title: Subgenual Cingulate-Amygdala Functional Disconnection and Vulnerability to Melancholic Depression.
abstract: The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the etiology of predisposing vulnerability traits and underscores the importance of identifying neurobiologically valid phenotypes. Distinctive fMRI biomarkers of vulnerability to MDD subtypes are currently lacking. This study investigated whether remitted melancholic MDD patients, who are at an elevated lifetime risk for depressive episodes, demonstrate distinctive patterns of resting-state connectivity with the subgenual cingulate cortex (SCC), known to be of core pathophysiological importance for severe and familial forms of MDD. We hypothesized that patterns of disrupted SCC connectivity would be a distinguishing feature of melancholia. A total of 63 medication-free remitted MDD (rMDD) patients (33 melancholic and 30 nonmelancholic) and 39 never-depressed healthy controls (HC) underwent resting-state fMRI scanning. SCC connectivity was investigated with closely connected bilateral a priori regions of interest (ROIs) relevant to MDD (anterior temporal, ventromedial prefrontal, dorsomedial prefrontal cortices, amygdala, hippocampus, septal region, and hypothalamus). Decreased (less positive) SCC connectivity with the right parahippocampal gyrus and left amygdala distinguished melancholic rMDD patients from the nonmelancholic rMDD and HC groups (cluster-based familywise error-corrected p⩽0.007 over individual a priori ROIs corresponding to approximate Bonferroni-corrected p⩽0.05 across all seven a priori ROIs). No areas demonstrating increased (more positive) connectivity were observed. Abnormally decreased connectivity of the SCC with the amygdala and parahippocampal gyrus distinguished melancholic from nonmelancholic rMDD. These results provide the first resting-state neural signature distinctive of melancholic rMDD and may reflect a subtype-specific primary vulnerability factor given a lack of association with the number of previous episodes.
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, Institute of Brain, Behaviour and Mental Health, Neuroscience and Psychiatry Unit, Manchester, UK.|The University of Manchester and Manchester Academic Health Sciences Centre, School of Psychological Sciences, Neuroscience and Aphasia Research Unit, Manchester, UK.
authors.forename: Clifford I
authors.initials: CI
authors.lastname: Workman
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, School of Psychological Sciences, Neuroscience and Aphasia Research Unit, Manchester, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Lythe
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, Institute of Brain, Behaviour and Mental Health, Neuroscience and Psychiatry Unit, Manchester, UK.
authors.forename: Shane
authors.initials: S
authors.lastname: McKie
authors.affiliation: Cognitive and Behavioral Neuroscience Unit, D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Moll
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, School of Psychological Sciences, Neuroscience and Aphasia Research Unit, Manchester, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gethin
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, Institute of Brain, Behaviour and Mental Health, Neuroscience and Psychiatry Unit, Manchester, UK.
authors.forename: John Fw
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, Institute of Brain, Behaviour and Mental Health, Neuroscience and Psychiatry Unit, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.affiliation: The University of Manchester and Manchester Academic Health Sciences Centre, School of Psychological Sciences, Neuroscience and Aphasia Research Unit, Manchester, UK.|Institute of Psychiatry, Psychology, and Neuroscience, Department of Psychological Medicine, Centre for Affective Disorders, King's College London, London, UK.
authors.forename: Roland
authors.initials: R
authors.lastname: Zahn
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D003866:Depressive Disorder / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology