Elsevier

Biological Psychiatry

Volume 66, Issue 5, 1 September 2009, Pages 451-459
Biological Psychiatry

Archival Report
Abnormal Amygdala-Prefrontal Effective Connectivity to Happy Faces Differentiates Bipolar from Major Depression

https://doi.org/10.1016/j.biopsych.2009.03.024Get rights and content

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.

Section snippets

Participants

The University of Pittsburgh Institutional Review Board approved the study protocol. Sixteen healthy control participants (HC) with no previous personal or family history of psychiatric illness in first and second degree relatives participated in the study. Thirty-one adults: 15 with bipolar disorder, Type I, in depressed episode (BD); and 16 with major depressive disorder in depressed episode (MDD), diagnosed according to DSM-IV criteria and the Structured Clinical Interview for DSM-IV,

Behavioral Analyses

There were no differences among groups in labeling of emotional face in both experiments (p > .05) (Table 1). Moreover, no emotion labeling differences were found between the two depressed groups (p > .1) (Table 1).

Functional Integration—DCM: Between-Group Differences in EC

There was a significant group difference upon left-sided top-down OMPFC–amygdala EC during the happy experiment [χ2(2) = 11.5, p = .003] (Table 2). Relative to HC, both MDD and BD had significantly reduced EC (MDD: U = 52, p = .004, Cohen's d effect size (d) = .95 and BD: U = 52, p =

Discussion

This is the first study to examine EC between key neural regions in emotion regulatory neural systems in bipolar and major depression. We found that different patterns of abnormal left-sided top-down OMPFC–amygdala during happy emotion labeling distinguished BD and MDD from HC, whereas only BD differed from HC on right-sided bottom-up amygdala–OMPFC EC. The MDD showed significantly greater negative left-sided top-down OMPFC–amygdala EC than HC, whereas BD showed significantly reduced positive

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