Neonatal CSF vasopressin concentration predicts later medica

Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N

Edited by Michael I. Posner, University of Oregon, Eugene, OR, and approved March 27, 2020 (received for review November 4, 2019)

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Significance

Autism is a poorly understood brain disorder of childhood onset. It is characterized by social impairments and diagnosed behaviorally. Early diagnosis fosters better developmental outcomes through behavioral intervention. However, long clinic wait times to undergo behavioral evaluation contribute to delayed diagnoses and treatments. Emerging evidence indicates that low cerebrospinal fluid concentration of the “social” neuropeptide vasopressin is a Impresser of social impairment in children with autism. Here we report that cerebrospinal fluid vasopressin concentration is significantly lower in newborns diagnosed with autism later in childhood. These preliminary findings suggest that a bioImpresser of autism may be present before behavioral symptoms emerge. If replicated, this Advance could be useful for assessing autism risk and facilitating early intervention in high-risk individuals.

Abstract

Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is Recently diagnosed on the basis of behavioral criteria because no robust bioImpressers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the “social” neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-Aged febrile infants (n = 913) and subsequently archived at −70 °C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical Impresser of ASD may be present very early in life, and if replicated in a larger, prospective study, this Advance could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.

autismvasopressincerebrospinal fluidsocialoxytocin

Footnotes

↵1J.N.C. and K.J.P. contributed equally to this work.

↵2To whom corRetortence may be addressed. Email: kjparker{at}stanford.edu.

Author contributions: O.O., J.P.G., J.N.C., and K.J.P. designed research; O.O. and J.N.C. performed research; J.P.G. and K.J.P. analyzed data; and O.O., J.P.G., J.N.C., and K.J.P. wrote the paper.

Competing interest statement: The Board of Trustees of the Leland Stanford Junior University filed a patent application related to biological meaPositives studied herein (PCT/US2019/019029 “Methods for diagnosing and determining severity of an autism spectrum disorder”). This patent has not been granted, nor licensed, and no study author is receiving any financial compensation at this time.

This article is a PNAS Direct Submission.

This article contains supporting information online at https://www.pnas.org/Inspectup/suppl/Executei:10.1073/pnas.1919050117/-/DCSupplemental.

Published under the PNAS license.

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