title: Self-blame-Selective Hyperconnectivity Between Anterior Temporal and Subgenual Cortices and Prediction of Recurrent Depressive Episodes.
abstract: OBJECTIVE
  Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emotions related to blaming others (eg, "indignation or anger toward others"). This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, "feeling guilty for everything"), known to have a key role in cognitive vulnerability to MDD. It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments.
  
  
  OBJECTIVE
  To use fMRI in remitted MDD at baseline to test the hypothesis that RSATL-SCSR connectivity for self-blaming relative to other-blaming emotions predicts subsequent recurrence of depressive episodes.
  
  
  METHODS
  A prospective cohort study from June 16, 2011, to October 10, 2014, in a clinical research facility completed by 75 psychotropic medication-free patients with remitted MDD and no relevant comorbidity. In total, 31 remained in stable remission, and 25 developed a recurring episode over the 14 months of clinical follow-up and were included in the primary analysis. Thirty-nine control participants with no personal or family history of MDD were recruited for further comparison.
  
  
  METHODS
  Between-group difference (recurring vs stable MDD) in RSATL connectivity, with an a priori SCSR region of interest for self-blaming vs other-blaming emotions.
  
  
  RESULTS
  We corroborated our hypothesis that during the experience of self-blaming vs other-blaming emotions, RSATL-SCSR connectivity predicted risk of subsequent recurrence. The recurring MDD group showed higher connectivity than the stable MDD group (familywise error-corrected P < .05 over the a priori SCSR region of interest) and the control group. In addition, the recurring MDD group also exhibited RSATL hyperconnectivity with the right ventral putamen and claustrum and the temporoparietal junction. Together, these regions predicted recurrence with 75% accuracy.
  
  
  CONCLUSIONS
  To our knowledge, this study is the first to provide a robust demonstration of an fMRI signature of recurrence risk in remitted MDD. Additional studies are needed for its further optimization and validation as a prognostic biomarker.
authors.affiliation: Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Lythe
authors.affiliation: Cognitive and Behavioral Neuroscience Unit, D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Moll
authors.affiliation: Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England3doctoral student at The University of Manchester, Manchester, England.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gethin
authors.affiliation: Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England4Neuroscience and Psychiatry Unit, Institute of Brain, Behaviour and Mental Health, T.
authors.forename: Clifford I
authors.initials: CI
authors.lastname: Workman
authors.affiliation: Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England.
authors.forename: Sophie
authors.initials: S
authors.lastname: Green
authors.affiliation: Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Lambon Ralph
authors.affiliation: Neuroscience and Psychiatry Unit, Institute of Brain, Behaviour and Mental Health, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England.
authors.forename: John F W
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England5Department of Psychological Medicine, Centre for Affective Disorders, Institute of P.
authors.forename: Roland
authors.initials: R
authors.lastname: Zahn
mesh_terms: D000328:Adult; D000786:Anger / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D063132:Connectome; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology*; D005500:Follow-Up Studies; D006167:Guilt; D006801:Humans; D008279:Magnetic Resonance Imaging; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012306:Risk; D012649:Self Concept