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Amygdala functional connectivity in major depression – disentangling markers of pathology, risk and resilience

  • Carolin Wackerhagen (a1), Ilya M. Veer (a1), Susanne Erk (a1), Sebastian Mohnke (a1), Tristram A. Lett (a1) (a2), Torsten Wüstenberg (a1), Nina Y. Romanczuk-Seiferth (a1), Kristina Schwarz (a3), Janina I. Schweiger (a3), Heike Tost (a3), Andreas Meyer-Lindenberg (a3), Andreas Heinz (a1) and Henrik Walter (a1)...

Abstract

Background

Limbic-cortical imbalance is an established model for the neurobiology of major depressive disorder (MDD), but imaging genetics studies have been contradicting regarding potential risk and resilience mechanisms. Here, we re-assessed previously reported limbic-cortical alterations between MDD relatives and controls in combination with a newly acquired sample of MDD patients and controls, to disentangle pathology, risk, and resilience.

Methods

We analyzed functional magnetic resonance imaging data and negative affectivity (NA) of MDD patients (n = 48), unaffected first-degree relatives of MDD patients (n = 49) and controls (n = 109) who performed a faces matching task. Brain response and task-dependent amygdala functional connectivity (FC) were compared between groups and assessed for associations with NA.

Results

Groups did not differ in task-related brain activation but activation in the superior frontal gyrus (SFG) was inversely correlated with NA in patients and controls. Pathology was associated with task-independent decreases of amygdala FC with regions of the default mode network (DMN) and decreased amygdala FC with the medial frontal gyrus during faces matching, potentially reflecting a task-independent DMN predominance and a limbic-cortical disintegration during faces processing in MDD. Risk was associated with task-independent decreases of amygdala-FC with fronto-parietal regions and reduced faces-associated amygdala-fusiform gyrus FC. Resilience corresponded to task-independent increases in amygdala FC with the perigenual anterior cingulate cortex (pgACC) and increased FC between amygdala, pgACC, and SFG during faces matching.

Conclusion

Our results encourage a refinement of the limbic-cortical imbalance model of depression. The validity of proposed risk and resilience markers needs to be tested in prospective studies. Further limitations are discussed.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike licence (http://creativecommons.org/licenses/by-nc-sa/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is included and the original work is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

Author for correspondence: Carolin Wackerhagen, E-mail: carolin.wackerhagen@charite.de

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Amygdala functional connectivity in major depression – disentangling markers of pathology, risk and resilience

  • Carolin Wackerhagen (a1), Ilya M. Veer (a1), Susanne Erk (a1), Sebastian Mohnke (a1), Tristram A. Lett (a1) (a2), Torsten Wüstenberg (a1), Nina Y. Romanczuk-Seiferth (a1), Kristina Schwarz (a3), Janina I. Schweiger (a3), Heike Tost (a3), Andreas Meyer-Lindenberg (a3), Andreas Heinz (a1) and Henrik Walter (a1)...

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