Significance The neuropeptide oxytocin (OXT) is critically involved in mammalian social functioning, and initial clinical research suggests that OXT biology may be altered in individuals with autism spectrum disorder (ASD). Here we provide important evidence that blood OXT concentrations are highly heritable within families, yet also strongly predict social functioning in ASD children, their unaffected siblings, and healthy control children. These findings also extend to OXT receptor genotypes which are significantly associated with differences in social functioning independent of disease status. These findings indicate that dysregulated OXT biology is not uniquely associated with ASD social phenotypes as widely theorized, but instead variation in OXT biology contributes to important individual differences in human social functioning, including the severe social impairments which characterize ASD.
Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.
Historically, electronic devices have been generally prohibited during hyperbaric oxygen (HBO2) therapy due to risk of fire in a pressurized, oxygen-rich environment. Point-of-care ultrasound (POCUS), however, has emerged as a useful imaging modality in diverse clinical settings. Hyperbaric chambers treating critically ill patients would benefit from the application of POCUS at pressure to make real-time patient assessments. Thus far, POCUS during HBO2 therapy has been limited due to required equipment modifications to meet safety standards. Here we demonstrate proof of concept, safety, and successful performance of an off-the-shelf handheld POCUS system (SonoSite iViz) in a clinical hyperbaric environment without need for modification.
