Prosociality and Negative Emotionality Mediate the Association of Serotonin Transporter Genotype With Childhood ADHD and ODD

Abstract

Although there is evidence that the promoter polymorphism of the serotonin transporter (5-HTTLPR) gene is associated with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), the pathways underlying these associations are largely unknown. Given their theoretical and biological plausibility, we tested whether individual differences in key temperament dimensions (i.e., prosociality, negative emotionality, daring) constituted potential pathways from 5-HTTLPR to ADHD and ODD. Using a well-characterized sample of 194 six to nine-year-old children with and without ADHD, we utilized multiple mediation procedures with bootstrapping to evaluate prosociality, negative emotionality, and daring as independent mediators of 5-HTTLPR with separate parent and teacher ratings of ADHD and ODD. Controlling for ODD, prosociality and negative emotionality significantly mediated the association of 5-HTTLPR and parent-reported ADHD. Similarly, controlling for ADHD, prosociality and negative emotionality each uniquely mediated the association of 5-HTTLPR and parent-reported ODD. For teacher-reported ADHD, prosociality significantly mediated the association of 5-HTTLPR (controlling for ODD) whereas controlling for ODD, negative emotionality significantly mediated the prediction of teacher-reported ODD from 5-HTTLPR. Specifically, the number of 5-HTTLPR long alleles was inversely associated with prosociality and positively associated with negative emotionality; prosociality was inversely associated and negative emotionality was positively associated with ADHD and ODD. We consider the role of temperament in genetically sensitive designs as well as its potential value in the development and delivery of effective interventions.

Notes

Note: Mean differences evaluated by one-way analysis of variance or chi-square. ADHD = attention deficit/hyperactivity disorder; WISC-IV = Wechsler Intelligence Scale for Children–Fourth Edition; FSIQ = Full-Scale IQ; ODD = oppositional defiant disorder; CD = conduct disorder.

^a n = 101.

^b n = 93.

Note: Models predicting attention-deficit/hyperactivity disorder (ADHD) controlled for ODD diagnostic status whereas models predicting oppositional defiant disorder (ODD) controlled for ADHD diagnostic status. All models controlled for race-ethnicity. BCa bootstrap CI = bias corrected and accelerated confidence intervals; Point est. = point estimate of the indirect effect. Boldface indicates significant mediation.