Acute and sustained effects of cognitive emotion regulation in major depression

Abstract

Dysfunctional regulation of mood and emotion is a key component of major depressive disorder and leads to sustained negative feelings. Using functional MRI (fMRI), we investigated the temporal dynamics of emotion regulation in patients with major depressive disorder and in healthy controls, testing for acute and sustained neural effects of active emotion regulation. Moderately depressed individuals (n = 17) and never-depressed healthy control subjects (n = 17) underwent fMRI during performance of an active cognitive emotion regulation task while viewing emotionally arousing pictures. In a second task, completed 15 min later, subjects were presented with the same stimuli in a passive viewing task. Whole-brain analyses and connectivity measures were used to determine acute and sustained effects of emotion regulation on brain activation and coupling between regions. On the group level, patients were able to downregulate negative emotions and corresponding amygdala activation, but this ability decreased with increasing symptom severity. Moreover, only healthy control subjects showed a sustained regulation effect in the amygdala after a 15 min delay, whereas depressed patients did not. Finally, patients exhibited diminished prefrontal activation and reduced prefrontolimbic coupling during active regulation. Although emotion regulation capacity in medicated depressive patients appears to be preserved depending on symptom severity, the effect is not sustained. Correlational analyses provide evidence that this diminished sustained-regulation effect might be related to reduced prefrontal activation during regulation.

Figure 1.

Regional brain activation during active regulation (task 1). Healthy controls and MDD patients showed significantly reduced bilateral amygdala activation during regulation of negative emotion (p < 0.05 family-wise error corrected for ROI). The amount of downregulation in MDD patients depended on symptom severity: the higher the scores in the HAMD scale, the less the downregulation effect in the right amygdala (r = 0.7, p = 0.016, two-tailed). Bar plots indicate size of the effect at the maximum activated voxel in the amygdala for the contrast negative no regulation > negative regulation. Note: plots were depicted only for the right amygdala, the same pattern was observed for the left amygdala. NoREG, No regulation condition; REG, Regulation condition.

Figure 2.

Regional brain activation during active regulation (task 1). Healthy controls exhibited significant activation of the DLPFC and inferior parietal cortex during active regulation of negative emotions (p < 0.05, family-wise error corrected for whole brain). The activation increase in the right DLPFC was positively correlated with the amount of downregulation in the right amygdala (r = 0.68, p = 0.003, two-tailed). Compared with healthy controls, MDD patients showed reduced DLPFC activation during regulation, as seen in a significant group-by-regulation interaction (p < 0.05, family-wise error corrected for ROI). Bar plots indicate size of effect at the maximum activated voxel in right DLPFC for the contrast negative regulation > no regulation (healthy controls) and the group-by-regulation contrast [healthy controls (regulation > no regulation) > MDD patients (regulation > no regulation)]. AMY, Amygdala; NoREG, no regulation condition; REG, regulation condition.

Figure 3.

Results of psychophysiological interaction analysis (task 1). Healthy controls showed increased coupling between left amygdala (seed) and right DLPFC, inferior parietal cortex, posterior cingulate gyrus, and ventromedial prefrontal cortex (p < 0.001 uncorrected at voxel level, p < 0.05 corrected at the cluster level). Compared with healthy controls, MDD patients showed significantly reduced coupling between amygdala and DLPFC. Bar plots indicate size of effect at the voxel showing the maximum coupling effect.

Figure 4.

Regional brain activation during passive viewing (task 2). Healthy controls exhibited a significant sustained regulation effect in the bilateral amygdala. (Note that there was no activation in DLPFC or IPL during task 2 even when the threshold was lowered to an uncorrected p < 0.05). The amount of this sustained regulation effect in the amygdala was positively correlated with DLPFC activation during active regulation in task 1 (r = 0.058, p = 0.007, two-tailed). Compared with healthy controls, MDD patients did not show a sustained regulation effect in the amygdala, as seen in a significant group-by-regulation interaction (p < 0.05 family-wise error corrected for ROI). Bar plots indicate size of the effect at the maximum activated voxel in the right amygdala for the group by regulation contrast [healthy controls (no regulation > regulation) > MDD patients (no regulation > regulation)]. AMY, Amygdala; NoREG, no regulation during task 1; REG, regulation during task 1; prev, previous.