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

Area of Science:

• Neuroscience
• Genetics
• Developmental Psychology

Background:

• Effortful Control, crucial for goal-directed behavior, is a heritable endophenotype linked to psychopathology.
• Understanding genetic and environmental interactions is key to explaining individual differences in self-regulation.

Purpose of the Study:

• To investigate the interaction between functional polymorphisms in BDNF val66met and 5-HTTLPR genes and childhood adversities in predicting Effortful Control.
• To identify specific genotypes that confer sensitivity or resilience to environmental influences on behavioral regulation.

Main Methods:

• A longitudinal population-based study with 1032 participants.
• Assessment of Effortful Control using the Early Adolescent Temperament Questionnaire.
• Genotyping of BDNF val66met (rs6265) and 5-HTTLPR (rs25531) polymorphisms.
• Evaluation of pregnancy, delivery, childhood, and long-term adversities through parent interviews and questionnaires.

Main Results:

• Effortful Control was significantly predicted by the interaction of BDNF val66met, 5-HTTLPR, and childhood events.
• Children with specific genotypes (l'/l'-met-carrier, l'/s'-val/val, s'/s'-val/val) demonstrated plasticity, being sensitive to childhood events.
• The BDNF val/val-5-HTTLPR l'/l' genotype was resilient, showing no significant impact from childhood events.
• Pregnancy/delivery adversities and long-term difficulties predicted Effortful Control largely independently of genotype.

Conclusions:

• Genetic plasticity in Effortful Control is modulated by the interplay between BDNF and 5-HTTLPR genotypes and childhood experiences.
• The BDNF val/val-5-HTTLPR l'/l' genotype represents a non-plastic pathway regarding childhood adversity.
• Findings highlight the complex gene-environment interactions shaping crucial self-regulatory abilities.