Subgenual cingulate-amygdala functional disconnection and vulnerability to melancholic depression

TY - JOUR

T1 - Subgenual cingulate-amygdala functional disconnection and vulnerability to melancholic depression

AU - Workman, Clifford I

AU - Lythe, Karen Elizabeth

AU - Mckie, Shane

AU - Moll, Jorge

AU - Gethin, Jennifer A

AU - Deakin, John Francis William

AU - Elliott, Rebecca

AU - Zahn, Roland Alessandro

PY - 2016/1/19

Y1 - 2016/1/19

N2 - The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the aetiology 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. Sixty-three medication-free remitted MDD (rMDD) patients (33 melancholic, 30 non-melancholic) 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 (ROI) 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 non-melancholic 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 non-melancholic 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.

AB - The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the aetiology 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. Sixty-three medication-free remitted MDD (rMDD) patients (33 melancholic, 30 non-melancholic) 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 (ROI) 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 non-melancholic 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 non-melancholic 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.

U2 - 10.1038/npp.2016.8

DO - 10.1038/npp.2016.8

M3 - Article

SN - 0893-133X

JO - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

ER -