Monoaminergic Genetic Variants, Prefrontal Cortex–Amygdala Circuit, and Emotional Symptoms in Children With ADHD: Exploration Based on the Gene–Brain–Behavior Relationship

Abstract

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.