Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder

Proc Natl Acad Sci U S A. 2020 May 12;117(19):10609-10613. doi: 10.1073/pnas.1919050117. Epub 2020 Apr 27.

Abstract

Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers 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-old 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 marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.

Keywords: autism; cerebrospinal fluid; oxytocin; social; vasopressin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine Vasopressin / analysis
  • Arginine Vasopressin / cerebrospinal fluid
  • Autism Spectrum Disorder / cerebrospinal fluid
  • Autism Spectrum Disorder / diagnosis*
  • Autistic Disorder / cerebrospinal fluid
  • Autistic Disorder / diagnosis*
  • Biomarkers / cerebrospinal fluid
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Medical Records
  • Neuropeptides
  • Neurophysins / analysis
  • Neurophysins / cerebrospinal fluid
  • Oxytocin
  • Prospective Studies
  • Protein Precursors / analysis
  • Protein Precursors / cerebrospinal fluid
  • Social Behavior
  • Vasopressins / analysis*
  • Vasopressins / cerebrospinal fluid

Substances

  • AVP protein, human
  • Biomarkers
  • Neuropeptides
  • Neurophysins
  • Protein Precursors
  • Vasopressins
  • Arginine Vasopressin
  • Oxytocin