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Plasma Vasopressin Concentrations Predict CSF Vasopressin Concentrations in Human Neonates and Are Associated with Social Functioning in Children with Autism

Friday, May 16, 2014
Atrium Ballroom (Marriott Marquis Atlanta)
D. S. Carson1, C. L. Howerton2, J. P. Garner2, R. A. Libove1, S. A. Hyde1, J. M. Phillips1, A. A. Penn3, A. Y. Hardan1 and K. J. Parker1, (1)Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, (2)Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, (3)Departments of Fetal and Transitional Medicine, Neonatology, and the Center for Neuroscience Research, Children’s National Medical Center, Washington, DC
Background:  The neuropeptide arginine vasopressin (AVP) has been linked to a variety of physiological processes, and more recently, to complex psychological processes including human social cognition. Several studies have outlined the potential for utilizing plasma AVP concentrations as a biomarker of disease status in neuropsychiatric disorders, including autism. Plasma AVP concentrations as a biomarker of social functioning are most meaningful if they are associated with brain AVP activity. The relationship between central and peripheral nervous system AVP activity, however, is not well understood. Given the growing interest in the role of AVP in neurodevelopmental disorders, there is an urgent need to clarify the relationship between cerebrospinal fluid (CSF) and plasma AVP concentrations in young children and test whether AVP is a biomarker of social functioning in children with and without 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.