Neuroimaging Correlates of Emotional Response-Inhibition Discriminate Between Young Depressed Adults With and Without Sub-threshold Bipolar Symptoms

ABSTRACT Background A significant number of subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neurobiology of MDD+ subjects is more akin to bipolar disorder depression (BDD) or to MDD subjects without any subthreshold bipolar symptoms (MDD−). Method This study included 118 medication-free young adult subjects (16 – 30 yrs.): 20 BDD, 28 MDD+, 41 MDD−, and 29 HC subjects. Participants underwent fMRI during emotional and non-emotional Go/No-go tasks during which they responded for Go stimuli and inhibited response for happy, fear, emotional (happy + fear) and non-emotional (gender) faces No-go stimuli. Linear mixed effects (LME) analysis for group effects and Gaussian Process Classifier (GPC) analyses was conducted. Results MDD− group compared to both the BDD and MDD+ groups, exhibited significantly lower activation in parietal, temporal and frontal regions (cluster-wise corrected p <0.05) for emotional inhibition conditions vs. non-emotional condition. No significant differences were found between BDD and MDD+ groups. GPC classification of emotional vs non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD− subjects (AUC: 0.70; balanced accuracy: 70% (p = 0.006)) as well as MDD+ and MDD− subjects (AUC: 0.72; balanced accuracy: 67% (p = 0.015)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (p = 0.091)). Notably, classification of the MDD− group was weighted for left amygdala activation pattern. Conclusion Using an fMRI emotional Go-Nogo task, MDD− subjects can be discriminated from BDD subjects and MDD+.