title: Reduced default mode network suppression during a working memory task in remitted major depression.
abstract: Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Lucie
authors: L
authors: Bartova
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Bernhard M
authors: BM
authors: Meyer
authors: Department of Psychology, Dresden University of Technology, Dresden, Germany.
authors: Kersten
authors: K
authors: Diers
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Ulrich
authors: U
authors: Rabl
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Christian
authors: C
authors: Scharinger
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Ana
authors: A
authors: Popovic
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Gerald
authors: G
authors: Pail
authors: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Klaudius
authors: K
authors: Kalcher
authors: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Roland N
authors: RN
authors: Boubela
authors: Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
authors: Julia
authors: J
authors: Huemer
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Dominik
authors: D
authors: Mandorfer
authors: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Christian
authors: C
authors: Windischberger
authors: Center of Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Harald H
authors: HH
authors: Sitte
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Siegfried
authors: S
authors: Kasper
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Nicole
authors: N
authors: Praschak-Rieder
authors: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Ewald
authors: E
authors: Moser
authors: Department of Psychology, Dresden University of Technology, Dresden, Germany.
authors: Burkhard
authors: B
authors: Brocke
authors: Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. Electronic address: lukas.pezawas@meduniwien.ac.at.
authors: Lukas
authors: L
authors: Pezawas
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D003865:Major Depressive Disorder / Q000150:complications*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D009434:Neural Pathways / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
keywords: Default mode network; Functional magnetic resonance imaging; Major depressive disorder; Remission; Rumination; Working memory