Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses
Aleksandrina Skvortsova1, Dieuwke S Veldhuijzen, Gustavo Pacheco-Lopez
1From the Health, Medical and Neuropsychology Unit (Skvortsova, Veldhuijzen, Pacheco-Lopez, van Middendorp, Evers), Faculty of Social and Behavioural Sciences, Leiden University; Leiden Institute for Brain and Cognition (Skvortsova, Veldhuijzen, Pacheco-Lopez, Bakermans-Kranenburg, Wilderjans, van Middendorp, Evers), Leiden, the Netherlands; Department of Health Sciences (Pacheco-Lopez), Metropolitan Autonomous University, Campus Lerma, Lerma, Edo. Mex., Mexico; Leiden Consortium on Individual Development (Bakermans-Kranenburg), Leiden University, Leiden; Department of Psychology, Education and Child Studies (van IJzendoorn), Erasmus University Rotterdam, Rotterdam, the Netherlands; Primary Care Unit (van IJzendoorn), School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Social, Health, and Organizational Psychology (Smeets), Utrecht University, Utrecht; Methodology and Statistics Research Unit (Wilderjans), Institute of Psychology, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Research Group of Quantitative Psychology and Individual Differences (Wilderjans), University of Leuven - KU Leuven, Leuven, Belgium; Department of Anaesthesiology (Dahan), Leiden University Medical Center, Leiden, the Netherlands; Health Psychology (van den Bergh), University of Leuven - KU Leuven, Leuven, Belgium; Departments of Public Health and Primary Care (Chavannes) and Psychiatry (van der Wee, Evers), Leiden University Medical Center, Leiden, the Netherlands; and Department of Psychiatry (Grewen), University of North Carolina, Charlotte, North Carolina.
Objective:
There is evidence that placebo effects may influence hormone secretion. However, few studies have examined placebo effects in the endocrine system, including oxytocin placebo effects. We studied whether it is possible to trigger oxytocin placebo effects using a classical conditioning paradigm.
Methods:
Ninety-nine women were assigned to a conditioned, control, or drug control group. In the two-phase conditioning paradigm, participants in the conditioned and drug control groups received an oxytocin nasal spray combined with a distinctive smell (conditioned stimulus [CS]) for three acquisition days, whereas the control group received placebo spray. Subsequently, the conditioned and control groups received placebo spray with the CS and the drug control group received oxytocin spray for three evocation days. Salivary oxytocin was measured several times during each day. Pain sensitivity and facial evaluation tests previously used in oxytocin research were also administered.
Results:
On evocation day 1, in the conditioned group, oxytocin significantly increased from baseline to 5 minutes after CS (B[slope] = 19.55, SE = 5.88, p < .001) and remained increased from 5 to 20 (B = -10.42, SE = 5.81, p = .071) and 50 minutes (B = -0.70, SE = 3.37, p = .84). On evocation day 2, a trend for increase in oxytocin was found at 5 minutes (B = 15.22, SE = 8.14, p = .062). No placebo effect was found on evocation day 3 (B = 3.57, SE = 3.26, p = .28). Neither exogenous nor conditioned oxytocin affected pain or facial tasks.
Conclusions:
Results indicate that oxytocin release can be conditioned and that this response extinguishes over time. Triggering hormonal release by placebo manipulation offers various clinical possibilities, such as enhancing effects of pharmacological treatments or reducing dosages of medications.
Trial Registration:
The study was registered as a clinical trial on www.trialregister.nl (number NTR5596).
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