A new study carried out by scientists from University College London in the UK has reported on the discovery of a rare gene variant found in about 1 in every 200 people that could increase the risk of developing alcohol dependence, bipolar disorder and schizophrenia.
Their research found that people with the variant of the GRM3 gene, believed to be important in brain signaling, were approximately 2-3 times more likely to develop alcohol dependence or schizophrenia. Previous research by the same team has found that the same gene variant could triple the risk of developing bipolar disorder.
All three of these conditions are chronic and severe, often having dramatic impacts on peoples’ livelihoods and social relationships.
Treatment for schizophrenia and bipolar disorder focuses on eliminating the symptoms of the conditions, as the specific causes are unknown. The new research could, however, lead to new treatments as a further clue to the genesis of such conditions is unveiled. Co-author of the research Prof. David Curtis says:
”We could be looking at the next big drug target for treating mental illness. The work opens up new ways to prevent and treat mental illnesses by revealing the mechanisms involved in their development.”
The researchers, who published their results in Psychiatric Genetics, arrived at their findings through a genetic analysis of 6,280 participants. Of these people, 4,971 had been diagnosed with one of the three disorders, and their results were compared with the results of the 1,309 healthy control participants.
The team found that the participants who had a variant of the GRM3 gene were also more likely to develop schizophrenia, bipolar disorder or alcohol dependency.
The association between the GRM3 variant and an increased risk of schizophrenia was confirmed by a global study that also involved research from University College London (UCL), as part of a consortium of over 200 institutions.
The study, also co-authored by Prof. Curtis and published in Nature, examined the genomes of 36,989 people who had developed schizophrenia and 113,075 otherwise healthy subjects taken from different sites across the world.
The consortium identified a total of 108 different genetic locations that were associated with schizophrenia. Of these, only the GRM3 gene has had a specific mutation identified as being responsible.
Prof. Curtis says that the consortium’s findings were “particularly compelling,” as “the odds of this occurring by chance are only one in a billion.”
Presently, the activity of the chemical dopamine is key to methods of treating schizophrenia. Dopamine is a neurotransmitter that helps to transmit signals between brain cells, and it is believed that overactive dopamine signaling could lead to areas of the brain communicating with each other that are supposed to remain separate.
Some scientists believe that overactive dopamine signaling could be responsible for one of the prominent symptoms of schizophrenia. Being able to “hear voices” may be due to speech and hearing areas of the brain communicating between each other.
However, there are other chemicals that brain cells use in order to communicate with each other. Glutamate is another neurotransmitter that is involved, and calcium “channels” are used to control brain cell activation. The consortium’s research found that genes related to these, including GRM3 were implicated in the development of schizophrenia.
Dr. Andrew McQuillen is head of the UCL Molecular Psychiatry team that first discovered GRM3, and he says that the findings could affect future research into treating the chronic conditions that the GRM3 variant has been linked to:
“Drug treatments for schizophrenia have barely changed over the past few decades, as they still target dopamine receptors. Schizophrenia treatments targeting glutamate receptors have been tested in the past without success. However, they might be more effective at treating patient groups with mutations in glutamate receptors such as GRM3.”
Dr. McQuillen also acknowledges that drugs targeting calcium channels have previously been tested with some success against bipolar disorder and that the consortium’s findings suggest that they are viable drug targets. He says he expects “we will see increased interest in drugs against both glutamate receptors and calcium channels as a result of the research.”
At present, it is reported that 2.4 million American adults have schizophrenia, 5.7 million experience bipolar disorder and more than 18 million have alcohol dependence. Any developments related to treatment for these chronic illnesses stand to improve the lives of a considerable portion of the American population.
Earlier in the month, Medical News Today reported on research that found another genetic variation could increase the risk of schizophrenia.