TY - JOUR
T1 - Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence
AU - White, Thomas P
AU - Loth, Eva
AU - Krabbendam, Lydia
AU - Rubia, Katya
AU - Whelan, Robert
AU - Banaschewski, Tobias
AU - Barker, Gareth J
AU - Bokde, Arun Lw
AU - Büchel, Christian
AU - Conrod, Patricia
AU - Flor, Herta
AU - Frouin, Vincent
AU - Heinz, Andreas
AU - Garavan, Hugh
AU - Gowland, Penny
AU - Ittermann, Bernd
AU - Lawrence, Claire
AU - Mann, Karl
AU - Paillère, Marie-Laure
AU - Nees, Frauke
AU - Paus, Tomas
AU - Pausova, Zdenka
AU - Rietschel, Marcella
AU - Robbins, Trevor
AU - Fauth-Bühler, Mira
AU - Smolka, Michael N
AU - Gallinat, Jürgen
AU - Shergill, Sukhwinder S
AU - Schumann, Gunter
PY - 2014
Y1 - 2014
N2 - Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level dependent (BOLD) activation are robust; however, despite observations that COMT is oestrogenically catabolised, 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 to 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.
AB - Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level dependent (BOLD) activation are robust; however, despite observations that COMT is oestrogenically catabolised, 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 to 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.
U2 - 10.1038/npp.2014.107
DO - 10.1038/npp.2014.107
M3 - Article
C2 - 24820538
SN - 1740-634X
VL - N/A
SP - N/A
JO - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
IS - N/A
M1 - N/A
ER -