PTSD, Environment and Gene Variants in COMT

A new study reports that variants in the gene for catechol-O-methyltransferase (COMT) Val158Met and the amount of "traumatic load" influences the likelihood of PTSD and other reports show that COMT may be located both in the glia and certain neurons. The toxic destruction  of dopamine neurons in striatum does not result in loss of COMT and therefore, striatal dopaminergic neurons do not contain a high level of this protein. In areas where COMT neurons are present such as the prefrontal cortex, variants may influence the dopamine signaling and increase the length of time for this neural transmitters elimination. These findings provide a foundation for understanding the difference in cognitive performance including executive functioning, of COMT variants as well as, their association with mental health disorders. (Yavich)

Notes:

• We suggested in an earlier blog that because hyperammonemia may influence cellular pathways associated with PTSD -- conditions that influence endogenous levels of ammonia from exogenous environmental factors or alterations in metabolism may have implications on development of this disorder.
• "COMT catalyzes the methylation of various endobiotic and xenobiotic substances preventing quinone formation and redox cycling, and therefore might protect DNA from oxidative damage."  Availability and variants of this protein therefore may influence the biological effect related to toxic exposures. (Hung) 

References:

• Hyperammonemia, Subordination, Hypoxia Influence Stress Hormone CRF Production in Fish.

Kolassa, I.-T. T., Kolassa, S., Ertl, V., Papassotiropoulos, A., and De Quervain, D. J.-F. J. (2010). The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase val(158)met polymorphism. Biological psychiatry, 67(4):304-308. http://www.citeulike.org/user/HEIRS/article/6250832
Hung, R. J., Boffetta, P., Brennan, P., Malaveille, C., Gelatti, U., Placidi, D., Carta, A., Hautefeuille, A., and Porru, S. (2004). Genetic polymorphisms of mpo, comt, mnsod, nqo1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis, 25(6):973-978. http://www.citeulike.org/user/HEIRS/article/6643978
Strawn, J. R., Pyne-Geithman, G. J., Ekhator, N. N., Horn, P. S., Uhde, T. W., Shutter, L. A., Baker, D. G., and Geracioti, T. D. (2010). Low cerebrospinal fluid and plasma orexin-a (hypocretin-1) concentrations in combat-related posttraumatic stress disorder. Psychoneuroendocrinology. http://www.citeulike.org/user/HEIRS/article/6644003