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Richard E. Frye, MD, PhD
Director of Autism Research, ACHRI
Associate Professor, Department of Pediatrics University of Arkansas for Medical Sciences, College of Medicine
Phone: 501-364-4662

Research Overview

Dr. Frye has a broad background in neurodevelopmental disorders, physiology, psychology, and biostatistics. Recently, his research has focused on the assessment, diagnosis, and treatment of children with autism spectrum disorder (ASD) in order to improve quality of life and promote recovery. Over the past year, he has completed three key clinical research studies on children with neurodevelopmental disorders. In the first study, just recently published in Molecular Psychiatry, it was demonstrated that children with ASD have a high incidence of the folate receptor alpha autoantibody, an autoantibody that prevents folate from entering the brain, and children with ASD and this autoantibody demonstrate a favorable behavioral and cognitive response to a reduced form of folate known as folinic acid. The second study focused on defining the clinical, behavioral, cognitive, genetic (single nucleotide polymorphisms and gene expression), and metabolic (oxidative stress) characteristics of an important subgroup of children with ASD, specifically those with mitochondrial disease. The third study was an open-label clinical trial that examined the metabolic and behavioral effects of tetrahydrobiopterin, a treatment that is hypothesized to treat both core symptoms of ASD and metabolic abnormalities associated with ASD (neurotransmitter deficits, redox and nitric oxide abnormalities).

Dr. Frye has been previously funded by NINDS to examine brain reorganization in individuals with developmental phonological dyslexia, ASD, cryptogenic epilepsy, and premature birth, using magnetoencephalography, diffusion tensor imaging, and surface morphology. His goal as the Director of Autism Research at the Arkansas Children's Hospital Research Institute is to develop a program that closely integrates basic science, translation, and clinical research.  

Recent Publications

Frye RE, DeLatorre R, Taylor HB, Slattery J, Melnyk S, Chowdhury N, James SJ. Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study. Transl Psychiatry. 2013 Mar 5;3:e237. doi: 10.1038/tp.2013.14.

Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, James SJ. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry. 2012 Jul 10;2:e134. doi: 10.1038/tp.2012.61.

Frye, R.E., Liederman, J., McGraw Fisher, J., Wu, M.H. Laterality of temporoparietal causal connectivity during the pre-stimulus period correlates with phonological decoding task performance in dyslexic and typical readers. Cerebral Cortex, 2012 Aug;22(8):1923-34.

Frye, R.E., Sequeira, J.M., Quadros, E.V., James, S.J., Rossignol, D. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2012 Jan 10. doi: 10.1038/mp.2011.175. [Epub ahead of print]

Rossignol, D., Frye, R.E. Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. Mol Psychiatry. 2012 Mar;17(3):290-314. doi: 10.1038/mp.2010.136. Epub 2011 Jan 25. Review.

Current Research Funding

Medical Etiologies of Neurodevelopmental Disorders: Cerebral Folate Deficiency. Autism Research Institute. 2011-2012.

Mitochondrial Dysfunction in Autism: Patient Characteristics and Relation to Mitochondrial Toxins. The Jane Botsford Johnson Foundation. 2010-2012.

Biomarkers of central nervous system tetrahydrobiopterin concentration and response to tetrahydrobiopterin supplementation in children with idiopathic cognitive developmental disorders, BioMarin Pharmaceutics Inc. 2010-2012.


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