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Front Psychiatry. 2018 Jul 24;9:326. doi: 10.3389/fpsyt.2018.00326. eCollection 2018.

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

Author information

1
Service de Psychiatrie et de Psychologie Médicale de l'Adulte, Centre Expert Dépression Résistante FondaMental, CHRU de Toulouse, Hôpital Purpan, ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France.
2
Pôle de Psychiatrie Générale et Universitaire, Centre Expert Dépression Résistante FondaMental, CH Charles Perrens, UMR INRA 1286, NutriNeuro, Université de Bordeaux, Bordeaux, France.
3
CHRU de Tours, Centre Expert Dépression Résistante FondaMental, Inserm U1253 iBrain, Inserm CIC 1415, Tours, France.
4
Department of Emergency Psychiatry and Postacute Care, Lapeyronie Hospital, CHU Montpellier, Expert Center for Resistant Depression, Fondation Fondamental, Montpellier, France.
5
CIC 1436, Service de Pharmacologie Clinique, CHU de Toulouse, INSERM, Université de Toulouse, UPS, Toulouse, France.
6
Centre Anti Poison CHU Toulouse Purpan, ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France.
7
Service de Psychiatrie et de Psychologie Médicale de l'Adulte, Centre Expert Dépression Résistante FondaMental, CHRU de Toulouse, Hôpital Purpan, Toulouse, France.
8
CHRU de Tours, Unité de Radiopharmacie, Tours, France.
9
UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
10
INSERM CIC 1415, University Hospital, Tours, France.
11
Institut des handicaps des Handicaps Neurologiques, Psychiatriques et Sensoriels, FHU HoPeS, CHU Toulouse, France.
12
Unité de Soutien Méthodologique à la Recherche Clinique (USMR), CHU de Toulouse, Toulouse, France.
13
Departement de Médecine Nucléaire, CHU Toulouse, Toulouse, France.
14
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France.
15
INSERM U1061, Université de Montpellier, Montpellier, France.
16
Centre Hospitalier Régional Universitaire Montpellier, Montpellier, France.
17
PhyMedExp, Université de Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France.
18
Département de Médecine Nucléaire, CHU de Montpellier, Montpellier, France.
19
Département de Neuroradiologie, Hôpital Gui de Chauliac, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France.
20
Institut d'Imagerie Fonctionnelle Humaine, Hôpital Gui de Chauliac, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France.
21
Laboratoire Charles Coulomb, CNRS UMR 5221, Université de Montpellier, Montpellier, France.
22
Département d'Imagerie Médicale, Centre Hospitalier Universitaire Caremeau, Nîmes, France.
23
CHRU de Tours, INSERM U1253, Université François Rabelais de Tours, Tours, France.
24
Service de Médecine Nucléaire, CHRU Tours, Tours, France.
25
Service de Neuro radiologie, CHRU Tours, Tours, France.
26
Departement de Médecine Nucléaire, Hopital Pellegrin, Bordeaux, France.
27
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR-5287), Université de Bordeaux, Bordeaux, France.
28
CHU Bordeaux Neurocentre Magendie, INSERM U1215, Université de Bordeaux, Bordeaux, France.
29
Pôle de Psychiatrie Générale et Universitaire, Centre Expert Dépression Résistante FondaMental, CH Charles Perrens, Bordeaux, France.
30
INRA, Nutrition and Integrative Neurobiology (NutriNeuro), UMR 1286, University of Bordeaux, Bordeaux, France.
31
Pôle de Psychiatrie des Hôpitaux Universitaires, Centre Expert Dépression Résistante FondaMental, Hôpital Henri Mondor-Albert Chenevier, AP-HP, Créteil, France.
32
INSERM U955, Translational Psychiatry, Paris-Est University, Créteil, France.
33
Department of Clinical Psychiatry, Clinical Investigation Center 1431-INSERM, EA 481 Neurosciences, University of Bourgogne Franche-Comté, University Hospital of Besancon and FondaMental Foundation, Créteil, France.

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:

DPA-714; TSPO; cytokines; depression; depressive disorder; inflammation; neuroinflammation

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