"Less is more": a dose-response account of intranasal oxytocin pharmacodynamics in the human brain

Daniel Martins; Katja Brodmann; Mattia Veronese; Ottavia Dipasquale; Ndaba Mazibuko; Uwe Schuschnig; Fernando Zelaya; Aikaterini Fotopoulou; Yannis Paloyelis

doi:10.1016/j.pneurobio.2022.102239

"Less is more": a dose-response account of intranasal oxytocin pharmacodynamics in the human brain

Daniel Martins, Katja Brodmann, Mattia Veronese, Ottavia Dipasquale, Ndaba Mazibuko, Uwe Schuschnig, Fernando Zelaya, Aikaterini Fotopoulou, Yannis Paloyelis

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20 Citations (Scopus)

Abstract

Intranasal oxytocin is attracting attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU), we demonstrate that intranasal oxytocin-induced changes in local regional cerebral blood flow (rCBF) in the amygdala at rest, and in the covariance between rCBF in the amygdala and other key hubs of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects on local rCBF might vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity, which corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain. DATA AVAILABILITY: Participants did not consent for open sharing of the data. Therefore, data can only be accessed from the corresponding author upon reasonable request.

Original language	English
Article number	102239
Journal	Progress in Neurobiology
Volume	211
Early online date	2 Feb 2022
DOIs	https://doi.org/10.1016/j.pneurobio.2022.102239
Publication status	Published - Apr 2022

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10.1016/j.pneurobio.2022.102239Licence: CC BY

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title = "{"}Less is more{"}: a dose-response account of intranasal oxytocin pharmacodynamics in the human brain",

abstract = "Intranasal oxytocin is attracting attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU), we demonstrate that intranasal oxytocin-induced changes in local regional cerebral blood flow (rCBF) in the amygdala at rest, and in the covariance between rCBF in the amygdala and other key hubs of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects on local rCBF might vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity, which corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain. DATA AVAILABILITY: Participants did not consent for open sharing of the data. Therefore, data can only be accessed from the corresponding author upon reasonable request.",

author = "Daniel Martins and Katja Brodmann and Mattia Veronese and Ottavia Dipasquale and Ndaba Mazibuko and Uwe Schuschnig and Fernando Zelaya and Aikaterini Fotopoulou and Yannis Paloyelis",

note = "Funding Information: We would like to thank all volunteers contributing data to this study. This study was part-funded by: an Economic and Social Research Council Grant ( ES/K009400/1 ) to YP; scanning time support by the National Institute for Health Research ( NIHR ) Biomedical Research Center at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London to YP; an unrestricted research grant by PARI GmbH to YP. Funding Information: We would like to thank all volunteers contributing data to this study. This study was part-funded by: an Economic and Social Research Council Grant (ES/K009400/1) to YP; scanning time support by the National Institute for Health Research (NIHR) Biomedical Research Center at South London and Maudsley NHS Foundation Trust and King's College London to YP; an unrestricted research grant by PARI GmbH to YP. Publisher Copyright: {\textcopyright} 2022 The Authors",

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doi = "10.1016/j.pneurobio.2022.102239",

language = "English",

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AU - Dipasquale, Ottavia

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AU - Schuschnig, Uwe

AU - Zelaya, Fernando

AU - Fotopoulou, Aikaterini

AU - Paloyelis, Yannis

N1 - Funding Information: We would like to thank all volunteers contributing data to this study. This study was part-funded by: an Economic and Social Research Council Grant ( ES/K009400/1 ) to YP; scanning time support by the National Institute for Health Research ( NIHR ) Biomedical Research Center at South London and Maudsley NHS Foundation Trust and King’s College London to YP; an unrestricted research grant by PARI GmbH to YP. Funding Information: We would like to thank all volunteers contributing data to this study. This study was part-funded by: an Economic and Social Research Council Grant (ES/K009400/1) to YP; scanning time support by the National Institute for Health Research (NIHR) Biomedical Research Center at South London and Maudsley NHS Foundation Trust and King's College London to YP; an unrestricted research grant by PARI GmbH to YP. Publisher Copyright: © 2022 The Authors

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JO - Progress in Neurobiology

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"Less is more": a dose-response account of intranasal oxytocin pharmacodynamics in the human brain

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