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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.

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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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