Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype

Charlotte Nymberg*, Tianye Jia, Steven J Lubbe, Barbara Ruggeri, Sylvane Desrivieres, Gareth Barker, Christian Büchel, Mira Fauth-Buehler, Anna Cattrell, Patricia Conrod, Herta Flor, Juergen Gallinat, Hugh Garavan, Andreas Heinz, Bernd Ittermann, Claire Lawrence, Karl Mann, Frauke Nees, Angelica Salatino-Oliveira, Marie Laure Paillère MartinotTomas Paus, Marcella Rietschel, Trevor Robbins, Michael Smolka, Tobias Banaschewski, Katya Rubia, Eva Loth, Gunter Schumann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in reward sensitivity and response inhibition. The relative contribution of these frontostriatal mechanisms to ADHD symptoms and their genetic determinants is largely unexplored. Methods Using functional magnetic resonance imaging and genetic analysis of the monoamine oxidase A (MAOA) gene, we investigated how striatal and inferior frontal activation patterns contribute to ADHD symptoms depending on MAOA genotype in a sample of adolescent boys (n = 190). Results We demonstrate an association of ADHD symptoms with distinct blood oxygen level-dependent (BOLD) responses depending on MAOA genotype. In A hemizygotes of the expression single nucleotide polymorphism rs12843268, which express lower levels of MAOA, ADHD symptoms are associated with lower ventral striatal BOLD response during the monetary incentive delay task and lower inferior frontal gyrus BOLD response during the stop signal task. In G hemizygotes, ADHD symptoms are associated with increased inferior frontal gyrus BOLD response during the stop signal task in the presence of increased ventral striatal BOLD response during the monetary incentive delay task. Conclusions Depending on MAOA genotype, ADHD symptoms in adolescent boys are associated with either reward deficiency or insufficient response inhibition. Apart from its mechanistic interest, our finding may aid in developing pharmacogenetic markers for ADHD.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalBiological psychiatry
Volume74
Issue number8
DOIs
StatePublished - Oct 15 2013

Keywords

  • Attention-deficit/hyperactivity disorder
  • genetics inferior frontal gyrus
  • monoamine oxidase A
  • neuroimaging
  • ventral striatum

ASJC Scopus subject areas

  • Biological Psychiatry

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