Effects of a Beta-Adrenergic Antagonist on Social and Cognitive Functioning in Autism Spectrum Disorder

Thursday, May 15, 2014
Atrium Ballroom (Marriott Marquis Atlanta)
R. M. Zamzow1, B. J. Ferguson1, M. L. Lewis1, A. S. Ragsdale1, J. P. Stichter2 and D. Q. Beversdorf3, (1)University of Missouri-Columbia, Columbia, MO, (2)Special Education, University of Missouri, Columbia, MO, (3)University of Missouri, Columbia, MO
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication impairments and restricted, repetitive behaviors.  Current pharmacological interventions for ASD focus primarily on psychiatric symptoms, including agitation and obsessive behaviors.  Few agents target core symptomatology, such as social and cognitive functioning.  It has been previously hypothesized that stress contributes to social and cognitive deficits in ASD.  Propranolol, a non-selective beta-adrenergic antagonist with known anxiolytic effects, is a potential therapeutic agent for ASD, as it blocks the noradrenergically mediated sympathetic response system.  This agent has been previously reported to improve verbal fluency and working memory in ASD.

Objectives: The present study explores the effects of propranolol on performance on social and cognitive tasks in ASD.  In addition, we sought to determine if those with higher baseline levels of sympathetic reactivity, measured by heart rate variability (HRV), exhibit the greatest response to propranolol, establishing a potential treatment response marker.

Methods: Twenty individuals with ASD participated in two study sessions, during which baseline HRV, assessed via electrocardiography, was measured for 5 minutes.  Participants were then administered propranolol (40 mg) or placebo in a counterbalanced, double-blinded manner.  60 minutes following drug administration, participants performed several cognitive and social tasks.  To assess social functioning, participants were given the Conversational Reciprocity component of the General Social Outcomes Measure (GSOM CR), in which participants engaged in a short conversation with the researcher.  To assess verbal problem solving and verbal memory, the Anagrams task and the Hopkins Verbal Learning Test (HVLT) were administered.

Results: Paired samples t-tests revealed a significant improvement in the total score [t(19) = 2.40, p = .03] and the nonverbal communication score [t(19) = 2.18, p = .04] for the GSOM CR in the propranolol condition, as compared to the placebo condition.  A trend for an increased sharing information score for this task in the propranolol condition was also observed [t(19) = 1.76, p = .09].  In addition, there was a significant decrease in the latency to correct response for the Anagrams task, in the propranolol condition, as compared to the placebo condition [t(18) = 2.17, p = .045].  Lastly, there was a trend for a between drug difference in the discrimination index for the HVLT, in which this score was higher in the propranolol condition [t(19) = 1.80, p = .09].  Simple linear regressions revealed a significant positive relationship between baseline HRV and response to propranolol for the GSOM CR total score [F(1,18) = 5.38, p = .03, R2 = .23].  A trend for a positive relationship between baseline HRV and response to propranolol for the sharing information component of this task was also demonstrated [F(1,18) = 3.11, p = .095, R2= .15].

Conclusions: Propranolol appears to improve both social functioning and aspects of cognition in ASD.  In addition, improvements in social functioning may be predicted by baseline sympathetic reactivity, where participants with greater heart rate variability demonstrate greater response to propranolol.  Overall, these findings contribute to insight regarding potential therapeutic interventions for core symptomatology in ASD.