Moderating effects of childhood deprivation and threat on the relationship between polygenic score and internalizing...

Childhood internalizing symptoms are linked to psychiatric disorders in adulthood. Both genetic factors and environmental adversities, such as deprivation and threats, contribute to their development. This study aimed to explore the interaction between an individual's polygenic score (PGS) for internalizing symptoms and their experiences of childhood deprivation and threats in predicting the development of such symptoms.

A sample of 1797 children, aged 9 to 18 years, was assessed using the Strengths and Difficulties Questionnaire to evaluate internalizing symptoms and the Development and Well-Being Assessment to identify adverse events during two time points. A generalized mixed model was used to analyze the interaction between the PGS for internalizing symptoms and adverse events (specifically deprivation and threat). The PGS was calculated using the PRS-CS software.

Our analysis showed that in low-deprivation contexts, a higher PGS was associated with increased internalizing symptoms (EMM): coefficient = -0.131, p = 0.027). However, this relationship was not significant in contexts of moderate or high deprivation (p > 0.05). Moreover, sex-specific interactions indicated that deprivation has a more pronounced effect on females, while threats have a stronger impact on males.

The study finds that individuals with a high genetic risk, indicated by a high PGS, predominantly exhibit increased symptoms in low-deprivation environments, suggesting that genetic susceptibility is most apparent under stable conditions. This finding underscores the critical impact of adverse childhood experiences on mental health, illustrating how environmental factors can significantly modify the expression of genetic risk.