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 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
Biological Psychiatry. 2013-10-01; 74(8): 607-614
DOI: 10.1016/j.biopsych.2013.03.027

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Authors :Nymberg C, Jia T, Lubbe S, 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; IMAGEN Consortium.

Collaborators: Williams SC, Reed LJ, Topper L, Smith L, Morgan C, Stacey D, Wong
CP, Carvalho F, Kühn S, Häke I, Strache N, Albrecht L, Ivanov N, Reuter J,
Palafox C, Schilling C, Lüdemann K, Romanowski A, Ströhle A, Wolff E, Rapp M,
Brühl R, Ihlenfeld A, Walaszek B, Schubert F, Jones J, Lalor E, McCabe E,
Shiothcháin AN, Whelan R, Spanagel R, Leonardi-Essmann F, Sommer W, Struve M,
Steiner S, Vollstedt-Klein S, Stolzenburg E, Schmäl C, Gowland P, Heym N, Newman
C, Tahmasebi ZP, Melka MG, Hübner T, Ripke S, Mennigen E, Müller K, Ziesch V,
Bromberg U, Meindl S, Peters J, Schneider S, Fadai T, Lueken L, Yacubian J,
Finsterbusch J, Artiges E, Martinot JL, Lemaitre H, Bordas N, Bricaud Z, Briand
FG, Massicotte J, Miranda R, Penttilä J, Boddaert N, Barbot A, Schwartz Y,
Lalanne C, Frouin V, Fritsch V, Dalley J, Mar A, Subramaniam N, Theobald D,
Richmond N, de Rover M, Molander A, Jordan ER, Robinson E, Moreno M, Arroyo M,
Stephens D, Ripley T, Crombag H, Pena Y, Lathrop M, Zelenika D, Heath S,
Lanzerath D, Heinrichs B, Spranger TM, Fuchs B, Speiser C, Klaassen A, Klaassen
I, Constant P, Mignon X, Thomsen T, Zysset S, Vestboe A, Ireland J, Rogers J.

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.


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