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

doi:10.3389/fgene.2018.00284

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

Front Genet. 2018 Jul 31:9:284. doi: 10.3389/fgene.2018.00284. eCollection 2018.

Authors

Sabina K Millenet¹, Frauke Nees^{1

2}, Stefan Heintz¹, Christiane Bach^{1

3}, Josef Frank⁴, Sabine Vollstädt-Klein⁵, Arun Bokde⁶, Uli Bromberg⁷, Christian Büchel⁷, Erin B Quinlan⁸, Sylvane Desrivières⁸, Juliane Fröhner⁹, Herta Flor^{2

10}, Vincent Frouin¹¹, Hugh Garavan¹², Penny Gowland¹³, Andreas Heinz¹⁴, Bernd Ittermann¹⁵, Herve Lemaire¹⁶, Jean-Luc Martinot¹⁷, Marie-Laure P Martinot¹⁸, Dimitri O Papadoulos¹¹, Tomáš Paus¹⁹, Luise Poustka²⁰, Marcella Rietschel⁴, Michael N Smolka⁹, Henrik Walter¹⁴, Rob Whelan²¹, Gunter Schumann⁸, Tobias Banaschewski¹, Sarah Hohmann¹

Affiliations

¹ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
² Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
³ Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, Germany.
⁴ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁵ Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁶ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁷ University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁸ Centre for Population Neuroscience and Stratified Medicine and MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁹ Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
¹⁰ Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
¹¹ NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
¹² Department of Psychiatry and Psychology, University of Vermont, Burlington, VT, United States.
¹³ Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
¹⁴ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹⁵ Physikalisch-Technische Bundesanstalt, Braunschweig Institute Berlin, Germany.
¹⁶ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry," Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre; and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
¹⁷ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry," University Paris Sud - Paris Saclay, University Paris Descartes; Service Hospitalier Frédéric Joliot, Orsay; and Maison de Solenn, Paris, France.
¹⁸ Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry," University Paris Sud - Paris Saclay, University Paris Descartes; and AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France.
¹⁹ Rotman Research Institute, Baycrest Centre for Geriatric Care, Department of Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
²⁰ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, Göttingen, Germany.
²¹ Trinity College Dublin, Dublin, Ireland.

Abstract

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.

Keywords: ADHD; COMT; adolescence; moderation; social impairment.

Abstract

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