Metabolism & Biomarkers
Autism is associated with an imbalance in glutathione-dependent redox metabolism. Glutathione synthesis and intracellular redox balance are linked to folate and methylation metabolism, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct ASD endophenotype that is closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Biomarkers that reflect these metabolic abnormalities have recently been investigated to find ASD metabolic endophenotype that may lead to a better understanding of the pathophysiological mechanisms underlying core and associated ASD symptoms and may lead to new treatments.
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.
Published Articles
Results are displayed in descending order beginning with most recent publications.
Preprint: High Sensitivity for Detection of Primary Diagnostic Variants in Autism, Including De Novo Variants, with Trio Whole Genome Sequencing and Data Reanalysis
Omri Bar , Elizabeth Vahey , Mark Mintz , Richard E. Frye , Richard G. Boles. Preprints.org. 14 Aug 2023.
Is a Folate Deficiency Worsening Your Child’s Autism?
Posted by: Potomac Psychiatry
Posted on: April 13, 2023
Read Now
Synchrony 2022: Catalyzing Research and Treatments to Benefit Individuals with Neurodevelopmental Disorders including Autism Spectrum Disorders
Nanda, H.; Frye, R.E. Synchrony 2022: Catalyzing Research and Treatments to Benefit Individuals with Neurodevelopmental Disorders including Autism Spectrum Disorders. J. Pers. Med. 2023, 13, 490. https://doi.org/10.3390/jpm13030490
Biochemical, Genetic and Clinical Diagnostic Approaches to Autism-Associated Inherited Metabolic Disorders
Senarathne, U.D.; Indika, N.-L.R.; Jezela-Stanek, A.; Ciara, E.; Frye, R.E.; Chen, C.; Stepien, K.M. Biochemical, Genetic and Clinical Diagnostic Approaches to Autism-Associated Inherited Metabolic Disorders. Genes 2023, 14, 803. https://doi.org/10.3390/genes14040803
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.
Metabolomic Signatures of Autism Spectrum Disorder
Brister D, Rose S, Delhey L, Tippett M, Jin Y, Gu H, Frye RE. J Pers Med. 2022 Oct 17;12(10):1727. doi: 10.3390/jpm12101727. PMID: 36294866; PMCID: PMC9604590.
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.
Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis
Brister D, Werner BA, Gideon G, McCarty PJ, Lane A, Burrows BT, McLees S, Adelson PD, Arango JI, Marsh W, Flores A, Pankratz MT, Ly NH, Flood M, Brown D, Carpentieri D, Jin Y, Gu H, Frye RE. Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis. Metabolites. 2022 Apr 20;12(5):371. doi: 10.3390/metabo12050371. PMID: 35629876; PMCID: PMC9148155.
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.
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.
Resting State Functional Magnetic Resonance Imaging Elucidates Neurotransmitter Deficiency in Autism Spectrum Disorder
McCarty PJ, Pines AR, Sussman BL, Wyckoff SN, Jensen A, Bunch R, Boerwinkle VL, Frye RE. J Pers Med. 2021 Sep 28;11(10):969. doi: 10.3390/jpm11100969. PMID: 34683111; PMCID: PMC8537605.
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.
Physiological mediators of prenatal environmental influences in autism spectrum disorder
Frye RE, Cakir J, Rose S, Palmer RF, Austin C, Curtin P. Bioessays. 2021 Sep;43(9):e2000307. doi: 10.1002/bies.202000307. Epub 2021 Jul 14. PMID: 34260745.
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.
Mitochondria May Mediate Prenatal Environmental Influences in Autism Spectrum Disorder
Frye RE, Cakir J, Rose S, Palmer RF, Austin C, Curtin P, Arora M. J Pers Med. 2021 Mar 18;11(3):218. doi: 10.3390/jpm11030218. PMID: 33803789; PMCID: PMC8003154.
Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology
Frye RE, Cakir J, Rose S, Delhey L, Bennuri SC, Tippett M, Melnyk S, James SJ, Palmer RF, Austin C, Curtin P, Arora M. Mol Psychiatry. 2021 May;26(5):1561-1577. doi: 10.1038/s41380-020-00885-2. Epub 2020 Sep 22. PMID: 32963337; PMCID: PMC8159748.
Early life metal exposure dysregulates cellular bioenergetics in children with regressive autism spectrum disorder
Frye RE, Cakir J, Rose S, Delhey L, Bennuri SC, Tippett M, Palmer RF, Austin C, Curtin P, Arora M. Transl Psychiatry. 2020 Jul 7;10(1):223. doi: 10.1038/s41398-020-00905-3. PMID: 32636364; PMCID: PMC7341836.
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.
Association With Monocyte Cytokine Profiles and Mitochondrial Respiration
Jyonouchi H, Geng L, Toruner GA, Rose S, Bennuri SC, Frye RE. Serum microRNAs in ASD: Front Psychiatry. 2019 Sep 10;10:614. doi: 10.3389/fpsyt.2019.00614. PMID: 31551826; PMCID: PMC6748029.
A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses.
Barone R, Alaimo S, Messina M, Pulvirenti A, Bastin J; MIMIC-Autism Group; Ferro A, Frye RE, Rizzo R. Front Psychiatry. 2018 Dec 7;9:636. doi: 10.3389/fpsyt.2018.00636. PMID: 30581393; PMCID: PMC6292950.
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.
Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: A comparison and validation study
Howsmon DP, Vargason T, Rubin RA, Delhey L, Tippett M, Rose S, Bennuri SC, Slattery JC, Melnyk S, James SJ, Frye RE, Hahn J. Bioeng Transl Med. 2018 Jun 19;3(2):156-165. doi: 10.1002/btm2.10095. PMID: 30065970; PMCID: PMC6063877.
Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers
Khemakhem AM, Frye RE, El-Ansary A, Al-Ayadhi L, Bacha AB. Metab Brain Dis. 2017 Dec;32(6):1983-1997. doi: 10.1007/s11011-017-0085-2. Epub 2017 Aug 22. PMID: 28831647.
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.
Other Resources
BEYOND BEHAVIORAL EVALUATIONS
from Autism File
Preprint: High Sensitivity for Detection of Primary Diagnostic Variants in Autism, Including De Novo Variants, with Trio Whole Genome Sequencing and Data Reanalysis
Omri Bar , Elizabeth Vahey , Mark Mintz , Richard E. Frye , Richard G. Boles. Preprints.org. 14 Aug 2023.
Is a Folate Deficiency Worsening Your Child’s Autism?
Posted by: Potomac Psychiatry
Posted on: April 13, 2023
Read Now
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
Success of blood test for autism affirmed
Rensselaer Polytechnic Institute
June 19, 2018
Read Article
Cellular Research in Autism
Title: https://www.youtube.com/watch?v=6ObkNn4me1s
Date: September 30, 2015
Location: Neurological Health Foundation
Presented by: Dr. Richard Frye, MD PhD
Cunningham Panel
Cunningham Panel
This test measures the levels of four proteins called autoantibodies and the activity of one enzyme protein. The four autoantibodies are believed to attach to nerve cells in the brain and cause them to function abnormally while the activity of the enzyme known as CamKinase II is believe to interfere with the function of nerve cells if its activity is too high. These measurements are complicated to interpret so you should discuss them with you doctor.
Mitochondrial Cheek Swab Test (MITOSWAB)
Mitochondrial Cheek Swab Test (MITOSWAB)
This test measures three activity enzyme proteins in the powerhouse of the cells in your body known as the mitochondria. The three enzyme proteins are called citrate synthase, complex I and complex IV. There will also be a measurement of the total amount of protein collected by the swab to make sure that there is enough protein for a valid measurement. The activity of the three proteins that are measures can be normal, abnormally low or abnormally high. These measurements are complicated to interpret so you should discuss them with you doctor.
Folate Receptor Alpha Autoantibody Test (FRAT)
Folate Receptor Alpha Autoantibody Test (FRAT)
This test measures two proteins in the blood called autoantibodies whichinterfere with the ability of the vitamin folate to be used by the brain and other parts of the body.The two autoantibodies are called ‘blocking’ and ‘blinding’ and then each may be ‘negative’, ‘low’, ‘medium’ or ‘high.’