Neural antecedents of emotional disorders: a functional magnetic resonance imaging study of subsyndromal emotional symptoms in adolescent girls

Abstract

Background: Emotional symptoms (ES) emerge forme fruste in adolescence, before manifesting as fully fledged emotional disorders. Studies indicate that subsyndromal ES precede the onset of emotional disorders. We hypothesized that adolescents showing subsyndromal ES will show perturbations in the emotion regulatory frontolimbic network (FLN) during emotion processing.

Methods: Fifty-eight female adolescents underwent functional magnetic resonance imaging while viewing an image-based emotion-processing task. Within this sample, 33 (56.9%) displayed emotional symptoms and 25 (43.1%) did not. Clinical measures, including assessments of mood and anxiety, were administered and participants were allocated to one of two groups based on the presence (ES+) or absence (ES-) of subsyndromal ES. Group comparisons were used to identify differential patterns of neural engagement and their relationship to clinical variables.

Results: Groups displayed emotion-specific differences in FLN activity with increased frontal activity in ES+ girls during positive emotion processing and decreased frontal and limbic activity during negative emotion processing. Trait anxiety was the strongest clinical predictor of group membership (ES+ versus ES-) and displayed a significant negative correlation with hippocampal neural activity during negative emotion processing. In addition, between the groups, the hippocampus displayed a pattern of reverse coupling with the amygdala and insula that was also significantly correlated with trait anxiety.

Conclusions: There is divergence in the pattern of FLN neural processing in adolescent female subjects determined by emotional symptoms. Future research is needed to corroborate these findings and to underline their implications longitudinally.

Keywords: Adolescents; anxiety; depression; emotional disorders; emotional network; fMRI.

Figure 1

In all subjects, compared to neutral images, negative images produced increased neural activity in the frontal (IFG and ACC) and limbic (Ag, Hipp, and Ins) regions. Positive images produced increased neural activity only in the frontal regions (IFG and ACC). Legend: Ag = amygdala; Ins = insula; Hipp = hippocampus; ACC = anterior cingulate cortex; IFG = inferior frontal gyrus.

Figure 2

Between-group analyses revealed that activity was significantly reduced both in the frontal (IFG, ACC) and limbic (Hipp) regions in adolescents with subsyndromal emotional symptoms (ES+) during the processing of negative emotion, whereas it was increased only in the frontal regions (IFG and ACC) during positive image processing. Legend: Ins = insula; Ag = amygdala; IFG = inferior frontal gyrus.

Figure 3

a. Hippocampal correlation: During negative emotion-processing the left hippocampus was the only ROI that significantly correlated with trait anxiety (the strongest predictor of group membership). As trait anxiety increased, the hippocampus signal decreased (negative correlation). b. Hippocampal coupling: Results from psychophysiological interaction analysis showing regions where adolescents with (ES+) and without (ES−) subsyndromal emotional symptoms displayed a significant difference in hippocampus coupling during negative emotion-processing. Specifically, these included the insula (MNI coordinates −33, −18, −21, cluster size 25 voxels, z-score 3.10), amygdala (MNI coordinates 30, 9, 27, cluster size 13 voxels, z-score 3.01), and inferior frontal gyrus (MNI coordinates −54, 03, 3, cluster size 14 voxels, z-score 2.67). This is indicated by the figure which shows the direction of coupling and effect size.

Figure 4

Schematic summary of the differences between adolescents with (ES+) and without (ES−) subsyndromal emotional symptoms in the coupling of the hippocampus with frontal and limbic ROIs. Legend: Trait anxiety significantly correlated with the coupling strength between the hippocampus and both the amygdala and the insula, respectively. Trait anxiety was high when hippocampus coupled negatively with the amygdala and insula but low when it coupled positively. Solid line = significant correlation; dashed line = trend level correlation; ACC = anterior cingulate cortex; IFG = inferior frontal gyrus; Ins = insula; Ag = amygdala; Hipp = hippocampus.