title: Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development.
abstract: BACKGROUND
  Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined.
  
  
  METHODS
  A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile.
  
  
  RESULTS
  There was a significant Time × Condition × 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. There were no group differences for AVP. Hormone levels were associated with social profiles.
  
  
  CONCLUSIONS
  For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or 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 on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University, PMB 40, 230 Appleton Place, Nashville, TN 37203 USA ; Vanderbilt Kennedy Center for Research on Human Development, Nashville, TN USA ; Department of Psychology, Vanderbilt University, Nasvhille, TN USA.
authors.forename: Blythe A
authors.initials: BA
authors.lastname: Corbett
authors.affiliation: University of California, Davis, CA USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Bales
authors.affiliation: Virginia Polytechnic Institute and State University, Blacksburg, VA USA.
authors.forename: Deanna
authors.initials: D
authors.lastname: Swain
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University, PMB 40, 230 Appleton Place, Nashville, TN 37203 USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sanders
authors.affiliation: University of California, Davis, CA USA.
authors.forename: Tamara A R
authors.initials: TA
authors.lastname: Weinstein
authors.affiliation: Department of Pediatrics, Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Muglia
keywords: Arginine vasopressin; Autism; Autism spectrum disorder; Cortisol; Hormone; Hydrocortisone; LHPA axis; Oxytocin; Stress