Background: Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder. Methods: Thirty-one depressed individuals-15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18-55 years, matched for age, age of illness onset, illness duration, and depression severity-and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC). Results: During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects. Conclusions: Abnormal, left-sided, top-down OMPFC-amygdala and right-sided, bottom-up, amygdala-OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression.
Bibliographical noteFunding Information:
Dr. Phillips reports having support from National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Award and 5R01 MH076971-01. Dr. Almeida reports having support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Foundation (#190105-2). Dr. Hassel reports having support from NARSAD. Dr. Mechelli, Dr. Versace, Dr. Quevedo and Dr. Kupfer reported no biomedical financial interests or potential conflicts of interest.
- bipolar disorder
- dynamic causal modeling
- major depression disorder
- orbitomedial prefrontal cortex