Risk gene for cannabis psychosis

Research by King’s College London’s Institute of Psychiatry suggests that a specific gene called AKT1 may be key in understanding why some people develop psychosis from smoking cannabis when others do not. 

However, the authors point out that further research is needed before the findings can be clinically significant.

Previous research has shown a link between smoking cannabis and psychosis. There is also emerging data that cannabis exposure during adolescence may increase the risk of developing schizophrenia. Predicting who is at risk of developing cannabis psychosis could therefore be used to advise people who smoke cannabis.

Researchers, led by Dr Marta Di Forti at King’s Institute of Psychiatry, studied the AKT1 gene, which is involved in dopamine signaling and known to be abnormal in psychosis. They studied 489 patients with their first episode of psychosis and 278 healthy controls.

They performed genetic tests on all volunteers, and assessed their use of cannabis. They found that cannabis users who carry a particular variant in the AKT1 gene had a two-fold increased probability of a psychotic disorder and this increased up to seven-fold if they used cannabis daily.

Dr Di Forti says: “We found that cannabis users who carry a particular variant in the AKT1 gene had a two-fold increased probability of a psychotic disorder and this increased up to seven-fold if they used cannabis daily. Although using cannabis increases the risk of schizophrenia, most cannabis users come to no harm. It has therefore been suggested that those who develop psychosis may carry some genetic vulnerability.

“Our findings help to explain why one cannabis user develops psychosis while his friends continue smoking without problems. Such findings could also help to design health educational campaigns tailored to reach those young people at particular risk.”

Dr. John Krystal, Editor of Biological Psychiatry says: “While the AKT1 genotype does not rise to the level of a clinically useful test of the risk for cannabis psychosis, it does show that this source of psychosis risk has a genetic underpinning.

“This advance also points to cellular signaling mechanisms mediated by Akt1 as being relevant to the biology of cannabis psychosis. This may suggest research directions for novel therapeutics for cannabis psychosis.”

Full paper: Di Forti, M. et al. “Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users” Biological Psychiatry, Volume 72, Issue 10 (November 15, 2012) doi: 10.1016/j.biopsych.2012.06.020

For further information, please contact Seil Collins, Press Officer, King’s College London’s Institute of Psychiatry, at +44 0207 848 5377 or seil.collins@kcl.ac.uk.

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Researchers in 'most powerful genetic studies of psychosis to date'

Two genome wide studies involving more than 50,000 participants have identified new genetic risk factors for schizophrenia and bipolar disorder. The research was conducted by over 250 scientists from more than 20 countries – one of the largest collaborative efforts in psychiatry to date.

The results of the Psychiatric Genome-Wide Association Study (GWAS) Consortium were published in two research papers in the October issue of Nature Genetics.  

The schizophrenia study found a total of seven locations on the genome to be implicated in the disease, five of which had not been identified before. The bipolar GWAS study revealed four locations on the genome associated with the disorder, one of which has not been previously identified. Combining the findings from both studies revealed that three gene locations were involved in both disorders, confirming the genetic overlap between schizophrenia and bipolar disorder.

Schizophrenia and bipolar disorder are common and often devastating brain disorders. Some of the most prominent symptoms of schizophrenia are hallucinations and delusions. Bipolar disorder is characterized by severe, episodic mood swings. The conditions are known to be caused by a combination of genetic and environmental risk factors.

Professor David Collier from the Institute of Psychiatry at King’s College London, who was involved in both studies says: ‘Although we have known that psychiatric disorders such as schizophrenia and bipolar disorder have a strong genetic basis, it has proven very difficult to identify the genetic risk factors involved. This is because the causes of these illnesses are highly complex, with many different genes and environmental factors involved. In order to try and solve this puzzle, hundreds of scientists researching schizophrenia have pooled their research results resulting in a major and unprecedented research cooperation, involving tens of thousands of volunteer patients.'

Prof Collier adds: ‘These are the most powerful genetic studies of psychosis to date, and have enabled us to identify a host of new genetic risk factors. These include one gene, a ‘micro RNA’ which may be acting as a master regulator, influencing the biological pathways in the brain, which once perturbed lead to schizophrenia.

‘Our findings are a significant advance in our knowledge of the underlying causes of psychosis - especially in relation to the development and function of the brain. Unravelling the biology of these disorders brings great hope for the development of new therapies – we can attempt to develop therapeutic drugs which target the molecules in the brain involved in the development of psychosis.’

IoP researchers at the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre who contributed to the bipolar GWAS study included Professor Anne Farmer, Professor Peter McGuffin, Dr Gerome Breen, Amanda Elkin and Richard Williamson and Professor David Collier who also contributed to the schizophrenia GWAS study.

The research was funded by over 40 US National Institutes of Health grants and a similar number of government grants from many countries involved, along with substantial private and foundation support.

Notes to editors:

Sklar, P. at el. ‘Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4’, Nature Genetics (October 2011) doi:10.1038/ng.943
http://www.nature.com/ng/journal/v43/n10/full/ng.943.html

Gejman, P.V. et al. ‘Genome-wide association study identifies five new schizophrenia loci’, Nature Genetics (October 2011) doi:10.1038/ng.940 http://www.nature.com/ng/journal/v43/n10/full/ng.940.html

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