Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression


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.

Publication DOI: https://doi.org/10.1016/j.biopsych.2009.03.024
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
Additional Information: © 2009, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: emotions,differential diagnosis,bipolar disorder,humans,prefrontal cortex,major depressive disorder,facial expression,adult,neural pathways,case-control studies,amygdala,neurological models,female,male
Publication ISSN: 1873-2402
Last Modified: 07 Mar 2024 18:50
Date Deposited: 16 Jul 2013 13:33
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Related URLs: https://www.sci ... 4272?via%3Dihub (Publisher URL)
PURE Output Type: Article
Published Date: 2009-09-01
Authors: de Almeida, Jorge R.C.
Versace, Amelia
Mechelli, Andrea
Hassel, Stefanie (ORCID Profile 0000-0001-7240-1581)
Quevedo, Karina
Kupfer, David J.
Phillips, Mary L.



Version: Accepted Version

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