Opening the oxytocin file drawer, one lab at a time

Gidi Nave   March 20, 2016   1 Comment on Opening the oxytocin file drawer, one lab at a time

My first encounter with Moïra Mikolajczak was a couple of years ago. As I was writing a review on oxytocin and trust, I stumbled upon her work in Psychological Science. I was intrigued by her finding, that giving intranasal oxytocin to human subjects made them “trust” a computer more than it made them trust a human. This result contradicted a previous high profile publication claiming that oxytocin’s effects were specific to interactions between humans. I asked Moïra to share her data.

Apart from the data, Moïra also shared her recent adventures as a behavioral oxytocin researcher in humans. After what had probably been beginners’ luck, her lab could not replicate some of their initial findings. They had also failed to detect several of the effects expected from prominent behavioral oxytocin theories. She had just got back from a conference where she desperately tried to discuss her findings with several high-profile figures in the field. None were willing to share information about the amount of unpublished null findings in their labs.

The conversation with Moïra made me angry. Apart from socializing and drinking, the point of going to conferences is having researchers talk to each other about their work. True, in some cases scientists might have fears of getting scooped by others. But this is not the case for null results. Sharing your failures with other researchers is especially important: it can save them the time, money and frustration of chasing non-existing effects.

The chat with Moïra also made me hopeful. I was fortunate to meet an oxytocin researcher who was committed to finding the truth and understood the importance of transparent, collaborative scientific conduct. It sparked collaboration with Moïra and two of her colleagues in the university of Louvain, Anthony Lane and Olivier Luminet. Our project is published in this week’s special issue on oxytocin in the journal of Neuroendocrinology.

Moïra’s lab conducted quite a few oxytocin studies over the past decade. The experiments were methodologically similar to most other works in the field with respect to sample size and oxytocin administration procedures. But only one type of studies was publishable. Positive results were greeted with enthusiasm by editors and reviewers and found their homes in top journals. Negative (or “null”) results got rejected time after time and were sent to the file drawer.

In one case, a high impact journal published a suspiciously large behavioral effect of oxytocin found in a single blind study (i.e., the experimenter interacting with the subjects knew what the hypothesis was, and which subjects received oxytocin / placebo) conducted in Moïra’s lab. Her group failed to replicate their own findings twice, with larger samples and using a double blind protocol. The same exact journal rejected their (failed) replication paper.

Moïra saw a publication bias rapidly emerging in front of her own eyes and it became obvious that her publication profile no longer reflected what was really going on in the lab. She made a decision to clear her lab’s file drawer, and publish all of her lab’s studies in a single article. The numbers below summarize her lab’s behavioral oxytocin research.[1]

Oxytocin-drawer

Only a single task out of 25 produced a main effect of intranasal oxytocin: the task that failed to replicate twice (mentioned earlier). Five out of 25 experiments (20%) found significant interaction effects. It’s important to keep in mind that the probability of a type I errors is quite high when exploring interactions, unless the p-values are corrected for multiple hypothesis testing. None of the interaction effects survived such correction.

Our newly published paper summarizes the results obtained in Moïra’s lab in three meta-analyses that test the overall effects of intranasal oxytocin on (1) affective, (2) behavioral and (3) cognitive variables in isolation. Neither of these meta-analyses found a reliable effect. Finally, we meta-analyzed the studies based on their relation to three prominent theories: (1) oxytocin is an “affiliation” hormone; (2) oxytocin enhances saliency of social stimuli; (3) oxytocin facilitates approach behaviors. We could not reject the null hypothesis in either case.

To date, it is unclear how many unpublished oxytocin studies are lying in other labs’ file drawers. Keeping in mind that the average statistical power in behavioral oxytocin literature in humans is extremely low (12%-16%), that seminal works has failed to replicate, and given the uncertainty surrounding the physiological effects of intranasal oxytocin administration (and whether the substance gets to brain regions involved in cognition and behavior), I find it hard to believe that Moïra’s lab is an outlier. It is possible that hundreds (if not thousand) unpublished intranasal oxytocin studies are still lying in many labs’ file drawers.

Moïra’s lab has set exemplary standards of scientific transparency. I hope that other researchers will adhere to these standards and release their unpublished oxytocin data as soon as possible – and turn oxytocin research into a transparent scientific endeavor. This is crucial for estimating the true effects of oxytocin administration on various behavioral outcomes. Oxytocin has dramatic influences on social behaviors of animals, and despite all of the methodological difficulties some of the effects may reflect real phenomena. Opening the oxytocin file drawer will also save time, money and frustration for many oxytocin researchers.

[1] Some dependent variables were estimated using more than a single behavioral paradigm, and some studies included more than a single task – a practice that is common in many labs, which goal is maximizing the knowledge gained from each subject that is going through a pharmacological treatment.

 

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