Evidence for plasticity genotypes in a gene-gene-environment interaction: the TRAILS study

The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5-HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to regulate behavior in a goal-directed manner and is an interesting endophenotype for psychopathology because of its heritability and the association of low Effortful Control with both internalizing and externalizing problems. In a longitudinal population-based study Effortful Control was assessed with the parent version of the Early Adolescent Temperament Questionnaire at age 11. Pregnancy and delivery adversities and childhood events were assessed in a parent interview at age 11. Long-term difficulties until age 11 were assessed with a parent questionnaire at age 13.5. Blood or buccal cells were collected at age 16 for genotyping the rs6265 and rs25531 SNPs and the 5-HTTLPR length polymorphism. The study included 1032 complete data sets. Effortful Control was significantly predicted by the interaction between BDNF val66met, 5-HTTLPR and childhood events. The BDNF val66met val/val-5-HTTLPR l'/l' genotype was unaffected by childhood events, while having either at least one BDNF val66met met or 5-HTTLPR s' allele (l'/l'-met-carrier; l'/s'-val/val; s'/s'-val/val) made children sensitive to childhood events. Predictions of Effortful Control by pregnancy and delivery adversities and long-term difficulties were largely independent of genotype. We concluded that the l'/l'-met-carrier, l'/s'-val/val and the s'/s'-val/val genotypes showed greatest plasticity while the l'/l'-val/val genotype was unaffected by childhood events.