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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

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: M_age = 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.

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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).

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).

The first grade referred to the first year of vocational high schools in the current study.

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.

Alex, K. D., & Pehek, E. A. (2007). Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacology and Therapeutics, 113(2), 296–320. https://doi.org/10.1016/j.pharmthera.2006.08.004.CrossRefPubMed

Alexander, N., Osinsky, R., Mueller, E., Schmitz, A., Guenthert, S., Kuepper, Y., & Hennig, J. (2011). Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery. Behavioural Brain Research, 216(1), 53–58. https://doi.org/10.1016/j.bbr.2010.07.003.CrossRefPubMed

Belsky, J., & Beaver, K. M. (2011). Cumulative-genetic plasticity, parenting and adolescent self-regulation. Journal of Child Psychology and Psychiatry, 52(5), 619–626. https://doi.org/10.1111/j.1469-7610.2010.02327.x.CrossRefPubMed

Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135(6), 885–908. https://doi.org/10.1037/a0017376.CrossRefPubMed

Bradley, R. H., & Corwyn, R. F. (2002). Socioeconomic status and child development. Annual Review of Psychology, 53, 371–399. https://doi.org/10.1146/annurev.psych.53.100901.135233.CrossRefPubMed

Brandão, M. L., & Coimbra, N. C. (2019). Understanding the role of dopamine in conditioned and unconditioned fear. Reviews in Neurosciences, 30(3), 325–337. https://doi.org/10.1515/revneuro-2018-0023.CrossRef

Brummett, B. H., Babyak, M. A., Williams, R. B., Harris, K. M., Jiang, R., Kraus, W. E., Singh, A., Costa, P. T., Georgiades, A., & Siegler, I. C. (2014). A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress. PloS One, 9(12), e114451 https://doi.org/10.1371/journal.pone.0114451.CrossRefPubMedPubMedCentral

Brummett, B. H., Kuhn, C. M., Boyle, S. H., Babyak, M. A., Siegler, I. C., & Williams, R. B. (2012). Cortisol responses to emotional stress in men: Association with a functional polymorphism in the 5HTR2C gene. Biological Psychology, 89(1), 94–98. https://doi.org/10.1016/j.biopsycho.2011.09.013.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

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

Christianson, J. P., Ragole, T., Amat, J., Greenwood, B. N., Strong, P. V., Paul, E. D., Fleshner, M., Watkins, L. R., & Maier, S. F. (2010). 5-hydroxytryptamine 2C receptors in the basolateral amygdala are involved in the expression of anxiety after uncontrollable traumatic stress. Biological Psychiatry, 67(4), 339–345. https://doi.org/10.1016/j.biopsych.2009.09.011.CrossRefPubMed

Cohen, M. X., Young, J., Baek, J. M., Kessler, C., & Ranganath, C. (2005). Individual differences in extraversion and dopamine genetics predict neural reward responses. Cognitive Brain Research, 25(3), 851–861. https://doi.org/10.1016/j.cogbrainres.2005.09.018.CrossRefPubMed

Coley, R. L., Sims, J., & Carrano, J. (2017). Environmental risks outweigh dopaminergic genetic risks for alcohol use and abuse from adolescence through early adulthood. Drug and Alcohol Dependence, 175, 106–118. https://doi.org/10.1016/j.drugalcdep.2017.01.042.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

Denys, D., Klompmakers, A. A., & Westenberg, H. G. (2004). Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine. Psychopharmacology, 176(2), 195–203. https://doi.org/10.1007/s00213-004-1880-0.CrossRefPubMed

Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168(10), 1041–1049. https://doi.org/10.1176/appi.ajp.2011.11020191.CrossRef

Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., Plomin, R., & Craig, I. W. (2004). Gene-environment interaction analysis of serotonin system markers with adolescent depression. Molecular Psychiatry, 9(10), 908–915. https://doi.org/10.1038/sj.mp.4001546.CrossRefPubMed

Ellis, B. J., & Boyce, W. T. (2008). Biological sensitivity to context. Current Directions in Psychological Science, 17(3), 183–187. https://doi.org/10.1111/j.1467-8721.2008.00571.x.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

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

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.

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

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.

Keller, M. C. (2014). Gene×environment interaction studies have not properly controlled for potential confounders: The problem and the (simple) solution. Biological Psychiatry, 75(1), 18–24. https://doi.org/10.1016/j.biopsych.2013.09.006.CrossRefPubMed

Lee, B. T., & Ham, B. J. (2008). Serotonergic genes and amygdala activity in response to negative affective facial stimuli in Korean women. Genes, Brain, and Behavior, 7(8), 899–905. https://doi.org/10.1111/j.1601-183X.2008.00429.x.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

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., & Tein, J. Y. (2015). Life events, psychopathology, and suicidal behavior in Chinese adolescents. Journal of Affective Disorders, 86(2-3), 195–203. https://doi.org/10.1016/j.jad.2005.01.016.CrossRef

Ma, J., Xiao, H., Yang, Y., Cao, D., Wang, L., Yang, X., Qiu, X., Qiao, Z., Song, J., Liu, Y., Wang, P., Zhou, J., & Zhu, X. (2015). Interaction of tryptophan hydroxylase 2 gene and life events in susceptibility to major depression in a Chinese Han population. Journal of Affective Disorders, 188, 304–309. https://doi.org/10.1016/j.jad.2015.07.041.CrossRefPubMed

Mills-Koonce, W. R., Propper, C. B., Gariepy, J. L., Blair, C., Garrett-Peters, P., & Cox, M. J. (2007). Bidirectional genetic and environmental influences on mother and child behavior: The family system as the unit of analyses. Development and Psychopathology, 19(4), 1073–1087. https://doi.org/10.1017/S0954579407000545.CrossRefPubMed

Mumper, E. E., Dyson, M. W., Finsaas, M. C., Olino, T. M., & Klein, D. N. (2020). Life stress moderates the effects of preschool behavioral inhibition on anxiety in early adolescence. Journal of Child Psychology and Psychiatry, 61(2), 167–174. https://doi.org/10.1111/jcpp.13121.CrossRefPubMed

Nilsson, K. W., Åslund, C., Comasco, E., & Oreland, L. (2018). Gene-environment interaction of monoamine oxidase A in relation to antisocial behaviour: current and future directions. Journal of Neural Transmission, 125(11), 1601–1626. https://doi.org/10.1007/s00702-018-1892-2.CrossRefPubMedPubMedCentral

Peyrot, W. J., Milaneschi, Y., Abdellaoui, A., Sullivan, P. F., Hottenga, J. J., Boomsma, D. I., & Penninx, B. W. (2014). Effect of polygenic risk scores on depression in childhood trauma. British Journal of Psychiatry, 205(2), 113–119. https://doi.org/10.1192/bjp.bp.113.143081.CrossRef

Ringler, L. L., & Hayden, D. C. (2000). Adolescent bereavement and social support: Peer losses compared to other losses. Journal of Adolescent Research, 15(2), 209–230. https://doi.org/10.1177/0743558400152002.CrossRef

Shaif, N. A., Chang, D. H., Cho, D., Kim, S., Seo, D. B., & Shim, I. (2018). The antidepressant-like effect of lactate in an animal model of menopausal depression. Biomedicines, 6(4), 108 https://doi.org/10.3390/biomedicines6040108.CrossRefPubMedCentral

Spence, S. H., Rapee, R., Mcdonald, C., & Ingram, M. (2001). The structure of anxiety symptoms among preschoolers. Behaviour Research & Therapy, 39(11), 1293–1316. https://doi.org/10.1016/S0005-7967(00)00098-X.CrossRef

Starr, L. R., Vrshek-Schallhorn, S., & Stroud, C. B. (2019). Serotonergic multilocus genetic variation moderates the association between major interpersonal stress and adolescent depressive symptoms: Replication and candidate environment specification. Journal of Psychiatric Research, 117, 55–61. https://doi.org/10.1016/j.jpsychires.2019.06.020.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/S0954579416001310.CrossRefPubMed

Storey, J. D. (2002). A direct approach to false discovery rates. Journal of the Royal Statistical Society: Series B (Statistical Methodology), 64, 479–498. https://doi.org/10.1111/1467-9868.00346.CrossRef

Sullivan, P. F., Daly, M. J., & O’Donovan, M. (2012). Genetic architectures of psychiatric disorders: The emerging picture and its implications. Nature Reviews Genetics, 13(8), 537–551. https://doi.org/10.1038/nrg3240.CrossRefPubMedPubMedCentral

Suomi, S. J. (1997). Early determinants of behaviour: Evidence from primate studies. British Medical Bulletin, 53(1), 170–184. https://doi.org/10.1093/oxfordjournals.bmb.a011598.CrossRefPubMed

Thaler, L., Groleau, P., Joober, R., Bruce, K. R., Israel, M., Badawi, G., Sycz, L., & Steiger, H. (2013). Epistatic interaction between 5HTTLPR and TPH2 polymorphisms predicts novelty seeking in women with bulimia nervosa spectrum disorders. Psychiatry Research, 208(1), 101–103. https://doi.org/10.1016/j.psychres.2012.11.028.CrossRefPubMed

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.

White, M. J., Lawford, B. R., Morris, C. P., & Young, R. M. (2009). Interaction between DRD2 C957T polymorphism and an acute psychosocial stressor on reward-related behavioral impulsivity. Behavior Genetics, 39(3), 285–295. https://doi.org/10.1007/s10519-008-9255-7.CrossRefPubMed

Widaman, K. F., Helm, J. L., Castro-Schilo, L., Pluess, M., Stallings, M. C., & Belsky, J. (2012). Distinguishing ordinal and disordinal interactions. Psychological Methods, 17(4), 615–622. https://doi.org/10.1037/a0030003.CrossRefPubMedPubMedCentral

Yildirim, B. O., & Derksen, J. J. (2013). Systematic review, structural analysis, and new theoretical perspectives on the role of serotonin and associated genes in the etiology of psychopathy and sociopathy. Neuroscience and Biobehavioral Reviews, 37(7), 1254–1296. https://doi.org/10.1016/j.neubiorev.2013.04.009.CrossRefPubMed

Zhang, K., Wang, L., Cao, C., Li, G., Fang, R., Liu, P., Luo, S., Zhang, X., & Liberzon, I. (2018). A DRD2/ANNK1-COMT interaction, consisting of functional variants, confers risk of post-traumatic stress disorder in traumatized Chinese. Frontiers in Psychiatry, 9, 170 https://doi.org/10.3389/fpsyt.2018.00170.CrossRefPubMedPubMedCentral

Zhang, X., & Belsky, J. (2020). Three phases of gene×environment interaction research: Theoretical assumptions underlying gene selection. Development and Psychopathology, First View, 1–12. https://doi.org/10.1017/S0954579420000966.

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

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