Caregiving and 5‐HTTLPR Genotype Predict Adolescent Physiological Stress Reactivity: Confirmatory Tests of Gene × Environment Interactions

A theory‐driven confirmatory approach comparing diathesis–stress and differential susceptibility models of Gene × Environment (G × E) interactions was applied to examine whether 5‐HTTLPR genotype moderated the effect of early maternal caregiving on autonomic nervous system ( ANS ) stress reactivity in 113 adolescents aged 13–17 years. Findings supported a differential susceptibility, rather than diathesis–stress, framework. Carriers of one or more 5‐HTTLPR short alleles ( SS / SL carriers) reporting higher quality caregiving exhibited approach ANS responses to a speech task, whereas those reporting lower quality caregiving exhibited withdrawal ANS responses. Carriers of two 5‐HTTLPR long alleles ( LL carriers) were unaffected by caregiving. Findings suggest that 5‐HTTLPR genotype and early caregiving in interaction are associated with ANS stress reactivity in adolescents in a “for better and for worse” fashion, and they demonstrate the promise of confirmatory methods for testing G × E interactions.