Age-specific associations among functional COMT Val158Met polymorphism, resting parasympathetic nervous control and generalized anxiety disorder
- PMID: 30954919
- DOI: 10.1016/j.psyneuen.2019.03.020
Age-specific associations among functional COMT Val158Met polymorphism, resting parasympathetic nervous control and generalized anxiety disorder
Abstract
The functional Val158Met polymorphism (rs4680) of the Catechol-O-Methyltransferase (COMT) gene has been implicated in generalized anxiety disorder (GAD); however, the underlying neural mechanisms remain unexamined. Recent evidence reveals that low resting parasympathetic (vagal) control is an endophenotypic predictor of anxiety, while the effect of COMT rs4680 differs at different ages. Thus, we examined whether the COMT Val158Met variant could increase the risk of GAD through decreased resting parasympathetic nervous control in an age-specific manner. COMT rs4680 polymorphism was genotyped in 1,655 Han Chinese adults (1,142 healthy subjects and 513 patients with GAD; age: 20-65). High-frequency power (HF) of heart rate variability (HRV) was used to measure resting state parasympathetic nervous regulation. Non-genetic factors, such as gender, smoking status, medication use and comorbidity conditions, were treated as covariates. After adjusting for relevant covariates, there was a significant age x COMT genotype interaction on resting HF of HRV. In younger adults, Met allele carriers had a significantly lower HF index; however, older adults exhibited the opposite pattern, with Val/Val homozygotes exhibiting decreased HF values. Moreover, reduced HF-HRV is associated with increased risk of GAD. Finally, pathway analysis revealed a significant indirect effect of COMT on the risk of GAD via reduced resting HF-HRV, in the aforementioned age-dependent manner. Our findings are the first to demonstrate that COMT Val158Met polymorphism is associated with risk of GAD via reduced resting parasympathetic nervous control, an age-specific risk pathway.
Keywords: Age-specific pathway; COMT gene; Generalized anxiety disorder (GAD); Heart rate variability (HRV); Resting parasympathetic (vagal) control; Val(158)Met (rs4680) polymorphism.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Similar articles
-
To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele.Neuropsychobiology. 2024;83(1):41-48. doi: 10.1159/000535912. Epub 2024 Jan 16. Neuropsychobiology. 2024. PMID: 38228118 Free PMC article.
-
BDNF Val⁶⁶Met polymorphism to generalized anxiety disorder pathways: Indirect effects via attenuated parasympathetic stress-relaxation reactivity.J Abnorm Psychol. 2020 Apr;129(3):237-247. doi: 10.1037/abn0000507. Epub 2020 Feb 20. J Abnorm Psychol. 2020. PMID: 32077707
-
Association of catechol-O-methyltransferase Val(108/158) Met genetic polymorphism with schizophrenia, P50 sensory gating, and negative symptoms in a Chinese population.Psychiatry Res. 2016 Aug 30;242:271-276. doi: 10.1016/j.psychres.2016.04.029. Epub 2016 Apr 14. Psychiatry Res. 2016. PMID: 27315458
-
Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.Biol Psychiatry. 2005 Jan 15;57(2):139-44. doi: 10.1016/j.biopsych.2004.10.018. Biol Psychiatry. 2005. PMID: 15652872 Review.
-
Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity.J Neuroimmune Pharmacol. 2016 Sep;11(3):434-45. doi: 10.1007/s11481-016-9651-3. Epub 2016 Jan 23. J Neuroimmune Pharmacol. 2016. PMID: 26803486 Review.
Cited by
-
To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele.Neuropsychobiology. 2024;83(1):41-48. doi: 10.1159/000535912. Epub 2024 Jan 16. Neuropsychobiology. 2024. PMID: 38228118 Free PMC article.
-
Warriors, Worriers, and COVID-19: An Exploratory Study of the Catechol O-Methyltransferase Val158Met Polymorphism Across Populations.Cureus. 2020 Aug 28;12(8):e10103. doi: 10.7759/cureus.10103. Cureus. 2020. PMID: 32879833 Free PMC article.
-
The association of catechol-O-methyltransferase (COMT) rs4680 polymorphisms and generalized anxiety disorder in the Chinese Han population.Int J Clin Exp Pathol. 2020 Jul 1;13(7):1712-1719. eCollection 2020. Int J Clin Exp Pathol. 2020. PMID: 32782694 Free PMC article.
-
Sex-specific pathways among tri-allelic serotonin transporter polymorphism, trait neuroticism and generalized anxiety disorder.J Psychiatry Neurosci. 2020 Nov 1;45(6):379-386. doi: 10.1503/jpn.190092. J Psychiatry Neurosci. 2020. PMID: 32293839 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous