Review for "Molecular genetic associations between a prominent serotonin transporter gene polymorphism (5‐HTTLPR/rs25531) and individual differences in tendencies toward autistic traits and generalized internet use disorder in China and Germany"
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5-HTTLPR
Association between the low-activity variant of a polymorphism in the transcriptional control region of the serotonin transporter (5-HTTLPR) and neuroticism or harm avoidance was found in several but not all studies. The authors analyzed the influence of 5-HTTLPR variants on personality disorders.Patients with personality disorders (N=320) and healthy volunteers (N=281) were studied with the Revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. All were genotyped for 5-HTTLPR variants.No differences in 5-HTTLPR genotype distribution were detected between patients with cluster B and C personality disorders and comparison subjects. In contrast, among patients with a cluster C diagnosis, carriers of the low-activity short allele of the 5-HTTLPR exhibited higher neuroticism scores than noncarriers.These findings support the notion that there is no general association between the 5-HTTLPR and anxiety-related traits and that differential gene effects and/or gene-by-environment interactions are likely operative in distinct clinical subpopulations.
5-HTTLPR
Association (psychology)
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5-HTTLPR
Moderation
Depression
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5-HTTLPR
Subjective Well-Being
Candidate gene
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5-HTTLPR
Moderation
Depression
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Human observational studies have shown that, in interaction with life stress, the short or S-allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with an enhanced risk for depression. However, this gene-by-environment interaction (G×E) has recently been questioned by two meta-analyses. We aim to provide an overview and appraisal of recent developments and controversies.The statistical approach of the meta-analyses aimed at a very strict replication of the initial finding and, accordingly, included only a minority of all available studies. Furthermore, the negative results of the meta-analyses appear to be predominantly driven by a few large studies that used retrospective, self-report measures of life stress. In contrast, among 19 studies using interview-based or more objective measures of stress, there were 13 replications, five part-replications and only one nonreplication. Finally, a broader approach based on evidence from different research fields and methodologies supports a 5-HTTLPR by stress interaction.Whereas there is no doubt that the meta-analyses are methodologically sound, it appears that this technique is only in part suitable for appraising all of the available evidence. Furthermore, convergent evidence is accumulating from different research fields that 5-HTTLPR is indeed closely associated with different biological pathways associated with stress regulation and depression.
5-HTTLPR
Depression
Association (psychology)
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5-HTTLPR
Candidate gene
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Previous studies of the interaction between a functional polymorphism in the serotonin transporter gene-linked promoter region (5-HTTLPR) and stress in anxiety-related phenotypes have produced inconsistent results. The aim of the current study was to examine the effect of the 5-HTTLPR × stress interaction on anxiety symptoms in Chinese adolescents. A total of 651 healthy adolescents [323 females and 328 males; age 14–17 (mean = 16.27, standard deviation = 0.77)] participated in this study. At the initial assessment, participants completed self-report measures assessing anxiety symptoms, depressive symptoms and stressful life events. Additionally, anxiety symptoms and stressful life events were assessed once every 3 months for the subsequent 9 months. A hierarchical linear model (HLM) was used to investigate the 5-HTTLPR × stress interaction. The HLM indicated no main effect of 5-HTTLPR on anxiety symptoms. Significant 5-HTTLPR × stress interaction effect in predicting anxiety symptoms was found. Specifically, individuals with the 5-HTTLPR L allele exhibited more anxiety symptoms related to stressful life events. The association between stress and anxiety symptoms is moderated by 5-HTTLPR. The 5-HTTLPR L allele increases individuals' vulnerability to anxiety under stress situations.
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Objective: To test whether individuals with at least one copy of the short (S) or long (L)G allele of the serotonin transporter polymorphism (5-HTTLPR) exhibit greater increases in anxiety, compared with LALA individuals, under periods of high daily stress. Although this common polymorphism in the serotonin transporter gene has been identified as a vulnerability factor for anxiety, findings in the literature are mixed. Discrepant findings could be explained by recent research showing that 5-HTTLPR is functionally triallelic (LA versus LG or S), rather than biallelic (L versus S). Mixed findings could also result from a lack of attention to diathesis-stress models, whereby genetic vulnerability is considered latent until activated by stress (gene-environment interplay). Based on this model, we argue that genotype differences in anxiety should be stronger in the presence of stress. Methods: A total of 350 college students recorded their daily stressors and mood for two 30-day periods, separated by 1 year. Results: Across both years, diathesis-stress patterns were observed for reports of anxious mood as a function of 5-HTTLPR. Individuals with at least one copy of the S or LG allele at 5-HTTLPR experienced elevated anxious mood on days with more intense stressors, as compared with those who were LA homozygotes. Genotype differences in anxiety were less apparent on low stress days. No consistent allelic association of 5-HTTLPR was observed with any other mood states, trait anxiety, or neuroticism. Conclusion: Our findings highlight the potential value of focusing on genetic vulnerability in the context of everyday environmental triggers. 5-HTTLPR = serotonin transporter gene promoter polymorphism; 5-HTT = serotonin transporter protein; fMRI = functional magnetic resonance imaging; STAI = State-Trait Anxiety Inventory.
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Stressor
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