Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Antoine Yrondi 1 Bruno Aouizerate 2 Wissam El-Hage 3 Fanny Moliere 4 Claire Thalamas 5 Nicolas Delcourt 6 Marie Sporer 6 Simon Taib 6 Laurent Schmitt 6 Nicolas Arlicot 3 Deborah Meligne 7 Agnés Sommet 8, 7 Anne Salabert 7 Sébastien Guillaume 9 Philippe Courtet 10 Florence Galtier 11, 12 Denis Mariano-Goulart 13, 4 Nicolas Menjot de Champfleur 4, 14, 15 Emmanuel Bars 4 Thomas Desmidt 3 Mathieu Lemaire 16 Vincent Camus 17, 18 Maria Santiago-Ribeiro 19 Jean Cottier 18 Philippe Fernandez 20 Marie Meyer 21 Vincent Dousset 22 Olivier Doumy 2 Didier Delhaye 2 Lucile Capuron 23 Marion Leboyer 24 Emmanuel Haffen 25 Patrice Péran 1 Pierre Payoux 26 Christophe Arbus 27
Abstract : Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance. Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group-patients with current MDD (n = 20), (ii) remitted depressed group-patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups. Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice. Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=1.
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Soumis le : jeudi 9 août 2018 - 12:32:12
Dernière modification le : samedi 18 janvier 2020 - 01:07:03

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Antoine Yrondi, Bruno Aouizerate, Wissam El-Hage, Fanny Moliere, Claire Thalamas, et al.. Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study). Frontiers in Psychiatry, Frontiers, 2018, 9, pp.326. ⟨10.3389/fpsyt.2018.00326⟩. ⟨hal-01856019⟩

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