Abnormal dynamic functional connectivity of amygdalar subregions in untreated patients with first-episode major depressive disorder

Abstract

Background: Accumulating evidence supports the concept of the amygdala as a complex of structurally and functionally heterogeneous nuclei rather than as a single homogeneous structure. However, changes in resting-state functional connectivity in amygdalar subregions have not been investigated in major depressive disorder (MDD). Here, we explored whether amygdalar subregions - including the laterobasal, centromedial (CM) and superficial (SF) areas - exhibited distinct disruption patterns for different dynamic functional connectivity (dFC) properties, and whether these different properties were correlated with clinical information in patients with MDD.

Methods: Thirty untreated patients with first-episode MDD and 62 matched controls were included. We assessed between-group differences in the mean strength of dFC in each amygdalar subregion in the whole brain using general linear model analysis.

Results: The patients with MDD showed decreased strength in positive dFC between the left CM/SF and brainstem and between the left SF and left thalamus; they showed decreased strength in negative dFC between the left CM and right superior frontal gyrus (p < 0.05, family-wise error-corrected). We found significant positive correlations between age at onset and the mean positive strength of dFC in the left CM/brainstem in patients with MDD.

Limitations: The definitions of amygdalar subregions were based on a cytoarchitectonic delineation, and the temporal resolution of the fMRI was slow (repetition time = 2 s).

Conclusion: These findings confirm the distinct dynamic functional pathway of amygdalar subregions in MDD and suggest that the limbic-cortical-striato-pallido-thalamic circuitry plays a crucial role in the early stages of MDD.

Fig. 1

The mean dynamic functional connectivity (dFC) map of each amygdalar subregion in each group. (A) The subregions of the amygdala: the centromedial (CM; magenta), laterobasal (LB; blue) and superficial (SF; yellow). (B) The mean dFC map of each amygdalar subregion in the major depressive disorder (MDD) and control groups. Warm colours indicate positive mean connectivity and cool colours represent negative mean connectivity. Right SF Right LB Right CM Left SF Left LB Left CM

Fig. 2

Group differences in the mean positive strength of dynamic functional connectivity (dFC) in amygdalar subregions. Compared with the control group, the major depressive disorder group showed a decreased positive mean dFC between the left centromedial/superficial regions and the brainstem, as well as between the left superficial region and the left thalamus (p < 0.05, family-wise error–corrected). L = left; R = right.

Fig. 3

Group differences in the mean negative strength of dynamic functional connectivity (dFC) in amygdalar subregions. The major depressive disorder group showed a decreased negative mean dFC between the left centromedial region and right superior frontal gyrus (p < 0.05, family-wise error–corrected). L = left; R = right.

Fig. 4

The correlations between the dynamic functional connectivity (dFC) properties and clinical variables in patients with major depressive disorder. The mean dFC between the left centromedial (CM) region and the brainstem was positively correlated with age at onset. The mean dFC between the left superficial (SF) region and the brainstem was positively correlated with age at onset and disease duration. Fitted mean dFC between left CM and brainstem