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.
authors.affiliation: Medical Research Council-Social, Genetic and Developmental Psychiatry Centre (CN, TJ, SL, BR, SD, GB, AC, PC, EL, GS), Institute of Psychiatry, King's College London, London, United Kingdom. Electronic address: charlotte.nymberg@kcl.ac.uk.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nymberg
authors.forename: Tianye
authors.initials: T
authors.lastname: Jia
authors.forename: Steven
authors.initials: S
authors.lastname: Lubbe
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruggeri
authors.forename: Sylvane
authors.initials: S
authors.lastname: Desrivieres
authors.forename: Gareth
authors.initials: G
authors.lastname: Barker
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.forename: Mira
authors.initials: M
authors.lastname: Fauth-Buehler
authors.forename: Anna
authors.initials: A
authors.lastname: Cattrell
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.forename: Juergen
authors.initials: J
authors.lastname: Gallinat
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.forename: Claire
authors.initials: C
authors.lastname: Lawrence
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.forename: Angelica
authors.initials: A
authors.lastname: Salatino-Oliveira
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Paillère Martinot
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Trevor
authors.initials: T
authors.lastname: Robbins
authors.forename: Michael
authors.initials: M
authors.lastname: Smolka
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Katya
authors.initials: K
authors.lastname: Rubia
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology*; D001479:Basal Ganglia / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D012201:Reward
chemical_list: D008995:Monoamine Oxidase
keywords: Attention-deficit/hyperactivity disorder; genetics; inferior frontal gyrus; monoamine oxidase A; neuroimaging; ventral striatum