The candidate gene-environment interaction (cG × E) research field in psychiatry has traditionally been dominated by the diathesis–stress framework, where certain genotypes are assumed to confer increased risk for adverse outcomes in a stressful environment. In later years, theories of differential susceptibility or biological sensitivity have been presented, suggesting that cGs that interact with environmental events do not exclusively confer a risk for behavioural or psychiatric disorders but rather seem to alter the sensitivity to both positive and negative environmental influences.

The present study investigates the susceptibility properties of the 5HTTLPR gene in relation to depressive symptoms and delinquency in two separate adolescent community samples: n = 1457, collected in 2006; and n = 191, collected in 2001.

Two-, three- and four-way interactions between the 5HTTLPR, positive family environment, negative family environment, and sex were found in relation to both depressive symptoms and delinquency. However, the susceptibility properties of the 5HTTLPR gene were distinctly less pronounced in relation to depressive symptoms.

If the assumption that the 5HTTLPR gene induces differential susceptibility to both positive and negative environmental influences is correct, the previous failures to measure and control for positive environmental factors might be a possible explanation for former inconsistent findings within the research field.

The authors have not supplied their declaration of competing interest.