Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates

Sci Transl Med. 2018 May 2;10(439):eaam9100. doi: 10.1126/scitranslmed.aam9100.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. These monkeys showed differences in specific neuropeptide and kinase signaling pathways compared to socially competent male monkeys. Using a discovery and replication design, we identified arginine vasopressin (AVP) in cerebrospinal fluid (CSF) as a key marker of group differences in monkey sociality; we replicated these findings in an independent monkey cohort. We also confirmed in an additional monkey cohort that AVP concentration in CSF is a stable trait-like measure. Next, we showed in a small pediatric cohort that CSF AVP concentrations were lower in male children with ASD compared to age-matched male children without ASD (but with other medical conditions). We demonstrated that CSF AVP concentration was sufficient to accurately distinguish ASD cases from medical controls. These data suggest that AVP and its signaling pathway warrant consideration in future research studies investigating new targets for diagnostics and drug development in ASD.

Publication types

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

MeSH terms

  • Animals
  • Arginine Vasopressin / cerebrospinal fluid*
  • Biomarkers / metabolism
  • Macaca mulatta / cerebrospinal fluid
  • Macaca mulatta / physiology
  • Male
  • Primates / cerebrospinal fluid*
  • Primates / physiology
  • Signal Transduction / physiology
  • Social Behavior

Substances

  • Biomarkers
  • Arginine Vasopressin