Increased amygdala response to shame in remitted major depressive disorder

Abstract

Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD), and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8). This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15). Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

Figure 1. The MDD group showed higher activation in the right amygdala (panel a) and right posterior insula (panel b) for shame versus guilt compared with the control group (displayed are whole brain maps at voxel-level p = .005 uncorrected and cluster size of 4 voxels).

This was confirmed by a supporting data analysis using the mean regression coefficients of the activated clusters in the amygdala (24, −4, −18) and posterior insula (40, −16, 0). For both regions, there was a moral emotion by group interaction (amygdala: F,  = 10.5, p = .003; posterior insula: F,  = 16.9, p<.0001) and no main effect of moral emotion (amygdala: F,  = .126, p  = .725; posterior insula: F,  = .11, p = .75) or group (amygdala: F ,  = .30, p = .59; posterior insula: F ,  = .79, p = .38). The increased shame-response relative to guilt compared with the control group was also found in the remitted MDD subgroup not currently taking medication (amygdala: p = .01, t = 2.6; posterior insula: p<.0001, t = 4.1).