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Plasma Vasopressin Concentrations Predict CSF Vasopressin Concentrations in Human Neonates and Are Associated with Social Functioning in Children with Autism
Objectives: The study objectives were two-fold: 1) to test whether plasma AVP concentrations predicted CSF AVP concentrations in human neonates; and, 2) to test whether plasma AVP concentrations predicted social functioning in a large cohort of children with autism, their unaffected siblings, and neurotypical controls.
Methods: Experiment 1: Participants were seventeen human neonates undergoing clinically indicated sepsis evaluation for standard risk factors. Within 72 h of birth, and at the time of clinically indicated lumbar puncture, CSF was collected using standard sterile procedures and whole blood was drawn into chilled, EDTA-treated vacutainer tubes. AVP concentrations were quantified in CSF and plasma using a commercially available enzyme immunoassay kit (Enzo Life Sciences, Inc., Farmingdale, NY). Experiment 2: Participants were seventy-nine children with autism, 52 unaffected siblings, and 62 neurotypical control children between the ages of 3 to 12 years. Autism diagnosis was based on the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview Revised, and expert clinical opinion. Social phenotyping was conducted using the NEPSY-II Social and Perception Domain. Blood was collected from all participants and plasma samples were quantified using the AVP enzyme immunoassay.
Results: Experiment 1: Plasma AVP concentrations significantly and positively predicted CSF AVP concentrations in human neonates (p<0.01). Experiment 2: Plasma AVP levels did not differ by group or gender. An interaction effect was noted whereby plasma AVP concentrations significantly and positively predicted Theory of Mind in autistic children but not in non-autistic children (p=0.023).
Conclusions: These findings suggest that measurement of AVP in plasma samples might be a valid tool for inferential assessment of brain AVP activity, at least in pediatric populations. Further, our findings suggest that impairments in AVP signaling may be a biomarker of social impairments in children with autism, and that AVP biology may be a promising therapeutic target for enhancing social functioning in children with autism.