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

• Published in: Psychological medicine Vol. 50; no. 16; pp. 2740 - 2750
• Main Authors: Wackerhagen, Carolin, Veer, Ilya M., Erk, Susanne, Mohnke, Sebastian, Lett, Tristram A., Wüstenberg, Torsten, Romanczuk-Seiferth, Nina Y., Schwarz, Kristina, Schweiger, Janina I., Tost, Heike, Meyer-Lindenberg, Andreas, Heinz, Andreas, Walter, Henrik
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.12.2020
• Subjects: Amygdala; Bipolar disorder; Brain; Brain mapping; Compensation; Cortex; Cortex (cingulate); Depressive personality disorders; Emotions; Frontal gyrus; Functional connectivity; Functional magnetic resonance imaging; Genetics; Imbalance; Magnetic resonance imaging; Matching; Mental depression; Mental disorders; Negative emotions; Nervous system; Neural networks; Neurobiology; Neuroimaging; Original Articles; Pathogenesis; Pathology; Prospective studies; Resilience; Schizophrenia; Germany; functional connectivity; pathology; Amygdala; major depressive disorder; intermediate phenotype; risk; faces; resilience; familial risk
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291719002885

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. 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. 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. 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.