This collection of peer reviewed articles is intended to provide an overview of some of the best research on autism pathophysiology and treatment, with an emphasis on biological approaches. Included are gene-environment interactions on neurdevelopment/neuroplasticity, metabolism, immune function, gut physiology, environmental toxins/infectious processes and their impact on systems biology. Primarily intended for students and professionals of basic and clinical sciences, there is a link to each publication for web access. As the production of papers are rapidly accelerating, we will attempt to keep this list up to date. This site and these references document that there is growing evidence that autism spectrum disorders are biologically based whole body conditions that are largely environmentally modulated and have many preventable and treatable forms.

 

Frye RE, Melnyk S, MacFabe DF. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Translational Psychiatry 2013, 3: e220. doi: 10.1038/tp.2012.143

de Theije CG, Wu J, da Silva SL, Kamphuis PJ, Garssen J, Korte SM, Kraneveld AD (2011) Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management. Eur J Pharmacol. http://www.ncbi.nlm.nih.gov/pubmed/21810417

Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem 42:1032-1040. http://www.ncbi.nlm.nih.gov/pubmed/19306862?dopt=Citation

Al-Mosalem OA, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to energy metabolism in Saudi autistic children. Clin Biochem 42:949-957. http://www.ncbi.nlm.nih.gov/pubmed/19376103?dopt=Citation

Aneja A, Tierney E (2008) Autism: the role of cholesterol in treatment. Int Rev Psychiatry 20:165-170. http://www.ncbi.nlm.nih.gov/pubmed/18386207?dopt=Citation

Ashwood P, Van de Water J (2004) Is autism an autoimmune disease? Autoimmun Rev 3:557-562. http://www.ncbi.nlm.nih.gov/pubmed/15546805?dopt=Citation

Atladottir HO, Thorsen P, Schendel DE, Ostergaard L, Lemcke S, Parner ET (2010) Association of hospitalization for infection in childhood with diagnosis of autism spectrum disorders: a Danish cohort study. Arch Pediatr Adolesc Med 164:470-477. http://www.ncbi.nlm.nih.gov/pubmed/20439799

Braunschweig D, Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de WJ (2008) Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology 29:226-231. http://www.ncbi.nlm.nih.gov/pubmed/18078998?dopt=Citation

Buie T, et al. (2010a) Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125 Suppl 1:S1-18. http://www.ncbi.nlm.nih.gov/pubmed/20048083

Buie T, Fuchs GJ, III, Furuta GT, Kooros K, Levy J, Lewis JD, Wershil BK, Winter H (2010b) Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics 125 Suppl 1:S19-S29. http://www.ncbi.nlm.nih.gov/pubmed/20048084?dopt=Citation

Campbell DB, Buie TM, Winter H, Bauman M, Sutcliffe JS, Perrin JM, Levitt P (2009) Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics 123:1018-1024. http://www.ncbi.nlm.nih.gov/pubmed/19255034

Careaga M, Van de WJ, Ashwood P (2010) Immune dysfunction in autism: a pathway to treatment. Neurotherapeutics 7:283-292. http://www.ncbi.nlm.nih.gov/pubmed/20643381

Chauhan A, Audhya T, Chauhan V. Brain region-specific glutathione redox imbalance in autism. Neurochem Res 2012; 37: 1681–9.
http://www.ncbi.nlm.nih.gov/pubmed?term=chauhan%2C%20audhya

Chauhan A, Chauhan V (2006) Oxidative stress in autism. Pathophysiology 13:171-181. http://www.ncbi.nlm.nih.gov/pubmed/16766163

El-Ansary A, Al-Daihan S, Al-Dbass A, Al-Ayadhi L (2009) Measurement of selected ions related to oxidative stress and energy metabolism in Saudi autistic children. Clin Biochem. http://www.ncbi.nlm.nih.gov/pubmed/19781542?dopt=Citation

El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY (2011a) Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia. Lipids Health Dis 10:63. http://www.ncbi.nlm.nih.gov/pubmed/21513514?dopt=Citation

El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY (2011b) Plasma fatty acids as diagnostic markers in autistic patients from Saudi Arabia. Lipids Health Dis 10:62. http://www.ncbi.nlm.nih.gov/pubmed/21510882?dopt=Citation

Fahmy, S.F., El-hamamsy, M.H., Zaki, O.K., Badary, O.A.
l-Carnitine supplementation improves the behavioral symptoms in autistic children. Research in Autism Spectrum Disorders; 2013: 7:159–166
http://www.sciencedirect.com/science/article/pii/S1750946712000827

Fatemi SH, Reutiman TJ, Folsom TD, Huang H, Oishi K, Mori S, Smee DF, Pearce DA, Winter C, Sohr R, Juckel G (2008) Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res 99:56-70. http://www.ncbi.nlm.nih.gov/pubmed/18248790?dopt=Citation

Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ (2004) Relative carnitine deficiency in autism. J Autism Dev Disord 34:615-623. http://www.ncbi.nlm.nih.gov/pubmed/15679182

Finegold SM (2007) Therapy and epidemiology of autism-clostridial spores as key elements. Med Hypotheses. http://www.ncbi.nlm.nih.gov/pubmed/17904761

Finegold SM, et al. (2002) Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 35:S6-S16. http://www.ncbi.nlm.nih.gov/pubmed/12173102

Finegold SM (2011a) Desulfovibrio species are potentially important in regressive autism. Med Hypotheses 77:270-274. http://www.ncbi.nlm.nih.gov/pubmed/21592674?dopt=Citation

Finegold SM (2011b) State of the art; microbiology in health and disease. Intestinal bacterial flora in autism. Anaerobe. http://www.ncbi.nlm.nih.gov/pubmed/21524713?dopt=Citation

Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D, Liu M, Molitoris DR, Green JA, III (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe. http://www.ncbi.nlm.nih.gov/pubmed/20603222?dopt=Citation

Frye RE (2010) Central tetrahydrobiopterin concentration in neurodevelopmental disorders. Front Neurosci 4:52. http://www.ncbi.nlm.nih.gov/pubmed/20661295?dopt=Citation

Frye RE, Butler I, Strickland D, Castillo E, Papanicolaou A (2010a) Electroencephalogram discharges in atypical cognitive development. J Child Neurol 25:556-566. http://www.ncbi.nlm.nih.gov/pubmed/20299700

Frye RE, Huffman LC, Elliott GR (2010b) Tetrahydrobiopterin as a novel therapeutic intervention for autism. Neurotherapeutics 7:241-249. http://www.ncbi.nlm.nih.gov/pubmed/20643376

Frye RE, Rossignol DA (2011) Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res. http://www.ncbi.nlm.nih.gov/pubmed/21289536?dopt=Citation

Gargus JJ (2009) Genetic calcium signaling abnormalities in the central nervous system: seizures, migraine, and autism. Ann N Y Acad Sci 1151:133-156. http://www.ncbi.nlm.nih.gov/pubmed/19154521

Herbert MR (2005) Large brains in autism: the challenge of pervasive abnormality. Neuroscientist 11:417-440. http://www.ncbi.nlm.nih.gov/pubmed/16151044

Herbert MR (2010) Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 23:103-110. http://www.ncbi.nlm.nih.gov/pubmed/20087183

Herbert MR, Russo JP, Yang S, Roohi J, Blaxill M, Kahler SG, Cremer L, Hatchwell E (2006) Autism and environmental genomics. Neurotoxicology 27:671-684. http://www.ncbi.nlm.nih.gov/pubmed/16644012

Hu VW, Nguyen A, Kim KS, Steinberg ME, Sarachana T, Scully MA, Soldin SJ, Luu T, Lee NH (2009) Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis. PLoS ONE 4:e5775. http://www.ncbi.nlm.nih.gov/pubmed/19492049

Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486: 207–14.
http://www.ncbi.nlm.nih.gov/pubmed/22699609

James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW (2009) Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr 89:425-430. http://www.ncbi.nlm.nih.gov/pubmed/19056591

James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW (2006) Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 141:947-956. http://www.ncbi.nlm.nih.gov/pubmed/16917939

Jones LL, McDonald DA, Borum PR (2010) Acylcarnitines: role in brain. Prog Lipid Res 49:61-75. http://www.ncbi.nlm.nih.gov/pubmed/19720082?dopt=Citation

Kayser MA (2008) Inherited metabolic diseases in neurodevelopmental and neurobehavioral disorders. Semin Pediatr Neurol 15:127-131. http://www.ncbi.nlm.nih.gov/pubmed/18708003?dopt=Citation

Kossoff EH, Zupec-Kania BA, Rho JM (2009) Ketogenic Diets: An Update for Child Neurologists. J Child Neurol. http://www.ncbi.nlm.nih.gov/pubmed/19535814?dopt=Citation

Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, Ji L, Brown T, Malik M (2009) Elevated immune response in the brain of autistic patients. J Neuroimmunol 207:111-116. http://www.ncbi.nlm.nih.gov/pubmed/19157572?dopt=Citation

Li Z, Dong T, Proschel C, Noble M (2007) Chemically diverse toxicants converge on Fyn and c-Cbl to disrupt precursor cell function. PLoS Biol 5:e35. http://www.ncbi.nlm.nih.gov/pubmed/17298174

MacFabe, D.F. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microbial Ecology in Health & Disease 2012, 23: 19260

MacFabe DF, Cain NE, Boon F, Ossenkopp KP, Cain DP (2010) Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder. Behav Brain Res. http://www.ncbi.nlm.nih.gov/pubmed/20937326?dopt=Citation

MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, Taylor AR, Kavaliers M, Ossenkopp KP (2007) Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res 176:149-169. http://www.ncbi.nlm.nih.gov/pubmed/16950524

MacFabe DF, Rodriguez-Capote K, Hoffman JE, Franklin AE, Mohammad-Asef Y, Taylor A, Boon F, Cain D.P., Kavaliers M, Possmayer F, Ossenkopp KP (2008) A novel rodent model of autism: Intraventricular infusions of propionic acid increase locomotor activity and induce neuroinflammation and oxidative stress in discrete regions of adult rat brain. Am J Biochem & Biotech 4:146-166. http://www.scipub.org/fulltext/ajbb/ajbb42146-166.pdf

Manson JE (2008) Prenatal exposure to sex steroid hormones and behavioral/cognitive outcomes. Metabolism 57 Suppl 2:S16-S21. http://www.ncbi.nlm.nih.gov/pubmed/18803959?dopt=Citation

Meguid NA, Atta HM, Gouda AS, Khalil RO (2008) Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem 41:1044-1048. http://www.ncbi.nlm.nih.gov/pubmed/18582451?dopt=Citation

Meidenbauer JJ, Mantis JG, Seyfried TN (2011) The EL mouse: a natural model of autism and epilepsy. Epilepsia 52:347-357. http://www.ncbi.nlm.nih.gov/pubmed/21204822?dopt=Citation

Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG, Fussell JJ, Bellando J, Pavliv O, Rose S, Seidel L, Gaylor DW, Jill JS (2011) Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism. J Autism Dev Disord. http://www.ncbi.nlm.nih.gov/pubmed/21519954?dopt=Citation

Nguyen A, Rauch TA, Pfeifer GP, Hu VW (2010) Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J 24:3036-3051. http://www.ncbi.nlm.nih.gov/pubmed/20375269

Ossenkopp K. P., Foley K. A., Gibson J., Fudge M. A., Kavaliers M., Cain D. P. and Macfabe D. F. (2011) Systemic treatment with the enteric bacterial fermentation product, propionic acid, produces both conditioned taste avoidance and conditioned place avoidance in rats. Behav. Brain Res. 227, 134-141.
http://www.ncbi.nlm.nih.gov/pubmed/22085877?dopt=Citation

Palmieri L, Persico AM (2010) Mitochondrial dysfunction in autism spectrum disorders: Cause or effect? Biochim Biophys Acta 1797:1130-1137. http://www.ncbi.nlm.nih.gov/pubmed/20441769

Patterson PH (2011) Maternal infection and immune involvement in autism. Trends Mol Med. http://www.ncbi.nlm.nih.gov/pubmed/21482187?dopt=Citation

Pessah IN, Seegal RF, Lein PJ, LaSalle J, Yee BK, Van de WJ, Berman RF (2008) Immunologic and neurodevelopmental susceptibilities of autism. Neurotoxicology 29:532-545. http://www.ncbi.nlm.nih.gov/pubmed/18394707

Rossignol DA, Frye RE (2011) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. http://www.ncbi.nlm.nih.gov/pubmed/21263444?dopt=Citation

Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Vaisanen ML, Nelson MN, Wexler HM (2000) Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol 15:429-435. http://www.ncbi.nlm.nih.gov/pubmed/10921511

Sarachana T, Zhou R, Chen G, Manji HK, Hu VW (2010) Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines. Genome Med 2:23. http://www.ncbi.nlm.nih.gov/pubmed/20374639

Shoffner J, Hyams L, Langley GN, Cossette S, Mylacraine L, Dale J, Ollis L, Kuoch S, Bennett K, Aliberti A, Hyland K (2010) Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol 25:429-434. http://www.ncbi.nlm.nih.gov/pubmed/19773461

Shultz SR, Macfabe DF, Martin S, Jackson J, Taylor R, Boon F, Ossenkopp KP, Cain DP (2009) Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. Behav Brain Res 200:33-41. http://www.ncbi.nlm.nih.gov/pubmed/19154758

Shultz SR, Macfabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, Cain DP (2008) Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology 54:901-911. http://www.ncbi.nlm.nih.gov/pubmed/18395759

Smith RA, Farnworth H, Wright B, Allgar V (2009) Are there more bowel symptoms in children with autism compared to normal children and children with other developmental and neurological disorders?: A case control study. Autism 13:343-355. http://www.ncbi.nlm.nih.gov/pubmed/19535465?dopt=Citation

Suren P, Bakken IJ, Aase H, Chin R, Gunnes N, Lie KK, et al. Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in norwegian children. Pediatrics 2012; 130: e152–8.
http://www.ncbi.nlm.nih.gov/pubmed?term=suren%2C%20bakken

Tamiji J, Crawford DA (2010) The neurobiology of lipid metabolism in autism spectrum disorders. Neurosignals 18:98-112. http://www.ncbi.nlm.nih.gov/pubmed/21346377?dopt=Citation

Theoharides TC, Doyle R, Francis K, Conti P, Kalogeromitros D (2008) Novel therapeutic targets for autism. Trends Pharmacol Sci 29:375-382. http://www.ncbi.nlm.nih.gov/pubmed/18606459?dopt=Citation

Thomas, R.H, Meeking, M. M., Mepham, J.R., Tichenoff, L.J., Possmayer, F. Suya Liu and MacFabe, D.F. The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders. J. of Neuroinflammation –accepted May 2012

Thomas RH, Foley KA, Mepham JR, Tichenoff LJ, Possmayer F, Macfabe DF (2010) Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders. J Neurochem 113:515-529. http://www.ncbi.nlm.nih.gov/pubmed/20405543

Tuchman R, Moshe SL, Rapin I (2008) Convulsing toward the pathophysiology of autism. Brain Dev. http://www.ncbi.nlm.nih.gov/pubmed/19006654?dopt=Citation

Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67-81. http://www.ncbi.nlm.nih.gov/pubmed/15546155

Waldman M, Nicholson S, Adilov N, Williams J (2008) Autism prevalence and precipitation rates in California, Oregon, and Washington counties. Arch Pediatr Adolesc Med 162:1026-1034. http://www.ncbi.nlm.nih.gov/pubmed/18981350?dopt=Citation

Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci 2012; 57: 2096–102.
http://www.ncbi.nlm.nih.gov/pubmed/22535281

Wang LW, Tancredi DJ, Thomas DW (2011) The Prevalence of Gastrointestinal Problems in Children Across the United States with Autism Spectrum Disorders from Families with Multiple Affected Members. J Dev Behav Pediatr. http://www.ncbi.nlm.nih.gov/pubmed/21555957?dopt=Citation

Wei H, Zou H, Sheikh A, Malik M, Dobkin C, Brown T, Li X (2011) IL-6 is increased in the cerebellum of the autistic brain and alters neural cell adhesion, migration and synapse formation. J Neuroinflammation 8:52. http://www.ncbi.nlm.nih.gov/pubmed/21595886?dopt=Citation

Welch MG, Welch-Horan TB, Anwar M, Anwar N, Ludwig RJ, Ruggiero DA (2005) Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin. J Mol Neurosci 25:259-274. http://www.ncbi.nlm.nih.gov/pubmed/15800379

Williams B. L., Hornig M., Buie T., Bauman M. L., Cho P. M., Wick I., Bennett A., Jabado O., Hirschberg D. L. and Lipkin W. I. (2011) Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One 6, e24585.
http://www.ncbi.nlm.nih.gov/pubmed/21949732

Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JK (2010) Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls. J Proteome Res. http://www.ncbi.nlm.nih.gov/pubmed/20337404?dopt=Citation