Gabriel Robert, MD, PhD; Elise Bannier, PhD; Magali Comte, PhD; Lea Domain, MD; Isabelle Corouge, PhD; Thibaut Dondaine, PhD; Jean-Marie Batail, MD, PhD; Jean-Christophe Ferre, MD, PhD; Eric Fakra, MD, PhD; Dominique Drapier, MD, PhD
Background: Major depressive disorder (MDD) is characterized by impaired cortical–subcortical functional connectivity. Apathy adds to functional impairment, but its cerebral basis in MDD remains unknown. Our objective was to describe impairments in functional connectivity during emotional processing in MDD (with varying levels of congruency and attention), and to determine their correlation with apathy.
Methods: We used the Variable Attention Affective Task during functional MRI, followed by diffusion-weighted MRI, to assess 55 right-handed women (30 with MDD and 25 healthy controls) between September 2012 and February 2015. We estimated functional connectivity using generalized psychophysiologic interaction and anatomic connectivity with tract-based spatial statistics. We measured apathy using the Apathy Evaluation Scale.
Results: We found decreased functional connectivity between the left amygdala and the left anterior cingulate cortex (ACC) during negative stimuli in participants with MDD (t54 = 4.2; p = 0.035, family-wise error [FWE]–corrected). During high-attention stimuli, participants with MDD showed reduced functional connectivity between the right dorsolateral prefrontal cortex (dlPFC) and the right ACC (t54 = 4.06, pFWE = 0.02), but greater functional connectivity between the right dlPFC and the right amygdala (t54 = 3.35, p = 0.048). Apathy was associated with increased functional connectivity between the right dlPFC and the right ACC during high-attention stimuli (t28 = 5.2, p = 0.01) and increased fractional anisotropy in the right posterior cerebellum, the anterior and posterior cingulum and the bilateral internal capsule (all pFWE < 0.05).
Limitations: Limitations included a moderate sample size, concomitant antidepressant therapy and no directed connectivity.
Conclusion: We found that MDD was associated with impairments in cortical–subcortical functional connectivity during negative stimuli that might alter the recruitment of networks engaged in attention. Apathy-related features suggested networks similar to those observed in degenerative disorders, but possible different mechanisms.
Submitted Apr. 15, 2020; Revised Jul. 28, 2020; Revised Oct. 25, 2020; Accepted Nov. 1, 2020
Acknowledgments: The authors would like to thank Jacques Soulabaille, Stéphane Brousse and Odile Petton for scheduling the study and their help in gathering the healthy controls. This work is dedicated to the memory of Christian Barillot, director of the former Visages, now Empenn, Imaging research unit in Rennes from 2006 to 2020.
Affiliations: From the EA 4712 Comportement et noyaux gris centraux, Université de Rennes 1, France (Robert, Batail, Drapier); the Psychiatry Department, Centre Hospitalier Guillaume Régnier, 108 Boulevard Général Leclerc, 35000, Rennes, France (Robert, Domain, Batail, Drapier); the Radiology Department, CHU Rennes, 2 Rue Henri le Guilloux, 35000 Rennes, France (Bannier, Ferre); the University of Rennes, CNRS, Inria, Inserm, IRISA UMR 6074, Empenn–ERL U 1228, 35000 Rennes, France (Bannier, Corouge, Ferre, Barillot); the Institut de Neurosciences de la Timone, Campus Santé Timone, 27, Bd Jean Moulin 13005 Marseille, France (Comte); the University of Lille & CHU Lille, Inserm, U1171, Degenerative and Vascular Cognitive Disorders, 59000, Lille, France (Dondaine); and the Psychiatry Department, CHU Saint-Etienne, Team PsyR2–Centre de Recherche en Neuroscience de Lyon, (CRNL) CNRS UMR 5292–Inserm U1028, University of Lyon and Saint Etienne, France (Fakra).
Funding: This work is supported by the Fondation de l’Avenir (ET1-628) and the Fondation Deniker. MRI data acquisition is supported by the Neurinfo MRI research facility from the University of Rennes I. Neurinfo is granted by the the European Union (FEDER), the French State, the Brittany Council, Rennes Metropole, Inria, Inserm and the University Hospital of Rennes.
Competing interests: G. Robert received funding for scientific talks from Janssen and Otsuka-Lundbeck (once each in the last 5 years). None of these were related to the current work. No other competing interests declared.
Contributors: G. Robert, E. Fakra and D. Drapier designed the study. G. Robert, E. Bannier, I. Courouge, T. Dondaine, J.-M. Batail and J.-C. Ferre acquired the data, which E. Bannier, M. Comte, L. Domain, E. Fakra and D. Drapier analyzed. G. Robert, E. Bannier, L. Domain and J.-C. Ferre wrote the article, which G. Robert, E. Bannier, M. Comte, L. Domain, I. Courouge, T. Dondaine, J.-M. Batail, E. Fakra and D. Drapier reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BYNC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
Correspondence to: G.H. Robert, Pôle Hospitalo-Universitaire de Psychiatrie Adulte, Centre Hospitalier Guillaume Régnier, 35000 Rennes, France; email@example.com