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 Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. 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 ROI 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 copared to 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.

Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder

“…Additional processing steps included prewhitening, spatial smoothing (5-mm kernel), and registration to anatomic data and standard space (MNI 152). Amygdala RSFC maps for the left and right amygdalae were highly similar to each other; following our previous work ) and the work of others (Luking et al 2011), we conducted a second-level analysis to average the right and left amygdala RSFC maps. These mean amygdala RSFC z-score maps were used for subsequent analyses (described below).…”

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…[31] This relationship between amygdala activity and mood begins early in life; amygdala reactivity to negative facial expressions has been correlated with higher severity of depression in pre-schoolers. [32] Additionally, reduced amygdala-frontal connectivity has been associated with depression in both children [33] and adult women. [34] 2.1.3.…”

10.3 Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

“…Two previous studies examining at-risk children and adolescents found decreased connectivity between amygdala and frontal-parietal network in unaffected children of depressed mothers and in children with early onset depression (29), and decreased connectivity within the frontal-parietal cognitive control network in unaffected adolescent girls with parental depression (32).…”

“…The top-down IFG-amygdala circuitry is disrupted during emotion regulation in adults with mood disorders (66,67). A study of children with MDD and children of mothers with MDD also reported reduced negative correlation between the amygdala and lateral parietal regions including the supramarginal gyrus (29). The atypically high level of connectivity between amygdala and emotion regulation and cognitive-control regions might reflect emotion dysregulation in MDD.…”

“…In line with this evidence, MDD has been conceptualized as an imbalance between the DMN and the cognitive control network (24)(25)(26). Third, atypical connectivity between the amygdala and cortical structures has been found in adults (27,28) and children (29) with MDD and is thought to reflect deficits in emotion regulation.…”