TY - JOUR
T1 - Effect of Citalopram on Emotion Processing in Humans
T2 - A Combined 5-HT1A [11C]CUMI-101 PET and Functional MRI Study
AU - Selvaraj, Sudhakar
AU - Walker, Chris
AU - Arnone, Danilo
AU - Cao, Bo
AU - Faulkner, Paul
AU - Cowen, Philip J.
AU - Roiser, Jonathan P.
AU - Howes, Oliver
N1 - Funding Information:
This study was supported by an Academy of Medical Sciences, UK clinical lecturer starter grant to SS (grant number: AMS-SGCL6). This study was funded by a Medical Research Council (UK) grant to OH (grant number: MC-A656-5QD30); Maudsley Charity (no. 666), Brain and Behavior Research Foundation, and Wellcome Trust (no. 094849/Z/10/Z) grants to OH; and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. PF was supported by an MRC studentship. DA was supported by the Academy of Medical Sciences, UK (grant number: AMS SGCL8) and has received travel grants from Jansenn-Cilag and Servier. PJC has been a member of advisory boards of Servier and Lundbeck and has been a paid lecturer for Servier and Lundbeck. JPR has been a member of a media advisory board for Lundbeck and consults for Cambridge Cognition Ltd. Intravenous citalopram was kindly provided by Lundbeck, UK. OH has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Astra-Zeneca, Autifony, BMS, Eli Lilly, Heptares, Janssen, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand, and Roche. The other authors declare no conflict of interest. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.
Publisher Copyright:
© 2018 American College of Neuropsychopharmacology. All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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-HT 1A 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-HT 1A 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-HT 1A availability using [ 11 C]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 [ 11 C]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.
AB - 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-HT 1A 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-HT 1A 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-HT 1A availability using [ 11 C]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 [ 11 C]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.
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U2 - 10.1038/npp.2017.166
DO - 10.1038/npp.2017.166
M3 - Article
C2 - 28776580
AN - SCOPUS:85040454196
SN - 0893-133X
VL - 43
SP - 655
EP - 664
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 3
ER -