Sex differences in COMT polymorphism effects on prefrontal inhibitory control in adolescence.
Item Type:Journal Article
Citation:White TP, Loth E, Rubia K, Krabbendam L, Whelan R, Banaschewski T, Barker GJ, Bokde AL, Büchel C, Conrod P, Fauth-Bühler M, Flor H, Frouin V, Gallinat J, Garavan H, Gowland P, Heinz A, Ittermann B, Lawrence C, Mann K, Paillère ML, Nees F, Paus T, Pausova Z, Rietschel M, Robbins T, Smolka MN, Shergill SS, Schumann G, Sex differences in COMT polymorphism effects on prefrontal inhibitory control in adolescence., Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39, 11, 2014, 2560-9
npp2014107a.pdf (PDF) 446.8Kb
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.
Type of material:Journal Article
Series/Report no:Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Availability:Full text available