Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depressionCitation formats

  • External authors:
  • Dorottya Pap
  • Xenia Gonda
  • Eszter Molnar
  • Judit Lazary
  • Anita Benko
  • Emma Thomas
  • Diana Chase
  • Zoltan G. Toth
  • Krisztina Mekli
  • Hazel Platt
  • Gyorgy Bagdy
  • Gabriella Juhasz

Standard

Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression. / Pap, Dorottya; Gonda, Xenia; Molnar, Eszter; Lazary, Judit; Benko, Anita; Downey, Darragh; Thomas, Emma; Chase, Diana; Toth, Zoltan G.; Mekli, Krisztina; Platt, Hazel; Payton, Antony; Elliott, Rebecca; Anderson, Ian M.; Deakin, J. F William; Bagdy, Gyorgy; Juhasz, Gabriella.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 159, No. 8, 12.2012, p. 928-940.

Research output: Contribution to journalArticle

Harvard

Pap, D, Gonda, X, Molnar, E, Lazary, J, Benko, A, Downey, D, Thomas, E, Chase, D, Toth, ZG, Mekli, K, Platt, H, Payton, A, Elliott, R, Anderson, IM, Deakin, JFW, Bagdy, G & Juhasz, G 2012, 'Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression', American Journal of Medical Genetics - Neuropsychiatric Genetics, vol. 159, no. 8, pp. 928-940. https://doi.org/10.1002/ajmg.b.32098

APA

Pap, D., Gonda, X., Molnar, E., Lazary, J., Benko, A., Downey, D., ... Juhasz, G. (2012). Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression. American Journal of Medical Genetics - Neuropsychiatric Genetics, 159(8), 928-940. https://doi.org/10.1002/ajmg.b.32098

Vancouver

Pap D, Gonda X, Molnar E, Lazary J, Benko A, Downey D et al. Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression. American Journal of Medical Genetics - Neuropsychiatric Genetics. 2012 Dec;159(8):928-940. https://doi.org/10.1002/ajmg.b.32098

Author

Pap, Dorottya ; Gonda, Xenia ; Molnar, Eszter ; Lazary, Judit ; Benko, Anita ; Downey, Darragh ; Thomas, Emma ; Chase, Diana ; Toth, Zoltan G. ; Mekli, Krisztina ; Platt, Hazel ; Payton, Antony ; Elliott, Rebecca ; Anderson, Ian M. ; Deakin, J. F William ; Bagdy, Gyorgy ; Juhasz, Gabriella. / Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2012 ; Vol. 159, No. 8. pp. 928-940.

Bibtex

@article{2312ff2ad9654930b51889a8a83ef3e9,
title = "Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression",
abstract = "The catechol-o-methyltransferase (COMT) gene has been extensively investigated in depression with somewhat contradictory results but the role of impulsivity, as a possible intermediate phenotype in this disorder, has not been considered yet. In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in two independent population cohorts: Manchester (n=1267) and Budapest (n=942). First, we investigated the association between COMT genotypes, impulsivity, neuroticism and depression using haplotype trend regression, and constructed a model using structural equation modeling to investigate the interaction between these factors. Secondly, we tested the effect of executive function on this model in a smaller interviewed sample (n=207). Our results demonstrated that COMT haplotypes were significantly associated with impulsivity in the combined cohort, showing the same direction of effects in both populations. The COMT effect on depressive symptoms (in subjects without history of depression) and on executive function (interviewed sample) showed the opposite pattern to impulsivity. Structural equation models demonstrated that COMT and impulsivity acted, both together (through neuroticism) and independently, to increase the risk of depression. In addition, better executive function also operated as a risk factor for depression, possibly though reduced ability to flexibly disengage negative emotions. In conclusion, variations in the COMT gene exert complex effects on susceptibility to depression involving various intermediate phenotypes, such as impulsivity and executive function. These findings emphasise that modeling of disease pathways at phenotypic level are valuable for identifying genetic risk factors. {\circledC} 2012 Wiley Periodicals, Inc.",
keywords = "Cognition, COMT, Depression, Haplotype, Intermediate phenotype, Modelling",
author = "Dorottya Pap and Xenia Gonda and Eszter Molnar and Judit Lazary and Anita Benko and Darragh Downey and Emma Thomas and Diana Chase and Toth, {Zoltan G.} and Krisztina Mekli and Hazel Platt and Antony Payton and Rebecca Elliott and Anderson, {Ian M.} and Deakin, {J. F William} and Gyorgy Bagdy and Gabriella Juhasz",
year = "2012",
month = "12",
doi = "10.1002/ajmg.b.32098",
language = "English",
volume = "159",
pages = "928--940",
journal = "American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "John Wiley & Sons Ltd",
number = "8",

}

RIS

TY - JOUR

T1 - Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: Relevance for major depression

AU - Pap, Dorottya

AU - Gonda, Xenia

AU - Molnar, Eszter

AU - Lazary, Judit

AU - Benko, Anita

AU - Downey, Darragh

AU - Thomas, Emma

AU - Chase, Diana

AU - Toth, Zoltan G.

AU - Mekli, Krisztina

AU - Platt, Hazel

AU - Payton, Antony

AU - Elliott, Rebecca

AU - Anderson, Ian M.

AU - Deakin, J. F William

AU - Bagdy, Gyorgy

AU - Juhasz, Gabriella

PY - 2012/12

Y1 - 2012/12

N2 - The catechol-o-methyltransferase (COMT) gene has been extensively investigated in depression with somewhat contradictory results but the role of impulsivity, as a possible intermediate phenotype in this disorder, has not been considered yet. In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in two independent population cohorts: Manchester (n=1267) and Budapest (n=942). First, we investigated the association between COMT genotypes, impulsivity, neuroticism and depression using haplotype trend regression, and constructed a model using structural equation modeling to investigate the interaction between these factors. Secondly, we tested the effect of executive function on this model in a smaller interviewed sample (n=207). Our results demonstrated that COMT haplotypes were significantly associated with impulsivity in the combined cohort, showing the same direction of effects in both populations. The COMT effect on depressive symptoms (in subjects without history of depression) and on executive function (interviewed sample) showed the opposite pattern to impulsivity. Structural equation models demonstrated that COMT and impulsivity acted, both together (through neuroticism) and independently, to increase the risk of depression. In addition, better executive function also operated as a risk factor for depression, possibly though reduced ability to flexibly disengage negative emotions. In conclusion, variations in the COMT gene exert complex effects on susceptibility to depression involving various intermediate phenotypes, such as impulsivity and executive function. These findings emphasise that modeling of disease pathways at phenotypic level are valuable for identifying genetic risk factors. © 2012 Wiley Periodicals, Inc.

AB - The catechol-o-methyltransferase (COMT) gene has been extensively investigated in depression with somewhat contradictory results but the role of impulsivity, as a possible intermediate phenotype in this disorder, has not been considered yet. In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in two independent population cohorts: Manchester (n=1267) and Budapest (n=942). First, we investigated the association between COMT genotypes, impulsivity, neuroticism and depression using haplotype trend regression, and constructed a model using structural equation modeling to investigate the interaction between these factors. Secondly, we tested the effect of executive function on this model in a smaller interviewed sample (n=207). Our results demonstrated that COMT haplotypes were significantly associated with impulsivity in the combined cohort, showing the same direction of effects in both populations. The COMT effect on depressive symptoms (in subjects without history of depression) and on executive function (interviewed sample) showed the opposite pattern to impulsivity. Structural equation models demonstrated that COMT and impulsivity acted, both together (through neuroticism) and independently, to increase the risk of depression. In addition, better executive function also operated as a risk factor for depression, possibly though reduced ability to flexibly disengage negative emotions. In conclusion, variations in the COMT gene exert complex effects on susceptibility to depression involving various intermediate phenotypes, such as impulsivity and executive function. These findings emphasise that modeling of disease pathways at phenotypic level are valuable for identifying genetic risk factors. © 2012 Wiley Periodicals, Inc.

KW - Cognition

KW - COMT

KW - Depression

KW - Haplotype

KW - Intermediate phenotype

KW - Modelling

U2 - 10.1002/ajmg.b.32098

DO - 10.1002/ajmg.b.32098

M3 - Article

C2 - 23008195

VL - 159

SP - 928

EP - 940

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 8

ER -