Windows into Stress Biology: A Protocol Comparing Plasma, Saliva, and Oral Mucosal Transudate Biomarkers of Stress and Inflammation

Abstract

Background: As biopsychosocial research has moved toward non-invasive alternatives to venipuncture, questions remain: to what extent measurements of the same biomarker agree across biological matrices, and does that agreement hold at rest, under acute stress, and across analytes? Plasma reflects systemic circulating concentrations; whole saliva is shaped by autonomic activity and local oral biology; and oral mucosal transudate (OMT), a serum-derived filtrate, occupies a physiologically intermediate position. Each matrix may reflect a distinct signal, and differences may not be uniform across analytes or stress contexts. Methods: This protocol describes a within-subjects, single-session study enrolling 150 healthy adults. Following a rest period and baseline collection, participants complete the Trier Social Stress Test (TSST), after which biospecimens are collected a second time from plasma (venipuncture), saliva (Salivette and passive drool), and OMT (OraSure swab). IL-6, CRP, IL-1ra, sTNFαR2, cortisol, and uric acid are assayed across all three matrices, and alpha-amylase in saliva and OMT only. Participants complete self-report measures of affect, depressive symptoms, anxiety, perceived stress, sleep quality, and neuroticism. Concordance is evaluated via correlations, intraclass correlation coefficients, and Bland-Altman analyses, with psychosocial–biomarker associations compared across matrices. Discussion: Concordance is hypothesized to be strongest for cortisol, modest for inflammatory markers, and largely unknown for uric acid and alpha-amylase. Plasma increases are expected to be accompanied by proportional oral fluid changes, most reliably for cortisol, with psychosocial correlates broadly comparable across matrices. This is the first three-matrix comparison under resting and acute stress, informing responsible use of non-invasive collection in biopsychosocial research.

The authors' abstract, as published at the source. Psychosomatic Medicine, 2026 · DOI ↗