Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome

Abstract

Fragile X syndrome (FXS) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms. Individuals with FXS, males in particular, often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations. We investigated whether oxytocin (OT), a hormone with prosocial and anxiolytic effects, could alleviate symptoms of social anxiety in this population. A randomized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo, 24 IU OT and 48 IU OT. Measures of eye gaze frequency, heart rate, respiratory sinus arrhythmia (RSA), heart rate variability (HRV) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration. Ten low-functioning males with FXS (aged 13-28 years) traveled to Stanford for the initial visit: 8 completed the study. Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose. There was no effect of OT on heart rate, RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others. These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS. Further double-blind placebo-controlled studies of OT, conducted in combination with behavioral treatment programs, may be warranted.

Conflict of interest statement

Conflict of interest

Dr. Allan Reiss is currently a consultant for Novartis though was not associated with the company at the time of the study. No funding or other support was received from Novartis for the design or implementation of the study, analysis of the data, or manuscript preparation.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Eye gaze frequency observed in the social proximity and social interaction phases of the social challenge at each dose. Data are expressed as mean + SEM, n = 8 per group. There was a significant main effect of dose, with eye gaze frequency occurring at higher levels following the 24 IU dose compared to placebo. There was no difference in eye gaze frequency between the social proximity and social interaction phases. *p < 0.05 (ANOVA + LSD test).

Figure 2

Heart rate levels (beats per minute) recorded for each participant (P). Data are plotted in 1 min bins in the social proximity and social interaction phases of the social challenge at each dose. Open circles represent heart rate levels in the social proximity phase. Filled circles represent heart rate levels in the social interaction phase.

Figure 3

Mean heart rate, respiratory sinus arrhythmia (RSA) and heart rate variability (HRV) levels recorded at each dose, plotted in the social proximity and social interaction phases of the social challenge. Data are expressed as mean + SEM, n = 8 per group.

Figure 4

Salivary cortisol levels obtained at each dose, plotted prior to and following the social challenge. Data are expressed as mean + SEM, n = 8 per group. There was a significant main effect of dose, with salivary cortisol occurring at lower levels following the 48 IU dose compared to placebo. There was no difference in salivary cortisol levels prior to and following the social challenge *p < 0.05 (ANOVA + LSD test).