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.
Key Words
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Article info
Publication history
Published online: May 19, 2009
Accepted:
March 31,
2009
Received in revised form:
March 24,
2009
Received:
February 17,
2009
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
