Integrative concept of pathogenesis and GBINS personalized multidisciplinary approach to clinical management of children with neuropsychiatric syndromes, associated with genetic deficiency of folate cycle
Keywords:
autism spectrum disorders, attention deficit hyperactivity disorder, obsessive-compulsive syndrome, immunodiagnostics, biochemical correction, immunotherapyAbstract
Background and aim: The problem of children’s neuropsychiatric diseases is a priority task of modern medicine to resolve. Scientific achievements in genetics, molecular biology, and immunology shed light on the mechanisms of brain damage in children with ASD. Results: Today, the folate-centric concept of polygenic inheritance of predisposition to the development of neuropsychiatric syndromes in children with multisystem body lesions has been established. Biochemical and immune-dependent ways of formation of microbe-induced autoimmune inflammatory encephalopathy with neuropsychiatric clinical manifestations in the context of a folate-centric concept are discussed. Considering the new data, two personalized multidisciplinary approaches to managing children with ASD and other neuropsychiatric syndromes are proposed. The first approach of Bradstreet et al (2010) is based on an empirical analysis of a large group of laboratory biomarkers. In 2022 Frye R. developed a multidisciplinary personalized approach called Bas-VISTOR. It systematizes and stratifies diagnostic and therapeutic interventions according to biomarkers assessment. Conclusions: This article puts forward an improved personalized multidisciplinary approach to clinical management of patients with ASD and neuropsychiatric manifestations associated with genetic folate cycle deficiency ‑ Genetic-Biochemical-Immunological-Neurological-Symptomatic. The successful testing of evidence-based personalized multidisciplinary diagnostic and treatment strategies in clinical practice will make it possible to make a breakthrough in the clinical management of children with severe mental disorders. This will provide not only the possibility of recovery from the prognostically unfavorable and currently non-curable neuropsychiatric disorder but will also contribute to stop the large-scale threatening epidemic of neuropsychiatric syndromes in the modern pediatric population.
References
Hughes HK, Mills Ko E, Rose D, Ashwood P. Immune dysfunction and autoimmunity as pathological mechanisms in autism spectrum disorders. Front Cell Neurosci. 2018;405. doi: 10.3389/fncel.2018.00405.
Maenner MJ, Shaw KA, Baio J, et al. Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2016. MMWR Surveill Summ. 2020;69(4):1-12. doi: 10.15585/mmwr.ss6904a1.
Catalá-López F, Hutton B, Page MJ, et al. Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis. JAMA Pediatr. 2022;176(4):e216401. doi:10.1001/jamapediatrics.2021.6401.
O'Halloran L, Coey P, Wilson C. Suicidality in autistic youth: A systematic review and meta-analysis. Clinic Psych Rev. 2022;93:102144. doi: 10.1016/j.cpr.2022.102144.
Zheng Z, Zheng P, Zou X. Association between schizophrenia and autism spectrum disorder: A systematic review and meta-analysis. Autism Res. 2018;11(8):1110-1119. doi: 10.1002/aur.1977.
Frye RE. A Personalized Multidisciplinary Approach to Evaluating and Treating Autism Spectrum Disorder. J Pers Med. 2022;12(3);464. doi: 10.3390/jpm12030464.
Cakir J, Frye RE, Walker SJ. The lifetime social cost of autism: 1990–2029. Res Autism Spectr Disord. 2020;72:101502. doi: 10.1016/j.rasd.2019.101502.
Tick B, Bolton P, Happé F, et al. Heritability of autism spectrum disorders: a meta-analysis of twin studies. J Child Psychol Psychiatry. 2016;57(5):585-595. doi: 10.1111/jcpp.12499
Henske EP, Jóźwiak S, Kingswood JC, Sampson JR, Thiele EA. Tuberous sclerosis complex. Nat Rev Dis Primers. 2016;2:16035. doi: 10.1038/nrdp.2016.35.
Mpoulimari I, Zintzaras E. Synthesis of genetic association studies on autism spectrum disorders using a genetic model-free approach. Psychiatr Genet. 2022;32(3):91-104. doi: 10.1097/YPG.0000000000000316.
Li Y, Qiu S, Shi J, et al. Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis. BMC Pediatr. 2020;20:449. doi: 10.1186/s12887-020-02330-3.
Sadeghiyeh T, Dastgheib SA, Mirzaee-Khoramabadi K, et al. Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: A systematic review and meta-analysis. Asian J Psychiatr. 2019;46:54-61. doi: 10.1016/j.ajp.2019.09.016.
Mohammad NS, Shruti PS, Bharathi V, et al. Clinical utility of folate pathway genetic polymorphisms in the diagnosis of autism spectrum disorders. Psychiatr Genet. 2016;26(6):281-286. doi: 10.1097/YPG.0000000000000152.
Pu D, Shen Y, Wu J. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res. 2013;6(5):384-392. doi: 10.1002/aur.1300.
Rai V. Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility. Metab Brain Dis. 2016;31(4):727-735. doi: 10.1007/s11011-016-9815-0.
Haghiri R, Mashayekhi F, Bidabadi E, Salehi Z. Analysis of methionine synthase (rs1805087) gene polymorphism in autism patients in Northern Iran. Acta Neurobiol Exp (Wars). 2016;76(4):318-323.
Chen L, Shi XJ, Liu H, et al. Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N = 9109). Transl Psychiatry. 2021;11(1):15. doi: 10.1038/s41398-020-01135-3.
Frustaci A, Neri M, Cesario A, et al. Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. Free Radic Biol Med. 2012;52(10):2128-2141. doi: 10.1016/j.freeradbiomed.2012.03.011.
Guo BQ, Li HB, Ding SB. Blood homocysteine levels in children with autism spectrum disorder: An updated systematic review and meta-analysis. Psychiatry Res. 2020;291:113283. doi: 10.1016/j.psychres.2020.113283.
Wan L, Li Y, Zhang Z, Sun Z, He Y, Li R. Methylenetetrahydrofolate reductase and psychiatric diseases. Transl Psychiatry.2018;8(1):242. doi: 10.1038/s41398-018-0276-6.
Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015;132(1):e6–9 doi: 10.1161/CIRCULATIONAHA.114.013311.
James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(8):947-56. doi: 10.1002/ajmg.b.30366.
Khan S, Naeem A. MTHFR Deficiency in Biological Siblings Diagnosed With Autism and Attention-Deficit Hyperactivity Disorder (ADHD): A Report of Two Cases. Cureus. 2023;15(3): e36294. doi: 10.7759/cureus.36294.
Horiuchi F, Yoshino Y, Kumon H, et al. Identification of aberrant innate and adaptive immunity based on changes in global gene expression in the blood of adults with autism spectrum disorder. J Neuroinflammation. 2021;18(1):102. doi: 10.1186/s12974-021-02154-7
Belardo A, Gevi F, Zolla L. The concomitant lower concentrations of vitamins B6, B9 and B12 may cause methylation deficiency in autistic children. J Nutr Biochem. 2019;70:38-46. doi: 10.1016/j.jnutbio.2019.04.004.
Bjørklund G, Doşa MD, Maes M, et al. The impact of glutathione metabolism in autism spectrum disorder. Pharm Res. 2021;166, 105437. doi: 10.1016/j.phrs.2021.105437.
Frye RE. Mitochondrial dysfunction in autism spectrum disorder: Unique abnormalities and targeted treatments. Seminars Pediatric Neurol. 2020;35:100829. doi: 10.1016/j.spen.2020.100829.
Frye RE, Rossignol DA. Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatr. 2014;2:66. doi: 10.3389/fped.2014.00066.
Rossignol DA, Frye RE. The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(8): 784. doi: 10.3390/jpm11080784.
Rossignol DA, Frye RE. Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(11):1141. doi: 10.3390/jpm11111141.
Heuer L, Ashwood P, Schauer J, et al. Reduced Levels of Immunoglobulin in Children With Autism Correlates With Behavioral Symptoms. Autism Res. 2008;1(5):275-283. doi: 10.1002/aur.42.
Jyonouchi H, Geng L, Streck DL, Toruner GA. Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. J Neuroinflam. 2012;9:4-16. doi: 10.1186/1742-2094-9-4.
Rossignol DA, Frye RE. A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder. J Pers Med. 2021;11(6):488. doi: 10.3390/jpm11060488.
Baj J, Sitarz E, Forma A, et al. Alterations in the Nervous System and Gut Microbiota after beta-Hemolytic Streptococcus Group A Infection-Characteristics and Diagnostic Criteria of PANDAS Recognition. Int J Mol Sci. 2020;21(4):1476. doi: 10.3390/ijms21041476.
Luleyap HU, Onatoglu D, Yilmaz MB, et al. Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene-308 g/a, -850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey. Indian J Hum Genet. 2013;19(2):196-201. doi: 10.4103/0971-6866.116116.
Wang Z, Ding R, Wang J. The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis. Nutrients. 2020;13(1):E86. doi: 10.3390/nu13010086.
Yektaş Ç, Alpay M, Tufan AE. Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls. Neuropsychiatr Dis Treat. 2019;15:2213-2219. doi: 10.2147/NDT.S212361.
Furlano RI, Anthony A, Day R, et al. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr. 2001;138(3):366-372. doi: 10.1067/mpd.2001.111323.
Isung J, Williams K, Isomura K, et al. Association of Primary Humoral Immunodeficiencies With Psychiatric Disorders and Suicidal Behavior and the Role of Autoimmune Diseases. JAMA Psychiatry. 2020;77(11):1147-1154. doi: 10.1001/jamapsychiatry.2020.1260.
Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neurosci Biobehav Rev. 2015;55:294-321. doi: 10.1016/j.neubiorev.2015.04.015.
Warren RP, Foster ANN, Margaretten NC. Reduced natural killer cell activity in autism. J Am Acad Child Adolesc Psych. 1987 26(3):333-335. doi: 10.1097/00004583-198705000-00008.
Warren RP, Yonk LJ, Burger RA, et al. Deficiency of suppressor inducer T cells in autism. Immunol Invest. 1990;19:245-251. doi: 10.3109/08820139009041839.
Cabanlit M, Wills S, Goines P, Ashwood P, Van De Water JUDY. Brain‐specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Annals NY Acad Sci. 2007;1107(1):92-103. doi: 10.1196/annals.1381.010.
Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2013;18(3):369-381. doi: 10.1038/mp.2011.175.
Binstock T. Intra-monocyte pathogens delineate autism subgroups. Med Hypotheses. 2001;56(4):523-531. doi: 10.1054/mehy.2000.1247.
Crawley JN, Heyer WD, LaSalle JM. Autism and cancer share risk genes, pathways, and drug targets. Trends Genet. 2016;32(3):139-146. doi: 10.1016/j.tig.2016.01.001.
McDougle CJ, Landino SM, Vahabzadeh A, et al. Toward an immune-mediated subtype of autism spectrum disorder. Brain Res. 2015;1617:72-92. doi: 10.1016/j.brainres.2014.09.048.
Maltsev DV. Results of the assessment of the immune status in children with autism spectrum disorders: immunodeficiency associated with genetic deficiency of the folate cycle. Immunol Allergol: Sci Pract. 2021;4:5–23. doi: 10.37321/immunology.2021.4-01 (in Ukrainian).
Careaga M, Rogers S, Hansen RL, Amaral DG, Van de Water J, Ashwood P. Immune endophenotypes in children with autism spectrum disorder. Biol Psychiatry. 2017;81:434–441. doi: 10.1016/j.biopsych.2015.08.036.
Maltsev D. Features of folate cycle disorders in children with ASD. Bangladesh J Med Sci. 2020;19(4):737-742. doi: 10.3329/bjms.v19i4.46634.
Maltsev D. The results of studying the microbial spectrum in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. Men’s Health, Gender and Psychosomatic Med. 2021;(1-2):26-39. doi: 10.37321/UJMH.2021.1-2-04 (in Ukrainian).
Mauracher AA, Gujer E, Bachmann LM, Güsewell S, Schmid JP. Patterns of immune dysregulation in primary immunodeficiencies: a systematic review. J Allergy Clin Immunol Pract. 2021;9(2):792-802. doi: 10.1016/j.jaip.2020.10.057.
Bouboulis DA, Mast PA. Infection-Induced Autoimmune Encephalopathy: Treatment with Intravenous Immune Globulin Therapy. A Report of Six Patients. Int J Neurol Res. 2016;2:256-258.
Chen N, Zhang X, Zheng K, et al. Increased risk of group B Streptococcus causing meningitis in infants with mannose-binding lectin deficiency. Clin Microbiol Infect. 2019;25(3):384.e1-384.e3. doi: 10.1016/j.cmi.2018.10.003.
Asogwa K, Buabeng K, Kaur A. Psychosis in a 15-Year-Old Female with Herpes Simplex Encephalitis in a Background of Mannose-Binding Lecithin Deficiency. Case Rep Psychiatry. 2017;2017:1429847. doi: 10.1155/2017/1429847.
Bagheri-Hosseinabadi Z, Imani D, Yousefi H, Abbasifard M. MTHFR gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis based on 16 studies. Clin Rheumatol. 2020;39(8):2267-2279. doi: 10.1007/s10067-020-05031-5.
Boughrara W, Aberkane M, Fodil M, et al. Impact of MTHFR rs1801133, MTHFR rs1801131 and ABCB1 rs1045642 polymorphisms with increased susceptibility of rheumatoid arthritis in the West Algerian population: A case-control study. Acta Reumatol Port. 2015;40(4):363-371.
Dimitroulas T, Sandoo A, Hodson J, Smith J, Douglas KM, Kitas GD. Associations between asymmetric dimethylarginine, homocysteine, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in rheumatoid arthritis. Scand J Rheumatol. 2016;45(4):267-273. doi: 10.3109/03009742.2015.1086433.
Maltsev DV. The results of the search for laboratory signs of autoimmune reactions to cerebral and extracerebral autoantigens in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. MSU. 2021;17(3):22-37. doi: 10.32345/2664-4738.3.2021.03.
Carlus SJ, Abdallah AM, Bhaskar LV, Morsy MM, Al-Harbi GS, Al-Mazroea AH, Al-Harbi KM. The MTHFR C677T polymorphism is associated with mitral valve rheumatic heart disease. Eur Rev Med Pharmacol Sci. 2016;20(1):109-114.
Aydin SZ, Atagunduz P, Inanc N, Bicakcigil M, Tasan D, Temel M, Direskeneli H. Mannose binding lectin levels in spondyloarthropathies. J Rheumatol. 2007;34(10):2075-2077. PubMed: 17896801.
Yigit S, Inanir A, Tural S, Filiz B, Tekcan A. The effect of IL-4 and MTHFR gene variants in ankylosing spondylitis. Z Rheumatol. 2015;1:60-66. doi: 10.1007/s00393-014-1403-2.
Naghibalhossaini F, Ehyakonandeh H, Nikseresht A, Kamali E. Association Between MTHFR Genetic Variants and Multiple Sclerosis in a Southern Iranian Population. Int J Mol Cell Med. 2015;4(2):87-93. PMID: 26261797.
Sævarsdóttir S, Vikingsdottir T, Vikingsson A, Manfredsdottir V, Geirsson AJ, Valdimarsson H. Low mannose binding lectin predicts poor prognosis in patients with early rheumatoid arthritis. A prospective study. J Rheumatol. 2001;28(4):728–734.
Glesse N, Monticielo OA, Mattevi VS, et al. Association of mannose-binding lectin 2 gene polymorphic variants with susceptibility and clinical progression in systemic lupus erythematosus. Clin Exp Rheumatol. 2011;29(6):983-990.
Jin Z, Ji Z, Hu J. Mannose-binding lectin gene site mutations and the susceptibility of rheumatic heart disease. Zhonghua Yi Xue Za Zhi. 2001;81(21):1284-1286. PMID: 16200716.
Li M, Tang Y, Zhao EY, Chen CH, Dong LL. Relationship between MTHFR gene polymorphism and susceptibility to bronchial asthma and glucocorticoid efficacy in children. Zhongguo Dang dai er ke za zhi= Ch J Contempor Pediatr. 2021;23(8):802-808. doi: 10.7499/j.issn.1008-8830.2105035.
Wang T, Zhang HP, Zhang X, Liang ZA, Ji YL, Wang G. Is Folate Status a Risk Factor for Asthma or Other Allergic Diseases? Allergy Asthma Immunol Res. 2015;7(6):538-546. doi: 10.4168/aair.2015.7.6.538.
Birbian N, Singh J, Jindal SK, Joshi A, Batra N, Singla N. Association of the wild-type A/A genotype of MBL2 codon 54 with asthma in a North Indian population. Dis Markers. 2012;32(5):301-308. doi: 10.3233/DMA-2012-0892.
El-Hadidy MA, Abdeen HM, Abd El-Aziz SM, Al-Harrass M. MTHFR gene polymorphism and age of onset of schizophrenia and bipolar disorder. Biomed Res Int. 2014;2014:318483. doi: 10.1155/2014/318483.
Peerbooms OL, van Os J, Drukker M, et al. Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability? Brain Behav Immun. 2011;25(8):1530-1543. doi: 10.1016/j.bbi.2010.12.006.
Foldager L, Köhler O, Steffensen R, Thiel S, Kristensen AS, Jensenius JC, Mors O. Bipolar and panic disorders may be associated with hereditary defects in the innate immune system. J Affect Disorders. 2014;164:148-154. doi: 10.1016/j.jad.2014.04.017.
Peng Q, Lao X, Huang X, Qin X, Li S, Zeng Z. The MTHFR C677T polymorphism contributes to increased risk of Alzheimer's disease: evidence based on 40 case-control studies. Neurosci Lett. 2015;586:36-42. doi: 10.1016/j.neulet.2014.11.049.
Chen F, Wen T, Lv Q, Liu F. Associations between Folate Metabolism Enzyme Polymorphisms and Lung Cancer: A Meta-Analysis. Nutr Cancer. 2020;72(7):1211-1218. doi: 10.1080/01635581.2019.1677924.
Li C, Yichao J, Jiaxin L, Yueting Z, Qin L, Tonghua Y. Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis. J Buon. 2015;20(6):1534-1545.
Promthet S, Pientong C, Ekalaksananan T, et al. Risk factors for rectal cancer and methylenetetrahydrofolate reductase polymorphisms in a population in Northeast Thailand. Asian Pac J Cancer Prev. 2012;13(8):4017-4023. doi: 10.7314/APJCP.2012.13.8.4017.
Qi X, Sun X, Xu J, Wang Z, Zhang J, Peng Z. Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk in Chinese population. Tumour Biol. 2014;35(3):1757-1762. doi: 10.1007/s13277-013-1529-x.
Singh A, Pandey S, Pandey LK, Saxena AK. In human alleles specific variation of MTHFR C677T and A1298C associated “risk factor” for the development of ovarian cancer. J Exp Ther Oncol. 2015;11(1):67-70.
Wang Y, Yang H, Duan G. MTHFR gene A1298C polymorphisms are associated with breast cancer risk among Chinese population: evidence based on an updated cumulative meta-analysis. Int J Clin Exp Med. 2015;8(11):20146. PMID: 26884927.
Swierzko AS, Szala A, Sawicki S, et al. Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours. Cancer Immunol Immunother. 2014;63(11):1129-1140. doi: 10.1007/s00262-014-1579-y.
Russo AJ, Krigsman A, Jepson B, Wakefield A. Low serum myeloperoxidase in autistic children with gastrointestinal disease. Clinic Exp Gastroenter. 2009;2:85-94. doi: 10.2147/ceg.s6051.
Kovacs M, Papp M, Lakatos PL, et al. Low mannose-binding lectin (MBL) is associated with paediatric inflammatory bowel diseases and ileal involvement in patients with Crohn disease. J Crohns Colitis. 2013;7(2):134-141. doi: 10.1016/j.crohns.2012.03.008.
Rai V, Yadav U, Kumar P, Yadav SK, Mishra OP. Maternal methylenetetrahydrofolate reductase C677T polymorphism and down syndrome risk: a meta-analysis from 34 studies. PLoS One. 2014;9(9):e108552. doi: 10.1371/journal.pone.0108552.
Nisihara RM, Utiyama SR, Oliveira NP, Messias-Reason IJ. Mannan-binding lectin deficiency increases the risk of recurrent infections in children with Down's syndrome. Hum Immunol. 2010;71(1):63-66. doi: 10.1016/j.humimm.2009.09.361.
Borges MC, Hartwig FP, Oliveira IO, Horta BL. Is there a causal role for homocysteine concentration in blood pressure? A Mendelian randomization study. Am J Clin Nutr. 2016;103(1):39-49. doi: 10.3945/ajcn.115.116038.
Madsen HO, Videm V. Association of mannose-binding-lectin deficiency with severe atherosclerosis. Lancet. 1998;352(9132):959-960.
Chen H, Yang X, Lu M. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch Gynecol Obstet. 2016;293(2):283-290. doi: 10.1007/s00404-015-3894-8.
Kilpatrick DC, Starrs L, Moore S, Souter V, Liston WA. Mannan binding lectin concentration and risk of miscarriage. Human Reprod. 1999;14(9):2379-2380. doi: 10.1093/humrep/14.9.2379.
Yang Y, Luo Y, Yuan J, et al. Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation. Arch Gynecol Obstet. 2016;293(6):1197-1211. doi: 10.1007/s00404-015-3944-2.
Maltsev DV, Stefanyshyn VM. Efficacy of combined immunotherapy with propes and inflamafertin in selective deficiency of nk and nkt cells in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. Cur Pediatric Res. 2021;25(4):536-540. doi: 10.37897/RJN.2021.2.13.
Nicolson GL, Gan R, Nicolson NL, Haier J. Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders. J Neurosci Res. 2007;85(5):1143-1148. doi: 10.1002/jnr.21203.
Valayi S, Eftekharian MM, Taheri M, Alikhani MY. Evaluation of antibodies to cytomegalovirus and Epstein-Barr virus in patients with autism spectrum disorder. Hum Antibodies. 2017;26(3):165-169. doi: 10.3233/HAB-180335.
Kuhn M, Grave S, Bransfield R, Harris S. Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and autism spectrum disorder.Med Hypotheses. 2012;78(5):606-615. doi: 10.1016/j.mehy.2012.01.037.
Hughes HK, Ashwood P. Anti-Candida albicans IgG antibodies in children with autism spectrum disorders. Front Psychiatry. 2018;26(9):627. doi: 10.3389/fpsyt.2018.00627.
Nayeri T, Sarvi S, Moosazadeh M, Hosseininejad Z, Sharif M, Amouei A, Daryani A. Relationship between toxoplasmosis and autism: A systematic review and meta-analysis. Microb Pathog. 2020;147:104434. doi: 10.1016/j.micpath.2020.104434.
Ghaziuddin M, Al-Khouri I, Ghоaziuddin N. Autistic symptoms following herpes encephalitis. Eur Child Adolesc Psychiatry. 2002;11(3):142-146. doi: 10.1007/s00787-002-0271-5.
Sakamoto A, Moriuchi H, Matsuzaki J, Motoyama K, Moriuchi M. Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit. Brain Dev. 2015;37(2):200-205. doi: 10.1016/j.braindev.2014.03.016.
Monge-Galindo L, Pérez-Delgado R, López-Pisón J, Lafuente-Hidalgo M, del Olmo-Izuzquiza IR, Peña-Segura JL. Mesial temporal sclerosis in paediatrics: its clinical spectrum. Our experience gained over a 19-year period. Rev Neurol. 2010;50(6):341-348. PMID: 20309832.
Wipfler P, Dunn N, Beiki O, Trinka E, Fogdell-Hahn A. The Viral Hypothesis of Mesial Temporal Lobe Epilepsy Is Human Herpes Virus-6 the Missing Link? A systematic review and meta-analysis. Seizure. 2018;54:33-40. doi: 10.1016/j.seizure.2017.11.015.
Harberts E, Yao K, Wohler JE, Maric D, Ohayon J, Henkin R, Jacobson S. Human herpesvirus-6 entry into the central nervous system through the olfactory pathway. PNAS. 2011;108(33):13734-13739. doi: 10.1073/pnas.110514310.
Lecointe D, Fabre M, Habes D, Mielot F, Bernard O, Nordmann P. Macrophage activation syndrome in primary human herpes virus-6 infection: a rare condition after liver transplantation in infants. Gastroenterol Clin Biol. 2000;24(12):1227-1228. PMID: 11173737.
Bobrowski-Khoury N, Ramaekers VT, Sequeira JM, Quadros EV. Folate receptor alpha autoantibodies in autism spectrum disorders: diagnosis, treatment and prevention. J Persona Med. 2021;11(8):710. doi: 10.3390/jpm11080710.
Li Ye, Viscidi RP, Kannan G, et al. Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-d-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology. Infect Immun. 2018;86(10):e00398-18. doi: 10.1128/IAI.00398-18.
Venâncio P, Brito MJ, Pereira G, Vieira JP. Anti-N-methyl-D-aspartate receptor encephalitis with positive serum antithyroid antibodies, IgM antibodies against mycoplasma pneumoniae and human herpesvirus 7 PCR in the CSF. Pediat Infect Dis J. 2014;33(8):882-883. doi: 10.1097/INF.0000000000000408.
Singh VK, Warren RP, Odell JD, Warren WL, Cole P. Antibodies to myelin basic protein in children with autistic behavior. Brain, Behav Immun. 1993;7(1):97-103. doi: 10.1006/brbi.1993.1010.
Kern JK, Geier DA, Mehta JA, Homme KG, Geier MR. Mercury as a hapten: A review of the role of toxicant-induced brain autoantibodies in autism and possible treatment considerations. J Trace Elem Med Biol. 2020;62:126504. doi: 10.1016/j.jtemb.2020.126504.
Snider LA, Lougee L, Slattery M, Grant P, Swedo SE. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry. 2005;57(7):788-792. doi: 10.1016/j.biopsych.2004.12.035.
Brimberg L, Sadiq A, Gregersen PK, Diamond B. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Mol Psychiatry. 2013;18(11):1171-1177. doi: 10.1038/mp.2013.101.
Mostafa GA, El-Sherif DF, Al-Ayadhi LY. Systemic auto-antibodies in children with autism. J Neuroimmun. 2014;272(1-2):94-98. doi: 10.1016/j.jneuroim.2014.04.011.
Prüss H. Autoantibodies in neurological disease. Nat Rev Immun. 2021;21(12):798-813. doi: 10.1038/s41577-021-00543-w
Whiteley P, Marlow B, Kapoor RR, Blagojevic-Stokic N, Sala R. Autoimmune encephalitis and autism spectrum disorder. Front Psychiatry. 2021;12:775017. doi: 10.3389/fpsyt.2021.775017.
Maltsev DV. Efficacy of rituximab in autism spectrum disorders associated with genetic folate cycle deficiency with signs of antineuronal autoimmunity. Intern Neurol J. 2021;12(3):472-486. doi: 10.22141/2224-0713.17.5.2021.238518.
Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ. Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry. 2015;20(4):440-446. doi: 10.1038/mp.2014.59.
Saghazadeh A, Ataeinia B, Keynejad K, Abdolalizadeh A, Hirbod-Mobarakeh A, Rezaei NA. meta-analysis of pro-inflammatory cytokines in autism spectrum disorders: Effects of age, gender, and latitude. J Psychiatr Res. 2019;115:90-102. doi: 10.1016/j.jpsychires.2019.05.019.
Thom RP, Keary CJ, Palumbo ML, et al. Beyond the brain: A multi-system inflammatory subtype of autism spectrum disorder. Psychopharmacology. 2019;236(10):3045-3061. doi: 10.1007/s00213-019-05280-6.
Maltsev DV. Evaluation of markers of inflammation and neuronal damage in patients with autism spectrum disorders associated with genetic deficiency of folate cycle. Immunol Allergy: Sci Pract. 2021;3:31-39. doi: 10.37321/immunology.2021.3-04 (in Ukrainian).
Lv MN, Zhang H, Shu Y, Chen S, Hu YY, Zhou M. The neonatal levels of TSB, NSE and CK-BB in autism spectrum disorder from Southern China. Transl Neurosci. 2016;7(1):6-11. doi: 10.1515/tnsci-2016-0002.
Zheng Z, Zheng P, Zou X. Peripheral blood S100B levels in autism spectrum disorder: A systematic review and meta-analysis. J Autism Dev Disord. 2020;51(8):2569-2577. doi: 10.1007/s10803-020-04710-1.
Maltsev D, Natrus L. The effectiveness of infliximab in autism spectrum disorders associated with folate cycle genetic deficiency. Psychiatry Psychother Clinic Psychol. 2020;11(3):583-594. doi: 10.22141/2224-0713.18.4.2022.959 (in Ukrainian).
Xu G, Snetselaar LG, Jing J, Liu B, Strathearn L, Bao W. Association of food allergy and other allergic conditions with autism spectrum disorder in children. JAMA network open. 2018;1(2):e180279-e180279. doi: 10.1001/jamanetworkopen.2018.0279.
Theoharides TC, Tsilioni I, Patel AB, Doyle R. Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders. Transl Psychiatry. 2016;6(6):e844. doi: 10.1038/tp.2016.77.
Theoharides TC. Is a subtype of autism an allergy of the brain? Clin Ther. 2013;35(5):584-91. doi: 10.1016/j.clinthera.2013.04.009.
Cao LH, He HJ, Zhao YY, et al. Food Allergy-Induced Autism-Like Behavior is Associated with Gut Microbiota and Brain mTOR Signaling. J Asthma Allergy. 2022;15:645-664. doi: 10.2147/JAA.S348609.
Yu Y, Huang J, Chen X, Fu J, et al. Efficacy and Safety of Diet Therapies in Children With Autism Spectrum Disorder: A Systematic Literature Review and Meta-Analysis. Front Neurol. 2022;13:844117. doi: 10.3389/fneur.2022.844117.
Ledda C, Cannizzaro E, Lovreglio P, et al. Exposure to Toxic Heavy Metals Can Influence Homocysteine Metabolism? Antioxidants (Basel). 2019;9(1):30. doi: 10.3390/antiox9010030.
Krigsman A, Walker SJ. Gastrointestinal disease in children with autism spectrum disorders: Etiology or consequence? World J Psychiatry. 2021;11(9):605. doi: 10.5498/wjp.v11.i9.605.
Fiorentino M, Sapone A, Senger S, et al. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016;7:49-66. doi: 10.1186/s13229-016-0110-z.
Azhari A, Azizan F, Esposito G. A systematic review of gut-immune-brain mechanisms in Autism Spectrum Disorder. Dev Psychobiol. 2019;61(5):752-771. doi: 10.1002/dev.21803.
Molina‐López J, Leiva‐García B, Planells E, Planells P. Food selectivity, nutritional inadequacies, and mealtime behavioral problems in children with autism spectrum disorder compared to neurotypical children. Intern J Eating Disor. 2021;54(12):2155-2166. doi: 10.1002/eat.23631.
Minshew NJ, Williams DL. The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol. 2007;64(7):945-950. doi: 10.1001/archneur.64.7.945.
Hardan AY, Fung LK, Frazier T, et al. A proton spectroscopy study of white matter in children with autism. Prog Neuropsychopharmacol Biol Psychiatry. 2016;66:48-53. doi: 10.1016/j.pnpbp.2015.11.005.
Marseglia LM, Nicotera A, Salpietro V, et al. Hyperhomocysteinemia and MTHFR polymorphisms as antenatal risk factors of white matter abnormalities in two cohorts of late preterm and full term newborns. Oxid Med Cell Longev. 2015;2015:543134. doi: 10.1155/2015/543134.
Øhlenschlæger T, Garred P, Madsen HO, Jacobsen S. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med. 2004;351:260-267. doi: 10.1056/NEJMoa033122.
Maltsev DV. Neuroradiological signs of encephalopathy in children with autism spectrum disorders associated with genetic folate cycle deficiency. Ukr Neurol J. 2021;(3-4):16-30. doi: 10.30978/UNJ2021-3-16 (in Ukrainian).
González-Toro MC, Jadraque-Rodríguez R, Sempere-Pérez Á, Martinez-Pastor P, Jover-Cerdá J, Gómez-Gosálvez F. Anti-NMDA receptor encephalitis: two paediatric cases. Rev Neurol. 2013;57(11):504-508. PMID: 24265144.
Pinillos-Pisón R, Llorente-Cereza MT, López-Pisón J. Congenital infection by cytomegalovirus. A review of our 18 years' experience of diagnoses. Rev Neurol. 2009;48(7):349-353. PMID: 19319815.
Maltsev DV. Results of a retrospective analysis of the use of normal intravenous human immunoglobulin in a high dose for the treatment of immune encephalopathy with a clinical picture of autism spectrum disorders in children with a genetic deficiency of the folate cycle. Intern Neurol J. 2021;17(8):31-43. doi: 10.22141/2224-0713.17.8.2021.250818.
Perlmutter SJ, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999;354(9185):1153-1158. doi: 10.1016/S0140-6736(98)12297-3.
Bradstreet JJ, Smith S, Baral M, Rossignol DA. Biomarker-guided interventions of clinically relevant conditions associated with autism spectrum disorders and attention deficit hyperactivity disorder. Altern Med Rev. 2010;15(1):15-32.
Liu H, Talalay P, Fahey JW. Biomarker-Guided Strategy for Treatment of Autism Spectrum Disorder (ASD). CNS Neurol Disord Drug Targets. 2016;15(5):602-613.
Frye RE, Rose S, Boles RG, Rossignol DA. A personalized approach to evaluating and treating Autism Spectrum Disorder. J Pers Med. 2022;12(2):147. doi: 10.3390/jpm12020147.
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