Venue : BBS conference room
Thesis defended in French
Juliette Montet
Nutrition and Neuropsychiatric Symptom Dimensions (NutriPsy)
Nutrineuro
Title
Role of early-life adversity in inflammation-related neuropsychiatric comorbidities in obesity: Implication of GTP-CH1 enzymatic pathway and dopamine metabolism
Abstract
Neuropsychiatric comorbidities are common in obesity, and numerous studies highlight the involvement of adiposity-related chronic low-grade inflammation in this effect. Cytokines alter dopamine metabolism by modulating the activity of the enzyme GTP cyclohydrolase 1 (GTP-CH1). This mechanism could contribute to the onset of several key symptoms, such as fatigue, decreased motivation, anhedonia, and psychomotor slowing in vulnerable individuals. Various data suggest that early life adversity (ELA) is an important factor in vulnerability to the neuropsychiatric effects of inflammation. Interestingly, ELA, like inflammation, can disrupt the activity of the GTP-CH1 pathway. The objective of this thesis is i) to evaluate the combined effect of ELA and obesity-related inflammation in neuropsychiatric comorbidities associated with obesity, and ii) to determine whether this effect is based on modulation of dopaminergic metabolism. The methodology used combines neuropsychiatric assessments, peripheral measurements of GTP-CH1 activity and inflammation, and [18F]DOPA PET brain imaging in a cohort of obese subjects. This work could contribute to the definition of new treatment perspectives for neuropsychiatric symptoms occurring in inflammatory contexts, which are known for their frequent resistance to conventional antidepressants.
Keywords
Obesity, inflammation, neuropsychiatric symptoms, early life adversity, dopamine
Selected publication
Montet J, Dexpert S, Darnaudéry M, Beau C, Forestier D, Ledaguenel P, Magne E, Aouizerate B, Capuron L. Role of early life adversities in inflammation-related neuropsychiatric comorbidity in obesity. Brain Behav Immun. 2025 Aug;128:612-619. doi: 10.1016/j.bbi.2025.04.039. Epub 2025 Apr 30. PMID: 40316033.
Jury
- Pr Philippe Fossati, PU-PH, APHP, Sorbonne Université, Rapporteur
- Pr Christine Poitou-Bernert, PU-PH, APHP, Sorbonne Université, Rapportrice
- Dr Raphaële Castagné, Chargée de recherche, Université Toulouse III Paul Sabatier, Examinatrice
- Dr Lucile Capuron, Directrice de recherche, Université de Bordeaux, Directrice de Thèse
- Pr Bruno Aouizerate, PU-PH, CH Charles Perrens, Univerité de Bordeaux, Examinateur invité
- Dr Eric Magne, Chirurgien, Clinique Tivoli, Bordeaux, Examinateur invité