For better and for worse: Evidence of differential susceptibility to environmental adversity in youth substance use from the cVEDA cohort

23/08/2026

AI Summary

Familial vulnerability and environmental adversity each increase adolescent substance use, with familial risk amplifying environmental effects.
Familial composite driven mainly by family history of alcohol dependence and psychiatric disorders; environmental composite dominated by adverse childhood experiences and unsafe school climate.
Findings indicate weak differential susceptibility consistent with a for better and for worse pattern; integrate family risk screening with school, childhood adversity, and parenting interventions.

Asian J Psychiatr. 2026 Aug 9;124:105116. doi: 10.1016/j.ajp.2026.105116. Online ahead of print.

ABSTRACT

BACKGROUND: Familial vulnerability and environmental adversity are both associated with adolescent substance-use, yet their joint effects remain insufficiently characterized. This study examined their interaction using a latent gene-environment (GxE) framework in the cVEDA cohort.

METHODS: The sample included 3786 adolescents and young adults aged 12-24 years. Familial vulnerability was indexed as the family-history density (FHD) scores derived from the pedigree for medical and psychiatric conditions, adjusted for degree of relatedness. Environmental adversity was captured using measures of childhood adversity, school climate, and parenting experiences. Substance use summarized as a global continuum of risk score from the WHO ASSIST. Weighted latent G×E models were estimated using an alternating optimization approach, adjusting for age and sex. Competing susceptibility patterns were compared, and predictive performance was evaluated using five-fold cross validation.

RESULTS: Familial vulnerability and environmental adversity were each associated with greater substance use involvement, with evidence that familial vulnerability amplified environmental effects. The latent familial composite was driven primarily by family history of alcohol dependence (η_p²=0.03) and other psychiatric disorders (η_p²=0.044). The latent environmental composite was dominated by adverse childhood experiences (η_p²=0.042) and unsafe school climate (η_p²=0.029), with smaller contributions from childhood neglect and negative parenting practices (η_p²<0.01). Model comparisons suggested a weak differential susceptibility pattern. Cross validation showed good discrimination (AUC=0.84).

CONCLUSIONS: Youth with greater familial vulnerability appear more environmentally sensitive, consistent with a “for-better-and-for-worse” pattern typical of differential susceptibility model. Integrating family risk screening with interventions targeting school climate, childhood adversity, and parenting may help identify targets for substance use prevention.

PMID:42628502 | DOI:10.1016/j.ajp.2026.105116

Document this CPD