Functional connectivity of the amygdala in early-childhood-onset depression

Abstract

Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD.

Method: A total of 51 children 7 through 11 years of age who had been prospectively studied since preschool age, completed resting state functional magnetic resonance imaging (fMRI) and were assigned to one of four groups: 1) C-MDD (N = 13), those children with a personal history of early-childhood-onset MDD; 2) M-MDD (N = 11), those with a maternal history of affective disorders; 3) CM-MDD (N = 13), those with both maternal and early-childhood-onset MDD; or 4) CON (N = 14), those without either a personal or maternal history of MDD. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in region-of-interest-based analyses of our child sample.

Results: We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when compared with CON, we found reduced connectivity between the amygdala and the "negative network" in children with C-MDD, M-MDD, and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the "positive network."

Conclusions: Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD, suggesting developmental continuity of this alteration into early childhood.

Figure 1

Negative and Postive Network Regions of Interest (ROIs) Note: Regions of interest comprising the A.) Negative Network (blue) and B.) Positive Network (red) along with the bilateral amygdala (yellow). See Tables S1 and S2, available online, for region coordinates and abbreviations.

Figure 2

Average Connectivity between the Amygdala and Negative and Positive Networks for all four groups Note: Average functional connectivity between the amygdala and the A.) Positive Network and B.) Negative Network in each of the four groups. Control = Neither Maternal (M) nor Childhood Onset (C) major depressive disorder (MDD) History; CM-MDD = Both Maternal and Childhood Onset MDD History. * p<.05, + p<.10

Figure 3

Individuals Differences in Childhood Emotion Management Scale Scores and Negative/Positive Network Connectivity Note: Scatterplot illustrating the relationship between individual differences in A.) the average Negative Network connectivity and Childhood Emotional Management Scale (CEMS) sadness dysregulation scores and B.) the average Positive Network connectivity and CEMS sadness coping scores