A Call for Experiments on Genetic Differential Susceptibility
from Part IV - Differential Susceptibility to Environmental Influences
Published online by Cambridge University Press: 04 September 2025
Belsky noted that for evolutionary-biological reasons, development may not follow a cumulative risk model. He theorized that ‘vulnerable’ children might actually be susceptible to environmental influences for better and for worse. Moreover, he argued that variation in susceptibility within the family would be evolutionarily advantageous for both parents and children. Stimulated by Belsky’s provocative thinking, and relying on randomized controlled trials that constitute the most stringent and powerful tests of the paradigm, we found meta-analytic support for (genetic) differential susceptibility. Examining the bold idea of within-family differential susceptibility, we included twins in our cohort-sequential randomized controlled trial and designed a series of experiments on mice. One of our mice studies revealed the expected crossover interaction. Heterozygous DRD4 mice who had grown up in an enriched environment licked and groomed their own offspring the most, while those who grew up in adverse circumstances showed the least licking and grooming. In humans, our experimental search for within-family differential susceptibility has not yet supported this bold conjecture. An explanation might be that the available polygenic scores for susceptibility were developed in the context of internalizing, not externalizing, problems. Susceptibility to environmental influences may be more domain specific (Belsky et al., 2022) than we originally thought.
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