Examining Autism Spectrum Disorders by Biomarkers: Example From the Oxytocin and Serotonin Systems

Abstract

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. Method 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<0.05) and this relationship was most prominent in children under 11 years old. Paralleling human findings, mice lacking Oxtr showed increased whole blood 5-HT levels (p=0.05), with this effect driven exclusively by mice younger than 4 months of age (p< 0.01). 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 do parallel studies in animal and human populations within a developmental context is a plausible approach to probe the root causes of ASD and identify potential interventions.

The combined role of serotonin and interleukin-6 as biomarker for autism

“…Although some researchers regarded 5-HT (Hammock et al, 2012) and cytokines (Abdallah et al, 2013) as a potential biomarker for autism, only association analysis was used in most of studies. However, it is not sufficient to define the biomarker only by correlation analysis.…”

Association of temperament and social behavior with oxytocin levels among toddlers

“…It has been reported that children with autism showed lower plasma OT levels [10,11] than children without autism. Our findings are in line with these previous studies, as autistic traits include persistency.…”

“…Other studies have investigated the association between social behavior and circulating OT levels among children with autism spectrum disorders [10,11] or schizophrenia [12]. Further, several studies reported the effectiveness of intranasal application of OT to improve social behavior among autism spectrum disorders or schizophrenia, in which social behavior is a central role [13][14][15][16][17].…”

“…As social behavior is associated with OT or related genes [10,11,[18][19][20][21], it is reasonable to hypothesize that temperament might be associated with OT levels because of the robust association between temperament and behavior [22]. Thomas and Chess were aware of the nine dimensions of temperament, which include activity, regularity, initial reaction, adaptability, intensity, mood, distractibility, persistence, attention span and sensitivity, which they based their interviews with parents of infants on [23].…”

Integrin β3 Haploinsufficiency Modulates Serotonin Transport and Antidepressant-Sensitive Behavior in Mice

“…Human blood of ITGB3 genotyped subjects was collected under an approved institutional review board protocol (the University of Illinois at Chicago) (Hammock et al, 2012). All subjects provided informed consent for research studies.…”