Are single peripheral measurements of baseline oxytocin in saliva and plasma reliable biomarkers of the physiology of the oxytocin system in humans?

BackgroundSingle measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid biomarkers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations. MethodsUsing radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. Dataset A comprised 17 healthy men sampled on four occasions approximately at weekly intervals. We administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo-controlled design and compared baseline levels and the effects of routes of administration. Dataset B comprised baseline plasmatic oxytocin measurements from 20 healthy men sampled on two separate occasions. Additionally, in dataset A, we tested whether salivary oxytocin can predict plasmatic oxytocin at baseline and after intranasal and intravenous oxytocin administration. ResultsSingle measurements of plasmatic and salivary oxytocin showed poor reliability across visits in both datasets. Intranasal administration of exogenous oxytocin increases salivary oxytocin, but intravenous administration of a considerable dose does not produce any changes. Saliva and plasma oxytocin did not correlate at baseline or after administration of exogenous oxytocin. ConclusionsOur findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid biomarkers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects.