Gene variant linked to schizophrenia, bipolar disorder and alcoholism

July 22, 2014

A rare gene variant discovered by UCL (University College London) scientists is associated with an increased risk of developing schizophrenia, bipolar disorder and alcoholism, confirms new research.

People with the variant are around 2 to 3 times more likely to develop or , reports a new UCL study. The variant, which is found in approximately one in every 200 people, is also associated with a threefold risk of developing , as previously shown by the same UCL group.

The research, published in Psychiatric Genetics, is based on genetic analysis of 4,971 people diagnosed with one of the three disorders compared with 1,309 healthy controls. It found that people with the variant of the GRM3 gene, thought to be important in brain signalling, were at increased risk of developing bipolar disorder, schizophrenia and alcohol dependence.

GRM3's association with schizophrenia was also confirmed by a global study involving a consortium of over 200 institutions including UCL. The research, published in Nature, involved searching the genomes of 36,989 people with schizophrenia and 113,075 healthy subjects from across the world. 108 different genetic locations were found to be associated with the disease, but GRM3 is the only one for which a specific mutation responsible has been identified.

"We could be looking at the next big drug target for treating mental illness," says Professor David Curtis (UCL Psychiatry), co-author on both papers. "The work opens up new ways to prevent and treat mental illnesses by revealing the mechanisms involved in their development. The result for GRM3 from the consortium is particularly compelling, as the odds of this occurring by chance are only one in a billion."

At present, schizophrenia is treated with drugs that reduce the activity of the chemical dopamine. Dopamine is important for transmitting messages between , but over-active dopamine signalling may cause parts of the brain that are supposed to be separate to communicate with each other. For example, some scientists suspect that such signalling between the speech and hearing centres of the brain may explain why people with schizophrenia 'hear voices'.

Yet dopamine is not the only chemical that brain cells use to communicate with each other. Glutamate is also involved and GRM3 codes for a protein which brain cells use to detect glutamate. Brain cell activation is controlled by calcium 'channels'. The latest research implicates both glutamate transmission and in schizophrenia development.

"Drug treatments for schizophrenia have barely changed over the past few decades, as they still target dopamine receptors," says study co-author Dr Andrew McQuillin, head of the UCL Molecular Psychiatry team that first discovered GRM3. "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.

"Drugs targeting calcium channels have been tested against bipolar disorder with some success, although only in open-label trials and not double-blind clinical trials. The results should therefore be interpreted with caution, although the Nature paper findings do suggest that calcium channels are a viable drug target. Overall I expect we will see increased interest in drugs against both glutamate receptors and calcium channels as a result of the research."

Explore further: Schizophrenia's genetic 'skyline' rising: Suspect common variants soar from 30 to 108

More information: medicalxpress.com/news/2014-07 … common-variants.html

Related Stories

Schizophrenia's genetic 'skyline' rising: Suspect common variants soar from 30 to 108

July 21, 2014
The largest genomic dragnet of any psychiatric disorder to date has unmasked 108 chromosomal sites harboring inherited variations in the genetic code linked to schizophrenia, 83 of which had not been previously reported. ...

New risk factor found for schizophrenia

February 6, 2014
(Medical Xpress)—Scientists have discovered a link between a largely unstudied gene and schizophrenia.

High levels of glutamate in brain may kick-start schizophrenia

April 18, 2013
An excess of the brain neurotransmitter glutamate may cause a transition to psychosis in people who are at risk for schizophrenia, reports a study from investigators at Columbia University Medical Center (CUMC) published ...

Researchers find epigenetic tie to neuropsychiatric disorders

July 21, 2014
Dysfunction in dopamine signaling profoundly changes the activity level of about 2,000 genes in the brain's prefrontal cortex and may be an underlying cause of certain complex neuropsychiatric disorders, such as schizophrenia, ...

Psychiatric disorders linked to a protein involved in the formation of long-term memories

June 17, 2013
Researchers have discovered a pathway by which the brain controls a molecule critical to forming long-term memories and connected with bipolar disorder and schizophrenia.

Recommended for you

Depression changes structure of the brain, study suggests

July 21, 2017
Changes in the brain's structure that could be the result of depression have been identified in a major scanning study.

Many kinds of happiness promote better health, study finds

July 21, 2017
A new study links the capacity to feel a variety of upbeat emotions to better health.

Study examines effects of stopping psychiatric medication

July 20, 2017
Despite numerous obstacles and severe withdrawal effects, long-term users of psychiatric drugs can stop taking them if they choose, and mental health care professionals could be more helpful to such individuals, according ...

Study finds gene variant increases risk for depression

July 20, 2017
A University of Central Florida study has found that a gene variant, thought to be carried by nearly 25 percent of the population, increases the odds of developing depression.

In making decisions, are you an ant or a grasshopper?

July 20, 2017
In one of Aesop's famous fables, we are introduced to the grasshopper and the ant, whose decisions about how to spend their time affect their lives and future. The jovial grasshopper has a blast all summer singing and playing, ...

Perceiving oneself as less physically active than peers is linked to a shorter lifespan

July 20, 2017
Would you say that you are physically more active, less active, or about equally active as other people your age?

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.