Skip to main content
Top
Gepubliceerd in:

13-09-2021 | Empirical Research

Monoaminergic Multilocus Genetic Variants Interact with Stressful Life Events in Predicting Changes in Adolescent Anxiety Symptoms: A One-year Longitudinal Study

Auteurs: Cong Cao, Kexin Sun, Lili Cao, Feifei Li

Gepubliceerd in: Journal of Youth and Adolescence | Uitgave 11/2021

Log in om toegang te krijgen
share
DELEN

Deel dit onderdeel of sectie (kopieer de link)

  • Optie A:
    Klik op de rechtermuisknop op de link en selecteer de optie “linkadres kopiëren”
  • Optie B:
    Deel de link per e-mail

Abstract

Research suggests that genetic variants linked to monoaminergic neurotransmitter function moderate the association between stress and anxiety symptoms, but examining gene-environment (G × E) interactions with individual genes limits power. As one of polygenetic approaches, the multilocus genetic profile score is derived theoretically from combining the effects of multiple candidate genes based on the “biological plausibility”. Using this approach, the current study examined the interaction between monoaminergic multilocus genetic variants and stressful life events on the changes in adolescent anxiety symptoms across a one-year timespan. In a Chinese Han adolescent sample which was derived from three vocational high schools (N = 587; T1: Mage = 16.47 ± 1.53 years; 50.8%, girls), the monoaminergic multilocus genetic profile score was calculated using 5-HTR2C rs6318, TPH2 rs4570625 and DRD2 rs1800497 polymorphisms. Results showed that this monoaminergic multilocus genetic profile score interacted with stressful life events in predicting changes in anxiety symptoms. Consistent with the G×E hypothesis of differential susceptibility, adolescents with more monoaminergic plasticity alleles not only suffered more from high levels of stressful life events, which increased the risk for anxiety symptoms, but also benefited more from low levels of stressful life events, which decreased the risk for anxiety symptoms. There were no significant G × E interactions when individual polymorphisms were examined in isolation. The results highlight the importance of examining aggregated influences of multiple genes in G × E interactions underlying the longitudinal development of adolescent anxiety symptoms.
Bijlagen
Alleen toegankelijk voor geautoriseerde gebruikers
Voetnoten
1
Notably, adolescent loss particularly due to the death of family members, relatives and friends is surprisingly common. Most adolescents (71%) have experienced a loss, reporting a median of 2 deaths (Ringler & Hayden, 2000). Moreover, adolescents are quite vulnerable to the adverse effect of loss. Loss due to death is tightly associated with physical and emotional problems, including depressive and anxiety symptoms (Heingold et al., 2004).
 
2
Additional three reasons were also attached here to explain why the current study did not focus on the MAOA-uVNTR, 5-HTTLPR and COMT genes: (i) although the additive effect of these three genes has already been well investigated in recent research, existing studies still have generated quite inconsistent findings on which specific alleles of these genes confers risk/plasticity. For instance, the MAOA-uVNTR contains 2 R, 3 R, 3.5 R, 4 R, 5 R, and 6 R alleles. The transcriptional efficiency of the 5 R allele is still controversial as it has been classified as both a low-activity allele and a high-activity allele (Nilsson et al., 2018). Meanwhile, the 2.5 R allele was considered as a risk/plastic allele in some studies (Coley et al. (2017)), but not in others (Belsky & Beaver, 2011). This was also true for the 5-HTTLPR and COMT genes (e.g., Belsky & Beaver, 2011; Coley et al. (2017); Stocker et al., 2017). (ii) previous research has showed a significant interaction between the COMT and DRD2 genes on mood disorders, especially among Chinese Han ethnicity (Zhang et al., 2018). Adding the epistatic (gene-by-gene interaction) effects into the additive effects could reduce the power (Vrshek-Schallhorn et al., 2015). (iii) the genotyping technique of MAOA-uVNTR and 5-HTTLPR (i.e., the genotyping for VNTR) differs from what was used in the current study (i.e., the genotyping for SNPs). This made the current study unfeasible to measure these two genetic variants (as well as other VNTR genetic variants).
 
3
The first grade referred to the first year of vocational high schools in the current study.
 
4
That is, the interactions of gender × G, gender × E, SES × G, SES × E were further controlled for. This test could minimize the possibility that significant findings are incorrectly attributed to interactive effects of G × E in cases in which the true underlying effect is the result of interactions of genes or environments with other covariates.
 
Literatuur
go back to reference Cao, C., Rijlaarsdam, J., van der Voort, A., Ji, L., Zhang, W., & Bakermans-Kranenburg, M. J. (2018). Associations between dopamine D2 receptor (DRD2) gene, maternal positive parenting and trajectories of depressive symptoms from early to mid-adolescence. Journal of Abnormal Child Psychology, 46(2), 365–379. https://doi.org/10.1007/s10802-017-0294-5.CrossRefPubMed Cao, C., Rijlaarsdam, J., van der Voort, A., Ji, L., Zhang, W., & Bakermans-Kranenburg, M. J. (2018). Associations between dopamine D2 receptor (DRD2) gene, maternal positive parenting and trajectories of depressive symptoms from early to mid-adolescence. Journal of Abnormal Child Psychology, 46(2), 365–379. https://​doi.​org/​10.​1007/​s10802-017-0294-5.CrossRefPubMed
go back to reference Chen, G. L., & Miller, G. M. (2012). Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 159B(2), 152–171. https://doi.org/10.1002/ajmg.b.32023.CrossRef Chen, G. L., & Miller, G. M. (2012). Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 159B(2), 152–171. https://​doi.​org/​10.​1002/​ajmg.​b.​32023.CrossRef
go back to reference Crystal, D. S., Chen, C., Fuligni, A. J., Stevenson, H. W., Hsu, C.-C., Ko, H.-J., Kitamura, S., & Kimura, S. (1994). Psychological maladjustment and academic achievement: A cross-cultural study of Japanese, Chinese, and American high school students. Child Development, 65(3), 738–753. https://doi.org/10.2307/1131415.CrossRefPubMed Crystal, D. S., Chen, C., Fuligni, A. J., Stevenson, H. W., Hsu, C.-C., Ko, H.-J., Kitamura, S., & Kimura, S. (1994). Psychological maladjustment and academic achievement: A cross-cultural study of Japanese, Chinese, and American high school students. Child Development, 65(3), 738–753. https://​doi.​org/​10.​2307/​1131415.CrossRefPubMed
go back to reference Global Burden of Disease Pediatrics Collaboration, Kyu, H. H., Pinho, C., Wagner, J. A., Brown, J. C., Bertozzi-Villa, A., Charlson, F. J., Coffeng, L. E., Dandona, L., Erskine, H. E., Ferrari, A. J., Fitzmaurice, C., Fleming, T. D., Forouzanfar, M. H., Graetz, N., Guinovart, C., Haagsma, J., Higashi, H., Kassebaum, N. J., Larson, H. J., & Vos, T. (2016). Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: Findings from the global burden of disease 2013 study. JAMA Pediatrics, 170(3), 267–287. https://doi.org/10.1001/jamapediatrics.2015.4276.CrossRef Global Burden of Disease Pediatrics Collaboration, Kyu, H. H., Pinho, C., Wagner, J. A., Brown, J. C., Bertozzi-Villa, A., Charlson, F. J., Coffeng, L. E., Dandona, L., Erskine, H. E., Ferrari, A. J., Fitzmaurice, C., Fleming, T. D., Forouzanfar, M. H., Graetz, N., Guinovart, C., Haagsma, J., Higashi, H., Kassebaum, N. J., Larson, H. J., & Vos, T. (2016). Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: Findings from the global burden of disease 2013 study. JAMA Pediatrics, 170(3), 267–287. https://​doi.​org/​10.​1001/​jamapediatrics.​2015.​4276.CrossRef
go back to reference Gutknecht, L., Jacob, C., Strobel, A., Kriegebaum, C., Müller, J., Zeng, Y., Markert, C., Escher, A., Wendland, J., Reif, A., Mössner, R., Gross, C., Brocke, B., & Lesch, K. P. (2007). Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation. International Journal of Neuropsychopharmacology, 10(3), 309–320. https://doi.org/10.1017/S1461145706007437.CrossRef Gutknecht, L., Jacob, C., Strobel, A., Kriegebaum, C., Müller, J., Zeng, Y., Markert, C., Escher, A., Wendland, J., Reif, A., Mössner, R., Gross, C., Brocke, B., & Lesch, K. P. (2007). Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation. International Journal of Neuropsychopharmacology, 10(3), 309–320. https://​doi.​org/​10.​1017/​S146114570600743​7.CrossRef
go back to reference Hayden, E. P., Klein, D. N., Dougherty, L. R., Olino, T. M., Laptook, R. S., Dyson, M. W., Bufferd, S. J., Emily Durbin, C., Sheikh, H. I., & Singh, S. M. (2010). The dopamine D2 receptor gene and depressive and anxious symptoms in childhood: Associations and evidence for gene-environment correlation and gene-environment interaction. Psychiatric Genetics, 20(6), 304–310. https://doi.org/10.1097/YPG.0b013e32833adccb. Hayden, E. P., Klein, D. N., Dougherty, L. R., Olino, T. M., Laptook, R. S., Dyson, M. W., Bufferd, S. J., Emily Durbin, C., Sheikh, H. I., & Singh, S. M. (2010). The dopamine D2 receptor gene and depressive and anxious symptoms in childhood: Associations and evidence for gene-environment correlation and gene-environment interaction. Psychiatric Genetics, 20(6), 304–310. https://​doi.​org/​10.​1097/​YPG.​0b013e32833adccb​.
go back to reference Heingold, A. A., Smith, D. W., Ruggiero, K. J., Saunders, B. E., Kilpatrick, D. G., & Resnick, H. S. (2004). Loss, trauma exposure, and mental health in a representative sample of 12–17-year-old youth: Data from the national survey of adolescents. Journal of Loss & Trauma, 9(1), 1–19. https://doi.org/10.1080/716100564.CrossRef Heingold, A. A., Smith, D. W., Ruggiero, K. J., Saunders, B. E., Kilpatrick, D. G., & Resnick, H. S. (2004). Loss, trauma exposure, and mental health in a representative sample of 12–17-year-old youth: Data from the national survey of adolescents. Journal of Loss & Trauma, 9(1), 1–19. https://​doi.​org/​10.​1080/​716100564.CrossRef
go back to reference Huang, J., Yang, X. B., Yun, Y. Z., Yan, S. S., Hao, W., Xiang, J. J., & Kang, C. (2019). Reliability and validity of Adolescent Self-rating Life Events Checklist among Chinese middle school students living in rural areas. Chinese Journal of School Health, 40(9), 1353–1359. Huang, J., Yang, X. B., Yun, Y. Z., Yan, S. S., Hao, W., Xiang, J. J., & Kang, C. (2019). Reliability and validity of Adolescent Self-rating Life Events Checklist among Chinese middle school students living in rural areas. Chinese Journal of School Health, 40(9), 1353–1359.
go back to reference Letourneau, N. L., de Koning, A., Sekhon, B., Ntanda, H. N., Kobor, M., Deane, A. J., Morin, A. M., Dewey, D., Campbell, T. S., & Giesbrecht, G. F., APrON Study Team. (2019). Parenting interacts with plasticity genes in predicting behavioral outcomes in preschoolers. The Canadian Journal of Nursing Research. https://doi.org/10.1177/0844562119863612. 844562119863612. Advance online publication.CrossRefPubMed Letourneau, N. L., de Koning, A., Sekhon, B., Ntanda, H. N., Kobor, M., Deane, A. J., Morin, A. M., Dewey, D., Campbell, T. S., & Giesbrecht, G. F., APrON Study Team. (2019). Parenting interacts with plasticity genes in predicting behavioral outcomes in preschoolers. The Canadian Journal of Nursing Research. https://​doi.​org/​10.​1177/​0844562119863612​. 844562119863612. Advance online publication.CrossRefPubMed
go back to reference Liu, X. C., Liu, L. Q., Yang, J., Chai, F. X., Wang, A. Z., Sun, L. M., zhao, G. F., & Ma, D. D. (1997). Reliability and validity test of adolescent life event scale. Chinese Journal of Clinical Psychology, 5, 34–36. Liu, X. C., Liu, L. Q., Yang, J., Chai, F. X., Wang, A. Z., Sun, L. M., zhao, G. F., & Ma, D. D. (1997). Reliability and validity test of adolescent life event scale. Chinese Journal of Clinical Psychology, 5, 34–36.
go back to reference Stocker, C. M., Masarik, A. S., Widaman, K. F., Reeb, B. T., Boardman, J. D., Smolen, A., Neppl, T. K., & Conger, K. J. (2017). Parenting and adolescents’ psychological adjustment: Longitudinal moderation by adolescents’ genetic sensitivity. Development and Psychopathology, 29(4), 1289–1304. https://doi.org/10.1017/S0954579416001310.CrossRefPubMed Stocker, C. M., Masarik, A. S., Widaman, K. F., Reeb, B. T., Boardman, J. D., Smolen, A., Neppl, T. K., & Conger, K. J. (2017). Parenting and adolescents’ psychological adjustment: Longitudinal moderation by adolescents’ genetic sensitivity. Development and Psychopathology, 29(4), 1289–1304. https://​doi.​org/​10.​1017/​S095457941600131​0.CrossRefPubMed
go back to reference Vrshek-Schallhorn, S., Stroud, C. B., Mineka, S., Zinbarg, R. E., Adam, E. K., Redei, E. E. & Hammen Constance & Graske & Michelle, G. (2015). Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression. Journal of Abnormal Psychology Association, 124(4), 776–790. https://doi.org/10.1037/abn0000098. Vrshek-Schallhorn, S., Stroud, C. B., Mineka, S., Zinbarg, R. E., Adam, E. K., Redei, E. E. & Hammen Constance & Graske & Michelle, G. (2015). Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression. Journal of Abnormal Psychology Association, 124(4), 776–790. https://​doi.​org/​10.​1037/​abn0000098.
Metagegevens
Titel
Monoaminergic Multilocus Genetic Variants Interact with Stressful Life Events in Predicting Changes in Adolescent Anxiety Symptoms: A One-year Longitudinal Study
Auteurs
Cong Cao
Kexin Sun
Lili Cao
Feifei Li
Publicatiedatum
13-09-2021
Uitgeverij
Springer US
Gepubliceerd in
Journal of Youth and Adolescence / Uitgave 11/2021
Print ISSN: 0047-2891
Elektronisch ISSN: 1573-6601
DOI
https://doi.org/10.1007/s10964-021-01496-y