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


CONCLUSIONS
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.
Division of Clinical Medicine, Brighton and Sussex Medical School, Falmer, Brighton, United Kingdom Institute of Psychiatry, King's College London, King's Health Partners, London, United Kingdom.
Ayana A
AA
Gibbs
Division of Clinical Medicine, Brighton and Sussex Medical School, Falmer, Brighton, United Kingdom.
Carla E
CE
Bautista
School of Psychology, University of Sussex, Falmer, Brighton, United Kingdom.
Florence D
FD
Mowlem
Institute of Psychiatry, King's College London, King's Health Partners, London, United Kingdom.
Kris H
KH
Naudts
The Department of Psychiatry, University of Muenster, Germany.
Dora T
DT
Duka
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D009025:Morpholines / Q000009:adverse effects / Q000494:pharmacology*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D000077593:Reboxetine; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D000077593:Reboxetine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase