Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness

Neuropsychobiology. 2012;65(1):45-54. doi: 10.1159/000329105. Epub 2011 Nov 17.

Abstract

Background: Stressful life experiences frequently precede the onset of major depression; however, the mechanisms that underlie this link are poorly understood. Importantly, some individuals are more susceptible to the depressogenic effects of stress than others. Carriers of the S or LG allele of the 5-HTTLPR/rs25531 polymorphisms (S' participants) have been found to be more prone to developing depression under stress relative to L or LA homozygotes (L' participants). Moreover, emerging evidence indicates that stress-induced anhedonia may be a mechanism underlying links between stress and depression. Given these findings, we hypothesized that exposure to a naturalistic stressor (school final examinations) would disrupt reward responsiveness (a key behavioral component of anhedonia), and that this effect would be strongest in S' participants.

Methods: To objectively assess reward responsiveness, we administered a probabilistic reward task to 70 Bulgarian high school students over two sessions in the 6-month period preceding school finals. For each participant, the two sessions were designated as the 'stress' and 'control' conditions based on self-reported perceived stress.

Results: A genotype×condition interaction emerged in males, with S' participants showing larger stress-related reduction in reward responsiveness relative to L' participants.

Conclusion: While in need of replication in a larger sample, our results indicate that stress associated with a real-life event is linked to reduced reward responsiveness, the susceptibility to which is modulated by 5-HTTLPR/rs25531 genotype. Although preliminary, these findings identify anhedonia as a promising mechanism linking 5-HTTLPR/rs25531 genotype and stress to depression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anhedonia / physiology*
  • Depressive Disorder / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Polymorphism, Genetic
  • Reward
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Stress, Psychological / genetics*
  • Students / psychology

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins