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
1 ToNIC - Toulouse Neuro Imaging Center
2 Hôpital Charles Perrens
3 Imagerie et cerveau
4 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
5 CIC - Biotherapie - Toulouse
6 Hôpital Purpan [Toulouse]
7 CHU Toulouse [Toulouse]
8 Service de Pharmacologie Médicale
9 Neuropsychiatrie : recherche épidémiologique et clinique
10 CHU - Hôpital Lapeyronie [Montpellier]
11 CHU Saint-Eloi
12 BC2M - Biocommunication en Cardio-Métabolique
13 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
14 UM - Université de Montpellier
15 L2C - Laboratoire Charles Coulomb
16 Université de Tours
17 Clinique Psychiatrique Universitaire
18 CHRU TOURS - Centre Hospitalier Régional Universitaire de Tours
19 Service de Médecine Nucléaire [Tours]
20 LAMPEA - Laboratoire méditerranéen de préhistoire Europe-Afrique
21 INERIS - Institut National de l'Environnement Industriel et des Risques
22 Neuroinflammation: imagerie et thérapie de la sclérose en plaques
23 NutriNeur0 - Nutrition et Neurobiologie intégrée
24 IMRB - Institut Mondor de Recherche Biomédicale
25 CAPS - Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093]
26 Department of Nuclear Medicine
27 Service d'anatomie et cytologie pathologiques [Purpan]
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.
Keywords : depression cytokines TSPO DPA-714 depressive disorder inflammation neuroinflammation
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https://hal.umontpellier.fr/hal-01856019
Contributeur : Dominique Mornet <>
Soumis le : jeudi 9 août 2018 - 12:32:12
Dernière modification le : samedi 18 janvier 2020 - 01:07:03

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UNIV-MONTPELLIER | CNRS | UNIV-TOURS | INRA | IMRB | INERIS | UPEC-UPEM | UNIV-BOURGOGNE | UNIV-AMU | LAMPEA | U1093 | MMSH | BS | U1061 | L2C | MIPS | UNIV-TLSE3 | UPEC

Citation

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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