Résumé
The emergence of antipsychotics and antidepressants has revolutionized the management of psychotic and depressive disorders, improving the quality of life for many patients. Initially focused on monoaminergic pathways, this approach led to the development of drugs targeting dopaminergic, serotonergic, and noradrenergic systems. However, a large number of patients exhibit resistance and/or intolerance to these treatments. These challenges are related to the lack of understanding of the neurobiological mechanisms underlying the pharmacological and adverse effects of current medications, as well as the inherent limitations of the monoaminergic hypothesis established to describe psychotic and depressive disorders. The questioning of the monoaminergic approach initiated a more in-depth exploration of the neurobiological pathways underpinning psychotic and depressive disorders. Advances in neuroscience and neuroimaging have highlighted the need for an integrative approach that allows to study these psychiatric disorders at the level of brain networks. The hypothesis of brain dysconnectivity between various regions of the central nervous system has emerged as a promising avenue to understand functional brain alterations and the complex symptoms observed in individuals with psychotic or depressive disorders. This approach has emphasized the key role of glutamatergic transmission. Furthermore, the discovery of the psychogenic, dissociative and antidepressant effects of ketamine has strengthened the studies suggesting an involvement of the glutamatergic system in the pathophysiology of these disorders. Hence, the thesis aims to describe the physiopathology of psychotic and depressive disorders and highlight the role of glutamatergic system both at the network and molecular level.