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Thesis defense – Camille Monchaux de Oliveira

17 December 2021 / 14:00

Venue: Centre Broca Nouvelle-Aquitaine

Language : in french

Depressive disorders are a major public health concern and display a rising prevalence worldwide. This effect can be explained by the increasing rate of individuals not responding to conventional antidepressant (ADs) treatments, but also by the rise of chronic conditions, often associated with low-grade inflammation and known to be associated with an increased risk of neuropsychiatric comorbidities. Moreover, a large proportion of depressed patients develop highly disabling side effects. These issues highlight the need to identify alternative strategies to current pharmaceutical treatments and the use of nutritional interventions may be a first-choice solution. Indeed, some nutrients and plant extracts have bioactive properties and can modulate many neurobiological systems, including those involved in the pathophysiology of depressive disorders, while reducing side effects. In that context, saffron therefore represents a promising candidate for the prevention and treatment of depressive disorders. Indeed, clinical and preclinical studies already reported improved depressive symptomatology after administration of saffron active compounds, although the mechanisms underlying these beneficial properties are still largely unknown. Better understanding those mechanisms is however essential in order to validate the therapeutic relevance of nutritional interventions with saffron extracts. In addition, it is important to identify the individuals who may be most likely to benefit from those interventions. Patients with a poor therapeutic response to conventional ADs may thus be the first concerned. Recent data suggest the involvement of inflammatory processes not only in the development of depressive disorders, but also in the poor response to ADs. Therefore, targeting inflammation appears to be a promising strategy to improve clinical response. Interestingly, several studies have demonstrated the immunomodulatory properties of saffron, suggesting that it may be particularly relevant to improve the therapeutic response in depressed patients with an inflammatory profile. In that context, the general objective of this thesis was therefore to clarify the role of nutritional interventions based on saffron supplementation in the management of depressive disorders and to determine the underlying mechanisms. For this purpose, we first demonstrated the beneficial effects of saffron on depressive-like behaviors, particularly in conditions modeling various risk factors for depression, such as stress. The neurobiological results suggest that it may act by particularly targeting central monoaminergic systems and the kynurenine pathway. In a second step, we validated an experimental strategy using two murine models of depression with different pathophysiological mechanisms, particularly regarding inflammatory processes, thus enabling to study their involvement in the development and treatment of depressive disorders. In conclusion, this thesis work allowed to establish preclinical evidence of the efficacy of a saffron extract in the management of depressive disorders and to start elucidating the underlying mechanisms. It also allowed to validate an experimental approach adapted to the in-depth study of the mechanisms underlying inflammatory depression and which should in turn help to better characterize the populations likely to benefit from nutritional approaches, as a replacement for or complement to pharmaceutical treatments, on the basis of their clinical profile. Taken together, this work should therefore contribute to improve the management and treatment of depressive disorders.

Key words: Depressive disorders, nutritional interventions, neurobiological systems, saffron, therapeutic response, inflammation, monoaminergic systems, kynurenine pathway


Saffron Extract-Induced Improvement of Depressive-Like Behavior in Mice Is Associated with Modulation of Monoaminergic Neurotransmission.
Monchaux De Oliveira C, Pourtau L, Vancassel S, Pouchieu C, Capuron L, Gaudout D, Castanon N. Nutrients. 2021  doi: 10.3390/nu13030904.


Pr Bruno AOUIZERATE, PU-PH, Université de Bordeaux,   Président

Dr David VAUZOUR, Chargé de Recherche, University of East Anglia, Norwich, Rapporteur

Dr Sylvie RABOT, Chargée de Recherche, Université Paris-Saclay, Rapporteur

Pr Emmanuel HAFFEN, PU-PH, Université de Bourgogne Franche-Comté, Examinateur

Dr Joelle CHABRY, Directrice de Recherche, Université de Nice-Sophia Antipolis, Examinateur

Dr Lucile CAPURON, Directrice de Recherche, Université de Bordeaux, Membre invitée

Dr Line POURTAU, Chef de Projet Neurosciences et Nutrition, Activ’Inside,  Membre invitée      

Dr Nathalie CASTANON, Chargée de Recherche, Université de Bordeaux, Directrice de thèse

Camille Monchaux

Thesis supervisor : Nathalie Castanon

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17 December 2021
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