Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers

J Neurosci. 2013 Oct 23;33(43):17023-8. doi: 10.1523/JNEUROSCI.2124-13.2013.

Abstract

Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / pharmacology*
  • Adult
  • Arousal / drug effects
  • Arousal / genetics
  • Case-Control Studies
  • Emotions
  • Gene Deletion
  • Genetic Association Studies
  • Genotype*
  • Healthy Volunteers
  • Homozygote
  • Humans
  • Male
  • Memory / drug effects*
  • Morpholines / pharmacology*
  • Polymorphism, Genetic
  • Reboxetine
  • Receptors, Adrenergic, alpha-2 / genetics*

Substances

  • ADRA2B protein, human
  • Adrenergic Uptake Inhibitors
  • Morpholines
  • Receptors, Adrenergic, alpha-2
  • Reboxetine