Abnormal Left and Right Amygdala-Orbitofrontal Cortical Functional Connectivity to Emotional Faces: State Versus Trait Vulnerability Markers of Depression in Bipolar Disorder
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Background Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD).Methods Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined.Results The BD versus HC showed significantly greater right amygdala-OFC FC (p < or = .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001).Conclusions In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC-FA relationships in BD and HC require further study.
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Studies of patients with bipolar disorder in a depressed phase reveal a mood-congruent bias in emotion perception tasks, including difficulty labelling happy faces and a tendency to misinterpret neutral facial stimuli as sad and happy faces as angry.
“studies examining patients with bipolar disorder in a depressed phase of illness reveal a mood congruent bias in emotion perception tasks, including difficulties labelling happy faces 97,102 and a tendency to misinterpret neutral facial stimuli as sad 144,183 and happy faces as angry.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [97]
A greater illness burden was associated with reduced functional connectivity between the amygdala and OFC in response to sad faces in a mixed sample of patients in depressed and remitted mood states.
“A greater illness burden was associated with reduced functional connectivity between the amygdala and OFC in response to sad faces in a mixed sample of patients in depressed and remitted mood states.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [97]
Greater left amygdala-OFC connectivity in response to sad faces and reduced bilateral connectivity between these regions in response to happy faces has been reported in depressed but not euthymic patients with bipolar disorder.
“Evidence of greater left amygdala-OFC connectivity in response to sad faces and reduced bilateral connectivity between these same regions in response to happy faces has also been reported in depressed but not euthymic patients with bipolar disorder.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [97]
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- Authors
- Versace, A., Thompson, W. K., Zhou, D., Almeida, J. R. C., Hassel, S., Klein, C. R., Kupfer, D. J., & Phillips, M. L.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Phillips, Mary L.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 67
- Issue
- 5
- Pages
- 422-431
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2835157
- OpenAlex
- W2087664470
- Cited by
- 194
- References
- 59
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 25 · 2020: 4 · 2019: 7 · 2018: 17 · 2017: 14 · 2016: 14 · 2015: 11 · 2014: 26 · 2013: 17 · 2012: 24
- FWCI
- 12.68
- 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 Institutes of Health (1 R01 MH076971-01, K25 MH076981-01)
- National Alliance for Research on Schizophrenia and Depression Independent Investigator Award (Nellie Blumenthal Investigator)
- National Science Foundation (DMS-0806106)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Brazil (190105-2)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- bipolar disorder, emotional facial expressions, depression vulnerability, hemispheric lateralization, white matter fractional anisotropy, antidepressant effects
- MeSH terms
- Adult, Affect, Amygdala, Bipolar Disorder, Major Depressive Disorder, Depressive Disorder, Major, Diagnosis, Differential, Face, Facial Expression, Female, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Nerve Net, Surveys and Questionnaires, Anisotropy, Prefrontal Cortex, Diagnostic and Statistical Manual of Mental Disorders
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