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The Relationship Between Valence, Task Difficulty, and the COMT Val 158 Met Polymorphism in Disengagement Processes

Published Online:https://doi.org/10.1027/0269-8803/a000075

The catechol-O-methyltransferase (COMT) Val158Met polymorphism (rs4680) moderates dopamine degradation in the prefrontal cortex. It has been shown that the Met allele is associated with an increased reactivity to negative stimuli. With regard to the tonic-phasic dopamine model it is hypothesized that this increased reactivity to negative stimuli derives from deficient disengagement from negative stimuli. The aim of this study was therefore to investigate whether this increased reactivity is reflected in prolonged disengagement from negative pictures. We used a novel forced spatial disengagement task in combination with eye tracking. This paradigm allows for varying task difficulty. Interestingly, contrary to our hypothesis, we found increased disengagement latencies for negative pictures in homozygous Val allele carriers compared to heterozygous participants. This effect was only seen in task conditions demanding less cognitive resources (prosaccade condition). We suggest that the COMT effect on emotional processing is task-specific and therefore heterosis effects can occur.

References

  • Axelrod, J. (1957). O-Methylation of epinephrine and other catechols in vitro and in vivo. Science, 126, 400–401. First citation in articleCrossrefGoogle Scholar

  • Bilder, R. M. , Volavka, J. , Lachman, H. M. , Grace, A. A. (2004). The catechol-O-methyltransferase polymorphism: Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology, 29, 1943–1961. First citation in articleGoogle Scholar

  • Colzato, L. S. , Waszak, F. , Nieuwenhuis, S. , Posthuma, D. , Hommel, B. (2010). The flexible mind is associated with the catechol-O-methyltransferase (COMT) Val158Met polymorphism: Evidence for a role of dopamine in the control of task-switching. Neuropsychologia, 48, 2764–2768. First citation in articleCrossrefGoogle Scholar

  • Dickinson, D. , Elvevag, B. (2009). Genes, cognition and brain through a COMT lens. Neuroscience, 164, 72–87. First citation in articleCrossrefGoogle Scholar

  • Domschke, K. , Deckert, J. , O’Donovan M, C. , Glatt, S. J. (2007). Meta-analysis of COMT val158met in panic disorder: Ethnic heterogeneity and gender specificity. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics), 144B, 667–673. First citation in articleCrossrefGoogle Scholar

  • Drabant, E. M. , Hariri, A. R. , Meyer-Lindenberg, A. , Munoz, K. E. , Mattay, V. S. , Kolachana, B. S. , … Weinberger, D. R. (2006). Catechol O-methyltransferase val(158)met genotype and neural mechanisms related to affective arousal and regulation. Archives of General Psychiatry, 63, 1396–1406. First citation in articleCrossrefGoogle Scholar

  • Egan, M. F. , Goldberg, T. E. , Kolachana, B. S. , Callicott, J. H. , Mazzanti, C. M. , Straub, R. E. , … Weinberger, D. R. (2001). Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proceedings of the National Academy of Sciences, 98, 6917–6922. First citation in articleCrossrefGoogle Scholar

  • Ettinger, U. , Kumari, V. , Collier, D. A. , Powell, J. , Luzi, S. , Michel, T. M. , … Williams, S. C. (2008). Catechol-O-methyltransferase (COMT) val158met genotype is associated with BOLD response as a function of task characteristic. Neuropsychopharmacology, 33, 3046–3057. First citation in articleCrossrefGoogle Scholar

  • Fischer, B. , Weber, H. , Biscaldi, M. , Aiple, F. , Otto, P. , Stuhr, V. (1993). Separate populations of visually guided saccades in humans: Reaction times and amplitudes. Experimental Brain Research, 92, 528–541. First citation in articleCrossrefGoogle Scholar

  • Gilchrist, I. D. , Proske, H. (2006). Anti-saccades away from faces: Evidence for an influence of high-level visual processes on saccade programming. Experimental Brain Research, 173, 708–712. First citation in articleCrossrefGoogle Scholar

  • Gogos, J. A. , Morgan, M. , Luine, V. , Santha, M. , Ogawa, S. , Pfaff, D. , Karayiorgou, M. (1998). Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proceedings of the National Academy of Sciences, 95, 9991–9996. First citation in articleGoogle Scholar

  • Hallett, P. E. (1978). Primary and secondary saccades to goals defined by instructions. Vision Research, 18, 1279–1296. First citation in articleCrossrefGoogle Scholar

  • Hariri, A. R. , Bookheimer, S. Y. , Mazziotta, J. C. (2000). Modulating emotional responses: Effects of a neocortical network on the limbic system. Neuroreport, 11, 43–48. First citation in articleCrossrefGoogle Scholar

  • Harrison, P. J. , Tunbridge, E. M. (2008). Catechol-O-methyltransferase (COMT): A gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders. Neuropsychopharmacology, 33, 3037–3045. First citation in articleCrossrefGoogle Scholar

  • Herrmann, M. J. , Wurflein, H. , Schreppel, T. , Koehler, S. , Mühlberger, A. , Reif, A. , … Fallgatter, A. J. (2009). Catechol-O-methyltransferase Val158Met genotype affects neural correlates of aversive stimuli processing. Cognitive, Affective, and Behavioral Neuroscience, 9, 168–172. First citation in articleCrossrefGoogle Scholar

  • Hong, J. , Shu-Leong, H. , Tao, X. , Lap-Ping, Y. (1998). Distribution of catechol-O-methyltransferase expression in human central nervous system. Neuroreport, 9, 2861–2864. First citation in articleCrossrefGoogle Scholar

  • Kempton, M. J. , Haldane, M. , Jogia, J. , Christodoulou, T. , Powell, J. , Collier, D. , … Frangou, S. (2009). The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: A fMRI study. International Journal of Neuropsychopharmacology, 12, 371–381. First citation in articleCrossrefGoogle Scholar

  • Kissler, J. , Keil, A. (2008). Look-don’t look! How emotional pictures affect pro- and anti-saccades. Experimental Brain Research, 188, 215–222. First citation in articleCrossrefGoogle Scholar

  • Lachman, H. M. , Papolos, D. F. , Saito, T. , Yu, Y. M. , Szumlanski, C. L. , Weinshilboum, R. M. (1996). Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics, 6, 243–250. First citation in articleCrossrefGoogle Scholar

  • Lang, P. J. (1980). Self-assessment manikin. Gainesville, FL: University of Florida. First citation in articleGoogle Scholar

  • Lang, P. J. , Bradley, M. M. , Cuthbert, B. N. (2005). International affective picture system (IAPS): Affective ratings of pictures and instruction manual. Gainsville, FL: University of Florida. First citation in articleGoogle Scholar

  • Laux, L. , Glanzmann, P. , Schaffner, P. , Spielberger, C. D. (1981). Das State-Trait-Angstinventar (Testmappe mit Handanweisung, Fragebogen STAI-G Form X1 und Fragebogen STAI-G Form X). Weinheim, Germany: Beltz. First citation in articleGoogle Scholar

  • Lotta, T. , Vidgren, J. , Tilgmann, C. , Ulmanen, I. , Melen, K. , Julkunen, I. , Taskinen, J. (1995). Kinetics of human soluble and membrane-bound catechol O-methyltransferase: A revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry, 34, 4202–4210. First citation in articleCrossrefGoogle Scholar

  • McLeod, H. L. , Fang, L. , Luo, X. , Scott, E. P. , Evans, W. E. (1994). Ethnic differences in erythrocyte catechol-O-methyltransferase activity in black and white Americans. Journal of Pharmacology and Experimental Therapeutics, 270, 26–29. First citation in articleGoogle Scholar

  • Meyer-Lindenberg, A. , Nichols, T. , Callicott, J. H. , Ding, J. , Kolachana, B. , Buckholtz, J. , … Weinberger, D. R. (2006). Impact of complex genetic variation in COMT on human brain function. Molecular Psychiatry, 11, 867–877. First citation in articleCrossrefGoogle Scholar

  • Mier, D. , Kirsch, P. , Meyer-Lindenberg, A. (2010). Neural substrates of pleiotropic action of genetic variation in COMT: A meta-analysis. Molecular Psychiatry, 15, 918–927. First citation in articleCrossrefGoogle Scholar

  • Montag, C. , Buckholtz, J. W. , Hartmann, P. , Merz, M. , Burk, C. , Hennig, J. , Renter, M. (2008). COMT genetic variation affects fear processing: Psychophysiological evidence. Behavioral Neuroscience, 122, 901–909. First citation in articleCrossrefGoogle Scholar

  • Nolan, K. A. , Bilder, R. M. , Lachman, H. M. , Volavka, J. (2004). Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: Differential effects of Val and Met alleles on cognitive stability and flexibility. American Journal of Psychiatry, 161, 359–361. First citation in articleCrossrefGoogle Scholar

  • Rasch, B. , Spalek, K. , Buholzer, S. , Luechinger, R. , Boesiger, P. , de Quervain, D. J. , Papassotiropoulos, A. (2010). Aversive stimuli lead to differential amygdala activation and connectivity patterns depending on catechol-O-methyltransferase Val158Met genotype. NeuroImage, 52, 1712–1719. First citation in articleCrossrefGoogle Scholar

  • Reuter, B. , Herzog, E. , Kathmann, N. (2006). Antisaccade performance of schizophrenia patients: Evidence of reduced task-set activation and impaired error detection. Journal of Psychiatric Research, 40, 122–130. First citation in articleCrossrefGoogle Scholar

  • Smolka, M. N. , Buhler, M. , Schumann, G. , Klein, S. , Hu, X. Z. , Moayer, M. , … Heinz, A. (2007). Gene-gene effects on central processing of aversive stimuli. Molecular Psychiatry, 12, 307–317. First citation in articleCrossrefGoogle Scholar

  • Smolka, M. N. , Schumann, G. , Wrase, J. , Grusser, S. M. , Flor, H. , Mann, K. , … Heinz, A. (2005). Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. Journal of Neuroscience, 25, 836–842. First citation in articleCrossrefGoogle Scholar

  • Weinberg, A. , Hajcak, G. (2010). Beyond good and evil: the time-course of neural activity elicited by specific picture content. Emotion, 10, 767–782. First citation in articleCrossrefGoogle Scholar

  • Weinshilboum, R. M. , Otterness, D. M. , Szumlanski, C. L. (1999). Methylation pharmacogenetics: Catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annual Review of Pharmacology and Toxicology, 39, 19–52. First citation in articleCrossrefGoogle Scholar

  • Wenban-Smith, M. G. , Findlay, J. M. (1991). Express saccades: Is there a separate population in humans? Experimental Brain Research, 87, 218–222. First citation in articleCrossrefGoogle Scholar

  • Wieser, M. J. , Pauli, P. , Mühlberger, A. (2009). Probing the attentional control theory in social anxiety: An emotional saccade task. Cognitive Affective Behavioral Neuroscience, 9, 314–322. First citation in articleCrossrefGoogle Scholar

  • Williams, L. M. , Gatt, J. M. , Grieve, S. M. , Dobson-Stone, C. , Paul, R. H. , Gordon, E. , Schofield, P. R. (2010). COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias. NeuroImage, 53, 918–925. First citation in articleCrossrefGoogle Scholar