2016 Marcel Dassault Prize for Mental Health ReseaFriday 16 December 2016
In France, one out of five people suffer from psychiatric disorders. By 2020, psychiatric disorders will become the leading cause of disabilities worldwide. Now more than ever, support for mental health research needs to be a priority, to better understand the causes and mechanisms of these disorders and their environmental risk factors, and to encourage the development of diagnostic and therapeutic innovation. For the 5th year, the FondaMental Foundation and the Dassault Group have joined forced to support the most promising research projects by awarding the Marcel Dassault Prize. This year, the Dassault Group has increased its sponsorship to 300,000 euros. The international jury has selected Nicolas Glaichenhaus for his project dealing with patients suffering from schizophrenia.
NICOLAS GLAICHENHAUS: FROM IMMUNOLOGY TO PSYCHIATRY
Nicolas Glaichenhaus has been Professor of Immunology at the University of Nice Sophia Antipolis since 1991, and a member of the Institut Universitaire de France since 1995.
After completing his thesis on gene expression regulation in eukaryotic cells, Nicolas Glaichenhaus was a postdoctoral intern at the University of California-Berkeley, where he began to specialise in immunology, specifically T-lymphocytes and their interactions with other cells in the body.
On returning to France in 1991, Nicolas Glaichenhaus received ATIP funding from the French Research Council (CNRS) to create a team within the Molecular and Cellular Pharmacology Institute, a CNRS research lab at the University of Nice Sophia Antipolis. The team has also been associated with INSERM since 2003.
Nicolas Glaichenhaus is the co-author of more than 100 publications, and his research has won several scientific awards, including the Medical Research Foundation award and the Bernard Halpern prize.
Alongside his research and teaching activities, Nicolas Glaichenhaus has been a member of numerous research assessment groups and steering committees in France and abroad.
THE RESEARCH PROJECTContext
Numerous treatments are now available for patients suffering from schizophrenia. Nevertheless, doctors lack markers for choosing the most effective therapeutic strategy for a given patient. For many years, doctors and researchers have been working to identify biological markers using genetic or immunological pathways and cerebral imaging. However, none of the markers identified so far have proven reliable enough to be used by doctors in their daily practice.
A unique approach: applying big data to immunology on behalf of precision medicine in psychiatry
Working in close collaboration with Michel Barlaud and Lionel Fillatre, two mathematicians from the University of Nice Sophia Antipolis, Nicolas Glaichenhaus proposes to use "supervised statistical classification" techniques to retrospectively analyse blood samples (inflammatory markers) and the clinical files of hundreds of patients suffering from schizophrenia, followed by the FondaMental Foundation Expert Centres.
Recent discoveries in immunology have revealed that dysfunctions in immune defence and inflammatory response could be a cause of or contributing factor to the development of psychotic disorders. This is why research on inflammatory blood markers is so promising. It provides a new understanding of schizophrenia that potentially opens the door to new diagnostic and therapeutic tools. Several studies suggest that for patients suffering from schizophrenia, these markers might be dependent on the interaction between a genetic profile and environmental risk factors (stress, infections, etc.).
By processing immunological and clinical data using big data methods, Nicolas Glaichenhaus hopes to develop a prediction algorithm that will enable a psychiatrist to identify the treatment with the highest probability of being effective for a given patient, on the basis of a simple blood sample.
A project based on encouraging preliminary results
To obtain proof of concept on the project’s feasibility, Nicolas Glaichenhaus was given access to a group of patients with a first psychotic episode, who had not been treated previously. He measured molecules from the inflammation produced by cytokines in the patients’ serum, before and after their treatment with Amisulpride, a first-line antipsychotic treatment. Data for the treatment’s responders and non-responders was analysed using advanced statistical classification methods. The analysis was used to generate a preliminary version of a mathematical algorithm that would predict, based on the concentration of a few cytokines before treatment, whether a patient would be a responder or non-responder to the first-line antipsychotic.
The project could lead to the development of new “theranostic” biomarkers
"Although the preliminary results we obtained with psychotic patients are encouraging, the predictive power of our algorithm, i.e. its selectivity and specificity, is still insufficient. To improve its predictive power, we will explore several solutions, including measuring the concentration of other cytokines, the integration of clinical data, and the incorporation of so-called “chart” constraints. Moreover, regardless of the predictive power of our algorithm, it cannot be used in daily clinical practice until we confirm its effectiveness with other groups of patients, and at different stages of the disorder. Lastly, assuming that our project produces the expected results, we would like to implement similar approaches to design clinical-biological markers for diagnostic purposes that will help psychiatrists identify, among patients who are experiencing an episode of depression, those which are unipolar (solely depressive) and those which are bi-polar (experiencing both depressive and manic episodes). We will be able to develop these projects thanks to the Marcel Dassault Prize and funding from the Dassault Group and the FondaMental Foundation."
Precision medicine offers immense hope for patients suffering from schizophrenia
We can hope that in the years ahead, psychiatrists will be able to identify the most suitable treatment for their patients, on the basis of a simple blood sample.
Schizophrenia in France
In France, 600,000 people are now suffering from schizophrenia. There are twice as many patients in cities than in rural areas, and the first symptoms generally appear between the ages of 15 and 25. The disorder is characterised by delirium, hallucinations, anxiety, and difficulties in feeling emotions and reasoning in a logical manner. Although the mechanisms that trigger the disorder are still poorly understood, studies over the past 20 years, notably by researchers at the FondaMental Foundation, have demonstrated that the immune system – the system which helps us fight external aggressions, such as infections and stress – plays a key role.
About the FondaMental Foundation
Motivated by the conviction that only quality research can help meet the medical and scientific challenges raised by these pathologies, the FondaMental Foundation is participating in the current scientific revolution in the field of psychiatry, a source of hope for patients and their loved ones (www.fondation-fondamental.org). The Foundation brings together healthcare professionals and research teams to work on what are considered to be the most disabling disorders. To meet the challenges posed by these pathologies, the FondaMental Foundation is pursuing four missions:
- Improve diagnostic precision
- Accelerate psychiatric research in France
- Train healthcare professionals and other players, by disseminating knowledge
- Inform and build awareness among the general public and decisions makers, to change their view of mental health disorders