Autism spectrum disorder (ASD) is a heritable but highly heterogeneous neuropsychiatric syndrome, which poses challenges for research relying solely on behavioral symptoms or diagnosis. Examining biomarkers may give us ways to identify individuals who demonstrate specific developmental trajectories and etiological factors related to ASD. Plasma oxytocin (OT) and whole-blood serotonin (5-HT) levels are consistently altered in some individuals with ASD. Reciprocal relationships have been described between brain oxytocin and serotonin systems during development. We therefore investigated the relationship between these peripheral biomarkers as well as their relationships with age. In our first study, we analyzed correlations between these two biomarkers in 31 children and adolescents who were diagnosed with autism and were not on medications. In our second study, we explored whether whole-blood 5-HT levels are altered in mice lacking the oxytocin receptor gene Oxtr. In humans, OT and 5-HT were negatively correlated with each other (p < .05) and this relationship was most prominent in children less than 11 years old. Paralleling human findings, mice lacking Oxtr showed increased whole-blood 5-HT levels (p = .05), with this effect driven exclusively by mice less than 4 months old (p < .01). Identifying relationships between identified ASD biomarkers may be a useful approach to connect otherwise disparate findings that span multiple systems in this heterogeneous disorder. Using neurochemical biomarkers to perform parallel studies in animal and human populations within a developmental context is a plausible approach to probe the root causes of ASD and to identify potential interventions.
|Original language||English (US)|
|Journal||Journal of the American Academy of Child and Adolescent Psychiatry|
|State||Published - Jul 2012|
Bibliographical noteFunding Information:
This work was supported in part by a Vanderbilt Luton Society Research Award (J.V., E.H.), a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (E.H.), a National Institutes of Health (NIH) grant K08MH081066 (J.V.), the National Institute of Child Health and Human Development (NICHD) grant P30HD15052 to the Vanderbilt Kennedy Center for Research on Human Development (E.H., J.V.), NIH Autism Center of Excellence grants P50 HD055751 (E.H.C.), and K23MH082121 (S.J.).
Disclosure: Dr. Veenstra-VanderWeele has received funding from Seaside Therapeutics, Novartis, and Roche Pharmaceuticals, and has served as a consultant for Novartis. Dr. Cook has served as a consultant for and has received funding from Seaside Therapeutics. Drs. Hammock, Yan, Morris, Anderson, Carter, and Jacob, and Mr. Kerr report no biomedical financial interests or potential conflicts of interest.