Objective: This study aimed to explore the association between monoaminergic genetic variants and emotional lability (EL) symptoms in children with ADHD. In addition, genetic effects on prefrontal cortex (PFC)-amygdala functional connectivity (FC) were investigated. Method: Children with ADHD and controls were genotyped for five monoaminergic genetic variants and were evaluated for EL symptoms. Imaging genetic exploration was conducted with previously reported aberrant PFC-amygdala resting-state functional connectivities (RSFCs) as target features. Results: A genotypic effect on EL symptoms was only found for NET1-rs3785143, indicating higher EL symptoms in TT genotype carriers than in C-allele carriers. Imaging genetic analyses indicated a marginal effect of NET1-rs3785143 on ADHD-altered FC between the superficial amygdala (SFA) and middle frontal gyrus (MFG). Mediation analysis suggested potential effects of NET1-rs3785143 via RSFC (SFA-MFG) on EL. Conclusion:NET1 variants might participate in the pathogenesis of EL in children with ADHD by influencing the function of the PFC-amygdala circuit.
Keywords: ADHD; emotional lability; imaging genetics; monoaminergic genetic variants; prefrontal cortex–amygdala.