Jungwon Cha1, Sidra Speaker2, Bo Hu3, Murat Altinay1, Parashar Koirala1, Harish Karne1, Jeffrey Spielberg4, Amy Kuceyeski5, Elvisha Dhamala5, Amit Anand6. 1. Center for Behavioral Health, Cleveland Clinic. 2. Cleveland Clinic Lerner College of Medicine. 3. Center for Quantitative Health Sciences, Cleveland Clinic. 4. Department of Psychiatry, University of Delaware. 5. Department of Radiology, Weill Cornell Medicine, Brain and Mind Research Institute, Weill Cornell Medicine. 6. Center for Behavioral Health, Cleveland Clinic. Electronic address: ananda@ccf.org.
Abstract
BACKGROUND: Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-). METHOD: This study included 118 medication-free young adults (15 - 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, and non-emotional (gender) faces No-go stimuli. Univariate linear mixed-effects (LME) analysis for group effects and multivariate Gaussian Process Classifier (GPC) analyses were 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. GPC classification of emotional (happy + fear) vs. non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD- subjects (AUC: 0.70; balanced accuracy: 70% (corrected p = 0.018)) as well as between MDD+ and MDD- subjects (AUC: 0.72; balanced accuracy: 67% (corrected p = 0.045)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (corrected p = 0.273)). Notably, classification of the MDD- group was weighted for left amygdala activation pattern. LIMITATIONS: Results also need to be tested in a different independent dataset. CONCLUSION: Using an fMRI emotional Go-Nogo task, MDD- subjects can be discriminated from BDD and MDD+ subjects.
BACKGROUND: Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-). METHOD: This study included 118 medication-free young adults (15 - 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, and non-emotional (gender) faces No-go stimuli. Univariate linear mixed-effects (LME) analysis for group effects and multivariate Gaussian Process Classifier (GPC) analyses were 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. GPC classification of emotional (happy + fear) vs. non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD- subjects (AUC: 0.70; balanced accuracy: 70% (corrected p = 0.018)) as well as between MDD+ and MDD- subjects (AUC: 0.72; balanced accuracy: 67% (corrected p = 0.045)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (corrected p = 0.273)). Notably, classification of the MDD- group was weighted for left amygdala activation pattern. LIMITATIONS: Results also need to be tested in a different independent dataset. CONCLUSION: Using an fMRI emotional Go-Nogo task, MDD- subjects can be discriminated from BDD and MDD+ subjects.
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