Blunted neural response to positive facial feedback and suicidal risk in patients with major depressive disorder

Individuals with major depressive disorder (MDD) exhibit a blunted neural response to happy (relative to neutral) facial feedback, indicated by attenuated feedback-related negativity (FRN). However, the relationship between FRN and suicide risk remains unclear.

The study included 110 MDD patients and 70 healthy controls (HCs) who completed an electroencephalogram social incentive delay task. According to the suicide risk module of the Mini International Neuropsychiatric Interview (MINI), patients were divided into low-suicide-risk (LSR, n = 34), moderate-suicide-risk (MSR, n = 36), and high-suicide-risk (HSR, n = 40) groups. FRN data were analyzed with repeated-measures analysis of variance across the groups. FRN source localization was conducted with standardized low-resolution brain electromagnetic tomography (sLORETA).

A significant group × condition interaction was found (F_{3, 176} = 3.138, p = 0.028, η²_p = 0.070). HCs showed significant mean amplitude differences between gain and neutral feedback (p = 0.028), but MDD groups did not (all ps > 0.05). Post-hoc analyses showed the HSR group had the lowest FRN amplitudes. Furthermore, FRN under the gain condition (FRN-gain) was correlated with clinical variables, including consummatory anhedonia and suicide risk (all ps < 0.05). FRN-gain source localization showed reduced orbitofrontal cortex, right fusiform gyrus, and insula activation, but increased left superior temporal gyrus activation in the HSR group.

The findings indicate the possibility of blunted neurophysiological responses to happy (vs. neutral) facial feedback and abnormal brain activation in high-suicide-risk MDD patients, which may be associated with increased suicide risk. Nevertheless, because the task lacked loss and non-social control conditions, the specificity of these findings to reward or social processing remains to be determined.