21 Oct Study Locates Gene Variation Linked to Greater Risk of Schizophrenia, Bipolar Disorder and Alcoholism
A recent study conducted at the University College London has added to a growing body of knowledge about how and where genetic mutations affect a person’s risk for developing certain illnesses. The new study identifies a specific and rarely occurring (showing up in just one out of every 200 individuals) gene variation linked to a higher risk for serious mental health conditions such as alcoholism, bipolar disorder or schizophrenia. Having a variant of the gene GRM3 increases a person’s likelihood of alcoholism or schizophrenia by as much as two or three times and the risk of bipolar disorder threefold.
The British Study
The new findings are based on genetic study of 4,971 individuals affected with one of the aforementioned conditions along with 1,309 non-affected (healthy) control subjects. The new research builds on findings from a previous larger-scale investigation into genetic underpinnings for these illnesses.
Study Points to GRM3 Gene
An international study looking for specific genetic markers linked to schizophrenia, for example, also identified GRM3 as a location where mutation can lead to development of the disorder. That study examined the genes of 36,989 individuals with schizophrenia at more than 200 research facilities. By comparing the genetic data from affected individuals with genomes of 113,075 non-affected controls, researchers were able to identify 108 gene locales in some way associated with schizophrenia. However, even in this larger scale worldwide study, GRM3 was the single gene location where variation has been clearly linked to the illness. Experts say that there is a one in a billion chance of this being a coincidence.
Why Gene Variants Matter
Knowing precisely where the problem starts can help drug manufacturers develop more narrowly targeted medications. Those might improve upon current treatments of schizophrenia but, even more exciting, treatments to prevent the illness are a possibility. Today, most medication used to treat schizophrenia works to calm dopamine activity in the brain by affecting dopamine receptors. Dopamine promotes region-to-region communication within the brain. It is believed that hyper-stimulated dopamine creates connectivity between brain areas not meant to be in communication.
For instance, one of the hallmark symptoms of schizophrenia is the experience of auditory hallucinations. People with the illness report hearing voices. Experts think that this may be the result of increased communication between the hearing area and the speech area inside the brain.
Creating Targeted Treatments
Toning down dopamine activity can reduce such symptoms, but dopamine is not the only chemical responsible for intra-brain messaging. Glutamate and calcium also play a role in cellular communication and are associated with the development of schizophrenia. Since GRM3 is involved with enabling cells to recognize glutamate, variations in GRM3 would reasonably be expected to affect brain communication. Medications that target glutamate receptors have not met with much success up to this point (especially in comparison to medications that affect dopamine receptors) but it is thought that they could perhaps be more beneficial to those with the identified GRM3 (a glutamate receptor) variant.
Scientists have used these findings to develop calcium-directed treatments for bipolar disorder. Those treatments have enjoyed limited success but have yet to be investigated in controlled double-blind trials. Still, understanding the specific ways the disorder is biologically driven is expected to lead to more effective treatments.
Conditions like alcoholism, bipolar disorder and schizophrenia can seriously impair a person’s ability to engage in routine activities of life. Developing treatments that go right to the source of symptoms could make an enormous difference in quality-of-life for people living with these illnesses.
People interested in reading further about these studies can find them published in research journals. The University College London study was printed in Psychiatric Genetics while the international study may be found in the publication Nature.
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