Linking a Gene to Schizophrenia
Changes in the Neuregulin-1 Gene are Linked with Schizophrenia
Oct 13, 2008
Schizophrenia is a remarkably common neuropsychiatric disorder. Some estimates have suggested that as many as 0.5% or more of all people over the age of 18 may have schizophrenia. While this disorder appears to run in families, it is unlike disorders where a single gene mutation is involved (such as in Duchenne muscular dystrophy or sickle cell anemia). No single gene defect explains schizophrenia. However, multiple genes have been linked to a higher incidence of this disease.
Schizophrenia and Gene Linkage Analysis Studies
As has been the case for many disorders where there appears to be some kind of genetic underpinning, research studies have identified several different gene alterations which appear to be more highly associated with the occurrence of schizophrenia. These types of studies, commonly known as genetic linkage analyses, compare variations in the DNA isolated from families with a higher risk of the disorder to families of similar ethnic origins with no such history.
Using various statistical analyses, it is determined whether the presence of a certain change in DNA is more or less predictive of the occurrence of the disorder. If a specific change occurs more frequently it might suggest that it increases susceptibility to the disorder. If a change occurs less frequently than in the general population, it might be assumed to be somewhat protective against developing the disorder. Linkage studies have identified several genes that have specific DNA sequence alterations that appear to be associated with a higher risk of schizophrenia including the genes known as dysbindin, D-amino acid oxidase (DAO), DISC-1 and neuregulin-1 (NRG1).
How Might Neuregulin-1 and Schizophrenia be Connected
The neuregulin-1 gene produces multiple protein products which are expressed throughout the central nervous system and are known to regulate the behavior of specific neurotransmitter receptors in specific brain regions and to also impact specific parts of the brain during development. The areas of the brain and the neurochemistry influenced by NRG1 are closely related to those believed to be impacted in the brain of patients afflicted with schizophrenia.
While specific changes in the DNA of the NRG1 gene appear to be associated with a higher risk of developing schizophrenia, they do not cause the disorder, but rather appear to act as an enhanced susceptibility factor. More recent data(1) have suggested that there may be an important linkage between certain changes in the gene for NRG-1 and the gene for one of its receptor proteins, known as erbB4 (or HER-4).
What Changes in the Brain in Schizophrenia
It is believed that changes in the balance of certain neurotransmitters may lie at the heart of schizophrenia, most likely dopamine and glutamate. There are no clearly obvious, remarkable changes in the overall physical structure of the schizophrenic brain as compared to normal, but smaller, less obvious changes occurring during development could well lead to an enhanced susceptibility. Thus external influences in the environment including extreme stress or a host of others could more readily trigger the development of the disorder.
For more information about schizophrenia visit the US National Institute of Mental Health website.
Reference: (1)
Benzel, I. et al. (2007) Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia. Behav Brain Funct. Jun 28;3:31.
 |
