Problems with measuring peripheral oxytocin: Can the data on oxytocin and human behavior be trusted?

Abstract

Research on the neurobiological and behavioral effects of oxytocin (OT), as well as on its possible therapeutic applications, has intensified in the past decade. Accurate determination of peripheral OT levels is essential to reach meaningful conclusions and to motivate, support and inform clinical interventions. Different, but concordant, methods for measuring plasma OT have been developed over the past four decades, but since 2004 several commercially available methods have been favored in research with humans. Evaluation of these methods reveals that they lack reliability when used on unextracted samples of human fluids, and that they tag molecules in addition to OT, yielding estimates that are wildly discrepant with an extensive body of earlier findings that were obtained using methods that are well validated, but more laborious. An accurate, specific, and readily available method for measuring OT that can be adopted as the standard in the field is urgently needed for advances in our understanding of OT's roles in cognition and behavior.

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Divergent findings like these, whose clarification is pivotal for advancement of behavioral and psychiatric neuroendocrinology, may partly result from methodological heterogeneity, which leads to an issue of particular concern. Reliability and validity of widely-used commercially available immunoassays to quantify peripheral OT concentrations have been put into question (McCullough et al, 2013). Across studies, the reported peripheral OT concentrations are highly variable depending on the applied methods, with values ranging from < 10 to over 1200 pg/ml (Brandtzaeg et al, 2016; McCullough et al, 2013).…”

“…Reliability and validity of widely-used commercially available immunoassays to quantify peripheral OT concentrations have been put into question (McCullough et al, 2013). Across studies, the reported peripheral OT concentrations are highly variable depending on the applied methods, with values ranging from < 10 to over 1200 pg/ml (Brandtzaeg et al, 2016; McCullough et al, 2013). Thus, there is an urgent need to standardize OT assay protocols to guarantee high-quality research, which is indispensable for obtaining meaningful results as well as reliability and comparability between studies.…”

Pilot study demonstrates that salivary oxytocin can be measured unobtrusively in preterm infants

“…On the other hand, other studies did detect oxytocin in the saliva of humans, including changes in that oxytocin after exposure to different behavioural paradigms 8, 9, 25. As stated in the introduction, these enzyme immunoassay‐based findings could be due to the cross‐reactivity of molecules other than oxytocin 12, but it is also possible that the detected molecules were indeed oxytocin from a central or even a local origin. The hypothalamus is not the only site that produces oxytocin molecules, as endothelial and epithelial cells at various other sites throughout the body have been reported to produce it 26.…”

“…Average collected saliva volumes in preterm infants are very small 10, and oxytocin may be broken down in saliva and thereby avoid detection by oxytocin‐specific antibodies used in commercially available enzyme immunoassays 11. Furthermore, the specificity of those antibodies allows detection of some other oxytocin‐like substances that can be misleading 12, especially when investigating the possibly very low concentrations of oxytocin in the saliva of preterm infants. We hypothesised that some of the barriers of measuring dynamic changes in oxytocin in the saliva of preterm infants could be overcome, by having a specialist laboratory perform a more sensitive radioimmunoassay 12 on the pooled saliva of multiple saliva collections before Kangaroo care and during Kangaroo care.…”

“…Furthermore, the specificity of those antibodies allows detection of some other oxytocin‐like substances that can be misleading 12, especially when investigating the possibly very low concentrations of oxytocin in the saliva of preterm infants. We hypothesised that some of the barriers of measuring dynamic changes in oxytocin in the saliva of preterm infants could be overcome, by having a specialist laboratory perform a more sensitive radioimmunoassay 12 on the pooled saliva of multiple saliva collections before Kangaroo care and during Kangaroo care. We conducted a pilot study to investigate the feasibility and obtrusiveness of doing this.…”