title: Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Affective Neuroscience Laboratory, Department of Psychology, Harvard University, Cambridge, MA, USA.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Nikolova
authors.forename: Ryan
authors.initials: R
authors.lastname: Bogdan
authors.forename: Diego A
authors.initials: DA
authors.lastname: Pizzagalli
mesh_terms: D000293:Adolescent; D059445:Anhedonia / Q000502:physiology*; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012201:Reward; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*; D013334:Students / Q000523:psychology
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
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