In Phoenix, at the height of the summer of 2025, we held out our microphone to Dr. Richard Eugene Frye for a conversation at the crossroads of medicine and scientific research. Founder of the Autism Discovery and Treatment Foundation, this eminent physician-scientist offers an illuminating perspective on autism, its biological and environmental determinants, as well as on the many roles mitochondria play in cellular health.
Within the framework of the ANR MitoDanger project, he shares a vision grounded in deep respect for patient individuality, shaped by decades of research in pediatric neurology, while also discussing the recent publication of his book The Folate Fix, dedicated to the key role of folate metabolism in certain forms of autism.

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By McKenzie Beard
Published March 19, 2025, 6:00 a.m. ET

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There is new hope regarding a possible treatment for autism, and it is being spearheaded by a doctor in the Phoenix area.

Child Neurologist Richard Frye has been testing the generic drug Leucovorin as a way of helping folic acid get through to the brain. Folic acid is essential for brain development. Dr. Frye said many patients saw significant improvements in their language skills.

"It's not just talking, but, what we found in our testing is that they were able to understand language in a more complicated fashion and understand the social nuances of language," Dr. Frye said.

Dr. Frye has published his findings in a book, as well as in peer-reviewed studies, and he hopes for additional outside research to confirm and expand on what may be a promising new treatment. FOX 10's Ellen McNamara has more.

(This video is provided for educational and informational purposes only, and does not constitute providing medical advice or professional services. The information provided should not be used for diagnosing or treating a health problem or disease, and those seeking personal medical advice should consult with a licensed physician.)

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A neurologist in Arizona says the generic drug leucovorin help children with autism absorb folic acid, allowing their brains to develop in a more neuro-typical way. The FDA has not approved the drug for this purpose though.

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By Dr. Céline Gounder
Updated on: September 24, 2025 / 7:50 PM EDT / CBS News

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Interview with Dr. Richard Frye, a pediatric neurologist and internationally recognized autism researcher, about Folinic Acid, Leucovorin and Autism. Dr. Frye focuses on the biological aspects of autism, including folate pathways, the immune system, metabolism, and mitochondrial function.

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Richard E. Frye MD, PhD

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Boles, R.G.; Bar, O.; Boles, P.T.; Hill, Z.R.; Frye, R.E. De Novo Variants Predominate in Autism Spectrum Disorder. Genes 2025, 16, 1099.

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Frye, R.E.; Cohen, I.L.; Sequeira, J.M.; Hill, Z.; Espinoza, A.; Brown, W.T.; Mevs, C.; Marchi, E.; Flory, M.; Jenkins, E.C.; et al. Transgenerational Effects and Heritability of Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorder. Int. J. Mol. Sci. 2025, 26, 8293.

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Hill, Z.; McCarty, P.J.; Boles, R.G.; Frye, R.E. A Mitochondrial Supplement Improves Function and Mitochondrial Activity in Autism: A Double-Blind Placebo-Controlled Cross-Over Trial. Int. J. Mol. Sci. 2025, 26, 2479.

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Castro K, Frye RE, Silva E, Vasconcelos C, Hoffmann L, Riesgo R, Vaz J. 3  2024. Journal of Personalized Medicine.; 14(8):823.

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Frye RE, Rincon N, Mccarty PJ, Brister D, Scheck AC, Rossignol DA. Neurobiology of Disease. 3 May 2024. https://doi.org/10.1016/j.nbd.2024.106520

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Frye RE, Mccarty PJ, Werner BA, Rose S, Scheck A. Front. Physiol. Sec. Mitochondrial Research. Vol 15 -2024. doi: 10.3389/fphys.2024.1306038

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Wells, L.; O’Hara, N.; Frye, R.E.; Hullavard, N.; Smith, E.  J. Pers. Med. 2024, 14, 166.

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Frye RE, McCarty PJ, Werner BA, Scheck AC, Collins HL, Adelman SJ, Rossignol DA, Quadros EV. J Pers Med. 1 Jan 2024.

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Omri Bar , Elizabeth Vahey , Mark Mintz , Richard E. Frye , Richard G. Boles. International Journal of Molecular Sciences. 18 Jan 2024.

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Omri Bar , Elizabeth Vahey , Mark Mintz , Richard E. Frye , Richard G. Boles. Preprints.org. 14 Aug 2023.

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Posted by: Potomac Psychiatry
Posted on:  April 13, 2023

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Poling, J. S., Frye, R. E., Shoffner, J., & Zimmerman, A. W. (2006). Developmental regression and mitochondrial dysfunction in a child with autism. Journal of child neurology, 21(2), 170–172. https://doi.org/10.1177/08830738060210021401

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Frye RE, Polling JS, Ma LC. Choroid plexus papilloma expansion over 7 years in Aicardi syndrome. J Child Neurol. 2007 Apr;22(4):484-7. doi: 10.1177/0883073807302759. PMID: 17621535; PMCID: PMC2536525.

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Frye RE, Fisher JM, Coty A, Zarella M, Liederman J, Halgren E. Linear coding of voice onset time. J Cogn Neurosci. 2007 Sep;19(9):1476-87. doi: 10.1162/jocn.2007.19.9.1476. PMID: 17714009; PMCID: PMC2393546.

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Frye RE, Fisher JM, Witzel T, Ahlfors SP, Swank P, Liederman J, Halgren E. Objective phonological and subjective perceptual characteristics of syllables modulate spatiotemporal patterns of superior temporal gyrus activity. Neuroimage. 2008 May 1;40(4):1888-901. doi: 10.1016/j.neuroimage.2008.01.048. Epub 2008 Feb 14. PMID: 18356082; PMCID: PMC2443388.

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Beauchamp MS, Yasar NE, Frye RE, Ro T. Touch, sound and vision in human superior temporal sulcus. Neuroimage. 2008 Jul 1;41(3):1011-20. doi: 10.1016/j.neuroimage.2008.03.015. Epub 2008 Mar 20. PMID: 18440831; PMCID: PMC2409200.

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Frye RE, Hasan K, Xue L, Strickland D, Malmberg B, Liederman J, Papanicolaou A. Splenium microstructure is related to two dimensions of reading skill. Neuroreport. 2008 Oct 29;19(16):1627-31. doi: 10.1097/WNR.0b013e328314b8ee. PMID: 18806688; PMCID: PMC2667961.

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Frye RE, Beauchamp MS. Receptive language organization in high-functioning autism. J Child Neurol. 2009 Feb;24(2):231-6. doi: 10.1177/0883073808329572. PMID: 19182164; PMCID: PMC2896833.

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Frye RE, Rezaie R, Papanicolaou AC. Functional Neuroimaging of Language Using Magnetoencephalography. Phys Life Rev. 2009 Mar 1;6(1):1-10. doi: 10.1016/j.plrev.2008.08.001. PMID: 20160985; PMCID: PMC2754842.

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Frye RE. Reversible posterior leukoencephalopathy syndrome in sickle-cell anemia. Pediatr Neurol. 2009 Apr;40(4):298-301. doi: 10.1016/j.pediatrneurol.2008.10.024. PMID: 19302944; PMCID: PMC2903963.

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Frye RE, Malmberg B, Desouza L, Swank P, Smith K, Landry S. Increased prefrontal activation in adolescents born prematurely at high risk during a reading task. Brain Res. 2009 Dec 15;1303:111-9. doi: 10.1016/j.brainres.2009.09.091. Epub 2009 Sep 29. PMID: 19796631; PMCID: PMC2783693.

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Frye RE, Liederman J, Malmberg B, McLean J, Strickland D, Beauchamp MS. Surface area accounts for the relation of gray matter volume to reading-related skills and history of dyslexia. Cereb Cortex. 2010 Nov;20(11):2625-35. doi: 10.1093/cercor/bhq010. Epub 2010 Feb 12. PMID: 20154011; PMCID: PMC2981021.

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Frye RE, Butler I, Strickland D, Castillo E, Papanicolaou A. Electroencephalogram discharges in atypical cognitive development. J Child Neurol. 2010 May;25(5):556-66. doi: 10.1177/0883073809344743. Epub 2010 Mar 18. PMID: 20299700; PMCID: PMC2896832.

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Pollonini L, Pophale S, Situ N, Wu MH, Frye RE, Leon-Carrion J, Zouridakis G. Information communication networks in severe traumatic brain injury. Brain Topogr. 2010 Jun;23(2):221-6. doi: 10.1007/s10548-010-0139-9. Epub 2010 Mar 12. PMID: 20224956.

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Frye RE, Malmberg B, McLean J 3rd, Swank P, Smith K, Papanicolaou A, Landry S. Increased left prefrontal activation during an auditory language task in adolescents born preterm at high risk. Brain Res. 2010 Jun 8;1336:89-97. doi: 10.1016/j.brainres.2010.03.093. Epub 2010 Apr 8. PMID: 20381475; PMCID: PMC2881563.

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Frye RE, Huffman LC, Elliott GR. Tetrahydrobiopterin as a novel therapeutic intervention for autism. Neurotherapeutics. 2010 Jul;7(3):241-9. doi: 10.1016/j.nurt.2010.05.004. PMID: 20643376; PMCID: PMC2908599.

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Frye RE, Hasan K, Malmberg B, Desouza L, Swank P, Smith K, Landry S. Superior longitudinal fasciculus and cognitive dysfunction in adolescents born preterm and at term. Dev Med Child Neurol. 2010 Aug;52(8):760-6. doi: 10.1111/j.1469-8749.2010.03633.x. Epub 2010 Feb 24. PMID: 20187879; PMCID: PMC2910222.

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Frye RE, Malmberg B, Swank P, Smith K, Landry S. Preterm birth and maternal responsiveness during childhood are associated with brain morphology in adolescence. J Int Neuropsychol Soc. 2010 Sep;16(5):784-94. doi: 10.1017/S1355617710000585. Epub 2010 Jul 8. PMID: 20609271.

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Hasan KM, Walimuni IS, Kramer LA, Frye RE. Human brain atlas-based volumetry and relaxometry: application to healthy development and natural aging. Magn Reson Med. 2010 Nov;64(5):1382-9. doi: 10.1002/mrm.22515. Epub 2010 Aug 25. PMID: 20740662.

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Kamali A, Kramer LA, Frye RE, Butler IJ, Hasan KM. Diffusion tensor tractography of the human brain cortico-ponto-cerebellar pathways: a quantitative preliminary study. J Magn Reson Imaging. 2010 Oct;32(4):809-17. doi: 10.1002/jmri.22330. PMID: 20882611; PMCID: PMC4492525.

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Frye RE, Wu MH, Liederman J, Fisher JM. Greater Pre-Stimulus Effective Connectivity from the Left Inferior Frontal Area to other Areas is Associated with Better Phonological Decoding in Dyslexic Readers. Front Syst Neurosci. 2010 Dec 2;4:156. doi: 10.3389/fnsys.2010.00156. PMID: 21160549; PMCID: PMC3001755.

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Hasan KM, Frye RE. Diffusion tensor-based regional gray matter tissue segmentation using the international consortium for brain mapping atlases. Hum Brain Mapp. 2011 Jan;32(1):107-17. doi: 10.1002/hbm.21004. PMID: 20799340; PMCID: PMC6869994.

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Frye, R., Rossignol, D. Mitochondrial Dysfunction Can Connect the Diverse Medical Symptoms Associated With Autism Spectrum Disorders. Pediatr Res 69, 41–47 (2011).

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Frye RE, Sreenivasula S, Adams JB. Traditional and non-traditional treatments for autism spectrum disorder with seizures: an on-line survey. BMC Pediatr. 2011 May 18;11:37. doi: 10.1186/1471-2431-11-37. PMID: 21592359; PMCID: PMC3123184.

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Wu MH, Frye RE, Zouridakis G. A comparison of multivariate causality based measures of effective connectivity. Comput Biol Med. 2011 Dec;41(12):1132-41. doi: 10.1016/j.compbiomed.2011.06.007. Epub 2011 Jul 13. PMID: 21742321.

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Frye RE, Liederman J, Hasan KM, Lincoln A, Malmberg B, McLean J 3rd, Papanicolaou A. Diffusion tensor quantification of the relations between microstructural and macrostructural indices of white matter and reading. Hum Brain Mapp. 2011 Aug;32(8):1220-35. doi: 10.1002/hbm.21103. Epub 2010 Jul 27. PMID: 20665719; PMCID: PMC6869925.

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Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol. 2011 Sep;53(9):783-792. doi: 10.1111/j.1469-8749.2011.03980.x. Epub 2011 Apr 19. PMID: 21518346.

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Rossignol DA, Frye RE. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry. 2012 Apr;17(4):389-401. doi: 10.1038/mp.2011.165. Epub 2011 Dec 6. PMID: 22143005; PMCID: PMC3317062.

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Frye RE, Wu MH. Multichannel least-squares linear regression provides a fast, accurate, unbiased and robust estimation of Granger causality for neurophysiological data. Comput Biol Med. 2011 Dec;41(12):1118-31. doi: 10.1016/j.compbiomed.2011.04.012. PMID: 21640990.

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Rossignol, D.A., Frye, R.E. Substantial Problems with Measuring Brain Mitochondrial Dysfunction in Autism Spectrum Disorder Using Magnetic Resonance Spectroscopy. J Autism Dev Disord 42, 640–642 (2012). https://doi.org/10.1007/s10803-011-1276-z

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Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2013 Mar;18(3):369-81. doi: 10.1038/mp.2011.175. Epub 2012 Jan 10. PMID: 22230883; PMCID: PMC3578948.

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Frye RE. Mitochondrial disease in 22q13 duplication syndrome. J Child Neurol. 2012 Jul;27(7):942-9. doi: 10.1177/0883073811429858. Epub 2012 Feb 28. PMID: 22378673.

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Rossignol, D., Frye, R. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17, 290–314 (2012). https://doi.org/10.1038/mp.2010.136

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Hasan KM, Walimuni IS, Frye RE. Global cerebral and regional multimodal neuroimaging markers of the neurobiology of autism: development and cognition. J Child Neurol. 2013 Jul;28(7):874-85. doi: 10.1177/0883073812452917. Epub 2012 Aug 16. PMID: 22899798.

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Frye RE, Liederman J, McGraw Fisher J, Wu MH. Laterality of temporoparietal causal connectivity during the prestimulus period correlates with phonological decoding task performance in dyslexic and typical readers. Cereb Cortex. 2012 Aug;22(8):1923-34. doi: 10.1093/cercor/bhr265. Epub 2011 Oct 6. PMID: 21980019; PMCID: PMC3394369.

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Li H, Xue Z, Ellmore TM, Frye RE, Wong ST. Network-based analysis reveals stronger local diffusion-based connectivity and different correlations with oral language skills in brains of children with high functioning autism spectrum disorders. Hum Brain Mapp. 2014 Feb;35(2):396-413. doi: 10.1002/hbm.22185. Epub 2012 Sep 24. PMID: 23008187; PMCID: PMC6869619.

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Leon-Carrion J, Leon-Dominguez U, Pollonini L, Wu MH, Frye RE, Dominguez-Morales MR, Zouridakis G. Synchronization between the anterior and posterior cortex determines consciousness level in patients with traumatic brain injury (TBI). Brain Res. 2012 Oct 2;1476:22-30. doi: 10.1016/j.brainres.2012.03.055. Epub 2012 Mar 29. PMID: 22534483.

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Frye, R., Melnyk, S. & MacFabe, D. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry 3, e220 (2013). https://doi.org/10.1038/tp.2012.143

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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(3):e237. doi: 10.1038/tp.2013.14. PMID: 23462988; PMCID: PMC3625913.

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Frye, R., DeLaTorre, R., Taylor, H. et al. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry 3, e273 (2013). https://doi.org/10.1038/tp.2013.51

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Ellmore TM, Li H, Xue Z, Wong ST, Frye RE. Tract-based spatial statistics reveal altered relationship between non-verbal reasoning abilities and white matter integrity in autism spectrum disorder. J Int Neuropsychol Soc. 2013 Jul;19(6):723-8. doi: 10.1017/S1355617713000325. Epub 2013 Apr 8. PMID: 23561717.

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Frye RE. A lack of statistical pitfalls in the comparison of multivariate causality measures for effective causality. Comput Biol Med. 2013 Aug 1;43(7):962-5. doi: 10.1016/j.compbiomed.2013.02.001. Epub 2013 Feb 26. PMID: 23485200.

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Frye RE, Rossignol D, Casanova MF, Brown GL, Martin V, Edelson S, Coben R, Lewine J, Slattery JC, Lau C, Hardy P, Fatemi SH, Folsom TD, Macfabe D, Adams JB. A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Front Public Health. 2013 Sep 13;1:31. doi: 10.3389/fpubh.2013.00031. PMID: 24350200; PMCID: PMC3859980.

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Frye RE, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW, Walters L, James SJ. Effectiveness of methylcobalamin and folinic Acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. Autism Res Treat. 2013;2013:609705. doi: 10.1155/2013/609705. Epub 2013 Oct 12. PMID: 24224089; PMCID: PMC3810468.

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Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, Melnyk S, James SJ. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One. 2014 Jan 8;9(1):e85436. doi: 10.1371/journal.pone.0085436. PMID: 24416410; PMCID: PMC3885720.

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Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, Melnyk S, James SJ. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One. 2014 Jan 8;9(1):e85436. doi: 10.1371/journal.pone.0085436. PMID: 24416410; PMCID: PMC3885720.

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Rossignol DA, Genuis SJ, Frye RE. Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry. 2014 Feb 11;4(2):e360. doi: 10.1038/tp.2014.4. PMID: 24518398; PMCID: PMC3944636.

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Rossignol DA, Frye RE. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 2014 Apr 22;5:150. doi: 10.3389/fphys.2014.00150. PMID: 24795645; PMCID: PMC4001006.

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Frye RE. Clinical potential, safety, and tolerability of arbaclofen in the treatment of autism spectrum disorder. Drug Healthc Patient Saf. 2014 May 10;6:69-76. doi: 10.2147/DHPS.S39595. PMID: 24872724; PMCID: PMC4025936.

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Frye RE, Rossignol DA. Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatr. 2014 Jun 27;2:66. doi: 10.3389/fped.2014.00066. PMID: 25019065; PMCID: PMC4073259.

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Frye RE, Slattery J, MacFabe DF, Allen-Vercoe E, Parker W, Rodakis J, Adams JB, Krajmalnik-Brown R, Bolte E, Kahler S, Jennings J, James J, Cerniglia CE, Midtvedt T. Approaches to studying and manipulating the enteric microbiome to improve autism symptoms. Microb Ecol Health Dis. 2015 May 7;26:26878. doi: 10.3402/mehd.v26.26878. PMID: 25956237; PMCID: PMC4425814.

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Richard E. Frye, Shannon Rose, John Slattery & Derrick F. MacFabe (2015) Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome, Microbial Ecology in Health and Disease, 26:1, DOI: 10.3402/mehd.v26.27458

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Frye RE. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder. Epilepsy Behav. 2015 Jun;47:147-57. doi: 10.1016/j.yebeh.2014.08.134. Epub 2014 Nov 4. PMID: 25440829.

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Hasan KM, Mwangi B, Cao B, Keser Z, Tustison NJ, Kochunov P, Frye RE, Savatic M, Soares J. Entorhinal Cortex Thickness across the Human Lifespan. J Neuroimaging. 2016 May;26(3):278-82. doi: 10.1111/jon.12297. Epub 2015 Oct 8. PMID: 26565394; PMCID: PMC4826319.

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Tilford JM, Payakachat N, Kuhlthau KA, Pyne JM, Kovacs E, Bellando J, Williams DK, Brouwer WB, Frye RE. Treatment for Sleep Problems in Children with Autism and Caregiver Spillover Effects. J Autism Dev Disord. 2015 Nov;45(11):3613-23. doi: 10.1007/s10803-015-2507-5. PMID: 26126749; PMCID: PMC4609586.

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Slattery J, MacFabe DF, Kahler SG, Frye RE. Enteric Ecosystem Disruption in Autism Spectrum Disorder: Can the Microbiota and Macrobiota be Restored? Curr Pharm Des. 2016;22(40):6107-6121. doi: 10.2174/1381612822666160905123953. PMID: 27592717.

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Frye, R., Cox, D., Slattery, J. et al. Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome. Sci Rep 6, 19544 (2016). https://doi.org/10.1038/srep19544

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Frye RE, Casanova MF, Fatemi SH, Folsom TD, Reutiman TJ, Brown GL, Edelson SM, Slattery JC, Adams JB. Neuropathological Mechanisms of Seizures in Autism Spectrum Disorder. Front Neurosci. 2016 May 10;10:192. doi: 10.3389/fnins.2016.00192. PMID: 27242398; PMCID: PMC4861974.

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Frye RE, Rossignol DA. Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes. Clin Med Insights Pediatr. 2016 Jun 15;10:43-56. doi: 10.4137/CMPed.S38337. PMID: 27330338; PMCID: PMC4910649.

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Niyazov DM, Kahler SG, Frye RE. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Mol Syndromol. 2016 Jul;7(3):122-37. doi: 10.1159/000446586. Epub 2016 Jun 3. PMID: 27587988; PMCID: PMC4988248.

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Slattery J, MacFabe DF, Frye RE. The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood. Clin Med Insights Pediatr. 2016 Oct 9;10:91-107. doi: 10.4137/CMPed.S38338. PMID: 27774001; PMCID: PMC5063840.

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Rose S, Bennuri SC, Wynne R, Melnyk S, James SJ, Frye RE. Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study. FASEB J. 2017 Mar;31(3):904-909. doi: 10.1096/fj.201601004R. Epub 2016 Nov 18. PMID: 27864377; PMCID: PMC5354548.

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Frye RE, Rose S, Chacko J, Wynne R, Bennuri SC, Slattery JC, Tippett M, Delhey L, Melnyk S, Kahler SG, MacFabe DF. Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines. Transl Psychiatry. 2016 Oct 25;6(10):e927. doi: 10.1038/tp.2016.189. PMID: 27779624; PMCID: PMC5290345.

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Rose S, Bennuri SC, Wynne R, Melnyk S, James SJ, Frye RE. Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study. FASEB J. 2017 Mar;31(3):904-909. doi: 10.1096/fj.201601004R. Epub 2016 Nov 18. PMID: 27864377; PMCID: PMC5354548.

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Delhey, L.M.; Nur Kilinc, E.; Yin, L.; Slattery, J.C.; Tippett, M.L.; Rose, S.; Bennuri, S.C.; Kahler, S.G.; Damle, S.; Legido, A.; Goldenthal, M.J.; Frye, R.E. The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. J. Clin. Med. 2017, 6, 18. https://doi.org/10.3390/jcm6020018

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Frye, R.E., Rose, S., Wynne, R. et al. Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines. Sci Rep 7, 4478 (2017). https://doi.org/10.1038/s41598-017-04821-3

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Frye, R.E., Rose, S., Wynne, R. et al. Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines. Sci Rep 7, 4478 (2017). https://doi.org/10.1038/s41598-017-04821-3

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Frye RE, Slattery JC, Quadros EV. Folate metabolism abnormalities in autism: potential biomarkers. Biomark Med. 2017 Aug;11(8):687-699. doi: 10.2217/bmm-2017-0109. Epub 2017 Aug 3. PMID: 28770615.

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Khemakhem, A.M., Frye, R.E., El-Ansary, A. et al. Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers. Metab Brain Dis 32, 1983–1997 (2017). https://doi.org/10.1007/s11011-017-0085-2

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Delhey L, Kilinc EN, Yin L, Slattery J, Tippett M, Wynne R, Rose S, Kahler S, Damle S, Legido A, Goldenthal MJ, Frye RE. Bioenergetic variation is related to autism symptomatology. Metab Brain Dis. 2017 Dec;32(6):2021-2031. doi: 10.1007/s11011-017-0087-0. Epub 2017 Aug 29. PMID: 28852932; PMCID: PMC5681971.

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Burger BJ, Rose S, Bennuri SC, et al. Autistic Siblings with Novel Mutations in Two Different Genes: Insight for Genetic Workups of Autistic Siblings and Connection to Mitochondrial Dysfunction. Frontiers in Pediatrics. 2017 ;5:219. DOI: 10.3389/fped.2017.00219. PMID: 29075622; PMCID: PMC5643424.

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Rose S, Bennuri SC, Murray KF, Buie T, Winter H, Frye RE. Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study. PLoS One. 2017 Oct 13;12(10):e0186377. doi: 10.1371/journal.pone.0186377. PMID: 29028817; PMCID: PMC5640251.

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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.

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Frye RE, Nankova B, Bhattacharyya S, Rose S, Bennuri SC, MacFabe DF. Front Immunol. 2017 Dec 22;8:1670. doi: 10.3389/fimmu.2017.01670. PMID: 29312285; PMCID: PMC5744079.

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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.

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Rose S, Bennuri SC, Davis JE, Wynne R, Slattery JC, Tippett M, Delhey L, Melnyk S, Kahler SG, MacFabe DF, Frye RE. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Transl Psychiatry. 2018 Feb 2;8(1):42. doi: 10.1038/s41398-017-0089-z. PMID: 29391397; PMCID: PMC5804031.

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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.

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Howsmon DP, Vargason T, Rubin RA, Delhey L, Tippett M, Rose S, Bennuri SC, Slattery JC, Melnyk S, James SJ, Frye RE, Hahn J. Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: A comparison and validation study. Bioeng Transl Med. 2018 Jun 19;3(2):156-165. doi: 10.1002/btm2.10095. PMID: 30065970; PMCID: PMC6063877.

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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.

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Connery K, Tippett M, Delhey LM, Rose S, Slattery JC, Kahler SG, Hahn J, Kruger U, Cunningham MW, Shimasaki C, Frye RE. Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism. Transl Psychiatry. 2018 Aug 10;8(1):148. doi: 10.1038/s41398-018-0214-7. PMID: 30097568; PMCID: PMC6086890.

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Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x. PMID: 30039193; PMCID: PMC6132446.

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Barone R, Alaimo S, Messina M, Pulvirenti A, Bastin J; MIMIC-Autism Group; Ferro A, Frye RE, Rizzo R. A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses. Front Psychiatry. 2018 Dec 7;9:636. doi: 10.3389/fpsyt.2018.00636. PMID: 30581393; PMCID: PMC6292950.

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