Hostname: page-component-745bb68f8f-b6zl4 Total loading time: 0 Render date: 2025-01-28T02:47:00.624Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Abstract

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

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.

Aims

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

Method

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.

Results

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

Conclusions

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.

Type
Papers
Information
The British Journal of Psychiatry , Volume 194 , Issue 6 , June 2009 , pp. 535 - 540
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 (http://creativecommons.org/licenses/by-nc/4.0/), 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
Copyright © Royal College of Psychiatrists, 2009

Footnotes

This research was funded by a Wellcome Trust studentship.

Declaration of interest

None.

References

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.Google Scholar
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 Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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: 189–202.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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 Scholar
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.Google Scholar
27 Mogg, K, Bradley, BP. A cognitive-motivational analysis of anxiety. Behav Res Ther 1998; 36: 809–48.Google Scholar
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.Google Scholar
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.Google Scholar
30 Rauch, SL, Shin, LM, Wright, CI. Neuroimaging studies of amygdala function in anxiety disorders. Ann NY Acad Sci 2003; 985: 389–410.Google Scholar
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: 64–75.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
42 Wise, RG, Tracey, I. The role of fMRI in drug discovery. J Magn ResonImaging 2006; 23: 862–76.Google Scholar
43 Iannetti, GD, Wise, RG. BOLD functional MRI in disease and pharmacological studies: room for improvement? Magn Reson Imaging 2007; 25: 978–88.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.