Research subject

Neuropsychiatric disorders, a public health priority worldwide, are the result of the accumulation and interactions throughout life of environmental, biological, genetic and epigenetic factors. Genetic data on these pathologies have significantly increased but must be now accompanied by greater knowledge about the role of the environment, which constitutes 70% to 90% of the risk of developing these pathologies.

Our unifying hypothesis states that environmental conditions, whether exogenous (psychosocial exposures, stress, lifestyle, pathogens, pollution and climate) or endogenous (diet, drugs, immunity, microbiota), shape our brain, the cognition and the behavior by acting on individual genetic vulnerability.

Our main objective is the identification and study of potentially modifiable environmental factors (vulnerability or protective) and biomarkers of neuropsychiatric pathologies that can be used to :

- Predict complex trajectories in order to prevent the onset of cognitive and mental disorders
- Inform public health prevention strategies
- Propose multimodal personalized medicine
- Develop innovative treatments.

Our multidisciplinary team (psychiatrists, neuro-epidemiologist, psychologists, pharmacist, biostatistician) studies suicidal behavior, eating disorders, schizophrenia and Alzheimer's disease (cognitive impairment in aging): 4 research axes.

Using an original approach, we identify risk factors and biological, cognitive and behavioural determinants common to these phenotypes and work on multi-causal etiological models. We have thus highlighted, on the one hand, common points between psychiatric and neurological disorders (white matter brain alterations, inflammation, decision making) and, on the other hand, we have identified specific homogeneous subgroups (vulnerable personalities, late depression, sleep disorders, social pain). These data pave the way for precision medicine.

Our epidemiological and clinical work is based on :

- Population_based cohort studies including the three-city Study (Bordeaux, Dijon, Montpellier http://www.three-city-study.com/) nearly 10,000 people aged 65 and over followed for 15 years, and its psychiatric part : the Esprit study. We also work with open access cohorts such as CONSTANCES (100 000 participants).

- Innovative clinical cohorts: Sui-predict, Smart-crisis, DIBLAN, G-PACTS, NISIS, SOLSTIS, GENESIS, DIAPEPSY, FACE.

These richly phenotyped cohorts allow us to perform multi-level analyses (lifestyle, iatrogeny, neuropsychology, genetics, biology, brain imaging, and recently COVID-19 exposure and infection). Some cohorts are also equipped with cuting edge sub-clinical biomarkers, integrating "omics" and markers from e-health (movement, sleep, social networks, biosensors) and robotics (social interactions).

- From longitudinal data, including lifetime exposure, we establish predictive statistical models.

Our work is then enriched by translational approaches conducted notably in collaboration with other IGF teams, in order to decipher physiopathological processes identified in our cohorts.

Our collaborations

- National : ISEM, Montpellier ; ISPED, Bordeaux ; Institut of Psychiatry &Neurosciences Paris ; Fondamental Foundation , Paris
- International : Melbourne & Canberra Univ, Australia ; Badajos Univ; Sevilla Univ; Jimenez Diaz, Foundation, Madrid

From environmental exposures to neuropsychiatric diseases

Research subject

Research theme: Cardiovascular diseases, including myocardial infarction and arrhythmias remain the leading cause of death in the world in 2019. By 2030, nearly 23.6 million people will die from cardiovascular disease, so it is essential to maintain our efforts in the field of cardioprotection.
Two parameters are paramount to preserve the cardiac performance: (i) the heart pacemaker activity activity, which generates the cardiac impulse and controls the ventricular rhythm, and (ii) the contraction efficiency of the myocardium. In this context, research projects of the team focus on the study of the cellular mechanisms involved, on the one hand, in the control of pacemaker activity and, on the other hand, in the processes of cell death leading to injury after myocardial infarction. The objectives of the team are to develop cardioprotective strategies to normalize heart rate and to inhibit cardiac cell apoptosis, in order to prevent ventricular remodeling leading to heart failure.

Strategy and techniques: The team uses mouse models of cardiac pathology such as transgenic mice with sick sinus syndrome, brady- or tachyarrhythmias. For the model of myocardial infarction, the reversible coronary ligation surgical model is used to best mimic the clinical context of myocardial ischemia-reperfusion. The technical platform of the team consists of all the devices for non-invasive pre-clinical monitoring with telemetric ECG recordings and echocardiography. Ex vivo experiments with isolated hearts (Langendorff) and in vitro recordings of contraction and electrical activity (DMT, patch-clamp, ..) are also performed to study the mechanistic aspects.

The team is part of the labex ICST (Ion Channel Science and Therapeutics and of the RegenHab FHU.