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COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.

Publication ,  Journal Article
Slade, GD; Sanders, AE; Ohrbach, R; Bair, E; Maixner, W; Greenspan, JD; Fillingim, RB; Smith, S; Diatchenko, L
Published in: J Dent Res
September 2015

When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according to biological susceptibility. We hypothesized that temporal escalation in stress exacerbates risk for TMD, and the effect is amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT), regulating catechol neurotransmitter catabolism. We used data from the Orofacial Pain: Prospective Evaluation and Risk Assessment prospective cohort study of 2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS) measured psychological stress. Genotyped DNA from blood samples determined COMT diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner-verified incident TMD. PSS scores at baseline were 20% greater (P < 0.001) in adults who developed incident TMD compared with TMD-free controls. Baseline PSS scores increased by 9% (P = 0.003) during follow-up in cases but remained stable in controls. This stress escalation was limited to incident cases with COMT diplotypes coding for low-activity COMT, signifying impaired catabolism of catecholamines. Cox regression models confirmed significant effects on TMD hazard of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a significant (P = 0.04) interaction of COMT diplotype and time-varying stress showed that a postbaseline increase of 1.0 standard deviation in PSS more than doubled risk of TMD incidence in subjects with low-activity COMT diplotypes (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence limits: 0.96, 2.09). Findings provide novel insights into dynamic effects of psychological stress on TMD pain, highlighting that effects are most pronounced in individuals whose genetic susceptibility increases responsiveness to catecholamine neurotransmitters.

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Published In

J Dent Res

DOI

EISSN

1544-0591

Publication Date

September 2015

Volume

94

Issue

9

Start / End Page

1187 / 1195

Location

United States

Related Subject Headings

  • Young Adult
  • Temporomandibular Joint Disorders
  • Stress, Psychological
  • Risk Factors
  • Pain
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Gene-Environment Interaction
 

Citation

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Slade, G. D., Sanders, A. E., Ohrbach, R., Bair, E., Maixner, W., Greenspan, J. D., … Diatchenko, L. (2015). COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain. J Dent Res, 94(9), 1187–1195. https://doi.org/10.1177/0022034515595043
Slade, G. D., A. E. Sanders, R. Ohrbach, E. Bair, W. Maixner, J. D. Greenspan, R. B. Fillingim, S. Smith, and L. Diatchenko. “COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.J Dent Res 94, no. 9 (September 2015): 1187–95. https://doi.org/10.1177/0022034515595043.
Slade GD, Sanders AE, Ohrbach R, Bair E, Maixner W, Greenspan JD, et al. COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain. J Dent Res. 2015 Sep;94(9):1187–95.
Slade, G. D., et al. “COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.J Dent Res, vol. 94, no. 9, Sept. 2015, pp. 1187–95. Pubmed, doi:10.1177/0022034515595043.
Slade GD, Sanders AE, Ohrbach R, Bair E, Maixner W, Greenspan JD, Fillingim RB, Smith S, Diatchenko L. COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain. J Dent Res. 2015 Sep;94(9):1187–1195.
Journal cover image

Published In

J Dent Res

DOI

EISSN

1544-0591

Publication Date

September 2015

Volume

94

Issue

9

Start / End Page

1187 / 1195

Location

United States

Related Subject Headings

  • Young Adult
  • Temporomandibular Joint Disorders
  • Stress, Psychological
  • Risk Factors
  • Pain
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Gene-Environment Interaction