Vulnerability to mental disorders

Mental disorders are complex diseases whose development progressively recruits a large set of brain areas and neurotransmission systems. Moreover, there are inter-individual differences in the vulnerability to develop these pathologies. Such vulnerability can be conceptualized and characterized through several levels including genetic, environmental and affective/psychiatric ones, which are interconnected. Nicotinic acetylcholine receptors (nAChRs) are homo- and hetero-pentameric cationic ligand-gated ion channels composed of α and β subunits that can co-assemble in various combinations of distinct brain distribution and functional properties. There is a growing body of evidence linking alterations in nAChR number and/or function to several mental conditions such as substance use dirsorders, Alzheimer’s disease or schizophrenia. Our main objective, through fundamental and preclinical research with an opening towards translational research, is to unravel how the nicotinic system may contribute to such conditions. More particularly, we aim at characterizing the impact of a polymorphism of α5 containing nAChRs, previously identified in smokers, on a set of processes associated not only with nicotine but also cocaine, alcohol and possibly food addiction, as well as with social behavior and aggressiveness. In parallel, we are developing novel approaches to refine our understanding of the role of α7 containing nAChRs in neuropsychiatric endophenotypes. Finally, we are interested in environmental predisposition to nicotine addiction and have been establishing a link between the gut microbiota and the effects of nicotine on the mesolimbic system.