Examining autism spectrum disorders by biomarkers: example from the oxytocin and serotonin systems.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA.
Elizabeth
E
Hammock
Jeremy
J
Veenstra-VanderWeele
Zhongyu
Z
Yan
Travis M
TM
Kerr
Marianna
M
Morris
George M
GM
Anderson
C Sue
CS
Carter
Edwin H
EH
Cook
Suma
S
Jacob
D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D016011:Normal Distribution; D010121:Oxytocin / Q000097:blood*; D018045:Receptors, Oxytocin / Q000235:genetics; D012701:Serotonin / Q000097:blood*
D015415:Biomarkers; C576074:OXTR protein, mouse; D018045:Receptors, Oxytocin; D012701:Serotonin; D010121:Oxytocin