title: Antidepressant short-term and long-term brain effects during self-referential processing in major depression.
abstract: Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression.
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle, ICM, Social and Affective Neuroscience (SAN) Laboratory, Paris, France. Electronic address: pauline.delaveau@yahoo.fr.
authors.forename: Pauline
authors.initials: P
authors.lastname: Delaveau
authors.affiliation: Institut de Recherches Internationales Servier, Suresnes, France.
authors.forename: Maritza
authors.initials: M
authors.lastname: Jabourian
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; AP-HP, Hôpitaux Universitaires Paris Ouest, Service de Psychiatrie de l'adulte et du sujet âgé, Paris, France; Inserm U894, Centre Psychiatrie et Neurosciences, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Lemogne
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle, ICM, Social and Affective Neuroscience (SAN) Laboratory, Paris, France; Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France.
authors.forename: Najib
authors.initials: N
authors.lastname: Allaïli
authors.affiliation: AP-HP, Department of Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Choucha
authors.affiliation: AP-HP, Department of Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Girault
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle, ICM, Social and Affective Neuroscience (SAN) Laboratory, Paris, France; Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France; AP-HP, Department of Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehericy
authors.affiliation: Institut de Recherches Internationales Servier, Suresnes, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Laredo
authors.affiliation: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle, ICM, Social and Affective Neuroscience (SAN) Laboratory, Paris, France; AP-HP, Department of Psychiatry, Pitié-Salpêtrière Hospital, Paris, France; Institut de Recherche Translationnelle en Neurosciences ICM-A-IHU, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fossati
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D016896:Treatment Outcome; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; C084711:agomelatine; D009281:Naphthalenes
keywords: Antidepressant; Functional magnetic resonance imaging (fMRI); Long-term; Major depressive disorder; Self-referential processing; Short-term