Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. As the pathophysiological abnormalities associated with ASD are studied, we hope that these revelations lead to associated treatments. Treatments targeting some of the abnormalities seen in ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways are being investigated. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. There are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future.
This page contains a selection of papers and other resources on this topic. You can also search this site and all types of content by creating a custom filter.
Results are displayed in descending order beginning with most recent publications.
The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment.
Frye RE, Lane A, Worner A, Werner BA, McCarty PJ, Scheck AC, Collins HL, Adelman SJ, Quadros EV, Rossignol DA. J Pers Med. 2022 Dec 8;12(12):2033. doi: 10.3390/jpm12122033. PMID: 36556254; PMCID: PMC9786140.
Long COVID Syndrome Presenting as Neuropsychiatric Exacerbations in Autism Spectrum Disorder: Insights for Treatment
Jyonouchi, H.; Geng, L.; Rossignol, D.A.; Frye, R.E. Long COVID Syndrome Presenting as Neuropsychiatric Exacerbations in Autism Spectrum Disorder: Insights for Treatment. J. Pers. Med. 2022, 12, 1815. https://doi.org/10.3390/jpm12111815
Modern Biomarkers for Autism Spectrum Disorder: Future Directions
Jensen AR, Lane AL, Werner BA, McLees SE, Fletcher TS, Frye RE. Mol Diagn Ther. 2022 Sep;26(5):483-495. doi: 10.1007/s40291-022-00600-7. Epub 2022 Jun 27. PMID: 35759118; PMCID: PMC9411091.
Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis
Rossignol DA, Frye RE. J Pers Med. 2021 Nov 3;11(11):1141. doi: 10.3390/jpm11111141. Erratum in: J Pers Med. 2022 Apr 29;12(5): PMID: 34834493; PMCID: PMC8622150.
A Personalized Multidisciplinary Approach to Evaluating and Treating Autism Spectrum Disorder
Frye RE. J Pers Med. 2022 Mar 14;12(3):464. doi: 10.3390/jpm12030464. PMID: 35330464; PMCID: PMC8949394.
Transdermal Electrical Neuromodulation for Anxiety and Sleep Problems in High-Functioning Autism Spectrum Disorder: Feasibility and Preliminary Findings
Foldes ST, Jensen AR, Jacobson A, Vassall S, Foldes E, Guthery A, Brown D, Levine T, Tyler WJ, Frye RE. Transdermal Electrical Neuromodulation for Anxiety and Sleep Problems in High-Functioning Autism Spectrum Disorder: Feasibility and Preliminary Findings. J Pers Med. 2021 Dec 6;11(12):1307. doi: 10.3390/jpm11121307. PMID: 34945779; PMCID: PMC8704341.
Ratings of the Effectiveness of Nutraceuticals for Autism Spectrum Disorders: Results of a National Survey
Adams, J.B.; Bhargava, A.; Coleman, D.M.; Frye, R.E.; Rossignol, D.A. Ratings of the Effectiveness of Nutraceuticals for Autism Spectrum Disorders: Results of a National Survey. J. Pers. Med. 2021, 11, 878. https://doi.org/10.3390/jpm11090878
The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis
Rossignol DA, Frye RE. J Pers Med. 2021 Aug 11;11(8):784. doi: 10.3390/jpm11080784. PMID: 34442428; PMCID: PMC8400809.
A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder
Rossignol DA, Frye RE. J Pers Med. 2021 May 30;11(6):488. doi: 10.3390/jpm11060488. PMID: 34070826; PMCID: PMC8229039.
Mitochondrial Fatty Acid β-Oxidation and Resveratrol Effect in Fibroblasts from Patients with Autism Spectrum Disorder
Barone R, Bastin J, Djouadi F, Singh I, Karim MA, Ammanamanchi A, McCarty PJ, Delhey L, Shannon R, Casabona A, Rizzo R, Frye RE. Mitochondrial Fatty Acid β-Oxidation and Resveratrol Effect in Fibroblasts from Patients with Autism Spectrum Disorder. J Pers Med. 2021 Jun 4;11(6):510. doi: 10.3390/jpm11060510. PMID: 34199819; PMCID: PMC8229571.
Emerging biomarkers in autism spectrum disorder: a systematic review
Frye RE, Vassall S, Kaur G, Lewis C, Karim M, Rossignol D. Ann Transl Med. 2019 Dec;7(23):792. doi: 10.21037/atm.2019.11.53. PMID: 32042808; PMCID: PMC6989979.
Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder
Zimmerman AW, Singh K, Connors SL, Liu H, Panjwani AA, Lee LC, Diggins E, Foley A, Melnyk S, Singh IN, James SJ, Frye RE, Fahey JW. Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder. Mol Autism. 2021 May 25;12(1):38. doi: 10.1186/s13229-021-00447-5. Erratum in: Mol Autism. 2021 Jun 16;12(1):44. PMID: 34034808; PMCID: PMC8146218.
Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder
Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV. Semin Pediatr Neurol. 2020 Oct;35:100835. doi: 10.1016/j.spen.2020.100835. Epub 2020 Jun 25. PMID: 32892962; PMCID: PMC7477301.
Mitochondrial Dysfunction in Autism Spectrum Disorder: Unique Abnormalities and Targeted Treatments
Frye RE. Semin Pediatr Neurol. 2020 Oct;35:100829. doi: 10.1016/j.spen.2020.100829. Epub 2020 Jun 23. PMID: 32892956.
Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms
Shimasaki C, Frye RE, Trifiletti R, Cooperstock M, Kaplan G, Melamed I, Greenberg R, Katz A, Fier E, Kem D, Traver D, Dempsey T, Latimer ME, Cross A, Dunn JP, Bentley R, Alvarez K, Reim S, Appleman J. Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms. J Neuroimmunol. 2020 Feb 15;339:577138. doi: 10.1016/j.jneuroim.2019.577138. Epub 2019 Dec 15. PMID: 31884258.
Mitochondrial Dysfunction Is Inducible in Lymphoblastoid Cell Lines From Children With Autism and May Involve the TORC1 Pathway
Bennuri SC, Rose S, Frye RE. Front Psychiatry. 2019 May 7;10:269. doi: 10.3389/fpsyt.2019.00269. PMID: 31133888; PMCID: PMC6514096.
Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder
Barone R, Rizzo R, Tabbì G, Malaguarnera M, Frye RE, Bastin J. Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder. Int J Mol Sci. 2019 Apr 16;20(8):1878. doi: 10.3390/ijms20081878. PMID: 30995737; PMCID: PMC6515064.
Rating of the Effectiveness of 26 Psychiatric and Seizure Medications for Autism Spectrum Disorder: Results of a National Survey
Coleman DM, Adams JB, Anderson AL, Frye RE. J Child Adolesc Psychopharmacol. 2019 Mar;29(2):107-123. doi: 10.1089/cap.2018.0121. Epub 2019 Feb 6. PMID: 30724573; PMCID: PMC6442266.
Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder
Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x. PMID: 30039193; PMCID: PMC6132446.
Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism
Connery K, Tippett M, Delhey LM, Rose S, Slattery JC, Kahler SG, Hahn J, Kruger U, Cunningham MW, Shimasaki C, Frye RE. Transl Psychiatry. 2018 Aug 10;8(1):148. doi: 10.1038/s41398-018-0214-7. PMID: 30097568; PMCID: PMC6086890.
Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins and Progress in Developing Therapeutic Agents
Frye RE. Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins and Progress in Developing Therapeutic Agents. CNS Drugs. 2018 Aug;32(8):713-734. doi: 10.1007/s40263-018-0556-y. PMID: 30105528; PMCID: PMC6105175.
Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials
Delhey LM, Tippett M, Rose S, Bennuri SC, Slattery JC, Melnyk S, James SJ, Frye RE. Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials. Front Neurosci. 2018 Feb 12;12:19. doi: 10.3389/fnins.2018.00019. PMID: 29483858; PMCID: PMC5816043.
Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry. 2018 Feb;23(2):247-256. doi: 10.1038/mp.2016.168. Epub 2016 Oct 18. PMID: 27752075; PMCID: PMC5794882.
Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society
Parikh S, Goldstein A, Karaa A, Koenig MK, Anselm I, Brunel-Guitton C, Christodoulou J, Cohen BH, Dimmock D, Enns GM, Falk MJ, Feigenbaum A, Frye RE, Ganesh J, Griesemer D, Haas R, Horvath R, Korson M, Kruer MC, Mancuso M, McCormack S, Raboisson MJ, Reimschisel T, Salvarinova R, Saneto RP, Scaglia F, Shoffner J, Stacpoole PW, Sue CM, Tarnopolsky M, Van Karnebeek C, Wolfe LA, Cunningham ZZ, Rahman S, Chinnery PF. Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2017 Dec;19(12):10.1038/gim.2017.107. doi: 10.1038/gim.2017.107. Epub 2017 Jul 27. PMID: 28749475; PMCID: PMC7804217.
Folate metabolism abnormalities in autism: potential biomarkers
Frye RE, Slattery JC, Quadros EV. Biomark Med. 2017 Aug;11(8):687-699. doi: 10.2217/bmm-2017-0109. Epub 2017 Aug 3. PMID: 28770615.
A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder
Richard E Frye, Richard G Boles, Shannon Rose and Daniel Rossignol
This book is a reprint of the Special Issue A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder that was published in JPM. This collection of articles provides the start of an overview of the current and future methods for applying a personalized medicine approach to the diagnosis, management, and treatment of autism.
Live interview with Dr. Richard Frye
Title: Interview/Live Chat
Date: May 14, 2021
Location: Autism Research Coalition Online
Featuring: Dr. Richard Frye, MD PhD
Richard E Frye, MD, PhD. is “All In” for Autistic Children
By: Becky Gillette
Posted: November 11, 2015
Propranolol is a blocker of beta-adrenergic receptor that acts both peripherally and centrally. Peripheral effects primarily target the autonomic nervous system where it affects primarily heart rate and blood pressure. Centrally targets include the wide spread norepinephrine circuits, including targets in the brainstem, cortex and most notably for ASD, amygdala. Propranolol has emerged as an interesting treatment for ASD that appears to improve social function