Changes in the neural correlates of implicit emotional face processing during antidepressant treatment in major depressive disorder
Open accessAbstract
An emerging hypothesis regarding the mechanisms underlying antidepressant pharmacotherapy suggests that these agents benefit depressed patients by reversing negative emotional processing biases (Harmer, 2008). Neuropsychological indices and functional neuroimaging measures of the amygdala response show that antidepressant drugs shift implicit and explicit processing biases away from the negative valence and toward the positive valence. However, few studies have explored such biases in regions extensively connected with the amygdala, such as the pregenual anterior cingulate cortex (pgACC) area, where pre-treatment activity consistently has predicted clinical outcome during antidepressant treatment. We used functional magnetic resonance imaging (fMRI) to investigate changes in haemodynamic response patterns to positive vs. negative stimuli in patients with major depressive disorder (MDD) under antidepressant treatment. Participants with MDD (n = 10) underwent fMRI before and after 8 wk sertraline treatment; healthy controls (n = 10) were imaged across an equivalent interval. A backward masking task was used to elicit non-conscious neural responses to sad, happy and neutral face expressions. Haemodynamic responses to emotional face stimuli were compared between conditions and groups in the pgACC. The response to masked-sad vs. masked-happy faces (SN-HN) in pgACC in the depressed subjects was higher in the pre-treatment condition than in the post-treatment condition and this difference was significantly greater than the corresponding change across time in the controls. The treatment-associated difference was attributable to an attenuated response to sad faces and an enhanced response to happy faces. Pre-treatment pgACC responses to SN-HN correlated positively with clinical improvement during treatment. The pgACC participates with the amygdala in processing the salience of emotional stimuli. Treatment-associated functional changes in this limbic network may influence the non-conscious processing of such stimuli by reversing the negative processing bias extant in MDD.
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Blunted dlPFC activation has been accompanied by exaggerated amygdalar activation when processing subliminal negative stimuli.
“Thus, blunted dlPFC activation has been accompanied by exaggerated amygdalar activation when (1) viewing and reappraising negative pictures [167], (2) processing subliminal negative stimuli [168, 169] (Fig. 4d) and negative words”
From Prefrontal cortex and depression (2022) · cites this paper as [169]
The Introduction reports an abnormally increased amygdala response to masked-sad faces in unmedicated depressed participants, supporting the exaggerated-amygdala part of the claim. The fMRI Results and Discussion describe changes in the pgACC, ventrolateral prefrontal cortex and lateral frontal polar cortex, but do not report blunted dlPFC activation accompanying that amygdala response. Passage-level page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSSRI treatment (sertraline) reduced activation in the pgACC (BA24/32) (as well as left medial OFC and left vlPFC) in response to masked sad vs. happy faces.
“For example, an early study reported that SSRI treatment (sertraline) reduced activation in the pgACC (BA24/32) (as well as left medial OFC and left vlPFC) in response to masked sad vs. happy faces [169].”
From Prefrontal cortex and depression (2022) · cites this paper as [169]
The fMRI Results report reduced masked-sad versus masked-happy (SN-HN) response in the right pgACC after sertraline treatment. They report reductions in the left medial OFC and left vlPFC for masked-sad versus masked-neutral (SN-NN) faces, not the sad-versus-happy contrast attributed to all three regions. The cited passages do not specify BA24/32 for the pgACC. (LLM, conf=0.90)
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- Authors
- Victor, T. A., Furey, M. L., Fromm, S. J., Öhman, A., & Drevets, W. C.
- Affiliations
- National Institutes of Health (US)
- Karolinska Institutet (SE)
- Corresponding author
- Victor, Teresa A.
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-11-01
- Volume
- 16
- Issue
- 10
- Pages
- 2195-2208
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2137202232
- Cited by
- 73
- References
- 65
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 30 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 8 · 2014: 4
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- William K. Warren Foundation
- Pfizer
- University of Pennsylvania
- National Institutes of Health
- Laureate Institute for Brain Research, University of Tulsa
- National Institute of Mental Health (Z01MH002792)
- NHLBI Division of Intramural Research
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, antidepressant treatment, sertraline, pregenual anterior cingulate cortex, amygdala, emotional face processing, implicit emotional processing, backward masking, hemodynamic response, treatment response prediction, limbic network, unconscious processes
- MeSH terms
- Adult, Antidepressive Agents, Brain, Brain Mapping, Cerebrovascular Circulation, Major Depressive Disorder, Emotions, Facial Expression, Female, Hemodynamics, Humans, Magnetic Resonance Imaging, Male, Neurons, Neuropsychological Tests, Time Factors, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Sertraline, Young Adult
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