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Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children

Abstract

The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=−0.92, P=0.0262, N=10) and CSF (r=−0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.

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Acknowledgements

We are grateful to the members of the Parker and Hardan laboratories, the nurses and doctors at Stanford Hospital & Clinics and Lucile Packard Children's Hospital, and, of course, the patients and their families for participating in this study. This research was supported by an Autism Speaks Meixner Postdoctoral Fellowship in Translational Research (7895; DSC), a Stanford University School of Medicine Dean’s Postdoctoral Fellowship (DSC), the Katherine D. McCormick Fund (KJP), the Mosbacher Family Fund for Autism Research (KJP), Stanford’s Bio-X NeuroVentures Program (KJP), the Weston Havens Foundation (KJP) and by an NIH/NCRR grant to the Stanford Center for Clinical Informatics (UL1 RR025744).

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Correspondence to D S Carson or K J Parker.

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Carson, D., Berquist, S., Trujillo, T. et al. Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children. Mol Psychiatry 20, 1085–1090 (2015). https://doi.org/10.1038/mp.2014.132

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