Does oxytocin increase trust in humans? Frequently asked questions

In a newly published paper, Colin CamererMichael McCullough and yours truly have reviewed the literature linking the neuropeptide Oxytocin with trust in humans.

As I often find myself in conversations about oxytocin –  in conferences, cocktail parties or flights – I’ve collected several frequently asked questions in this post. I will try to update it regularly, please feel free to post new questions (and alternative answers) of your own.

 Q: Is there an association between Oxytocin and trust in humans?

A: According to the scientific literature (as for late 2015), there is no strong evidence in favor this hypothesis. It doesn’t seem like spraying oxytocin onto one’s nose makes him or her more trusting, and there is no robust link between trust and either blood levels of oxytocin or oxytocin-related genetic variable. The absence of evidence, however, is not necessarily evidence of absence – it is possible that there are real effects that are too small to be detected by the current research methods, or that the effects depend on various unknown factors, such as gender, environment or other demographic variables.

Q: What about other findings linking oxytocin with things like romantic love, parenting or cooperation?

A: The oxytocin-trust studies are the seminal works that inspired most of oxytocin behavioral research and are among the few studies that underwent direct replication attempts by independent research groups. The failure to replicate these results, to my view, reduces the likelihood that other behavioral oxytocin findings (most of which never underwent replication attempts) reflect the true state of the world. It is possible that real discoveries are out there – but at the absence of independent replication attempts it is hard to say which ones. Also note that a recent meta-analysis concluded that most oxytocin studies are underpowered, and therefore the estimated false discovery rate is very high – around 80 (!!) percent. Moreover, promising well-cited results relating oxytocin to “mind reading” also do not seem as robust as one might hope.

Q: I would like to study the effects of oxytocin on behavior and got discouraged. What should I do?

There’s an urge for direct replications of previously published findings. My personal opinion is that this is a low-hanging fruit, given the interest of many fields (and the popular media) in the potential effects of oxytocin on social behavior (that are supported by animal research). Here is what you should do:

  1. Pick an oxytocin paper with an interesting result, preferably highly cited and from a top journal (Science, Nature, PNAS, Psychological Science).
  2. Conduct power analysis (you can use this calculator) based on the effect size of the original study. A standard power is 0.8, but the larger you go the better (even true effects are often over-estimated in the literature).
  3. Contact the authors of the original study and ask their collaboration. Ask them to provide all experimental materials, in order to make sure that your replication is as similar as possible to the original study. Don’t give up if they are non-cooperative, and remember to mention their levels of cooperation in your final paper, for good or bad.
  4. Submit a registered replication report or pre-register your study.
  5. Conduct your experiment.
  6. Write down a short paper and publish it (regardless of your result) as a short commentary / research report. You can also upload your data to databases such as psychology file drawer. Beware that not getting a p-value which is smaller than 0.05 does not necessarily mean a failure to replicate. I recommend using the “small telescope” approach in order to test such conclusion.
  7. Go back to step 1.

 Q: Does oxytocin reach the brain following intranasal administration?

We are not sure. Even though intranasal oxytocin has been around for quite some time, there is no consensus among researchers. My personal belief is that some molecules of oxytocin do cross the blood brain barrier after intranasal administration, but (and that’s an big but) we don’t know for sure if, how and when they reach target brain areas that plausibly control behavior and cognition. The current oxytocin literature relied on a single study from 2002 (hasn’t been replicated yet) with intranasal Arginine Vasopressin administration (a similar, but not identical molecule), and an equivalent study in oxytocin that was recently conducted (using a tiny sample size) did not find elevated levels of oxytocin in the cerebral and spinal fluid 45 minutes after administration (which is the time between administration and the behavioral task in most oxytocin studies).

 Q: How have we come to so strongly believe that oxytocin = trust?

The seminal oxytocin-trust papers used novel behavioral paradigms and were published in high profile journals. The papers are beautifully narrated and tell a surprising, yet simple and coherent story, which is based on animal research and gained them a lot of popular media attention. Media coverage included very strong claims of scientists about the link between oxytocin and trust  without mentioning that the results were preliminary or any other caveats. I’ll discuss more about this topic in future posts.

Q: How should one measure peripheral Oxytocin? 

For blood plasma, you can use RIA or ELISA – but make sure you conduct extraction as recommended in the kit’s manual. Remember to report in detail which method you have used: although their outputs correlate – it is not identical. Some scholars have used oxytocin measurements from urine or saliva, but there several researchers have raised  concerns regarding the bio-analytical validity of these measures (example 1example 2).

IMPORTANT: correlating biological measures with behaviors that are allegedly influenced by oxytocin, genetic variables or other invalid oxytocin measures (such as unextracted plasma oxytocin) DO NOT count as a bio-analytical validation.

 Q: I have an a-priori hypothesis about a specific environmental factor that might interact with oxytocin to influence target behavior. What should I do?

Pre-register your hypothesis here and run your study. Make sure you are well powered statistically, and report your result whether you found an effect or not.

 Q: How can I explore the interaction between oxytocin, environment, personality and behavior without inflating the rate of false discoveries?

Be careful. Using conventional hypothesis tests that are designed to test a single hypothesis, and then reporting only the “positive” results at the standard p-value of 0.05, will dramatically inflate the false discovery rate. Here is one possible approach for exploration without inflating the false-positive rates:

  1. Write down all of the environmental and personality factors that you would like to explore. Let’s call them E and P.
  2. Calculate N = (E+1) x (P+1): this is the number of hypotheses you are testing.
  3. Adjust your designated p-value using correction for multiple hypotheses testing, such as Bonferonni correction. Denote the new p-value by q.
  4. Conduct power analysis (you can use this calculator) based on the effect size you expect to find, and q (two-sided). A sample size that allows a power of 0.8 is standard, but the larger the better (effect sizes are often over-estimated) – go as large as you can.
  5. Run your study. Report your finding as “positive” only if your p-value is less than q. Publish your data with the necessary caveats otherwise.
  6. If you believe that some patterns in the data are worth further exploration – pre-register them as new a-priori hypotheses, and try to replicate these patterns in an independent sample of participants.

 

 

7 thoughts on “Does oxytocin increase trust in humans? Frequently asked questions

  1. sashibot

    My understanding is oxytocin is released after child birth and activated by breast feeding and helps to contract the uterus to stop bleeding. Is this context ever taken into account when designing studies, or am I misunderstanding it?

    Also, is it released in women during sex, right? Why would it not be related to bonding as opposed to trust? Like it’s not like you are trusting your baby, but bonding with it so you don’t abandon it. Is that what is thought to be going on?

    I am possibly way off, but who knows. Sometimes errant comments can help something fall into place. Again, 󾌵 great work, Gidi!

    Reply
    1. Gidi Nave Post author

      Great questions Sashi.

      Most of the oxytocin human studies were designed based on what is known already, from previous findings in humans and animals.

      There are also studies associating oxytocin with bonding, parenthood, etc. – basically almost every type of social behavior you can think of — from aggression and racism to romantic love and cooperation — has been “linked” to oxytocin by people who ran an experiment.

      The problem is that none of the findings seem to be robust. Scientists publish only positive findings and not negative ones, and I cannot think of a single study in the vast human oxytocin literature that was replicated by an independent research group.

      As long as this is the state of the literature, all of the literature should be regarded with a (very) healthy dose of skepticism.

      Reply
  2. yonatan

    Gidon,
    We learned about oxytocin this week, so it’s nice to see
    how it is related to your work : )
    GOOD LUCK and keep enjoying life !

    Reply
  3. Michelle

    Hi Gidi, thanks for this post (I will share it with my students). Regarding the Striepens et al. (2013) report, with elevated oxytocin in cerebrospinal fluid appearing much later than 45 minutes after nasal spray application: One point I would make is that the spinal fluid was probably collected with spinal tap at the base of the spinal cord, so it is not surprising that there was a long delay in the oxytocin (presumably entering near the 3rd ventricle) getting all the way down there. I think it takes 1-2 hours for cerebrospinal fluid to fully circulate through the brain’s ventricles and down the spinal canal. That said, I agree with you that we can’t be sure if meaningful amounts of oxytocin are reaching key brain areas (cerebral cortex, etc.) from the nasal spray.

    Reply
    1. Gidi Nave Post author

      Thanks Michele, great comment.
      With respect to the Striepens et al. (2013) report — it is also important to keep in mind that it is using a sample size of 4 people, with a control group of one subject.

      Drawing statistical conclusions from such a small sample using tools like ANOVA is quite problematic.

      NeuroSkeptic had a great post on it a couple of years ago:

      http://blogs.discovermagazine.com/neuroskeptic/2013/12/08/spinal-taps-save-oxytocin-research/

      Reply
  4. Konstantin

    Fascinating how whole strands of literature run in one direction and then most of it turns out to be false positives…

    Reply
  5. Pingback: Testing the null hypothesis of oxytocin’s effects in humans | Surface Your Real Self

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