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Background  There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the  5-HTTLPR  polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity −the intensity of an individual’s response to other’s emotions− has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between  5-HTTLPR  and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment.    Methods  Children ( N  = 521, 52.5% boys,  M age = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children’s self-reported negative and positive affect ( n  = 460) and facial electromyography activity (i.e.,  f EMG: the zygomaticus or “smile” muscle and the corrugator or “frown” muscle,  n  = 403). Parents reported on their negative and positive parenting behaviors.    Results  Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children’s  5-HTTLPR  genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor.    Conclusions  We found no evidence for an association between the  5-HTTLPR  polymorphism and children’s emotional reactivity. This finding is important, in discounting one potential underlying endophenotype of G×E between the  5-HTTLPR  and affective environmental stressors.

5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children