Catechol-O-methyltransferase val158met genotype determines effect of reboxetine on emotional memory in healthy male volunteers

Catechol-O-methyltransferase val158met genotype determines effect of reboxetine on emotional memory in healthy male volunteers

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J Psychiatry Neurosci 2014; 39(3): E24-E31

Ayana A. Gibbs, MBChB, PhD; Carla E. Bautista, BSc, MSc; Florence D. Mowlem, BSc; Kris H. Naudts, MD, PhD; Dora T. Duka, MD, PhD

Gibbs, Bautista — Division of Clinical Medicine, Brighton and Sussex Medical School, Falmer, Brighton, United Kingdom; Gibbs, Naudts — Institute of Psychiatry, King’s College London, King’s Health Partners, London, United Kingdom; Mowlem, Duka — School of Psychology, University of Sussex, Falmer, Brighton, United Kingdom

Abstract

Background: Catechol-O-methyltransferase (COMT) metabolizes catecholamines in the prefrontal cortex (PFC). A common polymorphism in the COMT gene (COMT val158met) has pleiotropic effects on cognitive and emotional processing. The met allele has been associated with enhanced cognitive processing but impaired emotional processing relative to the val allele.

Methods: We genotyped healthy, white men in relation to the COMT val158met polymorphism. They were given a single 4 mg dose of the selective noradrenaline reuptake inhibitor (NRI) reboxetine or placebo in a randomized, double-blind between-subjects model and then completed an emotional memory task 2 hours later.

Results: We included 75 men in the study; 41 received reboxetine and 34 received placebo. In the placebo group, met/met carriers did not demonstrate the usual memory advantage for emotional stimuli that was observed in val carriers. Reboxetine restored this emotional enhancement of memory in met/met carriers, but had
no significant effect in val carriers.

Limitations: We studied only men, thus limiting the generalizability of our findings. We also relied on self-reported responses to screening questions to establish healthy volunteer status, and in spite of the double-blind design, participants were significantly better than chance at identifying their intervention allocation.

Conclusions: Emotional memory is impaired in healthy met homozygotes and selectively improved in this group by reboxetine. This has potential translational implications for the use of reboxetine, which is currently licensed as an antidepressant in several countries, and edivoxetine, a new selective NRI currently in development.


*Both authors contributed equally to the work.

Submitted June 30, 2013; Revised Oct. 22, Nov 22, 2013; Accepted Nov. 25, 2013.

Acknowledgements: This study was funded by Brighton and Sussex Medical School.

Competing interests: None declared.

Contributors: A.A. Gibbs and D.T. Duka designed the study. A.A. Gibbs, C.E. Bautista and F.D. Mowlem acquired the data, which all authors analyzed. A.A. Gibbs, C.E. Bautista and F.D. Mowlem wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130131

Correspondence to: A. Gibbs, Clinical Imaging Sciences Centre, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom; a.gibbs@bsms.ac.uk