Effect of Citalopram on Emotion Processing in Humans: A Combined 5-HT [C]CUMI-101 PET and Functional MRI Study

Sudhakar Selvaraj, Chris Walker, Danilo Arnone, Bo Cao, Paul Faulkner, Philip J Cowen, Jonathan P Roiser, Oliver Howes

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Abstract

A subset of patients started on a selective serotonin reuptake inhibitor (SSRI) initially experience increased anxiety, which can lead to early discontinuation before therapeutic effects are manifest. The neural basis of this early SSRI effect is not known. Presynaptic dorsal raphe neuron (DRN) 5-HT1A receptors are known to have a critical role in affect processing. Thus we investigated the effect of acute citalopram on emotional processing and the relationship between DRN 5-HT1A receptor availability and amygdala reactivity. Thirteen (mean age 48±9 years) healthy male subjects received either a saline or citalopram infusion intravenously (10 mg over 30 min) on separate occasions in a single-blind, random order, crossover design. On each occasion, participants underwent a block design face-emotion processing task during fMRI known to activate the amygdala. Ten subjects also completed a positron emission tomography (PET) scan to quantify DRN 5-HT1A availability using [11C]CUMI-101. Citalopram infusion when compared with saline resulted in a significantly increased bilateral amygdala responses to fearful vs neutral faces (left p=0.025; right p=0.038 FWE-corrected). DRN [11C]CUMI-101 availability significantly positively correlated with the effect of citalopram on the left amygdala response to fearful faces (Z=2.51, p=0.027) and right amygdala response to happy faces (Z=2.33, p=0.032). Our findings indicate that the initial effect of SSRI treatment is to alter processing of aversive stimuli and that this is linked to DRN 5-HT1A receptors in line with evidence that 5-HT1A receptors have a role in mediating emotional processing.

© 2018, Macmillan Publishers Limited, part of Springer Nature. The attached document (embargoed until 04/02/2018) is an authorproduced version of a paper published in NEUROPSYCHOPHARMACOLOGY uploaded in accordancewith the publisher’s self- archiving policy. The final published version(version of record) is available online at the link below. Some minordifferences between this version and the final published version may remain. Wesuggest you refer to the final published version should you wish to cite from it.

Original languageEnglish
Pages (from-to)655-664
Number of pages10
JournalNEUROPSYCHOPHARMACOLOGY
Volume43
Issue number3
DOIs
Publication statusPublished - 4 Aug 2017

Keywords

  • Journal Article

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