Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

T.P White; E. Loth; K. Rubia; L. Krabbendam; RL Whelan; T. Banaschewski; G.J. Barker; ALW Bokde; C. Buchel; P. Conrod; M. Fauth-Bühler; H. Flor; V. Frouin; J. Gallinat; H. Garavan; P. Gowland; A. Heinz; B. Ittermann; C. Lawrence; K. Mann; M.L. Paillère; F. Nees; T. Paus; Z. Pausova; M. Rietschel; T. Robbins; M.N. Smolka; S.S. Shergill; G. Schumann

doi:10.1038/npp.2014.107

Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

T.P White, E. Loth, K. Rubia, L. Krabbendam, RL Whelan, T. Banaschewski, G.J. Barker, ALW Bokde, C. Buchel, P. Conrod, M. Fauth-Bühler, H. Flor, V. Frouin, J. Gallinat, H. Garavan, P. Gowland, A. Heinz, B. Ittermann, C. Lawrence, K. MannM.L. Paillère, F. Nees, T. Paus, Z. Pausova, M. Rietschel, T. Robbins, M.N. Smolka, S.S. Shergill, G. Schumann

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Article number	11
Pages (from-to)	2560-2569
Journal	Neuropsychopharmacology
Volume	2014
Issue number	39
DOIs	https://doi.org/10.1038/npp.2014.107
Publication status	Published - 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/npp.2014.107

Persistent URL (handle)

Persistent link

Cite this

White, T. P., Loth, E., Rubia, K., Krabbendam, L., Whelan, RL., Banaschewski, T., Barker, G. J., Bokde, ALW., Buchel, C., Conrod, P., Fauth-Bühler, M., Flor, H., Frouin, V., Gallinat, J., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Lawrence, C., ... Schumann, G. (2014). Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence. Neuropsychopharmacology, 2014(39), 2560-2569. Article 11. https://doi.org/10.1038/npp.2014.107

@article{3b8e3ce51a26424bbb084d432066d0be,

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.",

author = "T.P White and E. Loth and K. Rubia and L. Krabbendam and RL Whelan and T. Banaschewski and G.J. Barker and ALW Bokde and C. Buchel and P. Conrod and M. Fauth-B{\"u}hler and H. Flor and V. Frouin and J. Gallinat and H. Garavan and P. Gowland and A. Heinz and B. Ittermann and C. Lawrence and K. Mann and M.L. Paill{\`e}re and F. Nees and T. Paus and Z. Pausova and M. Rietschel and T. Robbins and M.N. Smolka and S.S. Shergill and G. Schumann",

year = "2014",

doi = "10.1038/npp.2014.107",

language = "English",

volume = "2014",

pages = "2560--2569",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "Springer Nature",

number = "39",

}

White, TP, Loth, E, Rubia, K, Krabbendam, L, Whelan, RL, Banaschewski, T, Barker, GJ, Bokde, ALW, Buchel, 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 2014, 'Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence', Neuropsychopharmacology, vol. 2014, no. 39, 11, pp. 2560-2569. https://doi.org/10.1038/npp.2014.107

TY - JOUR

T1 - Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

AU - White, T.P

AU - Loth, E.

AU - Rubia, K.

AU - Krabbendam, L.

AU - Whelan, RL

AU - Banaschewski, T.

AU - Barker, G.J.

AU - Bokde, ALW

AU - Buchel, C.

AU - Conrod, P.

AU - Fauth-Bühler, M.

AU - Flor, H.

AU - Frouin, V.

AU - Gallinat, J.

AU - Garavan, H.

AU - Gowland, P.

AU - Heinz, A.

AU - Ittermann, B.

AU - Lawrence, C.

AU - Mann, K.

AU - Paillère, M.L.

AU - Nees, F.

AU - Paus, T.

AU - Pausova, Z.

AU - Rietschel, M.

AU - Robbins, T.

AU - Smolka, M.N.

AU - Shergill, S.S.

AU - Schumann, G.

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 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.

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 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.

U2 - 10.1038/npp.2014.107

DO - 10.1038/npp.2014.107

M3 - Article

SN - 0893-133X

VL - 2014

SP - 2560

EP - 2569

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 39

M1 - 11

ER -

Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

Abstract

UN SDGs

Access to Document

Persistent URL (handle)

Fingerprint

Cite this