Examining the Relationship Between Oxytocin and Cortisol in a Double-Blind, Placebo-Controlled, Randomly Assigned Hydrosome Challenge Study in Autism Spectrum Disorder

Background: The hormones, cortisol and oxytocin (OT) are key neuromodulators of biological and behavioral responses and both have been implicated in the neuropathological profile of children with autism spectrum disorder (ASD).   Cortisol, a primary “stress hormone” is more variable and often elevated under conditions of social stress in ASD, when compared to typically developing (TD) children. OT known as the “social hormone” is a key moderator of social behavior and stress responsivity, and has been associated with social deficits in ASD.  In addition to mediating complex social behavior, OT plays an important role in stress buffering. However, the extent to which OT may moderate stress responsivity in ASD is uncertain.

Objectives:  The purpose of the investigation was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions.

Methods: Participants included children between 8 to 12 years of age with ASD (N = 14) and typical development (N = 11) each exposed to a single dose Hydrocortisone (pharmaceutical cortisol) challenge and placebo. A double-blind, placebo-controlled, randomly-assigned, crossover design was employed. The study was conducted over two visits with one-week intervals.  A low dose of Hydrocortisone and placebo were administered via liquid suspension that was prepared by investigational pharmacy. Height and weight were assessed to calculate body surface area (m²) to determine the administration of a single dose of Hydrocortisone in levels considered to be mild (5 mg per m² ). Demonstrable effects are detectable within one hour; thus, repeat blood sample collection for cortisol and OT was taken at baseline and at 60 min post administration. For each blood draw 6 ml was collected. The analysis of variance (ANOVA) statistical model included the within subject factor ‘Condition’ (Experimental/Placebo) and ‘Time’ (Pre and Post) and the between subject factor ‘Group’ (ASD vs. TD). Due to skewed distribution, cortisol was log transformed.

Results: Regarding OT, there was a significant difference for Time F(1,23) 8.95, p = 0.007) indicating the expected difference for both groups based on pre and post administration levels.  There was a trend for Condition x Group F (1,23) 3.64, = .07.  Notably, there was a significant Time x Condition x Group Interaction F(1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group.

Conclusions: For the TD group, an inverse relationship was observed such that OT decreased during placebo and increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT decreased during both the physiological challenge and the placebo condition suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT may play a contributory role in the heightened stress responsivity often observed in children with ASD especially under conditions of social stress.