Is Being Female Protective Against Autism Spectrum Disorders? Oxytocin and Vasopressin Levels In Children and Adolescents

Background: Male predominance of autism spectrum disorders (ASD) is estimated at 4 to 1. One theory for this higher male prevalence is that the female neuroendocrine system confers “protection” against autistic traits (Carter, 2007). According to this view, processes mediated by oxytocin (OT), and the lack of reliance on arginine vasopressin (AVP), make being female protective against autistic-like behavior. No previous studies have investigated sex differences in blood plasma OT and AVP levels in individuals with ASD.

Objectives: Primary aims included examining blood plasma levels of OT and AVP in girls and boys with ASD and typical development, and relating OT and AVP levels to autism and internalizing symptom measures. We hypothesized that: (1) neuropeptide levels would be significantly higher in typically developing individuals and would increase with age; (2) higher OT levels would be related to less social and repetitive behavior pathology and lower anxiety and depression; and (3) higher AVP levels would show the inverse of relationships in (2).

Methods: Plasma OT and AVP levels and standardized measures of autism and internalizing symptoms were obtained from 72 children ages 8-18: 39 with high-functioning ASD (18 girls, 21 boys) and 33 typically developing children (15 girls, 18 boys). OT and AVP levels were log-transformed and modeled as a function of time of blood draw, age, gender, and diagnosis. Spearman’s Rho was used to assess correlations between OT and VP levels and symptom measures.

Results: There were significant main effects of gender on OT levels (p = .04; girls higher, Cohen’s d = .47) and time of blood draw on AVP levels (p = .01), and marginally significant effects of diagnosis on OT (p = .09; ASD higher, Cohen’s d = .43) and gender on AVP (p = .08; boys higher, Cohen’s d = .44). There were no effects of age. Controlling for time of blood draw and age, OT values were positively associated with anxiety levels in girls and pragmatic language ability in boys and girls. OT and AVP levels were positively associated with restricted and repetitive behaviors in girls with ASD, while AVP levels were negatively associated with these behaviors in boys with ASD.

Conclusions: Results are consistent with the animal literature suggesting higher OT levels in females and higher AVP levels in males. However, our findings are inconsistent with several studies that have found lower OT in individuals with ASD, with trends in the opposite direction. The present results are suggestive of common and distinct roles of OT and AVP in boys and girls. Larger samples further exploring potential sex and diagnostic differences in OT and AVP are warranted.