A single dose of mirtazapine modulates neural responses to emotional faces in healthy people.
BACKGROUND
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 α(2)-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-hippocampal 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.
Rawlings
Nancy B
NB
Psychopharmacology and Emotion Research Laboratory, Department of Psychiatry, University of Oxford, Warneford Hospital, Neurosciences Building, Headington, Oxford, OX3 7JX, UK. nancy.rawlings@psych.ox.ac.uk
Norbury
Ray
R
Cowen
Philip J
PJ
Harmer
Catherine J
CJ
D000293:Adolescent; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage*; D000328:Adult; D000339:Affect / Q000187:drug effects; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage*; D001931:Brain Mapping; D004311:Double-Blind Method; D004739:England; D019260:Expressed Emotion; D005149:Facial Expression; D005239:Fear; D005260:Female; D006240:Happiness; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000078785:Mirtazapine; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D015990:Placebo Effect; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D055815:Young Adult
D058669:Adrenergic alpha-2 Receptor Antagonists; D000929:Antidepressive Agents, Tricyclic; D012702:Serotonin Antagonists; D008803:Mianserin; D000078785:Mirtazapine
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