Summary: Propranolol, a common ‘beta-blocker’ drug used to control blood pressure, could be a promising new treatment for those on the autism spectrum. The medication improved cognitive performance and positively altered the frontal-parietal control network, an area of the brain associated with word and information processing, in those with ASD.
Source: University of Missouri-Columbia
Drugs known as “beta-blockers” have been used since the 1960s as a low-cost, safe and effective means to lower heart rate and control blood pressure. But now researchers from the University of Missouri School of Medicine and the MU Thompson Center for Autism and Neurodevelopmental Disorders have discovered a version of the drug known as propranolol could provide cognitive and social benefits for those living with autism spectrum disorder.
One in 59 children in the United States has been diagnosed with a form of autism spectrum disorder, according to the Centers for Disease Control and Prevention. The signs of autism begin in early childhood and can affect individuals differently. However, many with autism share similar symptoms, including difficulties with social communication. That is the core symptom researchers targeted with a pilot study to look at how this drug affected processing of language in the brain.
“Propranolol is used for test anxiety and performance anxiety, so we suspected it might help with social anxiety,” said supervising investigator David Beversdorf, MD, professor of radiology, neurology and psychology at the MU School of Medicine and the Thompson Center. “I’d been studying its cognitive advantages and found some interesting benefits in language areas that prove difficult for those with autism. That’s why we started this imaging study to understand its effects, and we’re finding benefits involving both language and social interaction in single dose pilot studies.”
The study involved 13 individuals with autism spectrum disorder and 13 without the disorder. They had a mean age of 22.5 years-old. Each participant completed three MRI brain-imaging sessions after taking either a placebo, the beta-blocker propranolol or the beta-blocker nadolol–which is similar to propranolol except that it does not cross the vascular barrier into the brain–before being asked to name as many items as possible that belonged in a particular word category during the MRI screening. Led by John Hegarty, PhD, who completed this work as part of his doctorate in the Interdisciplinary Neuroscience Program at University of Missouri, Beversdorf’s team discovered in the autism group that propranolol improved performance compared to placebo on the word generation test, and the MRI results revealed the drug altered regions of the brain associated with word processing and improved specific task information processing.
“One of the interesting things we found in the autism group was the excessive connectivity in the frontal parietal control network–which affects how your brain allocates resources to other regions–became more similar to the levels of the non-autism group once propranolol was introduced,” Beversdorf said. “It’s an indicator as to why this drug may prove helpful.”
Beversdorf’s team is already working on a larger study involving propranolol. They’ve secured a federal grant from the Department of Defense (DOD) to examine the benefits of the drug on a larger and younger population of autism patients. Treating autism is challenging because of the many subtypes and factors that contribute to the disorder, so this study will monitor factors that might predict who will respond best to the drug.
“It’s important to recognize that different individuals are going to respond differently to each approach or medication,” Beversdorf said. “It’s critical to identify who is going to respond to individual therapies so treatment can be tailored to each patient. We need continued support to do this.”
Funding: Research reported in this publication was supported by a grant from the Health Resources and Services Administration, the University of Missouri School of Medicine Mission Enhancement Fund, the National Institute on Alcohol Abuse and Alcoholism, the University of Florida Center for Cognitive Aging and Memory, the McKnight Brain Research Foundation and the University of Missouri Molecular Life sciences Pre-doctoral Fellowship Program. The authors of the study declare that they have no conflicts of interest related to this study. The content is solely the responsibility of the authors and does not necessarily represent the views of the funding agencies.
In addition to Beversdorf, the study authors include University of Missouri colleagues Bradley Ferguson, PhD, assistant research professor, Department of Health Psychology; Shawn Christ, PhD, associate professor, Department of Psychology; and Jeffrey Johnson, PhD, assistant professor, Department of Psychology. Other collaborators include corresponding author John Hegarty, PhD, who is now a postdoctoral research fellow at the Stanford Autism Center; Rachel Zamzow, PhD; and Eric Porges, PhD, assistant professor, Department of Clinical and Health Psychology, University of Florida.
Beta-adrenergic antagonism alters functional connectivity during associative processing in a preliminary study of individuals with and without autism
Beta-adrenergic antagonism (e.g. propranolol) has been associated with cognitive/behavioral benefits following stress-induced impairments and for some cognitive/behavioral domains in individuals with autism spectrum disorder. In this preliminary investigation, we examined whether the benefits of propranolol are associated with functional properties in the brain. Adolescents/adults (mean age = 22.54 years) with (n = 13) and without autism spectrum disorder (n = 13) attended three sessions in which propranolol, nadolol (beta-adrenergic antagonist that does not cross the blood–brain barrier), or placebo was administered before a semantic fluency task during functional magnetic resonance imaging. Autonomic nervous system measures and functional connectivity between language/associative processing regions and within the fronto-parietal control, dorsal attention, and default mode networks were examined. Propranolol was associated with improved semantic fluency performance, which was correlated with the baseline resting heart rate. Propranolol also altered network efficiency of regions associated with semantic processing and in an exploratory analysis reduced functional differences in the fronto-parietal control network in individuals with autism spectrum disorder. Thus, the cognitive benefits from beta-adrenergic antagonism may be generally associated with improved information processing in the brain in domain-specific networks, but individuals with autism spectrum disorder may also benefit from additional improvements in domain-general networks. The benefits from propranolol may also be able to be predicted from baseline autonomic nervous system measures, which warrants further investigation.