Discovery of genetic mutations that increase risk of schizophrenia

Aug 11 2009

In collaboration with colleagues from across Europe, researchers from the University of Copenhagen and the Mental Health Services in the Capital Region of Denmark have found mutations in the human genome that lead to an increased risk of developing schizophrenia.

This discovery brings about a new understanding of the interplay between genes and the environment, i.e. why some individuals with specific genetic variations in, for example, the immune system are sensitive to a number of environmental factors (e.g. infections) when it comes to developing schizophrenia. The findings have just been published in the reputed scientific journal, Nature.

50,000 Patients Involved

It is the most extensive study of schizophrenia ever, in which over 50,000 patients and control subjects from fourteen countries in Europe have been examined. The study showed a correlation between congenital mutations within three different genome areas.

"The study has made it clear that schizophrenia is not a single or small set of ailments, but rather an extensive and varied group of conditions, which may occur for completely different reasons, and which may have myriad ways of expressing themselves," says Thomas Werge, Head of Research at the Sct. Hans Mental Health Centre, at Copenhagen's University Hospital.

Genetic studies and findings pave the way for an examination of complex illnesses such as schizophrenia, whereby we can gain insight into the biology of the illness, and accordingly develop drugs that target the causes and not just the symptoms.

Mutations Affect the Immune System

One of the genome areas that is mutated in individuals – who are at risk of developing schizophrenia – is associated with the human immune system. For some time now, researchers have been honing in on a connection between schizophrenia and the immune system based on a disproportionately large number of schizophrenic patients who are born in either winter or spring, when flu infections are frequent. Five mutations have now been mapped: they are all located closely together within a chromosome area that is important both in terms of human tissue type, and in terms of regulating the way in which our immune system responds to infections.

There is another mutation located on a chromosome in proximity to a gene that regulates memory and intelligence. It is precisely these two human faculties that are often unstable in patients with schizophrenia.

The last mutation is found in a gene that plays a role in the development of the brain.

Treatments

Last year, the research team published a study which showed that extensive chromosome changes can also lead to schizophrenia. As a result of the study, the Danish team was allocated more than DKK 20 million in funds from the Lundbeck Foundation, the Danish National Advanced Technology Foundation, and the Danish Medical Research Council. The appropriated funds will serve two functions: partly to develop new drugs that prevent or cure the actual illness, in lieu of the drugs presently used that merely subdue the schizophrenic symptoms, and partly to develop genetic analyses that diagnose schizophrenia.