Skip to main content Accessibility help
Hostname: page-component-99c86f546-swqlm Total loading time: 0.417 Render date: 2021-12-04T13:33:58.011Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Effect of a single dose of citalopram on amygdala response to emotional faces

Published online by Cambridge University Press:  02 January 2018

Susannah E. Murphy*
Department of Psychiatry, Warneford Hospital, Oxford
Raymond Norbury
University of Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Oxford
Ursula O'Sullivan
Department of Psychiatry, Warneford Hospital, Oxford, UK
Philip J. Cowen
Department of Psychiatry, Warneford Hospital, Oxford, UK
Catherine J. Harmer
Department of Psychiatry, Warneford Hospital, Oxford, UK
Dr Susannah Murphy, Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX. Email:
Rights & Permissions[Opens in a new window]


HTML view is not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Selective serotonin reuptake inhibitors (SSRIs) are typically thought to have a delay of several weeks in the onset of their clinical effects. However, recent reports suggest they may have a much earlier therapeutic onset. A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs.


To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces.


Twenty-six healthy volunteers were randomised to receive a single oral dose of citalopram (20 mg) or placebo. Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging.


Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo.


Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought.

Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NC
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial licence (, which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright © Royal College of Psychiatrists, 2009


This research was funded by a Wellcome Trust studentship.

Declaration of interest



1 Taylor, MJ, Freemantle, N, Geddes, JR, Bhagwagar, Z. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry 2006; 63: 1217–23.CrossRefGoogle ScholarPubMed
2 Posternak, MA, Zimmerman, M. Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry 2005; 66: 148–58.CrossRefGoogle Scholar
3 Harmer, CJ, Shelley, NC, Cowen, PJ, Goodwin, GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 2004; 161: 1256–63.CrossRefGoogle ScholarPubMed
4 Browning, M, Reid, C, Cowen, PJ, Goodwin, GM, Harmer, C. A single dose of citalopram increases fear recognition in healthy subjects. J Psychopharmacol 2007; 21: 684–90.CrossRefGoogle ScholarPubMed
5 Harmer, CJ, Bhagwagar, Z, Perrett, DI, Vollm, BA, Cowen, PJ, Goodwin, GM. Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology 2003; 28: 148–52.CrossRefGoogle ScholarPubMed
6 Drevets, WC. Neuroimaging abnormalities in the amygdala in mood disorders. Ann NY Acad Sci 2003; 985: 420–44.Google ScholarPubMed
7 Sheline, YI, Barch, DM, Donnelly, JM, Ollinger, JM, Snyder, AZ, Mintun, MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry 2001; 50: 651–8.CrossRefGoogle ScholarPubMed
8 Fu, CH, Williams, SC, Cleare, AJ, Brammer, MJ, Walsh, ND, Kim, J, et al. Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry 2004; 61: 877–89.CrossRefGoogle ScholarPubMed
9 Harmer, CJ, Mackay, CE, Reid, CB, Cowen, PJ, Goodwin, GM. Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biol Psychiatry 2006; 59: 816–20.CrossRefGoogle ScholarPubMed
10 Del-Ben, CM, Deakin, JF, McKie, S, Delvai, NA, Williams, SR, Elliott, R, et al. The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study. Neuropsychopharmacology 2005; 30: 1724–34.CrossRefGoogle ScholarPubMed
11 First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for DSM–IV Axis I Disorders (SCID–I). American Psychiatric Press, 1997.Google Scholar
12 Nelson, HE, Willison, J. National Adult Reading Test (NART). nferNelson, 1991.Google Scholar
13 Spielberger, CD, Gorsuch, RL, Lushene, RD. Manual for the State–Trait Anxiety Inventory (STAI). Consulting Psychologists Press, 1983.Google Scholar
14 Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–71.CrossRefGoogle ScholarPubMed
15 von Zerssen, D, Strian, F, Schwarz, D. Evaluation of depressive states, especially in longitudinal studies. Mod Probl Pharmacopsychiatry 1974; 7: 189202.CrossRefGoogle ScholarPubMed
16 Watson, D, Clark, LA, Tellegen, A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 1988; 54: 1063–70.CrossRefGoogle ScholarPubMed
17 Ekman, P, Friesen, WV. Pictures of Facial Affect. Consulting Psychologists Press, 1976.Google Scholar
18 Jenkinson, M, Bannister, P, Brady, M, Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 2002; 17: 825–41.CrossRefGoogle ScholarPubMed
19 Smith, SM. Fast robust automated brain extraction. Hum Brain Mapp 2002; 17: 143–55.CrossRefGoogle ScholarPubMed
20 Jenkinson, M Smith, S. A global optimisation method for robust affine registration of brain images. Med Image Anal 2001; 5: 143–56.CrossRefGoogle ScholarPubMed
21 Beckmann, CF, Jenkinson, M, Smith, SM. General multilevel linear modeling for group analysis in FMRI. Neuroimage 2003; 20: 1052–63.CrossRefGoogle Scholar
22 Woolrich, MW, Behrens, TE, Beckmann, CF, Jenkinson, M, Smith, SM. Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage 2004; 21: 1732–47.CrossRefGoogle ScholarPubMed
23 Worsley, KJ, Evans, AC, Marrett, S, Neelin, P. A three-dimensional statistical analysis for CBF activation studies in human brain. J Cereb Blood Flow Metab 1992; 12: 900–18.CrossRefGoogle ScholarPubMed
24 Talairach, J, Tournoux, P. Co-Planar Stereotactic Atlas of the Human Brain. Thieme, 1988.Google Scholar
25 Lancaster, JL, Woldroff, MG, Parsons, LM, Liotti, M, Freitas, CS, Rainey, L, et al. Automated Talairach atlas labels for function brain mapping. Hum Brain Mapp 2000; 10: 120–31.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
26 Bhagwagar, Z, Cowen, PJ, Goodwin, GM, Harmer, CJ. Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. Am J Psychiatry 2004; 161: 166–8.CrossRefGoogle ScholarPubMed
27 Mogg, K, Bradley, BP. A cognitive-motivational analysis of anxiety. Behav Res Ther 1998; 36: 809–48.CrossRefGoogle ScholarPubMed
28 Morris, JS, Frith, CD, Perrett, DI, Rowland, D, Young, AW, Calder, AJ, et al. A differential neural response in the human amygdala to fearful and happy facial expressions. Nature 1996; 383: 812–5.CrossRefGoogle ScholarPubMed
29 Drevets, WC, Videen, TO, Price, JL, Preskorn, SH, Carmichael, ST, Raichle, ME. A functional anatomical study of unipolar depression. J Neurosci 1992; 12: 3628–41.CrossRefGoogle ScholarPubMed
30 Rauch, SL, Shin, LM, Wright, CI. Neuroimaging studies of amygdala function in anxiety disorders. Ann NY Acad Sci 2003; 985: 389410.CrossRefGoogle ScholarPubMed
31 Davidson, RJ, Irwin, W, Anderle, MJ, Kalin, NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry 2003; 160: 6475.CrossRefGoogle ScholarPubMed
32 Stutzmann, GE, LeDoux, JE. GABAergic antagonists block the inhibitory effects of serotonin in the lateral amygdala: a mechanism for modulation of sensory inputs related to fear conditioning. J Neurosci 1999; 19: RC8.CrossRefGoogle ScholarPubMed
33 Drevets, WC, Bogers, W, Raichle, ME. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol 2002; 12: 527–44.CrossRefGoogle ScholarPubMed
34 Kent, JM, Coplan, JD, Gorman, JM. Clinical utility of the selective serotonin reuptake inhibitors in the spectrum of anxiety. Biol Psychiatry 1998; 44: 812–24.CrossRefGoogle ScholarPubMed
35 Burghardt, NS, Sullivan, GM, McEwen, BS, Gorman, JM, LeDoux, JE. The selective serotonin reuptake inhibitor citalopram increases fear after acute treatment but reduces fear with chronic treatment: a comparison with tianeptine. Biol Psychiatry 2004; 55: 1171–8.CrossRefGoogle ScholarPubMed
36 Attenburrow, MJ, Williams, C, Odontiadis, J, Reed, A, Powell, J, Cowen, PJ, et al. Acute administration of nutritionally sourced tryptophan increases fear recognition. Psychopharmacology (Berl) 2003; 169: 104–7.CrossRefGoogle ScholarPubMed
37 Neumeister, A, Hu, XZ, Luckenbaugh, DA, Schwarz, M, Nugent, AC, Bonne, O, et al. Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls. Arch Gen Psychiatry 2006; 63: 978–86.CrossRefGoogle ScholarPubMed
38 Whalen, PJ, Rauch, SL, Etcoff, NL, McInerney, SC, Lee, MB, Jenike, MA. Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J Neurosci 1998; 18: 411–8.CrossRefGoogle ScholarPubMed
39 Phillips, ML, Williams, LM, Heining, M, Herba, CM, Russell, T, Andrew, C, et al. Differential neural responses to overt and covert presentations of facial expressions of fear and disgust. Neuroimage 2004; 21: 1484–96.CrossRefGoogle ScholarPubMed
40 Bishop, SJ, Duncan, J, Lawrence, AD. State anxiety modulation of the amygdala response to unattended threat-related stimuli. J Neurosci 2004; 24: 10364–8.CrossRefGoogle ScholarPubMed
41 Pessoa, L, McKenna, M, Gutierrez, E, Ungerleider, LG. Neural processing of emotional faces requires attention. Proc Natl Acad Sci USA 2002; 99: 11458–63.CrossRefGoogle ScholarPubMed
42 Wise, RG, Tracey, I. The role of fMRI in drug discovery. J Magn ResonImaging 2006; 23: 862–76.Google ScholarPubMed
43 Iannetti, GD, Wise, RG. BOLD functional MRI in disease and pharmacological studies: room for improvement? Magn Reson Imaging 2007; 25: 978–88.CrossRefGoogle Scholar
Submit a response


No eLetters have been published for this article.
You have Access
Open access
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Effect of a single dose of citalopram on amygdala response to emotional faces
Available formats

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Effect of a single dose of citalopram on amygdala response to emotional faces
Available formats

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Effect of a single dose of citalopram on amygdala response to emotional faces
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *