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Association between salivary oxytocin levels and the amygdala and hippocampal volumes

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Salivary oxytocin levels have been widely measured and studied in relation to social behavior because of procedural simplicity and noninvasiveness. Although the relationship between oxytocin levels in the blood and the hippocampus and amygdala is now becoming clear with reliable blood oxytocin studies, few studies have examined the relationship between salivary oxytocin and the brain function and structure. This study aimed to investigate whether the salivary oxytocin level is associated with the volume of the amygdala and hippocampus in 178 adults (92 women and 86 men) in their third to seventh decade of life. We performed volumetric analysis of the amygdala and hippocampus using FreeSurfer and measured salivary oxytocin levels using enzyme-linked immunosorbent assay. The results showed contradictory effects of the salivary oxytocin level on the amygdala volume by sex and no significant effect on the hippocampal volume. Specifically, men showed a positive correlation between the salivary oxytocin level and amygdala volume, whereas women showed a negative correlation between the salivary oxytocin level and amygdala volume. The present study’s finding of sex differences in the association between salivary oxytocin and brain structure supports previous findings that there are sex differences in the oxytocin system.

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We thank Yoshie Matsumoto, Yang Li, Toko Kiyonari and Atsushi Miyazaki for their help with conducting the study and Takefumi Kikusui for his help with measuring salivary oxytocin levels.


This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number, JP19H04915. This research was supported by AMED under Grant Number JP18dm0307001.

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QS, JY, TM, and HT designed the research; KN and HT collected the data; QS and HT analyzed the data; QS, KN, MM, and HT conducted hormone analysis; and QS and HT drafted the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Haruto Takagishi.

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The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

All experimental protocols in this research project were approved by the Ethics Committee of Tamagawa University (approval no. TRE18-036). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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All participants provided written informed consent prior to the experiment.

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Shou, Q., Yamada, J., Nishina, K. et al. Association between salivary oxytocin levels and the amygdala and hippocampal volumes. Brain Struct Funct 227, 2503–2511 (2022).

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