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REVIEW ARTICLE

A multidimensional review of autism spectrum disorder in Türkiye and the world

Burak Çakar1* ,  Cansu Çadırcı2 ,  Kubilay Doğan Kılıç3,4
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1 Department of Histology and Embryology, Faculty of Medicine, İstinye University, İstanbul, Türkiye
2 Department of Histology and Embryology, Institute of Health Sciences, Aydın Adnan Menderes University, Aydın, Türkiye
3 Department of Histology and Embryology, Faculty of Medicine, Ege University, İzmir, Türkiye
4 Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany
Advanced Neurology, 025250073 https://doi.org/10.36922/AN025250073
Received: 17 June 2025 | Revised: 6 May 2026 | Accepted: 9 May 2026 | Published online: 28 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent difficulties in social communication, restricted and repetitive behaviors, and atypical sensory processing, significantly affecting the quality of life of individuals, families, and society. Its etiology is complex and multifactorial, involving interactions among genetic, epigenetic, and environmental factors that influence brain development, synaptic function, and neural connectivity. This narrative review aims to provide a comprehensive and multidimensional overview of ASD by synthesizing current evidence on neuropathology, neuroimaging findings, molecular and cellular mechanisms, and major genetic and environmental risk factors. In addition, global and national epidemiological data were summarized, followed by an overview of current diagnostic criteria, screening strategies, and both pharmacological and non-pharmacological interventions, including behavioral, educational, and psychosocial approaches. Emerging research on novel therapeutic targets was also discussed. This review was conducted as a narrative review based on a literature search of major academic databases, international health reports, and current clinical guidelines. Relevant studies were selected to provide a comprehensive and integrative perspective on ASD. Finally, this review highlights the relevance of ASD in midwifery practice, emphasizing the role of midwives in prenatal risk assessment, perinatal care, early recognition, family support, and interdisciplinary collaboration. By integrating biological, clinical, and professional perspectives, this article aims to inform healthcare professionals and contribute to a more holistic, family-centered approach to ASD.

Keywords
Autism spectrum disorder
Neurodevelopment
Neuropathology
Molecular mechanisms
Epidemiology
Midwifery
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
References
  1. Genovese A, Butler MG. Clinical assessment, genetics, and treatment approaches for autism spectrum disorder. Int J Mol Sci. 2020;21(13):4726. doi: 10.3390/ijms21134726
  2. Hughes HK, Moreno RJ, Ashwood P. Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD). Brain Behav Immun. 2023;108:1-11. doi: 10.1016/j.bbi.2022.12.001
  3. Hodges H, Fealko C, Soares N. Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. 2020;9(Suppl 1):S55-S65. doi: 10.21037/tp.2019.09.09
  4. Dover CJ, Le Couteur A. Autism spectrum disorder (ASD). In: Golding J, Middeldorp CM, eds. The Routledge International Handbook of Psychosocial Epidemiology. Routledge; 2016. doi: 10.4324/9781351258043-13
  5. Yu Y, Ozonoff S, Miller M. Assessment of autism spectrum disorder. Assessment. 2024;31(7):1757-1774. doi: 10.1177/10731911231173089
  6. Aishworiya R, Valica T, Hagerman R, Restrepo B. An Update on Psychopharmacological Treatment of Autism Spectrum Disorder. Focus. 2024;22(2):198-211. doi: 10.1176/appi.focus.24022006
  7. Fitzpatrick SE, Srivorakiat L, Wink LK, Pedapati EV, Erickson CA. Aggression in autism spectrum disorder: presentation and treatment options. Neuropsychiatr Dis Treat. 2016;12:1525-1538. doi: 10.2147/NDT.S84585
  8. McCracken JT, Anagnostou E, Arango C, et al. Drug development for autism spectrum disorder (ASD): Progress, challenges, and future directions. Eur Neuropsychopharmacol. 2021;48:3-31. doi: 10.1016/j.euroneuro.2021.05.010
  9. Rosen NE, Lord C, Volkmar FR. The diagnosis of autism: From Kanner to DSM-III to DSM-5 and beyond. J Autism Dev Disord. 2021;51(12):4253-4270. doi: 10.1007/s10803-021-04904-1
  10. Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014;383(9920):896-910. doi: 10.1016/S0140-6736(13)61539-1
  11. Lyall K, Croen L, Daniels J, et al. The changing epidemiology of autism spectrum disorders. Annu Rev Public Health. 2017;38:81-102. doi: 10.1146/annurev-publhealth-031816-044318
  12. Masi A, DeMayo MM, Glozier N, Guastella AJ. An overview of autism spectrum disorder, its heterogeneity, and treatment options. Neurosci Bull. 2017;33(2):183-193. doi: 10.1007/s12264-017-0100-y
  13. Yoon SH, Choi J, Lee WJ, Do JT. Genetic and epigenetic etiologies underlying autism spectrum disorder. J Clin Med. 2020;9(4):966. doi: 10.3390/jcm9040966
  14. Masini E, Loi E, Vega-Benedetti AF, et al. An overview of the main genetic, epigenetic and environmental factors involved in autism spectrum disorder focusing on synaptic activity. Int J Mol Sci. 2020;21(21):8290. doi: 10.3390/ijms21218290
  15. Courchesne E. Neuroanatomic imaging in autism. Pediatrics. 1991;87(5 Pt 2):781-790. doi: 10.1542/peds.87.5.781
  16. Verhoeven JS, De Cock P, Lagae L, Sunaert S. Neuroimaging of autism. Neuroradiology. 2010;52(1):3-14. doi: 10.1007/s00234-009-0583-y
  17. Hong SJ, Valk SL, Di Martino A, Milham MP, Bernhardt BC. Multidimensional neuroanatomical subtyping of autism spectrum disorder. Cereb Cortex. 2018;28(10):3572-3584. doi: 10.1093/cercor/bhx229
  18. Zabihi M, Poutanen T, Nolden S, et al. Fractionating autism based on neuroanatomical normative modeling. Transl Psychiatry. 2020;10:446. doi: 10.1038/s41398-020-01057-0
  19. Li X, Zhang K, He X, et al. Structural, functional, and molecular imaging of autism spectrum disorder. Neurosci Bull. 2021;37(5):735-751. doi: 10.1007/s12264-021-00673-0
  20. Minshew NJ, Keller TA. The nature of brain dysfunction in autism: functional brain imaging studies. Curr Opin Neurol. 2010;23(2):124-130. doi: 10.1097/WCO.0b013e32833782d4
  21. Hwang G, Wen J, Sotardi S, et al. Assessment of neuroanatomical endophenotypes of autism spectrum disorder and association with characteristics of individuals with schizophrenia and the general population. JAMA Psychiatry. 2023;80(5):498-507. doi: 10.1001/jamapsychiatry.2023.0409
  22. Pretzsch CM, Floris DL, Schäfer T, Bletsch A. Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism. Mol Psychiatry. 2023;28(5):2158-2169. doi: 10.1038/s41380-023-02016-z
  23. Pickett J, London E. The neuropathology of autism: A review. J Neuropathol Exp Neurol. 2005;64(11):925-935. doi: 10.1097/01.jnen.0000186921.42592.6c
  24. Fetit R, Hillary RF, Price DJ, Lawrie SM. The neuropathology of autism: a systematic review of post-mortem studies of autism and related disorders. Neurosci Biobehav Rev. 2021;129:35-62. doi: 10.1016/j.neubiorev.2021.07.014
  25. Palmen SJMC, van Engeland H, Hof PR, Schmitz C. Neuropathological findings in autism. Brain. 2004;127(12):2572-2583. doi: 10.1093/brain/awh287
  26. Pardo CA, Eberhart CG. The neurobiology of autism. J Neuropathol Exp Neurol. 2007;66(9):872-881. doi: 10.1111/j.1750-3639.2007.00102.x
  27. Schmitz C, Rezaie P. The neuropathology of autism: Where do we stand? Neuropathol Appl Neurobiol. 2008;34(1):4-11. doi: 10.1111/j.1365-2990.2007.00872.x
  28. Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31(3):137-145. doi: 10.1016/j.tins.2007.12.005
  29. Jiang CC, Lin LS, Long S, et al. Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications. Signal Transduct Target Ther. 2022;7(1):229. doi: 10.1038/s41392-022-01081-0
  30. Kumar S, Reynolds K, Ji Y, Gu R, Rai S, Zhou CJ. Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk. J Neurodev Disord. 2019;11:10. doi: 10.1186/s11689-019-9268-y
  31. Baranova J, Dragunas G, Botelho MCS, et al. Autism spectrum disorder: signaling pathways and prospective therapeutic targets. Mol Neurobiol. 2020;57(7):3110-3130. doi: 10.1007/s10571-020-00882-7
  32. Bou Najm D, Alame S, Chamoun WT. Unraveling the role of Wnt signaling pathway in the pathogenesis of autism spectrum disorder (ASD): a systematic review. Mol Neurobiol. 2025;62:4971-4992. doi: 10.1007/s12035-024-04558-x
  33. Wang RN, Green J, Wang Z, et al. Bone morphogenetic protein (BMP) signaling in development and human diseases. Genes Dis. 2014;1(1):87-105. doi: 10.1016/j.gendis.2014.07.005
  34. El Gohary TM, El Aziz NA, Darweesh M, Sadaa ES. Plasma level of transforming growth factor β 1 in children with autism spectrum disorder. EEgypt J Ear Nose Throat Allied Sci. 2015;16(1):69-73. doi: 10.1016/j.ejenta.2014.12.002
  35. Yousefi J, Khakzad MR, Hojati M, Ebrahimi SA, Hosseinpour M, Akhondian J. Is serum TGF-β1 and TGF- β2 levels correlated to autism intensity in children? Iran J Child Neurol. 2021;15(2):57-67. doi: 10.22037/ijcn.v15i1.21826
  36. Le Dréau G. BuMPing into neurogenesis: How the canonical BMP pathway regulates neural stem cell divisions throughout space and time. Front Neurosci. 2022;15:819990. doi: 10.3389/fnins.2021.819990
  37. Kashima R, Hata A. The role of TGF-β superfamily signaling in neurological disorders. Acta Biochim Biophys Sin (Shanghai). 2018;50(1):106-120. doi: 10.1093/abbs/gmx124
  38. Rahi S, Mehan S. Understanding abnormal SMO-SHH signaling in autism spectrum disorder: potential drug target and therapeutic goals. Cell Mol Neurobiol. 2022;42(4):931- 953. doi: 10.1007/s10571-020-01010-1
  39. Patel SS, Tomar S, Sharma D, Mahindroo N, Udayabanu M. Targeting sonic hedgehog signaling in neurological disorders. Neurosci Biobehav Rev. 2017;74(Pt A):76-97. doi: 10.1016/j.neubiorev.2017.01.008
  40. Al-Ayadhi LY. Relationship between Sonic hedgehog protein, brain-derived neurotrophic factor and oxidative stress in autism spectrum disorders. Neurochem Res. 2012;37(2):394- 400. doi: 10.1007/s11064-011-0624-x
  41. Upadhyay J, Patra J, Tiwari N, Salankar N, Ansari MN, Ahmad W. Dysregulation of multiple signaling neurodevelopmental pathways during embryogenesis: A possible cause of autism spectrum disorder. Cells. 2021;10(4):958. doi: 10.3390/cells10040958
  42. Iwata T, Hevner RF. Fibroblast growth factor signaling in development of the cerebral cortex. Dev Growth Differ. 2009;51(3):299-323. doi: 10.1111/j.1440-169X.2009.01104.x
  43. Guillemot F, Zimmer C. From cradle to grave: the multiple roles of fibroblast growth factors in neural development. Neuron. 2011;71(4):574-588. doi: 10.1016/j.neuron.2011.08.002
  44. Terwisscha van Scheltinga AF, Bakker SC, Kahn RS, Kas MJ. Fibroblast growth factors in neurodevelopment and psychopathology. Neuroscientist. 2013;19(5):479-494. doi: 10.1177/1073858412472399
  45. Esnafoglu E, Ayyıldız SN. Decreased serum fibroblast growth factor-2 levels in children with autism spectrum disorder. Psychiatry Res. 2017;257:79-83. doi: 10.1016/j.psychres.2017.07.028
  46. Guldiken G, Karayagmurlu A, Kucukgergin C, Coskun M. VEGF, IGF-1 and FGF-2 serum levels in children and adolescents with autism spectrum disorder with and without bipolar disorder. J Autism Dev Disord. 2024;54(10):3854- 3862. doi: 10.1007/s10803-023-06089-1
  47. Zhou J, Parada LF. PTEN signaling in autism spectrum disorders. Curr Opin Neurobiol. 2012;22(5):873-879. doi: 10.1016/j.conb.2012.05.004
  48. Yui K, Imataka G, Yoshihara S. Lipid-based molecules on signaling pathways in autism spectrum disorder. Int J Mol Sci. 2022;23(17):9803. doi: 10.3390/ijms23179803
  49. Lyu K, Li J, Chen M, et al. A bibliometric analysis of autism spectrum disorder signaling pathways research in the past decade. Front Psychiatry. 2024;15:1304916. doi: 10.3389/fpsyt.2024.1304916
  50. Rylaarsdam L, Guemez-Gamboa A. Genetic causes and modifiers of autism spectrum disorder. Front Cell Neurosci. 2019;13:385. doi: 10.3389/fncel.2019.00385
  51. Huguet G, Ey E, Bourgeron T. The genetic landscapes of autism spectrum disorders. Annu Rev Genomics Hum Genet. 2013;14:153-174. doi: 10.1146/annurev-genom-091212-153431
  52. Ronald A, Hoekstra RA. Autism spectrum disorders and autistic traits: A decade of new twin studies. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(3):255-274. doi: 10.1002/ajmg.b.31159
  53. Bhandari R, Paliwal JK, Kuhad A. Neuropsychopathology of autism spectrum disorder: complex interplay of genetic, epigenetic and environmental factors. In: Essa M, Qoronfleh M, eds. Personalized Food Intervention and Therapy for Autism Spectrum Disorder Management. Springer; 2020;24:97-141. doi: 10.1007/978-3-030-30402-7_4
  54. Robinson-Agramonte MLA, Noris García E, Fraga Guerra J, et al. Immune dysregulation in autism spectrum disorder: What do we know about it? Int J Mol Sci. 2021;23(1):303. doi: 10.3390/ijms23063033
  55. Tărlungeanu DC, Deliu E, Dotter CP, Günel M, Gleeson JG, Novarino G. Impaired amino acid transport at the blood– brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494.e18. doi: 10.1016/j.cell.2016.11.013
  56. Lord C, Brugha TS, Charman T, et al. Autism spectrum disorder. Nat Rev Dis Primers. 2020;6(1):5. doi: 10.1038/s41572-019-0138-4
  57. Gyawali S, Patra BN. Autism spectrum disorder: Trends in research exploring etiopathogenesis. Psychiatry Clin Neurosci. 2019;73(8):466-475. doi: 10.1111/pcn.12860
  58. Hyman SL, Levy SE, Myers SM. What causes autism spectrum disorder? In: Autism Spectrum Disorder: What Every Parent Needs to Know. 2nd ed. American Academy of Pediatrics; 2019. doi: 10.1542/9781610022705-ch02
  59. Hirota T, King BH. Autism spectrum disorder: A review. JAMA. 2023;329(2):157-169. doi: 10.1001/jama.2022.23661
  60. Hyman SL, Levy SE, Myers SM, Council on Children with Disabilities, Section on Developmental and Behavioral Pediatrics. Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics. 2020;145(1):e20193447. doi: 10.1542/peds.2019-3447
  61. Nadeem MS, Murtaza BN, Al-Ghamdi MA, et al. Autism - A comprehensive array of prominent signs and symptoms. Curr Pharm Des. 2021;27(11):1418-1433. doi: 10.2174/1381612827666210120095829
  62. Napolitano A, Schiavi S, La Rosa P, et al. Sex differences in autism spectrum disorder: Diagnostic, neurobiological, and behavioral features. Front Psychiatry. 2022;13:889636. doi: 10.3389/fpsyt.2022.889636
  63. Lau BY, Leong R, Uljarevic M, et al. Anxiety in young people with autism spectrum disorder: Common and autism-related anxiety experiences and their associations with individual characteristics. Autism. 2020;24(5):1111-1126. doi: 10.1177/1362361319886246
  64. Leader G, Abberton C, Cunningham S, et al. Gastrointestinal symptoms in autism spectrum disorder: A systematic review. Nutrients. 2022;14(7):1471. doi: 10.3390/nu14071471
  65. Zhang X, Li Y, Wang Y, et al. Intestinal symptoms among children aged 2–7 years with autism spectrum disorder in 13 cities of China. J Autism Dev Disord. 2023;53(11):4672- 4683. doi: 10.1007/s10803-023-06122-3
  66. Talantseva OI, Romanova RS, Shurdova EM, et al. The global prevalence of autism spectrum disorder: A three-level meta-analysis. Front Psychiatry. 2023;14:1071181. doi: 10.3389/fpsyt.2023.1071181
  67. Volkmar FR, McPartland JC. From Kanner to DSM-5: autism as an evolving diagnostic concept. Annu Rev Clin Psychol. 2014;10:193-212. doi: 10.1146/annurev-clinpsy-032813-153710
  68. Dougnon G, Matsui H. Modelling autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) using mice and zebrafish. Int J Mol Sci. 2022;23(14):7550. doi: 10.3390/ijms23147550
  69. Maenner MJ, Warren Z, Williams AR, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2020. MMWR Surveill Summ. 2023;72(2):1-14. doi: 10.15585/mmwr.ss7202a1
  70. Doenyas C, Ekici B, Unay ÖS, Gönen İ, Tatlı B. Autism in Turkey: demographics, behavior problems, and accompanying medical conditions in a sample of Turkish youth with autism spectrum disorder. Int J Dev Disabil. 2021;69(2):179-189. doi: 10.1080/20473869.2021.1937001
  71. Jensen AR, Lane AL, Werner BA, McLees SE, Fletcher TS, Frye RE. Modern biomarkers for autism spectrum disorder: Future directions. Mol Diagn Ther. 2022;26(4):483-495. doi: 10.1007/s40291-022-00600-7
  72. Baytar B, Yarar E. A critical discourse analysis of autism spectrum disorder news in Turkish online media. Uluslararası Dil Edebiyat ve Kültür Araştırmaları Dergisi. 2025;8(1):199-211. doi: 10.37999/udekad.1613363
  73. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–1222. doi: 10.1016/S0140-6736(20)30925-9
  74. Rogers C, Lepherd L, Ganguly R, Jacob-Rogers S. Perinatal issues for women with high functioning autism spectrum disorder. Women Birth. 2017;30(2):e89-e95. doi: 10.1016/j.wombi.2016.09.009
  75. Donovan J. Childbirth experiences of women with autism spectrum disorder in an acute care setting. Nurs Womens Health. 2020;24(4):e1-e9. doi: 10.1016/j.nwh.2020.04.001
  76. Moore L, Foley S, Larkin F. Understanding the experiences of receiving and providing maternity care for autistic adults: A Multi-perspectival Interpretative Phenomenological Analysis study. Autism. 2025;29(2):435-446. doi: 10.1177/13623613241274518
  77. Hollins Martin CJ, Martin CR. Midwifery basics human rights in childbearing 3: Providing sensitive antenatal care for autistic women and birthing people. Pract Midwife. 2022;25(7):24-28. doi: 10.55975/brwp4714
  78. Roquette Viana C, Caldeira S, Lourenço M, Simões Figueiredo A. Parenting children with autism spectrum disorder: A grounded theory study. Healthcare. 2021;9(7):872. doi: 10.3390/healthcare9070872
  79. Smith T, Scahill L, Dawson G, et al. Designing research studies on psychosocial interventions in autism. J Autism Dev Disord. 2007;37(2):354-366. doi: 10.1007/s10803-006-0173-3
  80. Yan Z. Targeting epigenetic enzymes for autism treatment. Trends Pharmacol Sci. 2024;45(9):764-767. doi: 10.1016/j.tips.2024.06.009
  81. Dougnon G, Matsui H. Three decades of neuroscience research using animal models of ADHD and ASD: A bibliometric analysis. Front Psychiatry. 2025;16:1528205. doi: 10.3389/fpsyt.2025.1528205
  82. Pensado-López A, Veiga-Rúa S, Carracedo Á, Allegue C, Sánchez L. Experimental models to study autism spectrum disorders: hiPSCs, rodents, and zebrafish. Genes. 2020;11(11):1376. doi: 10.3390/genes11111376
  83. Nomura J, Zuko A, Kishimoto K, et al. ESC models of autism with copy number variations reveal cell-type-specific translational vulnerability. Cell Genom. 2025;5(6):100877. doi: 10.1016/j.xgen.2025.100877
  84. Bethea TC, Sikich L. Early pharmacological treatment of autism: a rationale for developmental treatment. Biol Psychiatry. 2007;61(4):521-537. doi: 10.1016/j.biopsych.2006.09.021
  85. Farmer C, Thurm A, Grant P. Pharmacotherapy for the core symptoms in autistic disorder: Current status of the research. Drugs. 2013;73(4):303-314. doi: 10.1007/s40265-013-0021-7s
  86. Phan JM, Dwyer P, Elsherif MM, Friedel E, Kapp SK. Oxytocin in autism: rethinking treatment and research through a neurodivergent perspective. Psychoneuroendocrinology. 2025;171:107220. doi: 10.1016/j.psyneuen.2024.107220
  87. Darwish M, El Hajj R, Khayat L, Alaaeddine N. Stem cell secretions as potential therapeutic agents for autism spectrum disorder: A narrative review. Stem Cell Rev Rep. 2024;20(5):1252-1272. doi: 10.1007/s12015-024-10724-4
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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