Table 5.

Studies Investigating Level of Oxytocin in Autism Spectrum Disorder

Oxytocin receptor modulation and autism spectrum disorder
Authors	Sample	study aims	Main findings
Al‐Ayadhi [2005]	Seventy‐seven children with ASD participated in the study, 71 males (92.2%) and 6 females (7.8%). Seventy‐seven healthy age and sex matched controls	To investigate plasma levels of oxytocin and vasopressin in children with ASD. Also, to correlate plasma levels of those neuropeptides to the degree of ASD and age of the affected child. Another aim was to explore the role of Pitocin induction in the genesis of ASD.	Oxytocin (OT) and vasopressin levels were also found to be lower in 77 boys with ASD from central Saudi Arabia compared to the boys without ASD. No significant correlation between the severity of ASD, or the age of the affected child and plasma levels of oxytocin or vasopressin was found. A greater incidence of Pitocin‐induced labor among the group with ASD compared to the controls.
Andari et al. [2010]	13 patients with HF‐ASD and 13 matched healthy participants.	To investigate the behavioral effects of oxytocin in 13 participants with ASD.	Study found marked decreased levels of oxytocin (OT) in 13 high functioning autism patients with ASD compared to controls.
Crespi and Hurd [2015]	Questionnaire data and DNA samples from Caucasian undergraduate psychology students (175 males and 309 females) at the University of Alberta and Simon Fraser University.	Study aimed to investigate associations of genetically based indicators of serum oxytocin, and serum testosterone, with measures of autism‐spectrum and schizophrenia‐spectrum cognition in healthy individuals.	Low genetic index of testosterone, a high genetic index of oxytocin (OT), and/or a low ratio of testosterone to OT indices were positively correlated with high imagination (as measured by the Autism Quotient) and high positive and total schizotypy (as measured by the Schizotypal Personality Questionnaire). In the Autism Spectrum Quotient, the Imagination subscale measures areas of social imagination which overlap with mentalistic cognitions such as theory of mind, which previous studies have identified as being association with levels of OT.
Green et al. [2001]	28 males (97 ± 20 months; range, 70–139 months), diagnosed with DSM‐IV autistic disorder through observation and semistructured interview. 31 age‐matched nonpsychiatric controls (106 ± 22 months; range, 74–140 months).	To investigate whether there were changes in OT peptide forms in children with ASD compared to children without ASD.	Findings support the role of OT in ASD. Findings revealed that plasma OT is reduced in children with ASD and also has abnormal associations with social abilities. There are numerous pathways for this association such as alterations in either the brain OT axis, the peptide receptors, and/or in peptide synthesis and processing.
Lakatosova et al. [2013]	8 children with ASD.	To investigate the potential correlations between both peripheral levels of oxytocin (OT) and testosterone with ASD symptomology.	Findings revealed a positive correlation between OT levels and the Adaptation to change category of The Childhood Autism Rating Scale™, Second Edition (CARS‐2) and maladapative behavior scores as measured on The Vineland Adaptive Behavior Scales, Second Edition (Vineland‐II). There were no significant correlations between levels of testosterone and behavioral parameters. Elevated levels of OT were associated with more severe scores of adaptive behavior in ASD patients. It appears that, in individuals with ASD, OT recruits a different mechanism to modulate social behavior compared to the general population.
Miller et al. [2013]	75 preadolescent and adolescent girls and boys ages 8–18: 40 with high‐functioning ASD (19 girls, 21 boys) and 35 typically developing children (16 girls, 19 boys).	To investigate: (1) plasma levels of oxytocin (OT) and arginine vasopressin (AVP) in TYP girls and boys and those with ASD (2) to relate these levels of OT and AVP to measures of social, language, repetitive behavior, & internalizing symptoms	Study did not find any differences between the levels of OT and vasopressin in their sample of 75 patients with ASD compared to age‐matched controls in a United States population. Higher OT values were associated with greater anxiety in all girls. Higher OT values were also found to be associated with better pragmatic language in both boys and girls. AVP levels were positively associated with restricted & repetitive behaviors in girls with ASD. AVP levels were negatively (non‐significantly) associated with these behaviors in boys with ASD.
Modahl et al. [1998]	29 children with ASD and 30 age‐matched typically developing children, all prepubertal.	To investigate whether children with ASD have abnormalities in OT compared to controls using radioimmunoassay for levels of OT.	Children with ASD were found to have plasma OT levels which were significantly lower compared to those in the typically developing group. Moreover, in the typically developing group, OT was found to increase with age, an increase which was not exhibited in the individuals with ASD. Higher scores on social and developmental measures were associated with elevated OT for the children without ASD. However, in the children with ASD, lower scores on social and developmental measures were associated with elevated OT. In the children with ASD who were identified as being ‘aloof’ this association was even more marked.
Taurines et al. [2014]	19 children and adolescents with ASD, all male (mean age 10.7, SD = 3.8 years compared to two other groups, 17 healthy male children (mean age 13.6, SD = 2.1 years) and 19 male children with attention deficit hyperactivity disorder (ADHD) (mean age 10.4, SD = 1.9 years).	To investigate the changes in concentration levels of peripheral OT (OT plasma concentrations) using a validated radioimmunoassay.	Findings revealed a correlation between OT plasma concentrations with number of ASD symptom (as measured using the Autism Diagnostic Observation Schedule) in children with ASD.
Weisman et al. [2015]	All singleton live births in Denmark between 2000 and 2009 (n = 557,040) with a follow‐up through 2012. In this cohort, 2,110 children were later diagnosed with ASD.	To investigate oxytocin‐augmented labor and risk for ASD.	Findings showed that augmentation of labor with oxytocin (OT) was only modestly associated with an increased risk for ASD in males only. In the group of males exposed to OT augmentation, 560 were later diagnosed with ASD (incidence rate 103.2 per 100,000 person‐years). In the males not exposed to OT augmentation, 1,177 fulfilled the criteria for an ASD (incidence rate 81.4 per 100,000 person‐years).

SD, standard deviation; M, mean; ASD, autism spectrum disorders; OT, oxytocin; HF‐ASD, high‐functioning autism spectrum disorder; DNA, deoxyribonucleic acid; DSM‐IV, diagnostic and statistical manual of mental disorders, 4th edition; CARS‐2, the childhood autism rating scale™, second edition; Vineland‐II, the vineland adaptive behavior scales, second edition; AVP, arginine vasopressin.