Abstract
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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Acknowledgements
This research study was supported by NIH F31MH076420, K24MH065416, K23MH064678, K01MH072837, P41EB001975, and NARSAD. Support was also provided by the General Clinical Research Center of the University of Pittsburgh Medical Center (MO1RR000056) and the University of Pittsburgh Magnetic Resonance Research Center Pilot Imaging Program.
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In addition to the NIH grants listed above, Dr Pollock has received research support from Janssen Pharmaceuticals. He has served on the advisory board of Forest Laboratories and is a faculty member of the Lundbeck Institute. The other authors have no other disclosures or conflicts.
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Bigos, K., Pollock, B., Aizenstein, H. et al. Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity. Neuropsychopharmacol 33, 3221–3225 (2008). https://doi.org/10.1038/npp.2008.52
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DOI: https://doi.org/10.1038/npp.2008.52
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