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, 3) , Wissam El-Hage (4, 5) , Fanny Moliere (6, 7) , Claire Thalamas (8) , Nicolas Delcourt (1) , Marie Sporer (9) , Simon Taib (9) , Laurent Schmitt (9) , Nicolas Arlicot (4, 5) , Deborah Meligne (9) , Agnés Sommet (8) , Anne-Sophie Salabert (1) , Sébastien Guillaume (6, 7, 10) , Philippe Courtet (6, 7, 10) , Florence Galtier (6, 11) , Denis Mariano-Goulart (6, 12) , Nicolas Menjot de Champfleur (13, 14, 15, 16) , Emmanuel Bars (13, 14) , Thomas Desmidt (4) , Mathieu Lemaire (4) , Vincent Camus (4) , Maria Santiago-Ribeiro (4, 5) , Jean Cottier (4, 17) , Philippe Fernandez (18, 19) , Marie Meyer (18, 19) , Vincent Dousset (20, 21) , Olivier Doumy (2, 3) , Didier Delhaye (2) , Lucile Capuron (3) , Marion Leboyer (22, 23, 24) , Emmanuel Haffen (7, 25, 26) , Patrice Péran (1) , Pierre Payoux (1) , Christophe Arbus (1)

1 ToNIC - Toulouse NeuroImaging Center
2 Centre hospitalier Charles Perrens [Bordeaux]
3 NutriNeuro - Nutrition et Neurobiologie intégrée
4 iBraiN - Imaging, Brain & Neuropsychiatry
5 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
7 Fondation FondaMental [Créteil]
8 CIC 1436 - Centre d'investigation clinique de Toulouse
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
11 BC2M - Biocommunication en Cardio-Métabolique
12 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
13 Département de Neuroradiologie[Montpellier]
14 I2FH - Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier]
15 L2C - Laboratoire Charles Coulomb
16 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
17 Service de neuroradiologie [Tours]
18 Service de médecine nucléaire [Bordeaux]
19 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine
20 Institut François Magendie
21 CHU Bordeaux
22 Pôle de Psychiatrie [Hôpital Henri Mondor]
23 Groupe Henri Mondor-Albert Chenevier
24 IMRB - Institut Mondor de Recherche Biomédicale
25 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
26 NEURO - Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481)

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.

Mots clés: cytokines; TSPO; DPA-714; neuroinflammation; depressive disorder; depression; inflammation

Domaines: Sciences du Vivant [q-bio]

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, 2018, 9, pp.326. ⟨10.3389/fpsyt.2018.00326⟩. ⟨hal-01856019⟩