title: Sex differences in COMT polymorphism effects on prefrontal inhibitory control in adolescence.
abstract: Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level-dependent (BOLD) activation are robust; however, despite observations that COMT is estrogenically catabolized, sex differences in its prefrontal repercussions remain unclear. Here, in a large sample of healthy adolescents stratified by sex and Val(158)Met genotype (n=1133), we examine BOLD responses during performance of the stop-signal task in right-hemispheric prefrontal regions fundamental to inhibitory control. A significant sex-by-genotype interaction was observed in pre-SMA during successful-inhibition trials and in both pre-SMA and inferior frontal cortex during failed-inhibition trials with Val homozygotes displaying elevated activation compared with other genotypes in males but not in females. BOLD activation in the same regions significantly mediated the relationship between COMT genotype and inhibitory proficiency as indexed by stop-signal reaction time in males alone. These sexually dimorphic effects of COMT on inhibitory brain activation have important implications for our understanding of the contrasting patterns of prefrontally governed psychopathology observed in males and females.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: White
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.affiliation: Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Katya
authors.initials: K
authors.lastname: Rubia
authors.affiliation: Department of Educational Neuroscience, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lydia
authors.initials: L
authors.lastname: Krabbendam
authors.affiliation: 1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Whelan
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Gareth J
authors.identifier: 0000000252147421
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: 1] Institute of Psychiatry, King's College London, London, UK [2] Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.affiliation: 1] Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany [2] Department of Addictive Behaviour and Addiction Medicine, Heidelberg University, Heidelberg, Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Fauth-Bühler
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frouin
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: 1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Department of Physics and Astronomy, University of Nottingham, Nottingham, UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.affiliation: School of Psychology, University of Nottingham, Nottingham, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Lawrence
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 'Imaging & Psychiatry', University Paris Sud, Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Paillère
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: 1] School of Psychology, University of Nottingham, Nottingham, UK [2] Rotman Research Institute, University of Toronto, Toronto, ON, Canada [3] Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Behavioural and Clinical Neurosciences Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Robbins
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Sukhwinder S
authors.initials: SS
authors.lastname: Shergill
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
mesh_terms: D000293:Adolescent; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000502:physiology; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time; D012727:Sex Characteristics
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D010100:Oxygen