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 Martinot; Tomas Paus; Marcella Rietschel; Trevor Robbins; Michael Smolka; Tobias Banaschewski; Katya Rubia; Eva Loth; Gunter Schumann

doi:10.1016/j.biopsych.2013.03.027

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

Neurology

Research output: Contribution to journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	607-614
Number of pages	8
Journal	Biological psychiatry
Volume	74
Issue number	8
DOIs	https://doi.org/10.1016/j.biopsych.2013.03.027
State	Published - Oct 15 2013

Funding

This work was supported by the European Union–funded FP6 Integrated Project IMAGEN (Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology; Grant No. LSHM-CT-2007-037286), the FP7 projects ADAMS (Genomic Variations Underlying Common Neuropsychiatric Diseases and Disease Related Cognitive Traits in Different Human Populations) (Grant No. 242257), and the Innovative Medicine Initiative Project EU-AIMS (Grant No. 115300-2), as well as the United Kingdom National Institute for Health Research Biomedical Research Centre Mental Health and the Medical Research Council Programme Grant “Developmental Pathways into Adolescent Substance Abuse” (Grant No. 93558) and the Swedish Research Council.

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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10.1016/j.biopsych.2013.03.027

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Nymberg, C., Jia, T., Lubbe, S. J., Ruggeri, B., Desrivieres, S., Barker, G., Büchel, C., Fauth-Buehler, M., Cattrell, A., Conrod, P., Flor, H., Gallinat, J., Garavan, H., Heinz, A., Ittermann, B., Lawrence, C., Mann, K., Nees, F., Salatino-Oliveira, A., ... Schumann, G. (2013). Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype. Biological psychiatry, 74(8), 607-614. https://doi.org/10.1016/j.biopsych.2013.03.027

@article{d499a3cdab614300a3662ca859bd9e2f,

title = "Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype",

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.",

keywords = "Attention-deficit/hyperactivity disorder, genetics inferior frontal gyrus, monoamine oxidase A, neuroimaging, ventral striatum",

author = "Charlotte Nymberg and Tianye Jia and Lubbe, \{Steven J\} and Barbara Ruggeri and Sylvane Desrivieres and Gareth Barker and Christian B{\"u}chel and Mira Fauth-Buehler and Anna Cattrell and Patricia Conrod and Herta Flor and Juergen Gallinat and Hugh Garavan and Andreas Heinz and Bernd Ittermann and Claire Lawrence and Karl Mann and Frauke Nees and Angelica Salatino-Oliveira and \{Paill{\`e}re Martinot\}, \{Marie Laure\} and Tomas Paus and Marcella Rietschel and Trevor Robbins and Michael Smolka and Tobias Banaschewski and Katya Rubia and Eva Loth and Gunter Schumann",

note = "Funding Information: This work was supported by the European Union–funded FP6 Integrated Project IMAGEN (Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology; Grant No. LSHM-CT-2007-037286), the FP7 projects ADAMS (Genomic Variations Underlying Common Neuropsychiatric Diseases and Disease Related Cognitive Traits in Different Human Populations) (Grant No. 242257), and the Innovative Medicine Initiative Project EU-AIMS (Grant No. 115300-2), as well as the United Kingdom National Institute for Health Research Biomedical Research Centre Mental Health and the Medical Research Council Programme Grant “Developmental Pathways into Adolescent Substance Abuse” (Grant No. 93558) and the Swedish Research Council. ",

year = "2013",

month = oct,

day = "15",

doi = "10.1016/j.biopsych.2013.03.027",

language = "English (US)",

volume = "74",

pages = "607--614",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier Inc.",

number = "8",

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Nymberg, C, Jia, T, Lubbe, SJ, Ruggeri, B, Desrivieres, S, Barker, G, Büchel, C, Fauth-Buehler, M, Cattrell, A, Conrod, P, Flor, H, Gallinat, J, Garavan, H, Heinz, A, Ittermann, B, Lawrence, C, Mann, K, Nees, F, Salatino-Oliveira, A, Paillère Martinot, ML, Paus, T, Rietschel, M, Robbins, T, Smolka, M, Banaschewski, T, Rubia, K, Loth, E & Schumann, G 2013, 'Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype', Biological psychiatry, vol. 74, no. 8, pp. 607-614. https://doi.org/10.1016/j.biopsych.2013.03.027

TY - JOUR

T1 - Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype

AU - Nymberg, Charlotte

AU - Jia, Tianye

AU - Lubbe, Steven J

AU - Ruggeri, Barbara

AU - Desrivieres, Sylvane

AU - Barker, Gareth

AU - Büchel, Christian

AU - Fauth-Buehler, Mira

AU - Cattrell, Anna

AU - Conrod, Patricia

AU - Flor, Herta

AU - Gallinat, Juergen

AU - Garavan, Hugh

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Lawrence, Claire

AU - Mann, Karl

AU - Nees, Frauke

AU - Salatino-Oliveira, Angelica

AU - Paillère Martinot, Marie Laure

AU - Paus, Tomas

AU - Rietschel, Marcella

AU - Robbins, Trevor

AU - Smolka, Michael

AU - Banaschewski, Tobias

AU - Rubia, Katya

AU - Loth, Eva

AU - Schumann, Gunter

N1 - Funding Information: This work was supported by the European Union–funded FP6 Integrated Project IMAGEN (Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology; Grant No. LSHM-CT-2007-037286), the FP7 projects ADAMS (Genomic Variations Underlying Common Neuropsychiatric Diseases and Disease Related Cognitive Traits in Different Human Populations) (Grant No. 242257), and the Innovative Medicine Initiative Project EU-AIMS (Grant No. 115300-2), as well as the United Kingdom National Institute for Health Research Biomedical Research Centre Mental Health and the Medical Research Council Programme Grant “Developmental Pathways into Adolescent Substance Abuse” (Grant No. 93558) and the Swedish Research Council.

PY - 2013/10/15

Y1 - 2013/10/15

N2 - 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.

AB - 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.

KW - Attention-deficit/hyperactivity disorder

KW - genetics inferior frontal gyrus

KW - monoamine oxidase A

KW - neuroimaging

KW - ventral striatum

UR - https://www.scopus.com/pages/publications/84884670740

UR - https://www.scopus.com/inward/citedby.url?scp=84884670740&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2013.03.027

DO - 10.1016/j.biopsych.2013.03.027

M3 - Article

C2 - 23746540

AN - SCOPUS:84884670740

SN - 0006-3223

VL - 74

SP - 607

EP - 614

JO - Biological psychiatry

JF - Biological psychiatry

IS - 8

ER -

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

Abstract

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