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Expert Q&A: genetics and schizophrenia

Genes are often described as the blueprint for how we’re all created. Genetic information (DNA) is inherited from our parents and forms the instructions for how our bodies are made up.

Certain variations in people’s genetic make up may mean that you’re more likely to develop certain conditions – including mental illnesses like schizophrenia. Heritability is the term used to describe how much genetics contributes to the risk of developing a condition and research suggests that schizophrenia has one of the highest heritabilities of all the psychiatric disorders.

We know that people with schizophrenia die on average 20 years younger than the general population – so understanding the role genetics plays is crucial if we are to ensure people can be treated effectively and live the full life they deserve.

It’s why we’re delighted to be funding Dr James Walters, an academic psychiatrist at Cardiff University, whose project is looking into this important area of research.

What factors are causing this dramatic decrease in life-expectancy for people with schizophrenia?

It’s a complex picture but I think we’re beginning to understand the reasons. One of the main factors at play is that people with schizophrenia are at a higher risk of physical illnesses – the big two ones are cardiovascular and respiratory disease. The reason for this is probably mostly lifestyle related, and, in no little part, because people with schizophrenia are more likely to smoke cigarettes, and smoke heavily. It’s not fully known why this is the case but some theories suggest it’s related to reward mechanisms in the brain. Whatever the reason, one of the most effective ways of improving health in those with schizophrenia is to stop smoking (and exercise more often– so no different to anyone else).

Other factors impacting people’s physical health include medication, as the anti-psychotics we prescribe as treatment are associated with weight gain and other metabolic problems.

A small, but devastating part of the decrease in life-expectancy, is that people with schizophrenia are more likely to take their own life than the general population.

And finally, we know that people with schizophrenia are less likely to access health interventions or health services and when they do, they get investigated less thoroughly and treated less aggressively. Physical health hasn’t been prioritised in mental health settings and that is beginning to change.

How does your MQ-funded project help to tackle these issues?

My project is looking at the impact that genetic risk factors have on schizophrenia. We have gained important insights into the important role of genetics in schizophrenia in the last 5 years or so though there is still a lot to be discovered. One of the most important findings has been identifying a form of genetic variation called ‘copy number variants’ (CNVs) as strong risk factors for developing schizophrenia. CNVs are rare variations where genes are deleted (so the protein which is the product of the gene, isn’t produced) or duplicated (so there’s too much of the protein) – both of those factors increase someone’s risk of developing schizophrenia.

Although we’ve seen that CNVs increase someone’s risk of developing schizophrenia – we don’t yet understand the impact they’re having at a clinical level although we know that CNVs are also risk factors for conditions such as autism, intellectual disability and epilepsy. Crucially, we need to understand more about the physical health problems associated with CNVs.

If those with CNVs are identified and we know that they’re at increased risk of physical health problems then it means that we can target interventions and investigations at that group – and we’ll also be more prepared to pick up and treat those physical health problems more effectively. This will be the first time on a large scale where we have actually looked to see the effect of these CNVs on a population of people with schizophrenia.

So, do all people with schizophrenia have CNVs?

No – the vast majority of people with schizophrenia don’t have these large, rare CNVs. And we also know that there are lots of people in the population who carry CNVs without any apparent health implications. We’re only just beginning to explore why that might be.

If the majority of people with schizophrenia don’t have CNVs – then why do you think they’re important to research?

Because I think schizophrenia isn’t one condition and the reasons for symptoms developing will be different in different people so there’s lots of subtypes if you like. I believe the way we’re going to tackle it from a research perspective is by taking it on in small bits and this will be an important part of that pie. We also know that many of the same genes affected by CNVs harbour more common genetic risk variants and so what we learn from CNVs will hopefully have wider implications.

What does your project involve?

We’re looking at the CLOZUK sample, which is the largest genetic sample of people with schizophrenia in the world. The sample has genetic details of people who take the antipsychotic medication clozapine, which is used for treatment-resistant schizophrenia. We don’t yet have any clinical details to link with these samples, so what we’re able to do with this project is anonymously link the genetic sample with health records. We’ll be doing this across England, Scotland and Wales to see what impact CNVs are having on physical health outcomes.

Where would you like to go next with the study?

Genetics is one aspect of a very complicated picture but I believe it is a powerful way of telling us about how these conditions develop in a way that avoids some of the biases of many other research approaches. If we want to assess the impact that genetics has then we have to link up genetic data with clinical information. At the moment, our diagnostic categories and treatment strategies leave a lot to be desired – hopefully this project and work beyond will enable us to refine our diagnoses and ultimately get better treatments.

Also, one thing we’re really interested in is whether we can establish what the clinical and genetic factors are which predict someone doing well on clozapine and other antipsychotic medications. Clozapine is an under-prescribed medication – and can change the lives of some people as well as extend life expectancy – so it would be good if we could understand more about who should or shouldn’t be offered it.

Finally, why were you interested in researching schizophrenia?

I’ve always found it fascinating, ever since I was a medical student, mainly through talking to patients and trying to understand their experiences. It’s so complex – as well as genetics there are other really important risk factors that we need to know about in order to understand causes and design better treatments - medical, psychological or social interventions. And in the next ten years, with the help of organisations like MQ, I hope we can bring together research to inform better treatments. There’s a change in attitudes towards mental illness, and hopefully that will lead to more funding in research. I think we’re in a better position now than we ever have been.

Last updated: 8 August 2017

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