Abstract
The study of the evolution in the diagnosis and treatment of autism is a lesson in the dangers of medical beliefs or doctrines that are not grounded in medical science. The early descriptions of autism suggested that it was the result of childhood psychoses or psychodynamic disturbances of parent-child relationships. This flawed conceptualization of autism spectrum disorders (ASD) gave way to advances in medical science, which have established ASD as a neurobiological disorder of early brain development. There are many genetic, epigenetic, metabolic, hormonal, immunological, neuroanatomical and neurophysiological etiologies of ASD, as well as an array of gastrointestinal and other systemic co-morbid disorders. Thus, ASD are a biologically heterogeneous population with extensive neurodiversity. Early identification and understanding of ASD is crucial; interventions at younger ages are associated with improved outcomes. The advent of understanding the biological sub-phenotypes of ASD, along with targeted medical therapies, coupled with a multimodal therapeutic approach that encompasses behavioral, educational, social, speech, occupational, creative arts, and other forms of therapies has created a new and exciting era for individuals with ASD and their families: “personalized” and “precision” medical care based upon underlying biological sub-phenotypes and clinical profiles. For many individuals and their families dealing with the scourge of autism, their long and frustrating diagnostic journey is beginning to come to an end, with a hope for improved outcomes and quality of life.
Similar content being viewed by others
References
Rapin I, Tuchman RF. Where we are: overview and definitions. In: Tuchman R, Rapin I, editors. Autism: A Neurological Disorder of Early Brain Development, International Child Neurology Association. London: Mac Keith Press; 2006. p. 1–18.
Frazier TW, Youngstrom EA, Speer L, et al. Validation of proposed DSM-5 criteria for autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012;51:28–40.e3.
Mandy WP, Charman T, Skuse DH. Testing the construct validity of proposed criteria for DSM-5 autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012;51:41–50.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed.-text revision (TR). Washington, DC: American Psychiatric Association; 2000.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
Volkmar FR, Reichow B, McParland J. Classification of autism and related conditions: progress, challenges, and opportunities. Dialogues Clin Neurosci. 2012;14:229–37.
Volkmar FR, State M, Klin A. Autism and autism spectrum disorders: diagnostic issues for the coming decade. J Child Psychol Psychiatry. 2009;50:108–15.
Kanner L. Autistic disturbances of affective contact. Nervous Child. 1943;2:217–50.
Olmsted D, Blaxill M. Leo Kanner's mention of 1938 in his report on autism refers to his first patient. J Autism Dev Disord. 2016;46:340–1.
Asperger H. Die autistischen psychopathen im Kindesalter. Arch fur Psychiatrie und Nerven Krankheiten. 1944;117:76–136.
Heilpädagogik AH. Einführung in die psychopathologie des KindesfürÄrzte, Lehrer, psychologen und Fürsorgerinnen. Wien: Springer; 1952.
Fellowes S. Did Kanner actually describe the first account of autism? The mystery of 1938. J Autism Dev Disord. 2015;45:2274–6.
Frith U, Morton J, Leslie AM. The cognitive basis of a biological disorder: autism. Trends Neurosci. 1991;14:433–8.
Brumback RA, Harper CR, Weinberg WA. Nonverbal learning disabilities, Asperger’s syndrome, pervasive developmental disorder: should we care? J Child Neurol. 1996;11:427–9.
Klin A, Volkmar FR, Sparrow SS, Cicchetti DV, Rourke BP. Validity and neuropsychological characterization of Asperger syndrome: convergence with nonverbal learning disabilities syndrome. J Child Psychol Psychiatry Allied Discipl. 1995;36:1127–40.
Rourke BP, Tsatsanis KD. Nonverbal learning disabilities and Asperger syndrome. In: Klin A, Volkmar FR, editors. Asperger syndrome. New York, NY: The Guilford Press; 2000. p. 231–53.
Baker JP. Autism at 70 -redrawing the boundaries. N Engl J Med. 2013;369:1089–91.
Volkmar FR, Nelson DS. Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry. 1990;29:127–9.
Folstein SE. Genetic aspects of infantile autism. Annu Rev Med. 1985;36:415–9.
Rutter M. Childhood schizophrenia reconsidered. J Autism Child Schizophrenia. 1972;2:315–37.
Kolvin I. Studies in the childhood psychoses. I. Diagnostic criteria and classification. Br J Psychiatry. 1971;118:381–4.
Johnston MV, Blue ME. Neurobiology of autism. In: Tuchman R, Rapin I, editors. Autism: A Neurological Disorder of Early Brain Development, International Child Neurology Association. London: Mac Keith Press; 2006. p. 79–92.
Herbert MR, Caviness VS. Neuroanatomy and imaging studies. In: Tuchman R, Rapin I, editors. Autism: A Neurological Disorder of Early Brain Development, International Child Neurology Association. London: Mac Keith Press; 2006. p. 115–40.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association; 1980.
Hippler K, Klicpera C. A retrospective analysis of the clinical case records of ‘autistic psychopaths’ diagnosed by Hans Asperger and his team at the university Children’s hospital, Vienna. Philos Trans R Soc Lond Biol Sci. 2003;358:291–301.
Kirk SA, Kutchins H. The myth of the reliability of DSM. J Mind Behav. 1994;15:71–86.
Mintz M, Chadehumbe M, Barabas R, et al. The clinical utility of relevant exome panels for autism spectrum disorders and intellectual disabilities. Ann Neurol. 2014;76:S246. (Poster Presentation at the 43rdAnnual Meeting of the Child Neurology Society, Columbus, Ohio, 2014).
Eapen V, Črnčec R, Walter A. Exploring links between genotypes, phenotypes, and clinical predictors of response to early intensive behavioral intervention in autism spectrum disorder. Front Hum Neurosci. 2013;7:567.
Soden SE, Saunders CJ, Willig LK, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med. 2014;6:265ra168.
Mintz M, Allesandri M, Curatolo P. Treatment approaches for autistic spectrum disorders. In: Tuchman R, Rapin I, editors. Autism: A Neurological Disorder of Early Brain Development, International Child Neurology Association. London: Mac Keith Press; 2006. p. 281–307.
Iwata BA, Dorsey MF, Slifer KJ, Bauman KE, Richman GS. Toward a functional analysis of self-injury. J Appl Behav Anal. 1994;27:197–209.
Beavers GA, Iwata BA, Lerman DC. Thirty years of research on the functional analysis of problem behavior. J Appl Behav Anal. 2013;46:1–21.
Kasari C, Brady N, Lord C, Tager-Flusberg H. Assessing the minimally verbal school-aged child with autism spectrum disorder. Autism Res. 2013;6:479–93.
Visser EM, Berger HJ, Van Schrojenstein Lantman-De valk HM, et al. Cognitive shifting and externalising problem behaviour in intellectual disability and autism spectrum disorder. J Intellect Disabil Res. 2015;59:755–66.
Sansa G, Carlson C, Doyle W, et al. Medically refractory epilepsy in autism. Epilepsia. 2011;52:1071–5.
Roulet-Perez E, Deonna. Autism, Epilepsy and EEG Epileptiform Activity. In: Tuchman RF, Rapin I, editors. Autism: A Neurological Disorder of Early Brain Development, International Child Neurology Association. London: Mac Keith Press; 2006. p. 174–88.
Yasuhara A. Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD). Brain Dev. 2010;32:791–8.
Mintz M, LeGoff D, Scornaienchi J, et al. The underrecognized epilepsy spectrum: the effects of levetiracetam on neuropsychological functioning in relation to subclinical spike production. J Child Neurol. 2009;24:807–15.
Mintz M, Szklarski L, Chadehumbe M, et al. Unexpected subclinical spikes: clinical and neurophysiological correlations. Abstract No. 2.016. In: American Epilepsy Society annual meeting, www.aesnet.org. Washington: Seattle; 2014.
Tuchman RF, Rapin I. Regression in pervasive developmental disorders: seizures and epileptiform electroencephalogram correlates. Pediatrics. 1997;99:560–6.
Nass R, Devinsky O. Autistic regression with rolandic spikes. Neuropsychiatry Neuropsychol Behav Neurol. 1999;12:193–7.
Sanchez Fernandez I, Loddenkemper T, Galanopoulou AS, Moshe SL. Should epileptiform discharges be treated? Epilepsia. 2015;56:1492–504.
Chapman KE, Specchio N, Shinnar S, Holmes GL. Seizing control of epileptic activity can improve outcome. Epilepsia. 2015;56:1482–5.
Szklarski L, Mintz M. Dense-array electroencephalography (dEEG) improves compliance and acquisition without sedation or restraint for children and adults with behavioral challenges. Abstract No. 3.133. In: American Epilepsy Society Annual Meeting, www.aesnet.org. Pennsylvania: Philadelphia; 2015.
Nikolov RN, Bearss KE, Lettinga J, et al. Gastrointestinal symptoms in a sample of children with pervasive developmental disorders. J Autism Dev Disord. 2009;39:405–13.
Valicenti-McDermott MD, McVicar K, Cohen HJ, et al. Gastrointestinal symptoms in children with an autism spectrum disorder and language regression. Pediatr Neurol. 2008;39:392–8.
Buie T, Campbell DB, Fuchs GJ 3rd, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010;125:S1–18.
Buie T, Fuchs GJ 3rd, Furuta GT, et al. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics. 2010a;125:S19–29.
Buie T. Potential etiologic factors of microbiome disruption in autism. Clin Ther. 2015;37:976–83.
Zimmerman AW, Connors SL, Matteson KJ, et al. Maternal antibrain antibodies in autism. Brain Behav Immun. 2007;21:351–7.
Fatemi SH, Stary JM, Halt AR, Reatmuto GR. Dysregulation of reelin and bcl-2 proteins in autistic cerebellum. J Autism Dev Disord. 2001;31:529–35.
Jyonouchi H, Sun S, Itokazu N. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorders. Neuropsychobiology. 2002;46:76–84.
Jyonouchi H, Geng L, Ruby A, et al. Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology. 2005;51:77–85.
Sadamatsu M, Kanai H, Xu X, et al. Review of animal models for autism: implication of thyroid hormone. Congenit Anom. 2006;46:1–9.
Roman GC. Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents. J Neurol Sci. 2007;262:15–26.
Stein TP, Schluter MD, Steer RA, et al. Bisphenol A exposure in children with autism spectrum disorders. Autism Res. 2015;8:272–83.
Ming X, Julu PO, Brimacombe M, Connor S, Daniels ML. Reduced cardiac parasympathetic activity in children with autism. Brain Dev. 2005;27:509–16.
Zaki EA, Freilinger T, Klopstock T. Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome. Cephalalgia. 2009;29:719–28.
van Engeland H. The electrodermal orienting response to auditive stimuli in autistic children, normal children, mentally retarded children, and child psychiatric patients. J Autism Dev Disord. 1984;14:261–79.
Ming X, Brimacombe M, Chaaban J, Zimmerman-Bier B, Wganer GG. Autism spectrum disorders: concurrent clinical disorders. J Child Neurol. 2008;23:6–13.
Ming X, Stein TP, Barnes V, Rhodes N, Guo L. Metabolic perturbance in autism spectrum disorders: a metabolomics study. J Proteome Res. 2012;11:5856–62.
Williams PG, Sears LL, Allard A. Sleep problems in children with autism. J Sleep Res. 2004;13:265–8.
Malow BA, Marzec ML, McGrew SG, et al. Characterizing sleep in children with autism spectrum disorders: a multidimensional approach. Sleep. 2006;29:1563–71.
Schreck KA, Mulick JA, Smith AF. Sleep problems as possible predictors of intensified symptoms of autism. Res Dev Disabil. 2004;25:57–66.
Ming X, Walters AS. Autism spectrum disorders, attention deficit/hyperactivity disorder, and sleep disorders. Curr Opin Pulm Med. 2009;15:578–84.
Wiggs L, Stores G. Sleep patterns and sleep disorders in children with autistic spectrum disorders: insights using parent report and actigraphy. Dev Med Child Neurol. 2004;46:372–80.
Johnson KP, Malow BA. Sleep in children with autism spectrum disorders. Curr Neurol Neurosci Rep. 2008;8:155–61.
Lu JT, Campeau PM, Lee BH. Genotype-phenotype correlation- promiscuity in the era of next-generation sequencing. N Engl J Med. 2014;371:593–6.
Srivastava S, Cohen JS, Vernon H, et al. Clinical whole exome sequencing in child neurology practice. Ann Neurol. 2014;76:473–83.
Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013;369:1502–11.
Gardner A, Boles RG. Comment on treatment of psychiatric illness in patients with mitochondrial disease. Psychosomatics. 2011;52:497–8.
Verge B, Alonso Y, Miralles C. New evidence for the involvement of mitochondrial inheritance in schizophrenia: results from a cross-sectional study evaluating the risk of illness in relatives of schizophrenia patients. J Clin Psychiatry. 2012;73:684–90.
Gardner A, Boles RG. Mitochondrial energy depletion in depression with somatization. Psychother Psychosom. 2008;77:127–9.
Burnett BB, Gardner A, Boles RG. Mitochondrial inheritance in depression, dysmotility and migraine? J Affect Disord. 2005;88:109–16.
Legido A, Jethva R, Goldenthal MJ. Mitochondrial dysfunction in autism. Semin Pediatr Neurol. 2013;20:163–75.
Singh NA, Pappas C, Dahle EJ, et al. A role of SCN9A in human epilepsies, as a case of febrile seizure and as a potential modifier of Dravet syndrome. PLoS Genet. 2009;5:1–12.
Goldenthal MJ, Kuruvilla T, Damle S, et al. Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: comparison with studies in muscle biopsy. Mol Genet Metab. 2012;105:457–62.
Camilleri M, Carlson P, Zinsmeister AR, et al. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders. Am J Physiol Gastrointest Liver Physiol. 2009;296:G510–6.
Boles RG. High degree of efficacy in the treatment of cyclic vomiting syndrome with combined co-enzyme Q10, L-carnitine and amitriptyline, a case series. BMC Neurol. 2011;11:102.
Curtis LT, Patel K. Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): a review. J Altern Complement Med. 2008;14:79–85.
Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2013;18:369–81.
Frye RE, Delatorre R, Taylor H, et al. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry. 2013;3:e273.
Offit PA. Autism’s false prophets. New York: Columbia University Press; 2008.
Zwaigenbaum L, Bauman ML, Fein D, et al. Early screening of autism spectrum disorder: recommendations for practice and research. Pediatrics. 2015;136:S41.
Zwaigenbaum L, Bauman ML, Choueiri R, et al. Early intervention for children with autism spectrum disorder under 3 years of age: recommendations for practice and research. Pediatrics. 2015;136:S60-81.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Dr. Mintz serves on the editorial boards of the Journal of Child Neurology and Vision Development and Rehabilitation; has functioned as Principal Investigator for clinical trials research contracted through the Clinical Research Center of New Jersey, LLC (CRCNJ) sponsored by the following companies: Sunovion, Pfizer, Shire, Eisai, Inc, and Allergan; is the principle investigator for research funded by the State of New Jersey through the Governor’s Council for Medical Research and Treatment of Autism; is President, CEO, and Founder of The Center for Neurological and Neurodevelopmental Health, LLC, (CNNH) and CRCNJ; and is President of NeurAbilities, a 501(3)c Public Charity.
Source of Funding
None.
Rights and permissions
About this article
Cite this article
Mintz, M. Evolution in the Understanding of Autism Spectrum Disorder: Historical Perspective. Indian J Pediatr 84, 44–52 (2017). https://doi.org/10.1007/s12098-016-2080-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12098-016-2080-8