An international team of researchers led by Hans Moises of the University of Kiel announced today what appears to be a breakthrough in the search for the causes of schizophrenia. The discovery was presented at two scientific e-print servers, the internet's equivalent of scientific meetings.

The devastating effect of schizophrenia has recently been shown to the general public in the Oscar-winning movie A Beautiful Mind. Fifty million people are afflicted worldwide by the mysterious disease, including 2.5 million in the United States.

The team of researchers consists of scientists from the USA, India, China, the UK, Germany and Iceland. The group used a new association method developed by Dr. John Edwards at the University of Oxford.

Two genetic markers on both sides of the neuregulin-1 gene on the short arm of chromosome 8 revealed a highly significant association with schizophrenia. The marker close to the neuregulin-1 gene is strongly associated with the disorder thus identifying it as a major risk gene for schizophrenia.

The proteins of the gene are growth factors involved in the growth of the brain, especially of its supporting cells, the so-called glial cells, and of cancer, as well as of synaptic plasticity which is important for memory, and of motor neurons. All these areas have been found in numerous studies to be abnormal in schizophrenia. The discovery suggests a neuregulin deficiency in schizophrenia which could be treated with neuregulin-1.

"The neuregulin finding shows the postulated connection between the two major theories of schizophrenia, the genetic and the neurodevelopmental hypotheses," says Dr. Irving Gottesman of the University of Minnesota. It is also in agreement, according to Dr. Hans Moises, with his results obtained in 2001 by another analysis which suggested among other risk genes neuregulin-1 and a deficient protein synthesis of the brain as common final pathway in schizophrenia. Dr. Tomas Zoega says, "I am glad that our international Icelandic collaboration started many years ago has led to the identification of one of the genes involved. It will provide a rational empirical starting point for therapeutic intervention."

A genetically engineered neuregulin-1, termed recombinant human Glial Growth Factor 2 (rhGGF2), is already in late-stage preclinical development as treatment for neurodegenerative diseases such as multiple sclerosis at the Cambridge NeuroScience Inc in Massachusetts and the Bayer Corporation. Therefore it seems to be possible that neuregulin-1 might soon be available for the treatment of acute schizophrenic psychosis.

A copy of the paper describing the discovery is available at

• Research Paper: The Neuregulin 1 gene and Susceptibility to Schizophrenia (300K pdf file)