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MRC Fellowship awarded for new cannabis research

Posted on 08/12/2014
Dr Marta Di Forti has been awarded an MRC Clinician Scientist Fellowship

Marta Di Forti has been awarded one of the coveted Clinician Scientist Fellowships of the Medical Research Council (MRC). Dr Di Forti, a Clinical Research Worker at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), proposed a study investigating the biological mechanisms underlying the onset and outcome of cannabis associated psychosis.

The proposal includes detailed data on the history of cannabis use on 2,000 patients suffering their first episode of psychosis along with 2,000 healthy population controls. The analysis of these data will enable her to establish the patterns of cannabis use that best identify those at greatest risk of developing a psychotic disorder.

Most cannabis users do not develop psychosis, suggesting that individual susceptibility must also play a role. Using DNA samples from the study participants, Dr Di Forti aims to produce a summary score of genetic vulnerability to psychosis, for cases and controls, and investigate how differences in genetic vulnerability influence the individual’s risk of developing a psychotic disorder following cannabis use. On subsets of the whole sample, epigenetic and RNA expression data across the genome will be examined to see how exposure to cannabis use affects the way the DNA structure is expressed into RNA and then into proteins that impact on biological functions. This research will be the first to conduct such an integrated approach to establishing the biological changes cannabis exposure induces, and if changes in epigenetics and RNA expression can be used as biological markers to determine why certain cannabis users have developed psychotic illness.

A sub-set of the sample will be followed up at five years from onset of illness to assess outcome and repeat the measures of epigenetics and RNA expression. This is to identify the effect of cannabis use in causing poor outcome; what biological markers predict the greatest cannabis-associated decline; and if such biological changes are reversible when cannabis use ceases.

Dr Di Forti's project aims to produce important information concerning the relative frequency of cannabis-associated psychosis across five European countries. The findings concerning the patterns of use, and biological markers of susceptibility to the effect of cannabis, which provoke onset and persistence of psychosis, will be useful in clinical practice. They could indicate new drug targets to develop interventions aimed at reversing these epigenetic changes and inform better tailored public education campaigns.

The Clinician Scientist Fellowship at the MRC is very competitive and MRC Fellows are expected to maximise the impact of their research and act as an MRC ambassador for the next generation. Dr Di Forti’s epigenetic work will be carried out with Prof Jonathan Mill and Dr Chloe Wong and the cutting edge statistical analyses with the BRC Bioinformatics Department led by Dr Richard Dobson.

After graduating first in her medical school year in Palermo in Italy, Dr Di Forti came to London and joined the St George's training scheme. She completed her MRCPsych in 2002, and came to King’s in 2003 to work with Professor Robin Murray's team and in 2004 won a grant to research first episode psychosis. The study called Genetics and Psychosis (GAP) collected baseline data over six years and produced 26 papers and eight PhDs. The GAP follow up is still ongoing.

As well as research and teaching, Dr Di Forti works one day per week as a Consultant Psychiatrist  at the Lambeth Early Intervention team, part of the South London and Maudsley NHS Foundation Trust,  treating young people with their first episode of psychosis, most of whom have abused cannabis. The terms of the MRC Fellowship permit her to continue clinical work during the course of the research. Her aim is to discover more about gene-environment interactions that lead to psychosis and so contribute to better understanding and treatment of the condition.

“Christmas has come early for me this year" said Dr Di Forti. "I feel very privileged to have been given this opportunity to refine our understanding of the impact of cannabis use on the risk of psychosis and to move towards investigating its underlying biology. This is a project inspired by the young patients, mostly cannabis users, that I meet in my clinical practice at the Lambeth Early Onset team (LEO). I look forward, with the support of my outstanding sponsors and collaborators, to contributing to the prevention of cannabis associated psychosis, and to improving the care of patients suffering from psychosis associated with cannabis use. 

“One of the greatest limitations to progress in Psychiatry is the lack of reliable measures and biological markers for diagnosis and prediction of outcome.  As a consequence, patients with psychiatric illnesses and especially those suffering from psychosis are often stigmatized and discriminated against, as they are considered as suffering from a mysterious disease with no cure. I believe my research could play a small role in overcoming this stigma and discrimination.”

For further information contact Tom Bragg, Press Officer at IoPPN, King’s College London, on +44(0)2078485377 or email ioppn-pr@kcl.ac.uk

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