People who suffer from mental illness commonly speak of self-medicating with alcohol while many a doctor has stood by and wondered, Why does this tendency exist? Now, scientists at University College London (UCL) have identified a rare gene mutation that increases a person’s risk of developing schizophrenia, bipolar disorder, and alcoholism. In fact, people with the variant of the GRM3 gene, are two to three times more likely to develop schizophrenia or alcohol dependence and nearly three times more likely to develop bipolar disorder, according to research published in Psychiatric Genetics.
GRM3 is a protein-coding gene that is involved in brain signaling — the complex choreography of electrical signals and neurotransmitters dancing through the networks of your brain. Researchers have long thought of GRM3 as a promising schizophrenia gene candidate yet only recently did a global study confirm the relationship between gene and disease. The study, which was conducted by a consortium of over 200 institutions, analyzed the genomes of nearly 37,000 people with schizophrenia and 113,000 healthy volunteers worldwide. Upon comparison, a total of 108 different genetic locations — the exact position on a particular chromosome — were found to be associated with the disease.
Yet, GRM3 was the only gene in which a specific mutation, found in approximately one in every 200 people, could be positively identified as linked to the disease. These results are compelling, the scientists explained, as the odds of this occurring by chance are only one in a billion. Building on the findings from the consortium study, a research team at UCL decided to run a genetic analysis of nearly 5,000 people diagnosed with any one of the three disorders — bipolar disorder, schizophrenia, and alcohol dependence — and then compare this with genetic analysis of about 1,300 healthy volunteers.
What did the team discover? People with the GRM3 mutation were at increased risk of developing these three illnesses. "We could be looking at the next big drug target for treating mental illness," said Dr. David Curtis, a professor of psychiatry at UCL and co-author on both research papers.
Schizophrenia is currently treated with drugs that reduce the activity of the neurotransmitter dopamine, which transmits messages between brain cells. Over-active dopamine signaling, scientists believe, may cause parts of the brain supposed to be separate to communicate with each other. Some scientists suspect, for instance, that signaling between the speech and hearing centers of the brain may explain why people with schizophrenia "hear voices."
Dopamine, though, is far from the only signaling chemical in our brains. GRM3 codes for a protein which brain cells use to detect glutamate, another neurotransmitter in our brains, and one that becomes active within calcium channels. Since glutamate transmission and calcium channels have now been found to be crucial to schizophrenia, scientists should begin to investigate the development of drugs that interfere with glutamate receptors and calcium channels in order to combat the disease.
Source: O’Brien NL, Way MJ, Kandaswamy R, et al. The functional GRM3 Kozak sequence variant rs148754219 affects the risk of schizophrenia and alcohol dependence as well as bipolar disorder. Psychiatric Genetics. 2014.