Questioning oxytocin research

You may have heard of oxytocin as the “moral molecule” or the “hug hormone” or the “cuddle chemical”. Unleashed by hugs, available in a handy nasal spray, and possessed with the ability to boost trust, empathy and a laundry list of virtues, it is apparently the cure to all the world’s social ills. Except it’s not.” That was written by Ed Yong in July 2012. He was not the first of the last to question the hype.

And yet 6 months later we have io9 website with the headline, “10 Reasons Why Oxytocin Is The Most Amazing Molecule In The World”. And they are: it’s easy to get, a love potion that’s built right in, it helps Mom to be Mom, reduces social fears, healing and pain relief, a diet aid, an anti-depressant, stress relief, increases generosity, it’s what makes us human. It even helps autism! But “oxytocin increases in-group trust, it produces the opposite feeling for those in the out-group — so it’s not the “perfect drug” some might proclaim it to be.

But like right brained/left brained people it is a myth that just will not go away. The hype just continued with a number of clinics and authors making lots of money from it.

There is no doubt that oxytocin is a powerful hormone and does have some of these effects. But probably not all. Now it turns out that some, perhaps much, of the research is flawed. A new paper (citation below) looks at the tests used to measure oxytocin. They found much of the testing unreliable because of how samples were prepared. Christensen and others, looked at previously published results and found much variation in typical concentrations of oxytocin in human plasma including baseline levels.

There is considerable disagreement regarding typical levels for oxytocin. “we identified 47 publications … to demonstrate high variability in ‘‘normal’’ and expected oxytocin concentrations. Average concentrations within each publication ranged from 0.5 pg/mL to 3.6 ng/mL, with a mean of 169 pg/mL across all 47 studies. (note the big difference in units picagrams to nanograms) In analyzing the methods used in these publications, the largest apparent contributor to this variability, by far, was the use of pre-assay sample extraction. (to avoid components in the serum interfering in the test) Without any sort of extraction, 23 publications produced a mean concentration of 360.9 pg/mL (SD: 731.6), while extracted samples produced a mean of 10.4 pg/ mL (SD: 20.4) in the remaining 24 publications.” They also cautioned against using rodent data on behaviour in a human context, as rodent levels of oxytocin can be 2000 times those in humans – so there must be some differences in its physiology. They also question how much is known about the relationship between blood oxytocin and the amount in various regions of the brain. oxytocin

In their first experiment they used the two popular kits for measuring oxytocin on samples with and without extraction and with and without 10pg/ml of added oxytocin (to measure the percentage recovery in the test). The ELISA test had unacceptable variation without extraction and the RIA test could not recover the added oxytocin without extraction. They used the RIA test with extraction in the second experiment which was to test the effect of oxytocin on trust in the Prisoner’s Dilemma setting, with known partners and with strangers. Using these improved methods, they could not replicate the published effects.

This clearly demands re-investigations of the various effects attributed to oxytocin.

Here is the abstract: “Expanding interest in oxytocin, particularly the role of endogenous oxytocin in human social behavior, has created a pressing need for replication of results and verification of assay methods. In this study, we sought to replicate and extend previous results correlating plasma oxytocin with trust and trustworthy behavior. As a necessary first step, the two most commonly used commercial assays were compared in human plasma via the addition of a known quantity of exogenous oxytocin, with and without sample extraction. Plasma sample extraction was found to be critical in obtaining repeatable concentrations of oxytocin. In the subsequent trust experiment, twelve samples in duplicate, from each of 82 participants, were collected over approximately six hours during the performance of a Prisoner’s Dilemma task paradigm that stressed human interpersonal trust. We found no significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed with careful consideration of methods and appropriate biofluids for analysis.

Christensen, J., Shiyanov, P., Estepp, J., & Schlager, J. (2014). Lack of Association between Human Plasma Oxytocin and Interpersonal Trust in a Prisoner’s Dilemma Paradigm PLoS ONE, 9 (12) DOI: 10.1371/journal.pone.0116172

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