BODYMOOD – BODYMOOD

The Global Burden of Disease Study (2015) highlighted the significant and growing impact of mental disorders on global disability, with depressive disorders ranking as the third leading cause of years lived with disability. Although various treatments are available, it is clear that antidepressant drugs are effective in only about 65% of patients, and when efficient many of them experience relapse after initial improvement.
One of the reasons why treating mental health disorders remains a challenge nowadays relies on the traditional classification of mental disorders as conditions affecting only the brain, which does not always align with diagnostic realities, nor with basic research supporting alternative causal mechanisms beyond the brain. Understanding and treating mental illness effectively requires recognizing the complex interactions between the brain and the body, rather than focusing solely on clinical symptoms.
Examining mental illness, particularly mood disorders, from the perspective of body-brain axis dysfunction acknowledges that these disorders often become chronic and are frequently triggered by maladaptive immune responses. Supporting this notion are the numerous observations that depression is often associated with a peripheral inflammation, which arises in relation to gut microbiota dysregulation, or past infections. In this proposal, we hypothesize that peripheral inflammation can impact the central nervous system (CNS) through various mechanisms starting from gut microbiota dysbiosis, increased intestinal permeability, and inflammatory signals impacting the brain directly, or indirectly via perturbation of the brain borders, leading to a long-lasting change in affective behaviors.
By delineating clear experimental approaches for studying the way gut microbiota and immune signals shape brain functions, this proposal could significantly contribute to our understanding of the contribution of neuroimmune mechanisms involved in mood disorders. In particular, we aim to demonstrate how peripheral immune dysfunction can impact the CNS through various mechanisms that we aim to identify. Investigating the connections between the periphery and the brain could reveal insights into innovative adjunctive therapies such as manipulating the immune system or implementing lifestyle changes.