one in 6 of us will have a common mental health problem, life depression and anxiety.

Mental ill health even affects more people, and costs society more, than, for example, Dnahelix_genetic_fingerprintcancer. So, scientists, clinicians, and the government, are on the look out for biological markers, including genetic tests which could help diagnose people who are at risk of developing psychiatric conditions to catch them before they fully exhibit symptoms.

To find out more I met up with Professor Mike Owen from Cardiff University, and Prof Barbara Sahakian, from Cambridge University. I started by asking Mike why are there so many different psychiatric conditions? And how much does genetics play a role?

Mike -   There's a big range of different psychiatric disorders and they range from the very severe like schizophrenia or autism, intellectual disability and bipolar disorder, right through a spectrum to disorders like mild depression and anxiety that are often treated by general practitioners or clinical psychologists. 

As to the role of genetics, well actually, genetics plays a role in pretty much everything and perhaps to different degrees.  But much of our behaviour is influenced by genes.  It's not really surprising when you think about the fact that we're such a social species and natural selection is very likely to operate on genetic variance that influence behaviour. 

It's true to say that the more severe disorder seem to have a stronger genetic basis.  The heritability is higher.  As a kind of rule of thumb that the more severe disorders, the sort of relative contributions of sort of biology versus psychosocial influence is probably greater than the milder disorders.

Hannah -   So, if a baby is born, are they going to develop schizophrenia or autism for example?  Do they have the genes at birth for that illness?

Mike -   Well, yes.  What people inherit is a set of genes that renders them relatively more or less susceptible to developing the disorder.  There aren't genes for any of these conditions.  There are genes influenced - proteins influence nerve cells, influence circuits, influence et cetera, et cetera.  And we dealt a deck of cards if you like and that renders us more or less likely to develop particular psychiatric disorders, dependent upon a whole string of circumstances that occur throughout development.

Hannah -   Barbara...

Barbara -   Just by way of an example of what Mike was talking about, we had a paperDissection - learning from death with Matthew Owens and Ian Goodyer which looked at children who had had experienced adversity and was mainly psychological adversity, watching their parents fight and argue and scream at each other, hit each other in front of them.  And then we followed these children up to adolescence and we saw that they had this negative way of thinking which we could measure cognitively.  But it was this early adversity combined with this way of thinking and having the S-allele as a serotonin transporter gene which meant that in adolescence, unfortunately, they were at very high risk for developing depression.  So, it's this interesting combination as Mike said of these environmental factors combined with the genetic factors which is so important.

Hannah -   This seems to be applicable for a whole range of psychiatric conditions.  So you mentioned autism, schizophrenia, and also depression and anxiety.  In that case, do you think there'll be a case where there'll be early biological markers which will indicate?  So, you might be going to doctors for example, have some blood taken when you're a baby when you're first born and have your genes analysed and then you'll see whether you are at risk of developing a psychiatric condition down the line? And if there are certain things that you should be aware of during your lifetime, during the development of the rest of your brain that you should do to protect yourself.  Do you think that might happen in the future?

Mike -   Well, I'm often asked that question and despite having studied genetics for a long time, I'm never really sure of what the answer is.  I think that the brain is the most complicated system probably in the universe. 

I think people are perhaps a little naive in thinking that it's going to be terribly easy in the foreseeable future to predict very complicated disorders like psychiatric disorders.  But I do think that we will have some traction on being able to - people at different susceptibilities, there'll be rough and ready estimates on the whole.  Now, the exception to this is, there are some fairly rare genetic mutations that confer quite high risk of psychiatric disorders.  Many of the ones today, they actually confer risk, not just to schizophrenia, but also to autism, intellectual disability and ADHD.  And there, the risks are fairly high and people carrying these mutations are already getting put in touch with services, but they're usually sort of genetics services, possibly, paediatric neurologists.  I think clinical groups haven't yet got their heads around what to do about the increased risk of psychiatric disorders.  These are exceptions.  So, mutations like these factor a few percent of people with schizophrenia.  But of course, as we start doing more sequencing with the new technologies that we've got when we can sequence the whole genome pretty soon, maybe more of these rare things will come up.  But in the great mass of the population, I think it's going to be rather less straightforward, a bit more like predicting the weather perhaps.

Barbara -   I think also, there's obviously a lot of neuroethical issues associated with this type of area.  So, we have to be very concerned about those and thinking about those as things develop.  We know there's already so much stigma attached to mental health disorders which we have to work on obviously because I don't think it should be there because so many of us do have these problems.  We should be more forthcoming about them and I think it's changed quite a lot in the field of Alzheimer's disease, but it needs to change much more in regard to mental health disorders. 

As Mike says, it's more rare conditions where it's so definitive and so much with the rest of it depends on environmental influences and what are the sort of positive promoter factors that you can do to make sure somebody has a good quality of life and that they don't actually develop one of these things.  So maybe, what we'll move more towards is actually, working with young children and then working with them in schools to help develop programmes where they can develop their resilience and good brain health so that they don't succumb to these things.  And then also, looking out for them earlier so that we can sort of nip it in the bud and either stop it happening altogether or really detect early and treat effectively so it doesn't become chronic and lifelong.

Hannah -   And bearing in mind that 1 in 4 people will experience mental health at some point in their life before this biological genetic test might become available in the future.  What can we do?  What can I do to protect my mental health at the moment?  What can I do to help my nephew, who's 5, 6 protect his mental health in the future and my mother's actually?  What can we all do?

Barbara -   Well, I'm very much of the 'use it or lose it' idea and I think you have to Exercisekeep your mind active.  One way we know how to do this is through lifelong learning.  So, it's always good to be learning new things.  We know that new learning generates neurogenesis, new cells in the hippocampus.  So, that's very important.  There's other things like exercise.  We know that also is responsible for neurogenesis in the hippocampus.  So, there's things that we can do to really keep our minds functioning better for longer.  And there's these other things that we can do that are good for mental well-being.  So, the idea of connecting and being in the moment, the kind of mindfulness idea has been shown to be evidence-based method for well-being.  We devised about 5 of these for the mental capital and well-being project and by the foresight.  That was one of them and another one had to do with giving because actually, when they've looked at people giving to their favourite charities and they've had them in scanners, the reward system in the brain is actually activated.  So, the individual finds that very positive in rewarding as well as obviously, the person that they're giving to.  So, giving is good yourself as well as for the other person.  So that's another thing that we can do.  The other thing is support systems - social support systems that we need to be more attentive to developing close relationships with family members and friends, and the community.  That is also been shown to be beneficial for mental well-being.

Hannah -   Thank you very much, Barbara and also Mike for giving your time for discussing these issues with us.  I've got a few questions in from listeners which would be fabulous if you could spend some time answering. 

So, David Bailey and Steven Quill have been in touch saying, "Why are mental health problems so common and are they more common now than they were, say, a hundred years ago or a thousand years ago?"

Barbara -   Unfortunately, I couldn't answer by a hundred years ago or a thousand years ago, but certainly, there are certain forms mental ill health which are on the increase and those tend to be the stress-related ones.  It seems that globalisation, competing with other people for jobs and things like that is a very stressful event.  Unemployment is very stressful, debt is very stressful.  And so, in this times of austerity, the degree of stress tends to be raised and therefore, people find it that they're developing more anxiety and depression.

Mike -   Yeah, certainly.  I think the evidence, such that we have and it doesn't go back very far suggests that the severer disorders like Schizophrenia and bipolar are probably much the same.  Autism, as far as severe disorders go is an exception.  But the question is, is that because we're recognising it more or is there some environmental factor that's changed.  But I'm interested to sort of more generally.  I don't have a particular scientific answer with this sort of idea that in modern life is particularly likely to precipitate psychiatric disorders.  I mean, I suspect we're more psychologically minded.  In a sense, we have the kind of luxury to put ourselves in quite luxurious position in being able to sort of reflect on how we feel and how we are, to an extent that it wasn't present before.

Barbara -   Well, Mike has made a good point because we know that from the Quality Care Commission that the prescriptions for ADHD in terms of stimulant drugs such Ritalin has gone right up in the past 5 years.  The examples for why that might be that are given is that first of all, these disorders are recognise more.  So for instance, for somebody's grandfather, they might not have recognised that he had ADHD as a child.  So, the recognition is much greater.  The second thing is, years ago, we thought that ADHD finished in childhood or adolescence.  And now, we know that it continues on into adulthood.

Hannah -   On a similar note, Susan has been in touch saying, "I've been told that anxiety can stem from an innate 'flight or fight' response to stressful situations.  Is this true?"  So, our feelings of fear and anxiety is something that we have evolved it to have and it helps with our survival as a species.

Mike -   Well, anxiety is in many instances an adaptive response.  It is part of, is a manifestation of the 'fight or flight' process.  The problems arise when it starts to step out, escape from its box and to be present to an inappropriate or inappropriate situation.  So, it's a sort of, one can kind of speculate the same things about other psychiatric disorders like depression is.  Sadness is a natural part of life but when it escapes from its box that it becomes pathological or we call it pathological.

Hannah -   And it sometimes can be quite useful to feel sad and respond to a particular situation to try and help you to make sure that you don't encounter that situation again for example, that you learn from it.  And Susan is also saying, "Are there other behaviours, for example, ADHD that are thought to be linked to traits that would've been useful for survival for our ancestors?"

Barbara -   Well ADHD, actually, I've done a study where I've looked at entrepreneurs and entrepreneurial behaviour.  When I've actually asked some to fill in scales which are the same as what I asked for adults in the ADHD clinic to fill in, they actually score quite highly.  So the point is that if you can channel some of this activity that people have and the sort of enthusiasm for doing things, it actually is quite successful.  One reason it might be there is to help us to take advantage of time limited opportunities.  So, some of these traits or features of people with ADHD have - if they're channelled well - can be very useful.

Hannah -   Thanks to Professor Barbara Sahakian from Cambridge and Professor Mike Owen from Cardiff.


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