title: Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.
abstract: Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Dean S
authors.initials: DS
authors.lastname: Carson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America; Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Garner
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Shellie A
authors.initials: SA
authors.lastname: Hyde
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Libove
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Berquist
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Hornbeak
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jackson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Raena D
authors.initials: RD
authors.lastname: Sumiyoshi
authors.affiliation: Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Howerton
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Oncology, SCT and Cancer Biology, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Sadie L
authors.initials: SL
authors.lastname: Hannah
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Sonia
authors.initials: S
authors.lastname: Partap
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Phillips
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Antonio Y
authors.initials: AY
authors.lastname: Hardan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, 94305, United States of America.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Parker
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000097:blood* / Q000134:cerebrospinal fluid / Q000523:psychology*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009481:Neurophysins / Q000097:blood* / Q000134:cerebrospinal fluid*; D011498:Protein Precursors / Q000097:blood* / Q000134:cerebrospinal fluid*; D035781:Siblings / Q000523:psychology; D012919:Social Behavior; D014667:Vasopressins / Q000097:blood* / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: C438657:AVP protein, human; D015415:Biomarkers; D009481:Neurophysins; D011498:Protein Precursors; D014667:Vasopressins