Successful Pharmacologic Treatment of Major Depressive Disorder Attenuates Amygdala Activation to Negative Facial Expressions: A Functional Magnetic Resonance Imaging Study
Abstract
OBJECTIVE: Studies of the effects of pharmacotherapy for major depressive disorder (MDD) on limbic-subcortical-prefrontal brain networks show variable results. We quantified functional changes in the amygdala and the related limbic-subcortical-prefrontal structures after paroxetine treatment with functional magnetic resonance imaging relative to clinical responder status. METHOD: We scanned 22 patients with unipolar, DSM-IV-defined MDD (men and women aged 25-55 years; 17-item Hamilton Depression Rating Scale [HDRS(17)] score > 18) at study entry and after 6 (T0) and 12 (T1) weeks of paroxetine treatment. Our paradigm contrasted negative (fearful, angry), happy, and neutral faces relative to scrambled faces. Twenty-one age-matched (± 2.5 y) and sex-matched controls were scanned once. Patients received open-label paroxetine 20 mg/d for 6 weeks (T0). Nonresponders at T0 were randomly assigned to receive double-blind true dose escalation (paroxetine 30-50 mg/d) or placebo dose escalation for another 6 weeks (T1). The study was conducted from July 2005 to February 2007. RESULTS: At study entry, MDD patients showed increased ventral/limbic and decreased dorsal prefrontal activations to negative faces. At T0 and T1, respectively, 5/20 and 13/20 patients responded to paroxetine. After 12 weeks (at T1), overall amygdala activations remained unchanged relative to study entry. However, amygdala activations were significantly lower in treatment responders versus nonresponders (P = .001). Amygdala activations correlated with HDRS(17) scores (P < .04). Left amygdala activation correlated inversely with pregenual anterior cingulate cortex activation (P = .001). Dorsal cingulate gyrus and dorsolateral prefrontal activations increased after 6 and 12 weeks of treatment, regardless of clinical response. CONCLUSIONS: Successful paroxetine treatment decreases amygdala activation, presumably by improved frontolimbic control, in line with selective serotonin reuptake inhibitor-induced increased functional connectivity between the pregenual anterior cingulated cortex, prefrontal cortex, and amygdala. Changes in amygdala activation when processing negative faces might serve as an indicator for improved frontolimbic control, which is required for clinical response. TRIAL REGISTRATION: ISRCTN identifier: ISRCTN44111488.
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Amygdala reactivity to negative affective stimuli is a marker of negative affective bias in depression.
“Amygdala reac vity to nega ve informa on is a marker of nega ve affec ve processes in depression that is reduced by an depressant medica on.”
From Amygdala Reactivity, Antidepressant Discontinuation, and Relapse (2024) · cites this paper as [19]
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- Authors
- Ruhé, H. G., Booij, J., Veltman, D. J., Michel, M. C., & Schene, A. H.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Amsterdam Neuroscience (NL)
- Corresponding author
- Ruhé, Henricus G.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2011-08-09
- Volume
- 73
- Issue
- 04
- Pages
- 451-459
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2090519430
- Cited by
- 104
- References
- 0
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 26 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 12 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, paroxetine, amygdala activation, negative facial expressions, treatment response, prefrontal cortex, pregenual anterior cingulate cortex, selective serotonin reuptake inhibitors, functional connectivity, depression biomarkers, dose escalation
- MeSH terms
- Adult, Amygdala, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Facial Expression, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychiatric Status Rating Scales, Selective Serotonin Reuptake Inhibitors, Paroxetine, Functional Neuroimaging
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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