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A single dose of mirtazapine modulates neural responses to emotional faces in healthy people

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Abstract

Rationale

Single-dose administration of selective serotonin and noradrenaline reuptake blockers has been shown to alter emotional processing in both behavioral and fMRI studies in healthy volunteers. Mirtazapine is a clinically established antidepressant with different pharmacological actions from monoamine reuptake inhibitors, involving blockade of noradrenaline α2-adrenoceptors and multiple 5-HT receptor subtypes. The aim of this study was to investigate the effect of a single dose of mirtazapine on the neural processing of emotional faces in healthy volunteers.

Methods

Twenty-eight participants were randomized to receive either a single dose of mirtazapine (15 mg) or placebo. Two hours later, participants underwent an fMRI scan, in which they classified fearful and happy faces on the basis of gender. Mood and subjective experience were also measured.

Results

Whole-brain analysis showed significant group × emotion interactions in a right amygdala-hippocamal region and left fronto-striatal cortex. Post hoc analyses revealed significantly reduced activation to fear and greater activation to happy faces in both regions under mirtazapine.

Conclusions

Our findings indicate that a single dose of mirtazapine modulates neural activity to affective stimuli. Mirtazapine was found to decrease neural responses to fear and increase responses to happy facial expressions in regions implicated in the processing of emotional faces. These effects may be important for our understanding of the neural mechanisms of antidepressant action in anxiety and depression.

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Acknowledgement

Thanks to Martina Di Simplicio, Michael Browning, and Sarah McTavish.

Conflict of interest

CJH is on the advisory board for P1vital and holds shares in the company. She has also received consultancy fees from GlaxoSmithKline, Servier, P1vital, Lundbeck, and AstraZeneca. PJC has been a paid member of advisory boards of DSM, Eli Lilly, Servier, Wyeth, and Xytis and has been a paid lecturer for Eli Lilly, Servier, and GlaxoSmithKline. He has received remuneration for scientific advice given to legal representatives of GlaxoSmithKline.

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Authors and Affiliations

  1. Psychopharmacology and Emotion Research Laboratory (PERL), Department of Psychiatry, University of Oxford, Warneford Hospital, Neurosciences Building, Headington, Oxford, OX3 7JX, UK

    Nancy B. Rawlings & Catherine J. Harmer

  2. Psychopharmacology Research Unit (PPRU), Department of Psychiatry, University of Oxford, Warneford Hospital, Neurosciences Building, Headington, Oxford, OX3 7JX, UK

    Ray Norbury & Philip J. Cowen

Authors
  1. Nancy B. Rawlings
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  2. Ray Norbury
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  3. Philip J. Cowen
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  4. Catherine J. Harmer
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Corresponding author

Correspondence to Nancy B. Rawlings.

Additional information

* Development of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at tott0006@tc.umn.edu for more information concerning the stimulus set.

This study was supported by the MRC.

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Rawlings, N.B., Norbury, R., Cowen, P.J. et al. A single dose of mirtazapine modulates neural responses to emotional faces in healthy people. Psychopharmacology 212, 625–634 (2010). https://doi.org/10.1007/s00213-010-1983-8

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  • DOI: https://doi.org/10.1007/s00213-010-1983-8

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