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.

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

“…Some studies in pregnant women [51], adult suicide attempters [52], and adult patients undergoing surgical procedures [53] have indicated a lack of correlation between OXT concentrations in plasma and cerebrospinal fluid (CSF). However, a recent study on children and adult patients have reported a positive correlation of OXT levels between the two compartments and this relationship is stronger when only children are included in the analysis [54]. Also in studies with children, higher peripheral OXT levels have been shown to correspond with greater interaction skills in normal individuals [20].…”

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

“…Treatment effect generalizability was evaluated using (i) the RBS-R (44), which measures a comprehensive list of repetitive and stereotyped behaviors, and (ii) The Spence Children's Anxiety Scale (45), which assesses the severity of trait anxiety symptoms broadly in line with DSM dimensions of anxiety disorder. Anxiety was selected as an outcome measure because of its significant comorbidity with ASD (46), its negative relationship with endogenous OXT concentrations in humans (47), and OXT's anxiolytic effects in mice (48). Drug safety and tolerability were evaluated using (i) the DOTES, a rating scale that assesses the presence, frequency, and severity of side effects (38), and (ii) change from baseline in vital signs (i.e., blood pressure, heart rate, temperature) and in height and weight.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Moreover, most human studies rely on plasma OT concentrations for the prediction of behavioral phenotypes, assuming that these peripherally derived measures reflect central OT concentrations. This basic premise has been challenged by studies showing that there is no correlation between plasma and CSF OT concentrations (Altemus et al, 2004; Kagerbauer et al, 2013), but confirmed by others, which found significant between-compartment correlations (Carson et al, 2015). Divergent findings like these, whose clarification is pivotal for advancement of behavioral and psychiatric neuroendocrinology, may partly result from methodological heterogeneity, which leads to an issue of particular concern.…”