Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder Symptoms Are Stratified by MAOA Genotype

Charlotte Nymberg; Tianye Jia; Steven Lubbe; Barbara Ruggeri; Sylvane Desrivieres; Gareth Barker; Christian Buchel; 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 Paillere Martinot; Tomas Paus; Marcella Rietschel; Trevor Robbins; Michael Smolka; Tobias Banaschewski; Katya Rubia; Eva Loth; Gunter Schumann; IMAGEN Consortium

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 Lubbe, Barbara Ruggeri, Sylvane Desrivieres, Gareth Barker, Christian Buchel, 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 Paillere MartinotTomas Paus, Marcella Rietschel, Trevor Robbins, Michael Smolka, Tobias Banaschewski, Katya Rubia, Eva Loth, Gunter Schumann, IMAGEN Consortium

^*Corresponding author for this work

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

52 Citations (Scopus)

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
Article number	N/A
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
Publication status	Published - 15 Oct 2013

Keywords

Attention-deficit/hyperactivity disorder
genetics
inferior frontal gyrus
monoamine oxidase A
neuroimaging
ventral striatum
DEFICIT HYPERACTIVITY DISORDER
MONOAMINE-OXIDASE-A
VENTRAL STRIATAL ACTIVITY
REWARD ANTICIPATION
RESPONSE-INHIBITION
PREFERENTIAL TRANSMISSION
PROMOTER POLYMORPHISM
BRAIN ACTIVATION
CONDUCT DISORDER
NOVELTY-SEEKING
Acknowledged-BRC
Acknowledged-BRC-13/14

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10.1016/j.biopsych.2013.03.027

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Nymberg, C., Jia, T., Lubbe, S., Ruggeri, B., Desrivieres, S., Barker, G., Buchel, 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., ... IMAGEN Consortium (2013). Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder Symptoms Are Stratified by MAOA Genotype. Biological psychiatry, 74(8), 607-614. Article N/A. https://doi.org/10.1016/j.biopsych.2013.03.027

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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, DEFICIT HYPERACTIVITY DISORDER, MONOAMINE-OXIDASE-A, VENTRAL STRIATAL ACTIVITY, REWARD ANTICIPATION, RESPONSE-INHIBITION, PREFERENTIAL TRANSMISSION, PROMOTER POLYMORPHISM, BRAIN ACTIVATION, CONDUCT DISORDER, NOVELTY-SEEKING, Acknowledged-BRC, Acknowledged-BRC-13/14",

author = "Charlotte Nymberg and Tianye Jia and Steven Lubbe and Barbara Ruggeri and Sylvane Desrivieres and Gareth Barker and Christian Buchel 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 Martinot, {Marie-Laure Paillere} and Tomas Paus and Marcella Rietschel and Trevor Robbins and Michael Smolka and Tobias Banaschewski and Katya Rubia and Eva Loth and Gunter Schumann and {IMAGEN Consortium}",

year = "2013",

month = oct,

day = "15",

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

language = "English",

volume = "74",

pages = "607--614",

journal = "Biological psychiatry",

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Nymberg, C , Jia, T , Lubbe, S , Ruggeri, B , Desrivieres, S , Barker, G, Buchel, 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, Martinot, M-LP, Paus, T, Rietschel, M, Robbins, T, Smolka, M, Banaschewski, T, Rubia, K , Loth, E , Schumann, G & IMAGEN Consortium 2013, 'Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder Symptoms Are Stratified by MAOA Genotype', Biological psychiatry, vol. 74, no. 8, N/A, 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

AU - Ruggeri, Barbara

AU - Desrivieres, Sylvane

AU - Barker, Gareth

AU - Buchel, 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 - Martinot, Marie-Laure Paillere

AU - Paus, Tomas

AU - Rietschel, Marcella

AU - Robbins, Trevor

AU - Smolka, Michael

AU - Banaschewski, Tobias

AU - Rubia, Katya

AU - Loth, Eva

AU - Schumann, Gunter

AU - IMAGEN Consortium

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

KW - inferior frontal gyrus

KW - monoamine oxidase A

KW - neuroimaging

KW - ventral striatum

KW - DEFICIT HYPERACTIVITY DISORDER

KW - MONOAMINE-OXIDASE-A

KW - VENTRAL STRIATAL ACTIVITY

KW - REWARD ANTICIPATION

KW - RESPONSE-INHIBITION

KW - PREFERENTIAL TRANSMISSION

KW - PROMOTER POLYMORPHISM

KW - BRAIN ACTIVATION

KW - CONDUCT DISORDER

KW - NOVELTY-SEEKING

KW - Acknowledged-BRC

KW - Acknowledged-BRC-13/14

U2 - 10.1016/j.biopsych.2013.03.027

DO - 10.1016/j.biopsych.2013.03.027

M3 - Article

C2 - 23746540

SN - 1873-2402

VL - 74

SP - 607

EP - 614

JO - Biological psychiatry

JF - Biological psychiatry

IS - 8

M1 - N/A

ER -

Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder Symptoms Are Stratified by MAOA Genotype

Abstract

Keywords

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