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Warriors Versus Worriers: The Role of COMT Gene Variants

Published online by Cambridge University Press:  07 November 2014

Abstract

Behavioral phenotypes are generally complex, reflecting the action of multiple different genes. Nevertheless, there is growing evidence that key gene variants can alter activity within specific neuronal circuits and, therefore, influence particular cognitive-affective phenomena. One example is the catechol-O-methyltransferase (COMT) gene, which has a common variant at codon 158. Those with valine (Val158) alleles have increased greater COMT activity and lower prefrontal extracellular dopamine compared with those with the methionine (Met158) substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance. while individuals with Met158 alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val158 alleles are associated with schizophrenia, while Met158 alleles are associated with anxiety.

Type
Pearls in Clinical Neuroscience
Copyright
Copyright © Cambridge University Press 2006

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References

REFERENCES

1. Stein, DJ, Moeller, FG. The man who turned bad. CNS Spectr. 2005;10:8890.Google Scholar
2. Chambers, RA, Taylor, JR, Potenza, MN. Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry. 2003;160:10411052.Google Scholar
3. Stein, DJ, Hollander, E. Impulsive aggression and obsessive-compulsive disorder. Psychiatr Ann. 1993;23:389395.Google Scholar
4. Stein, DJ. Neurobiology of the obsessive-compulsive spectrum disorders. Biol Psychiatry. 2000;47:296304.Google Scholar
5. Winterer, G, Musso, F, Vucurevic, G, et al. COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits. Neuroimage. 2006 Jul 31; [Epub ahead of print].Google Scholar
6. Egan, MF, Goldberg, TE, Kolachana, BS, et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA. 2001;98:69176922.Google Scholar
7. Goldberg, TE, Egan, MF, Gscheidle, T, et al. Executive subprocesses in working memory: relationship to catectiol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry. 2003;60:889896.Google Scholar
8. Blasi, G, Mattay, VS, Bertolino, A, et al. Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci. 2005;25:50385045.Google Scholar
9. Bishop, SJ, Cohen, JD, Fossella, J, et al. COMT genotype influences prefrontal response to emotional distraction. Cogn Affect Behav Neurosci. 2006;6:6270.Google Scholar
10. Zubieta, JK, Heitzeg, MM, Smith, YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299:12401243.Google Scholar
11. Smolka, MN, Schumann, G, Wrase, J, et al. Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci. 2005;25:836842.Google Scholar
12. Kates, WR, Antshel, KM, Abdulsabur, N, et al. A gender-moderated effect of a functional COMT polymorphism on prefrontal brain morphology and function in velo-cardio-facial syndrome (22q11.2 deletion syndrome). Am J Med Genet B Neuropsychiatr Genet. 2006;141:274280.Google Scholar
13. Zinkstok, J, Schmitz, N, van Amelsvoort, T, et al. The COMT val(158)met polymorphism and brain morphometry in healthy young adults. Neurosci Lett. 2006;405:3439.Google Scholar
14. Meyer-Lindenberg, A, Kohn, PD, Kolachana, B, et al. Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nat Neurosci. 2005;8:594596.Google Scholar
15. Bilder, RM, Volavka, J, Czobor, P, et al. Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia. Biol Psychiatry. 2002;52:701707.Google Scholar
16. Malhotra, AK, Kestler, LJ, Mazzanti, C, et al. A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry. 2002;159:652654.Google Scholar
17. Heinz, A, Smolka, MN. The effects of catechol 0-methyltransferase genotype on brain activation elicited by affective stimuli and cognitive tasks. Rev Neurosci. 2006;17:359367.Google Scholar
18. Xu, K, Ernst, M, Goldman, D. Imaging genomics applied to anxiety, stress response, and resiliency. Neuroinformatics. 2006;4:5164.Google Scholar
19. Tunbridge, EM, Harrison, PJ, Weinberger, DR. Catechol-o-Methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol Psychiatry. 2006;60:141151.Google Scholar
20. Olsson, CA, Anney, RJ, Lotfi-Miri, M, et al. Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health. Psychiatr Genet. 2005;15:109115.Google Scholar
21. Diatchenko, L, Slade, GD, Nackley, AG, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005;14:135143.Google Scholar
22. McGrath, M, Kawachi, I, Ascherio, A, et al. Association between catechol-O-methyltransferase and phobic anxiety. Am J Psychiatry. 2004;161:17031705.Google Scholar
23. Munafo, MR, Bowes, L, Clark, TG, et al. Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol Psychiatry. 2005;10:765770.Google Scholar
24. Mattay, VS, Goldberg, TE, Fera, F et al. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA. 2003;100:61866191.Google Scholar
25. Caspi, A, Moffitt, TE, Cannon, M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;57:11171127.Google Scholar
26. Mill, J, Dempster, E, Caspi, A, et al. Evidence for monozygotic twin (MZ) discordance in methylation level at two CpG sites in the promoter region of the catechol-O-methyltransferase (COMT) gene. Am J Med Genet B Neuropsychiatr Genet. 2006;141:421425.Google Scholar
27. van Praag, HM, Asnis, GM, Kahn, RS, et al. Monoamines and abnormal behaviour. A multi-aminergic perspective. Br J Psychiatry. 1990;157:723734.Google Scholar
28. Weickert, TW, Goldberg, TE, Mishara, A, et al. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Biol Psychiatry. 2004;56:677682.Google Scholar
29. Arias, B, Serretti, A, Lorenzi, C, et al. Analysis of COMT gene (Val 158 Met polymorphism) in the clinical response to SSRIs in depressive patients of European origin. J Affect Disord. 2006;90:251256.Google Scholar
30. Bertolino, A, Caforio, G, Blasi, G, et al. Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry. 2004;161:17981805.Google Scholar
31. Lee, MS, Kim, HS, Cho, EK, et al. COMT genotype and effectiveness of entacapone in patients with fluctuating Parkinson's disease. Neurology. 2002;58:564567.Google Scholar
32. Yamanouchi, Y, Iwata, N, Suzuki, T, et al. Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone. Pharmacogenomics J. 2003;3:356361.Google Scholar
33. Rakvag, TT, Klepstad, P, Baar, C, et al. The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients. Pain. 2005;116:7378.Google Scholar
34. Craddock, N, Owen, MJ, O'Donovan, MC. The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry. 2006;11:446458.Google Scholar
35. De Luca, V, Tharmalingam, S, Sicard, T, Kennedy, JL. Gene-gene interaction between MAOA and COMT in suicidal behavior. Neurosci Lett. 2005;383:151154.Google Scholar
36. Zahn-Waxler, C. Warriors and worriers: gender and psychopathology. Dev Psychopathol. 1993;5:7989.Google Scholar
37. Brook, JS, Whiteman, M, Cohen, P. Warriors and worriers: a longitudinal study of gender differences in drug use. NIDA Research Monographs. 2000;271284.Google Scholar