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‘Mutating genes are key to treating schizophrenia’ says top neuroscientist

Major psychological disorders such as schizophrenia will continue to affect humans because men and women are continually generating genetic mutations that disrupt brain development.

This will be the key conclusion of Professor Sir Michael Owen, director of Cardiff University’s centre for neuropsychiatric genetics and genomics, when he gives the annual Darwin Lecture at the Royal Society of Medicine this week. Understanding such conditions at an evolutionary level will be crucial to developing treatments, Owen believes.

Thirty years ago, the new technology of DNA analysis raised hopes that schizophrenia – a condition that can track through families – would soon reveal links to one or two specific genes, said Owen. Treatments might then be relatively easy to develop, it was thought. Instead scientists found that hundreds of genes, each having a tiny effect, dictate whether or not a person will be susceptible to the condition. Characterised by profound behavioural changes, hallucinations, and delusions, these transformations in behaviour can have profound consequences, he added.

For example, men with schizophrenia have – on average – only a quarter as many children as males in the general population while women with the condition have about half as many as unaffected females. That low reproduction rate should have had one clear result, Owen told the Observer last week. “Schizophrenia cases should have declined and disappeared long ago as those affected were out bred by those unaffected. This has not happened. A steady level of 1% people continue to be affected.”

So how could the condition have persisted, scientists have asked. What underlying mechanisms are operating to keep schizophrenia fairly common today? Finding answers will be crucial to uncovering ways to treat the condition, Owen added.

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Some scientists argue that people with the condition have brains similar to individuals who are highly creative and the successes of the latter have maintained high levels of genes that make both creativity and schizophrenia more likely to appear in people. Others say siblings of people with schizophrenia – who share many genes – might have compensatory higher than average degrees of fertility and so are maintaining levels of predisposing genes in the population.

“These are important ideas but recent studies indicate they are wrong,” Owen said. “Instead it has become clear schizophrenia is being maintained at its current level because new mutations that predispose people to the condition are being generated spontaneously and constantly. One set of mutations gets swept out of the population over five to 10 generations but is replaced by a new set of mutations.”

In particular, gene mutations that affect brain cell synapses and the developing brain appear to have a strong effect in leading to cases of schizophrenia – and also other psychological conditions including autism and bipolar disorder. “In addition, there are environmental factors that must play a key role in the development of these conditions such as intrauterine infections or birth complications,” said Owen. “They are the price we pay for having brains of unrivalled complexity.”

As to developing treatments, that is going to be hard given that so many mutated genes – each having only a tiny effect – are involved in predisposing individuals to schizophrenia. “It is going to some major advances in medical science and of course we are working towards that now.”

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