Neuropsychiatric Disorders and the Gene COMT (Catechol-O-Methyltransferase)

The COMT gene has another symbol as “HEL-S-98n”. It is located at 22q11.21. It is an important enzyme in the process of metabolic degradation of catecholamines (Gogos et al., 1998).

The 158met variant on the nondeleted allele has been related to lower enzyme activity, higher catecholamine levels, and neuropsychiatric symptoms among patients with the 22q11.2 deletion syndrome (Graf et al. 2001). The val108/158met may also be involved in the cognitive function in the 22q11 deletion syndrome (Baker et al. 2005).

Genetic variations in COMT such as the SNPs rs737865 and rs4680 have been related to the risk of psychosis in Alzheimer disease (AD) (Sweet et al. 2005). A randomized crossover clinical trial showed that the COMT Val158Met polymorphism may influence the responses to entacapone among patients with Parkinson’s disease (Corvol et al. 2011).


Baker, K., Baldeweg, T., Sivagnanasundaram, S., Scambler, P., Skuse, D. COMT val108/158met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome. Biol. Psychiat. 58: 23-31, 2005.

Corvol, J.-C., Bonnet, C., Charbonnier-Beaupel, F., Bonnet, A.-M., Fievet, M.-H., Bellanger, A., Roze, E., Meliksetyan, G., Ben Djebara, M., Hartmann, A., Lacomblez, L., Vrignaud, C., Zahr, N., Agid, Y., Costentin, J., Hulot, J.-S., Vidailhet, M. The COMT Val158Met polymorphism affects the response to entacapone in Parkinson’s disease: a randomized crossover clinical trial. Ann. Neurol. 69: 111-118, 2011.

Gogos, J. A., Morgan, M., Luine, V., Santha, M., Ogawa, S., Pfaff, D., Karayiorgou, M. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc. Nat. Acad. Sci. 95: 9991-9996, 1998.

Graf, W. D., Unis, A. S., Yates, C. M., Sulzbacher, S., Dinulos, M. B., Jack, R. M., Dugaw, K. A., Paddock, M. N., Parson, W. W. Catecholamines in patients with 22q11.2 deletion syndrome and the low-activity COMT polymorphism. Neurology 57: 410-416, 2001.

Sweet, R. A., Devlin, B., Pollock, B. G., Sukonick, D. L., Kastango, K. B., Bacanu, S.-A., Chowdari, K. V., DeKosky, S. T., Ferrell, R. E. Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease. Molec. Psychiat. 10: 1026-1036, 2005.

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