Behavior Genetics

, Volume 34, Issue 5, pp 533–539 | Cite as

COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

  • Cindy M. de Frias
  • Kristina Annerbrink
  • Lars Westberg
  • Elias Eriksson
  • Rolf Adolfsson
  • Lars-Göran Nilsson


Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35–85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.

Adulthood aging COMT genetics memory 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akil, M., Kolachana, B. S., Rothmond, D. A., Hyde, T. M., Weinberger, D. R., and Kleinman, J. E. (2003). Catechol-Omethyltransferase genotype and dopamine regulation in human brain. J. Neurosci. 23:2008-2013.PubMedGoogle Scholar
  2. Antal, A., Kéri, S., Kincses, Z. T., Dibó, G., Szabó, A., Benedek, G., Janka, Z., and Vécsei, L. (2003). Dopaminergic contributions to the visual categorization of natural scenes: evidence from Parkinson's disease. Journal of Neural Transmission 110:757- 770.PubMedGoogle Scholar
  3. Bäckman, L., Ginovart, N., Dixon, R. A., Wahlin, T. B. R., Wahlin, Ã., Halldin, C., and Farde, L. (2000). Age-related cognitive deficits mediated by changes in the striatal dopamine system. Am. J. Psychia. 157:635-637.CrossRefGoogle Scholar
  4. Bilder, R. M., Volavka, J., Czobor, P., Malhotra, A. K., Kennedy J. L., Ni, X., Goldman R. S., Hoptman, M. J., Sheitman, B., Lindenmayer, J-P., Citrome, L., McEvoy, J. P., Kunz, M., Chakos, M., Cooper, T. B., and Lieberman, J. A. (2002). Neurocognitive correlates of the COMT Val158-Met polymorphism in chronic schizophrenia. Biol. Psychia. 52:701-707.CrossRefGoogle Scholar
  5. Coull, J. T., Frith, C. D., Dolan, R. J., Frackowiak R. S., and Grasby P. M. (1997). The neural correlates of the noradrenergic modulation of human attention, arousal and learning. Eur. J. Neurosci. 9:589-598.PubMedGoogle Scholar
  6. Craik, F. I. M. (2000). Age-related changes in human memory. In D. C. Park and N. Schwarz (eds.), Cognitive aging: a primer Philadelphia, PA: Psychology Press, pp. 75-92.Google Scholar
  7. Egan, M. F., Goldberg, T. E., Kolachana, B. S., Callicott, J. H., Mazzanti, C. M., and Straub, R. E. (2001). Effect of COMT Vall08/158Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci. USA 98:6917-6922.CrossRefPubMedGoogle Scholar
  8. Folstein, M. F., Folstein, S. E., and McHugh, P. R. (1975). Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatry Res. 12:189-198.CrossRefGoogle Scholar
  9. Gallinat, J., Bajbouj, M., Sander, T., Schlattmann, P., Xu, K., Ferro, E. F., Goldman, D., and Winterer, G. (2003). Association of the G1947A COMT (ValI08/158Met) gene polymorphism with prefrontal P300 during information processing. Biological Psychiatry 54:40-48.CrossRefPubMedGoogle Scholar
  10. Goldberg, T. E., Egan, M. F., Gscheidle, T., Coppola, R., Weickert, T., Kolachana, B. S., Goldman, D., and Weinberger, D. R. (2003). Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Archives of General Psychiatry 60:889-896.CrossRefPubMedGoogle Scholar
  11. de Geus, E. J. C., Wright, M. J., Martin, N. G., and Boomsma, D. I. (2001). Genetics of brain function and cognition. Behavior Genetics 31:489-495.CrossRefPubMedGoogle Scholar
  12. Joober, R., Gauthier, J., Lal, S., Bloom, D., Lalonde, P., Rouleau, G., Benkelfat, C., and Labelle, A. (2002). Catechol-O-methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting test. Archives of General Psychiatry 59:662-663.CrossRefPubMedGoogle Scholar
  13. Koller, W. C., and Rueda, M. G. (1998). Mechanism of action of dopaminergic agents in Parkinson's disease. Neurology 50(Suppl 6):S11-S14.PubMedGoogle Scholar
  14. Lachman, H. M., Papolos, D. F., Saito, T., Yu, Y. M., Szumlanski, C. L., and 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.PubMedGoogle Scholar
  15. Lotta, T., Vidgren, J., Tilgmann, C., Ulmanen, I., Melén, K., Julkunen, I., and 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.PubMedGoogle Scholar
  16. Malhotra, A. K., Kestler, L. J., Mazzanti, C., Bates, J. A., Goldberg, T., and Goldman, D. (2002). A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am. J. Psychiatry 159:652-654.CrossRefPubMedGoogle Scholar
  17. Mattay, V. S., Goldberg, T. E., Fera, F., Hariri, A. R., Tessitore, A., Egan, M. F., Kolachana, B., Callicott, J. H., and Weinberger, D. R. (2003). Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc. Natl. Acad. Sci. 100:6186-6191.CrossRefPubMedGoogle Scholar
  18. Meco, G., and Alessandri, A. (2000). Can COMT inhibitors improve cognitive functions in patients with Parkinson's disease? CNS Drugs 13:227-232.Google Scholar
  19. Nieoullon, A. (2002). Dopamine and the regulation of cognition and attention. Progress in Neurobiology 67:53-83.CrossRefPubMedGoogle Scholar
  20. Nilsson, L.-G. (2000). Can genes teach us anything about memory? In E. Tulving (ed.), Memory, consciousness, and the brain: The Tallinn conference Philadelphia, PA: Psychology Press, pp. 28-37.Google Scholar
  21. Nilsson, L.-G., Adolfsson, R., Bäckman, L., Cruts, M., Edvardsson, H., Nyberg, L., and Van Broeckhoven, C. (2002). Memory development in adulthood and old age: the betula prospective-cohort study. In P. Graf and N. Ohta (eds.), Lifespan development of human memory. MIT Press; Cambridge, MA, pp. 185-204.Google Scholar
  22. Nilsson, L.-G., Adolfsson, R., Bäckman, L., Cruts, M., Nyberg, L., Small, B., and Van Broeckhoven, C. (2003). Selective impairment of episodic recall in carriers of the ApoE e4 allele. Manuscript submitted for publication.Google Scholar
  23. Nilsson, L.-G., Adolfsson, R., Bäckman, L., de Frias, C. M., Molander, B., and Nyberg, L. (in press). Betula: A prospective cohort study on memory, health and aging. Aging, Neuropsychology and Cognition.Google Scholar
  24. Nilsson, L-G., Bäckman, L., Erngrund, K., Nyberg, L., Adolfsson, R., Bucht, G., Karlsson, S., Widing, M., and Winblad, B. (1997). The Betula prospective cohort study: memory, health, and aging, Aging, Neuropsychology, and Cognition 4:1-32.Google Scholar
  25. Nilsson, L.-G., Nyberg, L., and Bäckman, L. (2002). Genetic variation in memory functioning. Neuroscience and Biobehavioral Review 26:841-848.CrossRefGoogle Scholar
  26. Nordfors, L., Jansson, M., Sandberg, G., Lavebratt, C., Sengul, S., Schalling, M., and Arner, P. (2002). Large-scale genotyping of single nucleotide polymorphisms by Pyrosequencing trademark and validation against the 5'nuclease (Taqman (R)) assay. Human Mutation 19:395-401.CrossRefPubMedGoogle Scholar
  27. Nyberg, L., Maitland, S. B., Rönnlund, M., Bäckman, L., Dixon, R. A., Wahlin, Å., and Nilsson, L.-G. (2003). Selective adult age differences in an age-invariant multifactor model of declarative memory. Psychol. and Aging 18: 149-160.CrossRefGoogle Scholar
  28. Nyberg, L., and Tulving, E. (1996). Classifying human long-term memory: evidence from converging dissociations. European J. Cognitive Psychol. 8:163-183.CrossRefGoogle Scholar
  29. Plomin, R. (1997). Current directions in behavioral genetics: moving into the mainstream. Current Directions in Psychol. Sci. 6:85.CrossRefGoogle Scholar
  30. Tsai, S. J., Yu, Y. W., Chen, T. J., Chen, J. Y., Liou, Y. J., Chen, M. C., and Hong, C. J. (2003). Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females. Neuroscience Lett. 338:123-6.CrossRefGoogle Scholar
  31. Tulving, E. (1995). Organization of memory: quo vadis? In M. S. Gazzaniga (ed.), The cognitive neurosciences. Cambridge, MA: MIT Press, pp. 839-847.Google Scholar
  32. Weinberger, D. R., Egan, M. F., Bertolino, A., Callicott, J. H., Mattay, V. S., Lipska, B. K., Berman, K. F., and Goldberg, T. E. (2001). Neurobiology of schizophrenia and the role of atypical antipsychotics: prefrontal neurons and the genetics of schizophrenia. Bio. Psychiatry. 50:825-844.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Cindy M. de Frias
    • 1
    • 2
  • Kristina Annerbrink
    • 3
  • Lars Westberg
    • 3
  • Elias Eriksson
    • 3
  • Rolf Adolfsson
    • 4
  • Lars-Göran Nilsson
    • 2
    • 5
  1. 1.Aging Research Centre, Division of Geriatric EpidemiologyKarolinska InstituteStockholmSweden
  2. 2.Department of PsychologyStockholm UniversityStockholmSweden
  3. 3.Department of PharmacologyGöteborg UniversityGöteborgSweden
  4. 4.Department of Clinical Psychiatry, Division of PsychiatryUmeå UniversityUmeåSweden
  5. 5.Center for Advanced StudyNorwegian Academy of Science and LettersOsloNorway

Personalised recommendations