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

Abstract

BackgroundLimbic-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.MethodsWe 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.ResultsGroups 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.ConclusionOur 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.

Multimodal brain imaging connectivity analyses of emotional and motivational deficits in depression among women

“…However, first-degree relatives also show increased functional connectivity between the perigenual ACC and the amygdala compared with healthy controls and people with MDD, suggesting that this might be a mechanism for resilience. 49 As well, in a sample of 12 women, increased effective connectivity has been reported between the left-sided subgenual ACC and the amygdala while implicitly processing dynamic fearful faces. 50 Thus, both increased and decreased functional connectivity between the rostral ACC and the amygdala have been described.…”

“…48 Functional connectivity between the amygdala and the perigenual ACC was negatively associated with negative affect in controls. 49 Carriers of the 5-HTTP short allele have reduced functional connectivity between the subgenual region and the amygdala during the perception of threatening faces, compared with carriers of the long allele. 8 Reduced perigenual-amygdalar functional connectivity has been tested as an intermediate phenotype for at-risk individuals.…”

“…50 Thus, both increased and decreased functional connectivity between the rostral ACC and the amygdala have been described. Beyond task designs and sample size and characteristics, other modulating factors such as genotype, 51 MDD response, 6 MDD subtype 47 and state or trait specificity 47,49 could account for this variation. We found decreased fractional anisotropy in an extensive network, including where the most significant difference was in the anterior cingulum and the forceps minor.…”

Desynchronized Functional Activities Between Brain White and Gray Matter in Major Depression Disorder

“…A previous study that focused on large‐scale intrinsic brain networks reported that MDD patients tended to exhibit reduced connectivity within GM, especially in the networks associated with diverse cognitive, emotional, and self‐reflective functions 20 . Additional MDD studies have reported that resting‐state connections were decreased between a variety of GM regions, but mainly including the amygdala 21 and dorsolateral prefrontal and posterior cingulate corices 22 . Given these findings, it is possible that global GM‐connection impairments may be a potential pathological feature of MDD.…”

Kognitive Neurowissenschaft der psychischen Resilienz

“…Die kortikolimbische Regulation kehrt nicht nur psychopatho logische Zustände um, sondern zeigt sich auch bei gesunden Per sonen als neuronales Korrelat der Emotionsregulation [54]. Wei ter gibt es inzwischen eine Reihe neurokognitiver Resilienzstudien, die auf eine ausgeglichene kortikolimbische Regulation als Resi lienzmechanismus hinweisen [34,[55][56][57][58][59][60]. Diese Studien sind vor allem querschnittlich und kategorial, d. h. es wurden Gruppen un tersucht, die Stressoren erlebt hatten und dann diejenigen mit und ohne Traumafolgestörung verglichen.…”