Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study).
Front. Psychiatry. 2018-07-24; 9:
DOI: 10.3389/fpsyt.2018.00326
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1. 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).
Yrondi A(1), Aouizerate B(2), El-Hage W(3), Moliere F(4), Thalamas C(5), Delcourt
N(6), Sporer M(7), Taib S(7), Schmitt L(7), Arlicot N(8)(9)(10), Meligne D(11),
Sommet A(5)(12), Salabert AS(13)(14), Guillaume S(4)(15), Courtet P(4)(15),
Galtier F(16), Mariano-Goulart D(17)(18), Champfleur NM(19)(20)(21)(22), Bars
EL(19)(20), Desmidt T(23), Lemaire M(23), Camus V(23), Santiago-Ribeiro
MJ(9)(10)(24), Cottier JP(9)(25), Fernandez P(26)(27), Meyer M(26)(27), Dousset
V(28), Doumy O(2), Delhaye D(29), Capuron L(30), Leboyer M(31)(32), Haffen E(33),
Péran P(14), Payoux P(13)(14), Arbus C(1).
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.
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=d
epression&cntry=FR&rank=1.
DOI: 10.3389/fpsyt.2018.00326
PMCID: PMC6066663
PMID: 30087626