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

Jorge R.C. de Almeida, Amelia Versace, Andrea Mechelli, Stefanie Hassel, Karina Quevedo, David J. Kupfer, Mary L. Phillips

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)451-459
Number of pages9
JournalBiological Psychiatry
Volume66
Issue number5
DOIs
Publication statusPublished - 1 Sep 2009

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Amygdala
Bipolar Disorder
Emotions
Major Depressive Disorder
Prefrontal Cortex
Depression
Diagnostic Errors
Age of Onset
Diagnostic and Statistical Manual of Mental Disorders
Healthy Volunteers

Bibliographical note

© 2009, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

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

Cite this

de Almeida, J. R. C., Versace, A., Mechelli, A., Hassel, S., Quevedo, K., Kupfer, D. J., & Phillips, M. L. (2009). Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression. Biological Psychiatry, 66(5), 451-459. https://doi.org/10.1016/j.biopsych.2009.03.024
de Almeida, Jorge R.C. ; Versace, Amelia ; Mechelli, Andrea ; Hassel, Stefanie ; Quevedo, Karina ; Kupfer, David J. ; Phillips, Mary L. / Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression. In: Biological Psychiatry. 2009 ; Vol. 66, No. 5. pp. 451-459.
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abstract = "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.",
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de Almeida, JRC, Versace, A, Mechelli, A, Hassel, S, Quevedo, K, Kupfer, DJ & Phillips, ML 2009, 'Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression', Biological Psychiatry, vol. 66, no. 5, pp. 451-459. https://doi.org/10.1016/j.biopsych.2009.03.024

Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression. / de Almeida, Jorge R.C.; Versace, Amelia; Mechelli, Andrea; Hassel, Stefanie; Quevedo, Karina; Kupfer, David J.; Phillips, Mary L.

In: Biological Psychiatry, Vol. 66, No. 5, 01.09.2009, p. 451-459.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression

AU - de Almeida, Jorge R.C.

AU - Versace, Amelia

AU - Mechelli, Andrea

AU - Hassel, Stefanie

AU - Quevedo, Karina

AU - Kupfer, David J.

AU - Phillips, Mary L.

N1 - © 2009, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2009/9/1

Y1 - 2009/9/1

N2 - 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.

AB - 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.

KW - emotions

KW - differential diagnosis

KW - bipolar disorder

KW - humans

KW - prefrontal cortex

KW - major depressive disorder

KW - facial expression

KW - adult

KW - neural pathways

KW - case-control studies

KW - amygdala

KW - neurological models

KW - female

KW - male

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JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

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