Limited associations between salivary cytokines and depressive symptoms in university students

Objectives

Low-grade inflammation is increasingly implicated in depression, with pro-inflammatory cytokines such as IL-6 and TNF-α linked to psychiatric symptoms. Although prior research has largely focused on peripheral blood markers, salivary cytokines provide a non-invasive and practical alternative for assessing inflammatory activity. University students constitute a high-risk group for stress-related mental health problems due to academic and social pressures, yet the relationship between salivary cytokines and psychological functioning in this population remains underexplored. This study investigates these associations, hypothesizing that elevated depressive symptoms are linked to distinct inflammatory profiles and poorer psychological functioning.

Methods

Koç University students were recruited via the SONA system and institutional email announcements. Following a 30-minute rest period, saliva samples were collected at 9:00 a.m. using Salivette tubes. Samples were centrifuged at 1500×g for 15 minutes at 4°C to remove cellular debris, kept on ice during processing, and stored at −80°C until analysis. Participants subsequently completed questionnaires via Qualtrics. Salivary cytokine profiles were measured using the BioLegend LEGENDplex Human Inflammation Panel 1 kit. Cytokines that were undetectable or yielded unreliable measurements were excluded. Data from participants who failed attention check items were also removed. After exclusions, 61 participants remained. Spearman’s rho was used for correlation analyses, and group differences were assessed with the Mann–Whitney U test. Participants with PHQ-9 scores ≥10 were classified as the depressive group.

Results

The participants, aged between 18-24, consisted of 48 female (78.7%), 12 male (19.8%), and 1 other (1.6%). No significant difference between the depressive group (n=33) and the non-depressive group (n=28) was detected for any cytokine level. Bivariate correlation analysis yielded mostly non-significant results between scale scores and cytokine levels (IL1-β, MCP-1, IL-8, IL-18, and IL-23) except for a small correlation between IL-6 and perceived stress scale (p=.017, r=.305). Significant differences were observed between the depressive and non-depressive groups across all scales except for social ladder for parents (p=.965) and social ladder for the self (p=.33). The depressive group reported higher anxiety (GAD-7: 11.06±4.49 vs. 4.86±3.30, p<.001), perceived stress (PSS: 32.12±6.20 vs. 24.25±7.16, p<.001), chronic stress (24.03±9.99 vs. 18.64±10.99), and semester stress level (71.33±25.63 vs. 62.96±19.92, p=.048), but lower resilience (53.33±16.64 vs. 63.61±12.63, p=.016) and success perception (65.30±18.93 vs. 77.93±14.76, p=.003).

Conclusions

Strong inter-scale correlations support the internal consistency and validity of self-reported measures, and group differences delineate a clear psychological profile of depression in university students. The observed IL-6–PSS association should be interpreted cautiously due to its small effect size and lack of significance after multiple comparisons, though it warrants further investigation. Limitations include single-time-point cytokine assessment, reliance on self-report measures rather than structured clinical interviews, and a modest sample size. Future studies with larger samples, repeated biological measures, and diagnostic interviews are needed to clarify the relationship between salivary cytokine profiles and mental health.

References

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