Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment's impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (β = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (β = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(β_ASRS = 0.51; 95% CI: 0.26;0.77) and (β_SDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (β = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.