In her plenary lecture, recipient of the ECNP 2018 Neuropsychopharmacology Award, Professor Marion Leboyer (University of Paris, Créteil, France) outlined the 3 principles driving her award-winning research as: Dare to think outside the box, Share, and Care.
Dare to think outside the box, Share, and Care
Professor Leboyer predicted an era of precision in medicine in which different treatments are used for different patient subtypes. For instance, anti-inflammatory treatment would be considered for patients with evidence of inflammatory etiology.
A goal of psychiatry is to develop diagnostic tools to better identify homogenous subgroups of psychiatric disorders, paving the way for the identification of mechanism-based innovative treatments. Advances in deep phenotyping and big data analysis will allow patient stratification and precise therapeutic strategies including target-based treatments, cell therapy, psychosocial treatments, and biotherapy/neuromodulation.
A goal of psychiatry is to develop diagnostic tools to better identify homogenous subgroups of psychiatric disorders
Precision in medicine is making inroads towards optimizing the treatment of schizophrenia. In the past, it was not possible to predict treatment response, possibly due to patient heterogeneity. In the OPTiMiSE study, patients were stratified into 4 subtypes among which one was characterized by both an inflamed inflammatory signature and the most severe symptoms. Among patients with the inflammatory phenotype, lack of efficacy of antipsychotics could be predicted with 80% accuracy. Nonetheless, using a simple treatment algorithm to identify the need for switching treatment, symptomatic remission was achieved for most patients in the early stages of schizophrenia.1
Is inflammation the key missing link between environmental risk factors and psychiatric disorders?
Research conducted by Professor Leboyer and collaborators has identified inflammation as a key missing link between environmental risk factors and psychiatric disorders. The interaction between immunogenetics and environmental risk factors, such as infections, stress and unhealthy lifestyle, leads to low grade inflammation in the periphery, brain and gut, which induces many different pathways, including the production of brain auto-antibodies and human endogenous retrovirus (HERV).2-4
HERV at the gene-environment interface can trigger de novo genetic and auto-immune disorders. Elevated levels of the envelope protein of the activated endogenous HERV-W identified in response to infection, and leading to inflammation and neurotoxicity, may lead to development of bipolar disorder and schizophrenia.4,5 Consequently, development of an antibody to neutralize the envelope protein HERV-W is a target of precision medicine.
Development of an antibody to neutralize the envelope protein HERV-W is a target of precision in medicine
Inflammation increases antigen traffic through the leaky gut wall into the bloodstream leading to development of brain auto-antibodies against neurotransmitter receptors (e.g. the NMDA receptor) that can be identified before the onset of psychiatric disorders and in patients with schizophrenia,3 leading to the concept of ‘auto-immune psychosis’.6 In the future, directed treatments for auto-immune psychosis, such as immunomodulators, may be possible.
A key facilitator on the road to precision in psychiatry is the sharing of research data, platforms, and innovations to reduce the cost and risk of developing new treatment strategies. Professor Leboyer revealed her personal goal would be to develop a “virtual institute” for precision in psychiatry, building strong partnerships between academia, industry, governments and patients.
Develop a “virtual institute” for precision in psychiatry, building strong partnerships between academia, industry, governments and patients
A first step on this road is establishment of the Fondation FundaMental, a collaborative scientific initiative dedicated to the fight against major psychiatric disorders.
For more on the topic of how big data analysis could possibly aid in the movement towards precision medicine in psychiatry, see https://progress.im/en/content/promise-big-data-analysis-%E2%80%93-precision-psychiatry-and-therapeutic-targeting. For more on the gut-brain relationship, see this recent article from ECNP 2018: https://progress.im/en/content/probiotics-psychobiotics-nutrition-gut-and-brain