Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity
Open accessAbstract
Variability in serotonin (5-HT) function is associated with individual differences in normal mood and temperament, as well as psychiatric illnesses, all of which are influenced by amygdala function. This study evaluated the acute effects of 5-HT reuptake blockade on amygdala function using pharmacological functional MRI. Eight healthy men completed a double-blind balanced crossover study with the selective 5-HT reuptake inhibitor, citalopram (20 mg infused over 30 min), and normal saline. Amygdala reactivity in response to novel facial expressions was assessed on three successive scans, once before drug/placebo infusion, once early in the infusion, and once at the end of infusion. Acute citalopram administration resulted in concentration-dependent increases in human amygdala reactivity to salient stimuli. The current pattern of 5-HT-mediated amygdala reactivity may represent an important pathway through which SSRIs achieve an antidepressant effect. Intriguingly, our data may also reveal a mechanism contributing to clinical observations of extreme agitation, restlessness, and suicidal ideation in some individuals during acute SSRI treatment. Developing a comprehensive model of how 5-HT modulates human amygdala reactivity supporting behavioral and physiological arousal will be instrumental for our understanding of basic neurobehavioral processes, their dysfunction in psychiatric illnesses, and their contribution to mechanism of treatment response.
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Evidence following single-dose citalopram treatment on amygdala reactivity is mixed, with both increases and decreases reported.
“In reality, however, the evidence following single-dose treatment is rather mixed, and both increases in amygdala reactivity52 and decreases53 have been reported; see for example the recent review in ref 54 and metaanalysis in ref 55.”
From The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment (2015) · cites this paper as [52]
A study found increased activation comparing faces (emotional and neutral) and a sensorimotor control task with citalopram.
“but increased activation comparing faces (emotional and neutral) and a sensorimotor control task (Bigos et al., 2008).”
From Affective Cognition and its Disruption in Mood Disorders (2011) · cites this paper as Bigos et al., 2008
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“…an increase or no change in amygdala activation (decrease: Del-Ben et al., 2005; Grady et al., 2013; Harmer et al., 2006; Murphy et al., 2009; Windischberger et al., 2010; increase: Bigos et al., 2008; Selvaraj et al., 2017; no change: Brühl et al., 2009; Hornboll et al., 2018; Klomp et al., 2013).”
Background
- Authors
- Bigos, K. L., Pollock, B. G., Aizenstein, H. J., Fisher, P. M., Bies, R. R., & Hariri, A. R.
- Affiliations
- University of Pittsburgh (US)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Bigos, Kristin L
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2008-05-07
- Volume
- 33
- Issue
- 13
- Pages
- 3221-3225
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2858321
- OpenAlex
- W2170045804
- Cited by
- 164
- References
- 22
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 11 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 20 · 2014: 11 · 2013: 16 · 2012: 13
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pittsburgh
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (UL1TR000005)
- Medical Center, University of Pittsburgh
- National Institute of Mental Health (K23MH064678, F31MH076420, K24MH065416, K01MH072837)
- National Institute of Biomedical Imaging and Bioengineering (P41EB001975)
- National Center for Research Resources (M01RR000056, MO1RR000056)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- serotonin, citalopram, selective serotonin reuptake inhibitors, amygdala reactivity, facial expression processing, antidepressant mechanism, SSRI adverse effects, agitation, suicidal ideation
- MeSH terms
- Adult, Amygdala, Anxiety, Brain Chemistry, Depressive Disorder, Dose-Response Relationship, Drug, Double-Blind Method, Facial Expression, Humans, Male, Middle Aged, Neuropsychological Tests, Photic Stimulation, Serotonin, Citalopram, Akathisia, Drug-Induced, Selective Serotonin Reuptake Inhibitors, Presynaptic Terminals, Cross-Over Studies, Young Adult
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