Scientists move forward understanding of schizophrenia

November 17, 2005

A Scots-led medical research team has identified a new gene linked to major mental illness that links back to a previously discovered gene known to increase the risk of schizophrenia and depression. Scientists from the Universities of Edinburgh and Glasgow, together with scientists from the pharmaceutical company Merck, Sharp & Dohme Limited, report the discovery of the second gene, phosphodiesterase 4B (PDE4B) in the prestigious journal Science today (17 November). Their discoveries could lead to the eventual development of new drugs to treat mental health problems.

In 2000, researchers at the University of Edinburgh identified a gene they called Disrupted in Schizophrenia 1 (DISC1), which was found to increase the chances of people developing schizophrenia, bipolar disorder (manic depression) and major clinical depression.

Now, new research by the two Universities and by scientists from the pharmaceutical company Merck Sharpe and Dohme reveals that damage to the gene PDE4B is also seen to increase the risk of developing mental illness. PDE4B was already known to play an important role in how the brain thinks and builds memories, but had not previously been linked to mental disorder. In addition, researchers have discovered that DISC1 acts as a regulator for PDE4B, creating a 'pathway' between the two genes.

Professor David Porteous at the University of Edinburgh said: "This is another important breakthrough in our still limited understanding of major mental illness. It is the result of a long term research commitment to use the tools of genetics to better understand the root causes of mental disorder.

"This has been a fantastic combined effort. The collaboration between the Universities of Edinburgh and of Glasgow, jointly with our research colleagues at Merck Sharpe and Dohme has really made this happen.

"It is now clear that the DISC1 gene plays an important role in the risk of developing schizophrenia or bipolar affective disorder. The new genetic link we have made to PDE4B and how that links back to DISC1 sheds much needed light on these debilitating disorders. It also suggests a new way of thinking about developing better and effective medicines."

Professor Miles Houslay of the University of Glasgow said: "Over the past few years we've been working hard to help in the development of medicines for treating asthma and chronic obstructive pulmonary disease by inhibiting very similar enzymes to PDE4B. It has been so exciting to work together with the Edinburgh and Merck groups in finding this new link between the gene coding for PDE4B and schizophrenia. This new research has the potential for developing novel ways of diagnosing and treating this debilitating disease."

Peter Hutson, the Neuroscience Research Centre, Merck Sharp & Dohme, said: "Mental illness remains a scourge of society. Our insights into the important role that the proteins PDE4B and DISC1 may play in the mis-function of the brain that leads to schizophrenia will lead our thinking in the development of new treatments for this disorder"
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University of Edinburgh

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