Meta-analysis of the effect of 5HTTLPR polymorphism in fear learning

Studies of the association between polymorphisms of the serotonin transporter gene and fear learning have produced inconsistent results, raising questions about the strength of the relationship and the methodological conditions under which the relationship occurs. We conducted a meta-analysis of existing studies to provide an integrated statistical measure of the effect of the polymorphic region of the serotonin transporter gene (5-HTTLPR) in aversive associative learning (acquisition and extinction) in humans and rodents. The included studies were gathered through scientific database search engines. Selection criteria included experimental studies in which 5-HTTLPR and any measure of fear were considered as main variables. An effect size was calculated for each relevant experiment. 30 articles, with 33 experiments were included, 28 for acquisition, 13 for extinction. The integrated effect size (random effects model) for acquisition of fear was d = 0.33, 95 % CI [0.20, 0.50]. For extinction, the integrated effect size was d = 0.63, 95 % [CI 0.26, 1.00]. Test for publication bias was not significant neither for acquisition nor extinction. Thus, a medium but consistent effect was found between having the S allele of 5-HTTLPR and fear. The finding suggests a genetic vulnerability to anxiety in carriers of the polymorphism of the serotonin transporter that should be considered in future research.