Common and Distinct Amygdala-Function Perturbations in Depressed vs Anxious Adolescents
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CONTEXT: Few studies directly compare amygdala function in depressive and anxiety disorders. Data from longitudinal research emphasize the need for such studies in adolescents. OBJECTIVE: To compare amygdala response to varying attention and emotion conditions among adolescents with major depressive disorder (MDD) or anxiety disorders, relative to adolescents with no psychopathology. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Eighty-seven adolescents matched on age, sex, intelligence, and social class: 26 with MDD (14 with and 12 without anxiety disorders), 16 with anxiety disorders but no depression, and 45 without psychopathology. MAIN OUTCOME MEASURES: Blood oxygen level-dependent signal in the amygdala, measured by means of event-related functional magnetic resonance imaging. During imaging, participants viewed facial expressions (neutral, fearful, angry, and happy) while attention was constrained (afraid, hostility, and nose-width ratings) or unconstrained (passive viewing). RESULTS: Left and right amygdala activation differed as a function of diagnosis, facial expression, and attention condition both when patients with comorbid MDD and anxiety were included and when they were excluded (group x emotion x attention interactions, P < or = .03). Focusing on fearful face-viewing events, patients with anxiety and those with MDD both differed in amygdala responses from healthy participants and from each other during passive viewing. However, both MDD and anxiety groups, relative to healthy participants, exhibited similar signs of amygdala hyperactivation to fearful faces when subjectively experienced fear was rated. CONCLUSIONS: Adolescent MDD and anxiety disorders exhibit common and distinct functional neural correlates during face processing. Attention modulates the degree to which common or distinct amygdala perturbations manifest in these patient groups, relative to healthy peers.
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Neuroimaging studies in children and adolescents with MDD show heightened amygdala and OFC activation in response to emotional facial expressions, though conflicting findings exist.
“Neuroimaging studies conducted in children and adolescents with MDD also show heightened activation in the amygdala 56,60,74 and OFC 74 in response to emotional facial expressions (for conflicting findings, see Thomas and colleagues 42 ).”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [56]
The most consistent finding in childhood generalized anxiety disorder is increased amygdala activation during viewing of negative emotional expressions.
“The most consistent finding in childhood GAD is increased amygdala activation during viewing of negative emotional expressions.”
From Neural Substrates of Childhood Anxiety Disorders (2012) · cites this paper as [121]
In childhood generalized anxiety disorder, prefrontal activation differences to negative emotions are reported but inconsistent in direction; lower ventrolateral prefrontal activation is associated with higher anxiety severity and less treatment improvement.
“Multiple studies also report differences in PFC activation to negative emotions in GAD.”
From Neural Substrates of Childhood Anxiety Disorders (2012) · cites this paper as [121]
Studies of facial emotion encoding have found amygdala hyperactivation in adolescents with BI in early childhood and adolescents with GAD and/or SAD versus control groups when they attend to fearful relative to neutral faces.
“Studies of facial emotion encoding have found amygdala hyperactivation in adolescents with BI in early childhood (Perez-Edgar et al., 2007) and adolescents with GAD and/or SAD (Beesdo et al., 2009, McClure et al., 2007) versus control groups when they attend to fearful relative to neutral faces.”
From Gaining insight into adolescent vulnerability for social anxiety from developmental cognitive neuroscience (2014) · cites this paper as Beesdo et al., 2009
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- Authors
- Beesdo, K., Lau, J. Y. F., Guyer, A. E., McClure-Tone, E. B., Monk, C. S., Nelson, E. E., Fromm, S. J., Goldwin, M. A., Wittchen, H.-U., Leibenluft, E., Ernst, M., & Pine, D. S.
- Affiliations
- University of Oxford (GB)
- National Institutes of Health (US)
- University of Michigan (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-03-01
- Volume
- 66
- Issue
- 3
- Pages
- 275
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2891508
- OpenAlex
- W2145309562
- Cited by
- 250
- References
- 72
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 11 · 2021: 10 · 2020: 21 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 21 · 2015: 14 · 2014: 21 · 2013: 29 · 2012: 22
- FWCI
- 31.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- Sanofi
- F. Hoffmann-La Roche
- National Institutes of Health (ZIA‐MH002781)
- National Institute of Mental Health
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- amygdala, major depressive disorder, anxiety disorders, adolescents, facial expression processing, fearful faces, attentional modulation, amygdala hyperactivation, comorbidities, emotional processing, neural correlates of depression
- MeSH terms
- Adolescent, Affect, Amygdala, Anxiety Disorders, Brain, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Oxygen, Photic Stimulation, Reaction Time, Case-Control Studies
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