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Oxytocin and the social facilitation of placebo effects

Molecular Psychiatry volume 27, pages 2640–2649 (2022)Cite this article

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Abstract

Significant clinical improvement is often observed in patients who receive placebo treatment in randomized double-blind placebo-controlled trials. While a proportion of this “improvement” reflects experimental design limitations (e.g., reliance on subjective outcomes, unbalanced groups, reporting biases), some of it reflects genuine improvement corroborated by physiological change. Converging evidence across diverse medical conditions suggests that clinically-relevant benefits from placebo treatment are associated with the activation of brain reward circuits. In parallel, evidence has accumulated showing that such benefits are facilitated by clinicians that demonstrate warmth and proficiency during interactions with patients. Here, we integrate research on these neural and social aspects of placebo effects with evidence linking oxytocin and social reward to advance a neurobiological account for the social facilitation of placebo effects. This account frames oxytocin as a key mediator of treatment success across a wide-spectrum of interventions that increase social connectedness, thereby providing a biological basis for assessing this fundamental non-specific element of medical care.

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Fig. 1: Oxytocinergic modulation of reward processing and the social facilitation of placebo effects.
Fig. 2: Blood oxytocin concentration predicts placebo effects on social functioning in individuals with autism.

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Notes

  1. More broadly, an individual’s overall level of “social connectedness” is an important predictor of well-being, morbidity, and mortality. Social connectedness can be measured by assessing structural, functional, and/or qualitative aspects of an individual’s relationships (e.g., the size of their social network, their access to social support, and affective valences), and is increased by forging new social connections of the kind described here [46, 47].

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Acknowledgements

We are grateful to Olena Zyga for her input on the clinical implications of social connectedness on an early draft of this manuscript. This work was supported by National Institute of Mental Health Grant K01MH122730 (DLB), a seed grant from the Wu Tsai Neuroscience Institute at Stanford University (DLB & KPJ), a Stanford School of Medicine Dean’s fellowship (EI), and the Stanford Department of Psychiatry (KJP).

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  1. These authors contributed equally: Elena Itskovich, Daniel L. Bowling.

Authors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Elena Itskovich, Daniel L. Bowling, Joseph P. Garner & Karen J. Parker

  2. Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Joseph P. Garner & Karen J. Parker

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  1. Elena Itskovich
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All authors contributed to the conceptualization, investigation, writing, review, and editing of this manuscript.

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Itskovich, E., Bowling, D.L., Garner, J.P. et al. Oxytocin and the social facilitation of placebo effects. Mol Psychiatry 27, 2640–2649 (2022). https://doi.org/10.1038/s41380-022-01515-9

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