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P-800 - how do Antidepressants Work? a Positron Emission Tomography (pet) Study of Brain Serotonin Levels and Affect Regulation

Published online by Cambridge University Press:  15 April 2020

S. Selvaraj
Affiliation:
Psychosis Studies, King's College London, Institute of Psychiatry, London MRC Clinical Sciences Centre, Hammersmith Hospital, London
P. Faulkner
Affiliation:
Institute of Cognitive Neuroscience, University College London, London
E. Mouchlianitis
Affiliation:
MRC Clinical Sciences Centre, Hammersmith Hospital, London
F. Turkheimer
Affiliation:
Imperial College School of Medicine, University of London, London
L. Rosso
Affiliation:
Imperial College School of Medicine, University of London, London
J.P. Roiser
Affiliation:
Institute of Cognitive Neuroscience, University College London, London
P.J. Cowen
Affiliation:
Oxford University, School of Psychiatry, Oxford, UK
O. Howes
Affiliation:
Psychosis Studies, King's College London, Institute of Psychiatry, London MRC Clinical Sciences Centre, Hammersmith Hospital, London

Abstract

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Background

Serotonin (5-HT) is thought to be critical for affect regulation in the brain and many antidepressants are thought to primarily work by altering 5-HT levels. However there has not been a validated means of directly imaging of endogenous 5-HT levels in humans. The main aims of this project are to image the effect of Citalopram on brain endogenous 5-HT levels and to determine the relationship between brain 5-HT and affect regulation.

Methods

Thirteen healthy volunteers (mean age 50.9yrs, range 35–63) underwent two Positron Emission Tomography (PET) scans with [11C]-CUMI, a highly selective 5-HT1A agonist radioligand. Subjects received either a slow intravenous infusion of citalopram 10mg or saline starting 45 minutes before each PET scan in a randomized design. All subjects had a functional MRI emotion processing task (block design) known to activate the amygdala on a separate day.

Results

The citalopram infusion induced 6–11% increases in [11C]-CUMI binding potential in anterior cingulate, insula and cortical brain regions (p < 0.05 corrected for repeated measures).

BOLD response to fearful vs neutral faces in the left amygdala inversely correlated with baseline dorsal raphe BP (Pearson r2 =−0.90, p < 0.001) and directly correlated with dorsal raphe BP changes (r2=0.51, p = 0.07).

Conclusion

The increase in [11C]CUMI-101 availability would be consistent with a decrease in endogenous 5-HT availability in certain terminal regions. The relationship between brain emotion processing and [11C]-CUMI binding in the raphe indicates the 5-HT levels at presynaptic receptors regulate emotional processing and suggests presynaptic 5-HT as a treatment target for affective disorders.

Type
Abstract
Copyright
Copyright © European Psychiatric Association 2012
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