Cited by 192Anxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesTreatment of Major DepressionNeural and Behavioral Psychology Studies

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Increased Amygdala Responses to Sad But Not Fearful Faces in Major Depression: Relation to Mood State and Pharmacological Treatment

Arnone, Danilo, McKie, Shane, Elliott, Rebecca, Thomas, Emma J., Downey, Darragh, Juhasz, Gabriella, Williams, Steve R., Deakin, J.F. William, Anderson, Ian M.·2012·American Journal of Psychiatry

DOI 10.1176/appi.ajp.2012.11121774

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Abstract

OBJECTIVE: Increased amygdala response to negative emotions seen in functional MRI (fMRI) has been proposed as a biomarker for negative emotion processing bias underlying depressive symptoms and vulnerability to depressive relapse that are normalized by antidepressant drug treatment. The purpose of this study was to determine whether abnormal amygdala responses to face emotions in depression are related to specific emotions or change in response to antidepressant treatment and whether they are present as a stable trait in medication-free patients in remission. METHOD: Sixty-two medication-free unipolar depressed patients (38 were currently depressed, and 24 were in remission) and 54 healthy comparison subjects underwent an indirect face-emotion processing task during fMRI. Thirty-two currently depressed patients were treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring citalopram plasma concentrations. RESULTS: Patients with current depression had increased bilateral amygdala responses specific to sad faces relative to healthy comparison subjects and nonmedicated patients in stable remission. Treatment with citalopram abolished the abnormal amygdala responses to sad faces in currently depressed patients but did not alter responses to fearful faces. CONCLUSIONS: Aberrant amygdala activation in response to sad facial emotions is specific to the depressed state and is a potential biomarker for a negative affective bias during a depressive episode.

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“, 2008b) as well as treatment with a selective serotonin reuptake inhibitor antidepressant (Fu et al., 2004; Arnone et al., 2012) has been associated with nor-”
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Background
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“Furthermore, evidence from neuroimaging studies in depression have also demonstrated that decreased amygdala activation in response to positive stimuli may be associated with anhedonic symptoms caused by inappropriate salience attribution to positive information (Arnone et al. 2012; Stuhrmann et al. 2013).”
Background
Contrasting the amygdala activity and functional connectivity profile between antidepressant-free participants with major depressive disorder and healthy controls: A systematic review of comparative fMRI studies
Tassone, V. K., Demchenko, I., Salvo, J. J., Mahmood, R., Passa, A.-M. D., Kuburi, S., Rueda, A., & Bhat, V. (2022) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2022.111517 · Cited by 33
The Course of Disease in Major Depressive Disorder Is Associated With Altered Activity of the Limbic System During Negative Emotion Processing
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“…each fluctuate dynamically within individuals over time and have been associated with neural responses to aversive cues in between-person studies (Arnone et al., 2012; Goldstein-Piekarski et al., 2015; Larson and Ham, 1993; Mroczek and Almeida, 2004; Sliwinski et al., 2009; Swartz et al., 2015b,…”
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“The biased processing of emotional stimuli in depression has been linked to dysfunction in the amygdala 8,9 , the prefrontal cortex (PFC) 10,11 , the dorsal anterior cingulate 12,13 and their connections 14,15 .”
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Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls
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Self-citation
Decision-Making Dysfunctions of Counterfactuals in Depression: Who Might I have Been?
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TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder
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“Most previous patient-based studies showed an opposite pattern, suggesting that MDD patients are more sensitive to sad faces (Arnone et al., 2012; Surguladze et al., 2005) while SAD patients are more sensitive to fearful faces (Frick, Howner, Fischer, Kristiansson, & Furmark, 2013; Killgore and Yurgelun-Todd, 2005).”
Result
Right and left amygdalae activation in patients with major depression receiving antidepressant treatment, as revealed by fMRI
Chen, Y.-T., Huang, M.-W., Hung, I.-C., Lane, H.-Y., & Hou, C.-J. (2014) · Behavioral and Brain Functions · doi:10.1186/1744-9081-10-36 · Cited by 24
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“Amygdala responsivity is a potential marker of depressive state which shows a demonstrated specificity to sad faces with increased activation during a current depressive episode that normalises following treatment (Fu et al., 2004; Arnone et al., 2012).”
Background
Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls
Falcone, M., Smith, R. M., Chenoweth, M. J., Bhattacharjee, A. K., Kelsoe, J. R., Tyndale, R. F., & Lerman, C. E. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.152 · Cited by 21
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MethodSelf-citation
Association between dynamic resting-state functional connectivity and ketamine plasma levels in visual processing networks
Spies, M., Klöbl, M., Höflich, A. S., Hummer, A., Vanicek, T., Michenthaler, P., Kranz, G. S., Hahn, A., Winkler, D., Windischberger, C., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-46702-x · Cited by 22
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“At the same time, volumetric changes in the hippocampus have 305 been linked to symptomatic improvement following treatment (Arnone et al 2012a), suggesting state-dependency of 306 hippocampal volume.”
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Specificity of anhedonic alterations in resting-state network connectivity and structure: A transdiagnostic approach
Geller, W. N., Liu, K., & Warren, S. L. (2021) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2021.111349 · Cited by 18
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fMRI Response of Parietal Brain Areas to Sad Facial Stimuli in Mild Depression
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Negative Bias During Early Attentional Engagement in Major Depressive Disorder as Examined Using a Two-Stage Model: High Sensitivity to Sad but Bluntness to Happy Cues
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“…are consistent with previous behavioral findings in depression (Gotlib et al., 1988; Mogg et al., 1991; Koster et al., 2005; Kellough et al., 2008; Atchley et al., 2012; for reviews see Peckham et al., 2010; Winer and Salem, 2016) but also restrict the attentional impairment within the P1 time…”
Result

Authors: Arnone, D., McKie, S., Elliott, R., Thomas, E. J., Downey, D., Juhasz, G., Williams, S. R., Deakin, J. F. W., & Anderson, I. M.
Affiliations: University of Manchester (GB)
ORCID: Arnone, Danilo
McKie, Shane
Elliott, Rebecca
Downey, Darragh
Williams, Steve R.
Deakin, J.F. William
Anderson, Ian M.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2012-08
Volume: 169
Issue: 8
Pages: 841-850
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.2012.11121774
OpenAlex: W2057953148
Cited by: 192
References: 0
Citations by year: 2026: 5 · 2025: 7 · 2024: 13 · 2023: 3 · 2022: 11 · 2021: 34 · 2020: 9 · 2019: 15 · 2018: 15 · 2017: 12 · 2016: 14 · 2015: 20 · 2014: 19 · 2013: 11 · 2012: 3
FWCI: 22.75
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Topics: Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: major depressive disorder, amygdala, sad faces, fearful faces, citalopram, antidepressant treatment, remission, mood states, biomarkers, medication adherence
MeSH terms: Adult, Affect, Amygdala, Major Depressive Disorder, Depressive Disorder, Major, Facial Expression, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Citalopram, Biomarkers, Case-Control Studies, Antidepressive Agents, Second-Generation, Functional Neuroimaging

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Increased Amygdala Responses to Sad But Not Fearful Faces in Major Depression: Relation to Mood State and Pharmacological Treatment

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