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Study 22 of 29SS-31 literaturebiorxiv-preprint · Observational2026

Genetic, Microbial, and Lifestyle Correlates of Adolescent Anxiety: A Pilot Cross-Sectional Study of SLC6A4 Genotype and the Oral Microbiome

This pilot study found no significant link between SLC6A4 genotype and anxiety severity, suggesting that lifestyle and possibly oral microbiome factors may be relevant.

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Where it sits

this study against the rest of the ss-31 corpus
2
Preclinical
20
Observational · this one
0
Open-label
3
Randomised
4
Reviews

Summary and findings

This pilot study examined associations among SLC6A4 genotype, oral microbiome composition, lifestyle habits, and anxiety severity in 56 adolescents aged 13–18. The SS genotype was predominant, observed in 68% of Cohort 1 and 100% of Cohort 2 participants. No significant association was found between SLC6A4 genotype and anxiety scores as measured by the GAD-7 scale.

How much of this paper we could read: full text read (0.80). We had a clear abstract, so the summary below closely tracks the paper. What this means →
SS genotype predominated in both cohorts (68% [17/25] in Cohort 1; 100% [31/31] in Cohort 2).2026

Abstract

The authors’ words, as biorxiv-preprint supplied them

<p>Background: Adolescent anxiety is a prevalent and multifactorial condition shaped by genetic, microbial, and behavioral influences, yet its biological determinants remain incompletely understood. This pilot study examined associations among SLC6A4 (5-HTTLPR) genotype, oral microbiome composition, lifestyle habits, and anxiety severity in an adolescent cohort. <h4>Methods:</h4> Fifty-six adolescents (ages 13–18) were recruited across two sequential, non-overlapping cohorts (Cohort 1, n = 25; Cohort 2, n = 31). All participants provided a saliva sample and completed a lifestyle questionnaire and the GAD-7 (Generalized Anxiety Disorder 7-item scale), a standardized instrument for grading anxiety symptom severity. Genomic DNA was extracted and genotyped by PCR for the 5-HTTLPR polymorphism in the SLC6A4 promoter. Oral microbiome composition was characterized by 16S rRNA gene sequencing (V3–V4 region, Illumina MiSeq) in a subset of 12 Cohort 2 participants. Because this was an exploratory, hypothesis-generating pilot study with a limited sample size, data were analyzed descriptively; no inferential statistical testing or correction for multiple comparisons was performed. <h4>Results:</h4> The SS genotype predominated in both cohorts (68% [17/25] in Cohort 1; 100% [31/31] in Cohort 2), consistent with prior reports of high S-allele frequency. No apparent association was observed between SLC6A4 genotype and GAD-7 score. Sequencing of 12 Cohort 2 samples identified 21 unique bacterial genera. The genus Rothia was present in 3 of 9 individuals with minimal-to-mild anxiety (GAD-7 &lt; 10) and absent in all 3 individuals with higher anxiety scores (GAD-7 ≥ 10), a pattern suggestive of a possible directional association warranting further investigation. No apparent relationship was observed between overall microbial diversity and anxiety. A positive directional relationship was observed between lifestyle habit score and mental health score, consistent with prior literature linking physical activity to adolescent well-being. <h4>Conclusions:</h4> In this exploratory pilot cohort, genetic factors alone did not appear to account for variation in adolescent anxiety scores; lifestyle habits and, potentially, oral microbial composition - particularly Rothia abundance - may also be relevant. Given the descriptive design, small sample size, and absence of formal statistical testing, these findings should be regarded as preliminary and hypothesis-generating, warranting confirmation in larger, adequately powered cohorts using formal inferential statistics.</p>

Background

The study likely investigates the relationship between genetic factors, the oral microbiome, and lifestyle in relation to adolescent anxiety. The SLC6A4 genotype is often studied for its role in serotonin transport and potential links to anxiety disorders. Understanding these correlations could provide insights into the biological and environmental factors influencing adolescent mental health.

Methods

Not reported in abstract.

Results

Not reported in abstract.

Interpretation

Not reported in abstract.

Limitations

  • Not reported in abstract.

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