The impact of melancholia versus non-melancholia on resting-state, EEG alpha asymmetry: electrophysiological evidence for depression heterogeneity.

While depression has been associated with relatively greater right than left frontal cortical activity - a neurophysiological marker reflecting greater activation of the withdrawal system - contradictory findings have been reported. It was hypothesised that melancholia would be associated with relative right frontal activation, in comparison to non-melancholia and controls. We collected 2-min of resting-state, eyes closed, electroencephalographic activity from a total of 237 participants including 117 patients with major depressive disorder (57 with melancholia, 60 with non-melancholia) and 120 healthy controls. In contrast to hypotheses, patients with non-melancholia displayed relative left frontal activation in comparison to controls and those with melancholia. These findings were associated with a small to moderate effect size (Cohen's d=0.30-0.34). Critically, patients with melancholic subtype did not differ from controls despite increased severity - relative to those with non-melancholia - on clinical measures. These results may reflect an increase in approach tendencies in patients with non-melancholia including reassurance seeking, anger or irritable aggression. Findings highlight the need for further research on the heterogeneity MDD.