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.