Translating the Language of Mental Disorders: The Role of Neuregulin 1 Transmembrane Domain in Schizophrenia

Gregory Petershack

Mentor: Dr. Consuelo Walss-Bass

Schizophrenia is a chronic mental illness characterized by positive symptoms, such as delusions and hallucinations (psychosis), negative symptoms, such as social withdrawal and flattened affect, and cognitive abnormalities, that affects ~1% of the population. Currently, diagnosis of schizophrenia is based entirely on a psychiatrist’s perception of outward symptoms, which include some of the symptoms described above, as well as duration of disturbances. The problem with this subjective form of diagnosis is that the symptoms have no biological basis and they overlap with those observed in other mental illnesses, such as bipolar disorder, making it hard to correctly diagnose the disease. There is currently no biological test to diagnose schizophrenia. The focus of our laboratory is to identify genes and mutations that are involved in causing schizophrenia, with the goal of identifying the biological causes of the disease and to develop biological tests, such asa blood tests, that could be used to correctly diagnose this disease. Neuregulin1 (NRG1) gene has been identified as a possible causative gene in schizophrenia. Our laboratory discovered a mutation in the NRG1 gene which causes a change of Valine (V) to Leucine (L) in the transmembrane domain of the NRG1 protein, which alters the function of the protein and may thereby be involved in schizophrenia development (Walss-Bass et al 2006). It has been shown that this V>L mutation causes reduced cleavage of the protein (Dejaegere et al 2008). NRG1 is known to be protective against inflammation, causing a reduction in levels of inflammatory molecules (Guo et al 2008).