1. ¹Department of Pharmaceutical Sciences, University of Pittsburgh, PA, USA
2. ²Centre for Addiction and Mental Health, Rotman Research Institute, University of Toronto, ON, Canada
3. ³Department of Psychiatry, University of Pittsburgh, PA, USA
4. ⁴Center for Neuroscience, University of Pittsburgh, PA, USA

Correspondence: Dr KL Bigos, Clinical Brain Disorders Branch, National Institute of Mental Health, 10 Center Drive, Room 3C101, Bethesda, MD 20892, USA. Tel: +1 301 594 2429; Fax: +1 301 480 0169; E-mail: bigosk@mail.nih.gov

Received 2 November 2007; Revised 5 March 2008; Accepted 6 March 2008; Published online 7 May 2008.

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.