Neuregulin and Schizophrenia

Professor Daniel Weinberger discusses research that makes neuregulin a candidate gene for schizophrenia.

So what is the role of neuregulin in schizophrenia? The neuregulin story is very analogous to the dysbindin story. Neuregulin was discovered basically the same way. It was based on family studies doing the so-called linkage analysis across the genome looking for where markers that were spaced across the genome, which are just little polymorphic segments of DNA, would segregate, that is travel in families along with the illness phenotype. And when these studies were done, one of the other regions of the genome that showed a very good so-called ‘linkage signal' was a region of the short arm of the eighth chromosome. And lying in that region was a gene called neuregulin. And when people looked then specifically at neuregulin for whether variations in its sequence were more abundant in schizophrenics than in controls, they found a signal in neuregulin. And this has also been replicated in probably ten studies around the world. So that makes neuregulin look like a very good functional candidate gene for schizophrenia. How does neuregulin cause schizophrenia? Again, this is work that has only been two years outgoing, but neuregulin is a multi-functional complex protein involved in many aspects of brain development, as probably are all the schizophrenia genes by the way. And neuregulin is involved with the differentiation of nerve cells it’s involved with how nerves respond to the environment, it’s involved with things called neuroplasticity and neural signaling. And so we believe that neuregulin is a risk gene for schizophrenia, in terms of our current state of knowledge, by affecting subtle processes involved in brain development that are probably part of how the schizophrenic brain gets configured.