Elevated Amygdala Activity to Sad Facial Expressions: A State Marker of Bipolar but Not Unipolar Depression
Open accessAbstract
Background Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression.Methods Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series.Results The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity.Conclusions Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.
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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 [102]
Depressed patients with bipolar disorder have shown elevated amygdala activity and attenuated responses in the OFC and DLPFC to neutral and negative faces.
“Depressed patients with bipolar disorder have also shown elevated activity in the amygdala 102 and attenuated responses in the OFC and DLPFC to neutral and negative (e.g., angry, fearful, sad) faces.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [102]
Overall, these data suggest that patients with bipolar depression may be biased toward negative mood-congruent facial expressions, whereas those with unipolar depression have an attentional bias away from positive expressions.
“Overall, these data suggest that patients with bipolar depression may be biased toward negative mood-congruent facial expressions, whereas those with unipolar depression have an attentional bias away from positive expressions.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [102]
Early evidence of differences in connectivity patterns between the amygdala and OFC in response to displays of facial emotion in patients with bipolar depression may be a potential biomarker that is not present in those with unipolar depression.
“early evidence of differences in connectivity patterns between the amygdala and OFC in response to displays of facial emotion in patients with bipolar depression may be a potential biomarker that is not present in those with unipolar depression.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [102]
Patients with bipolar depression have shown enhanced activation in the amygdala in response to neutral and sad faces compared with controls, patients with remitted bipolar disorder and patients with MDD.
“Patients with bipolar depression have also shown enhanced activation in the amygdala in response to neutral and sad faces compared with controls, patients with remitted bipolar disorder and patients with MDD.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [102]
Depression is associated with amygdala hyper-responsivity to mild sad and neutral stimuli, though the cited study was restricted to bipolar disorder.
“depression is associated with amygdala hyper-responsivity to mild sad and neutral stimuli in particular, though that study was restricted to individuals with bipolar disorder (Almeida et al., 2010)”
From Neural correlates of emotional processing in depression: Changes with cognitive behavioral therapy and predictors of treatment response (2011) · cites this paper as Almeida et al., 2010
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- Authors
- Almeida, J. R. C., Versace, A., Hassel, S., 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
- 414-421
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2854029
- OpenAlex
- W1990144469
- Cited by
- 226
- References
- 53
- Citations by year
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- FWCI
- 13.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- 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)
- Funders
- Brain Imaging Research Center
- National Alliance for Research on Schizophrenia and Depression
- Independent Investigator Award
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- amygdala activity, bipolar depression, major depressive disorder, sad facial expressions, emotional facial expressions, emotional processing, state markers, differential diagnosis, neuroimaging, event-related potentials, left amygdala
- MeSH terms
- Adult, Affect, Amygdala, Bipolar Disorder, Depressive Disorder, Facial Expression, Female, Humans, Functional Laterality, Male, Biomarkers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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