COMT Val158Met Polymorphism and Social Impairment Interactively Affect Attention-Deficit Hyperactivity Symptoms in Healthy Adolescents

Sabina K. Millenet, Frauke Nees, Stefan Heintz, Christiane Bach, Josef Frank, Sabine Vollstädt-Klein, Arun Bokde, Uli Bromberg, Christian Büchel, Erin B. Quinlan, Sylvane Desrivières, Juliane Fröhner, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Herve Lemaire, Jean-Luc Martinot, Marie-Laure P. Martinot, Dimitri O. Papadoulos, Tomáš Paus, Luise Poustka, Marcella Rietschel, Michael N. Smolka, Henrik Walter, Rob Whelan, Gunter Schumann, Tobias Banaschewski, Sarah Hohmann

The dopaminergic system has been shown to have substantial effects on the etiology of attention-deficit hyperactivity disorder (ADHD). However, while some studies found a significant direct effect, others did not. In this context, social behavior might play an important role as a factor that is related both to the dopaminergic system and ADHD. In a large epidemiological sample of adolescents (N = 462; 16-17 years), we assessed the level of ADHD symptoms using the Strengths and Difficulties Questionnaire, social behavior using the Social Responsiveness Scale, and the allelic distribution of the dopaminergic catechol-O-methyltransferase (COMT) Val158Met polymorphism. We found a significant association between COMT and social impairment, insofar as Met-allele carriers showed increased levels of social impairment. Moreover, social impairment significantly determined an association between COMT and ADHD (explained variance: 19.09%). This effect did not significantly differ between males and females. COMT and social impairment might interactively affect ADHD symptomatology, and could thus represent significant gene-phenotypic risk factors for ADHD symptomatology. This might have interesting implications for prevention and intervention strategies with a focus on social behavior in genetically at-risk individuals.