Abnormal Amygdala-Prefrontal Effective Connectivity to Happy Faces Differentiates Bipolar from Major Depression
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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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These dysfunctional patterns of neural activity and connectivity are observed in both manic and depressed patients with bipolar disorder.
“These dysfunctional patterns of neural activity and connectivity are observed in both manic and depressed patients with bipolar disorder”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [101]
Almeida et al. (2009) reported disrupted OFC-amygdala connectivity in response to happy faces.
“Almeida et al. (2009) reported disrupted OFC-amygdala connectivity in response to happy faces and a non-significant trend towards the same effect of sad faces.”
From Affective Cognition and its Disruption in Mood Disorders (2011) · cites this paper as Almeida et al. (2009)
Almeida et al. (2009) reported a non-significant trend towards disrupted OFC-amygdala connectivity in response to sad faces.
“Almeida et al. (2009) reported disrupted OFC-amygdala connectivity in response to happy faces and a non-significant trend towards the same effect of sad faces.”
From Affective Cognition and its Disruption in Mood Disorders (2011) · cites this paper as Almeida et al. (2009)
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Healey, K. L., Morgan, J., Musselman, S. C., Olino, T. M., & Forbes, E. E. (2014) · Brain and Cognition · doi:10.1016/j.bandc.2013.12.004 · Cited by 53 · see citing works
- Authors
- Almeida, J. R. C. D., Versace, A., Mechelli, A., Hassel, S., Quevedo, K., Kupfer, D. J., & Phillips, M. L.
- Affiliations
- University of Pittsburgh (US)
- King's College London (GB)
- Corresponding author
- Phillips, Mary Louise
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 66
- Issue
- 5
- Pages
- 451-459
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2740996
- OpenAlex
- W1997180680
- Cited by
- 305
- References
- 56
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 15 · 2022: 9 · 2021: 44 · 2020: 9 · 2019: 9 · 2018: 23 · 2017: 12 · 2016: 28 · 2015: 22 · 2014: 23 · 2013: 26 · 2012: 27
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Aston Publications Explorer (Aston University) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression (5R01 MH076971-01)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, major depressive disorder, amygdala, effective connectivity, emotion regulation, top-down connectivity, hemispheric lateralization, antipsychotic drugs, dynamic causal modeling, differential diagnosis of depression
- MeSH terms
- Adult, Amygdala, Bipolar Disorder, Major Depressive Disorder, Diagnosis, Differential, Emotions, Facial Expression, Female, Humans, Male, Models, Neurological, Neural Pathways, Case-Control Studies, Prefrontal Cortex
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