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test_str = ("{{Hatnote|This article is about the classic autistic disorder; some writers use the word ''autism'' when referring to the range of disorders on the [[autism spectrum]] or to the various [[pervasive developmental disorder]]s.<ref name=Caronna/>}}\n"
"{{pp-semi-indef}}\n"
"{{pp-move-indef}}\n"
"{{bots|deny=Monkbot}} <!-- keep Monkbot from visiting this page -->\n"
"{{Use dmy dates|date=June 2015}}\n"
"<!-- NOTES:\n"
"1) Please follow the Wikipedia style guidelines for editing medical articles [[WP:MEDMOS]], and medical referencing standards at [[WP:MEDRS]].\n"
"2) Use <ref> for explicitly cited references.\n"
"3) Reference anything you put here with notable references, as this subject tends to attract a lot of controversy.-->\n"
"{{Infobox disease\n"
"| Name = Autism\n"
"| Image = Autism-stacking-cans 2nd edit.jpg\n"
"| Alt = Young red-haired boy facing away from camera, stacking a seventh can atop a column of six food cans on the kitchen floor. An open pantry contains many more cans.\n"
"| Caption = Repetitively stacking or lining up objects is associated with autism.\n"
"| field = [[Psychiatry]]\n"
"| DiseasesDB = 1142\n"
"| ICD10 = {{ICD10|F|84|0|f|80}}\n"
"| ICD9 = 299.00\n"
"| ICDO =\n"
"| OMIM = 209850\n"
"| MedlinePlus = 001526\n"
"| eMedicineSubj = med\n"
"| eMedicineTopic = 3202\n"
"| eMedicine_mult = {{eMedicine2|ped|180}}\n"
"| MeshID = D001321\n"
"| GeneReviewsNBK = NBK1442\n"
"| GeneReviewsName = Autism overview\n"
"}}\n"
"<!-- Definition and symptoms -->\n"
"'''Autism''' is a [[neurodevelopmental disorder]] characterized by impaired [[Interpersonal relationship|social interaction]], [[language acquisition|verbal]] and [[non-verbal communication]], and restricted and repetitive behavior. Parents usually notice signs in the first two years of their child's life.<ref name=CCD/> These signs often develop gradually, though some children with autism reach their [[developmental milestones]] at a normal pace and then [[Regressive autism|regress]].<ref name=Stefanatos/> The [[Diagnostic and Statistical Manual of Mental Disorders|diagnostic criteria]] require that symptoms become apparent in early childhood, typically before age three.<ref name=DSM5>{{vcite book | title = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition | chapter = Autism Spectrum Disorder, 299.00 (F84.0) | editor = American Psychiatric Association | year = 2013 | publisher = American Psychiatric Publishing | pagex = 50–59}}</ref>\n\n"
"<!-- Causes and diagnosis -->\n"
"While autism is highly heritable, researchers suspect both environmental and genetic factors as causes.<ref>{{cite journal |author=Chaste P, Leboyer M |title=Autism risk factors: genes, environment, and gene-environment interactions |journal=Dialogues in Clinical Neuroscience |volume=14 |pages=281–92 |year=2012 |pmid=23226953 |pmc=3513682 }}</ref> In rare cases, autism is strongly associated with [[Teratology|agents that cause birth defects]].<ref name=Arndt/> [[Controversies in autism|Controversies]] surround other proposed environmental [[Causes of autism|causes]];<ref name=Rutter/> for example, the [[MMR vaccine controversy|vaccine hypotheses]] have been disproven. Autism affects information processing in the [[Human brain|brain]] by altering how [[nerve cell]]s and their [[synapse]]s connect and organize; how this occurs is not well understood.<ref name=\"Levy\" /> It is one of three recognized disorders in the [[autism spectrum]] (ASDs), the other two being [[Asperger syndrome]], which lacks delays in cognitive development and language, and [[PDD-NOS|pervasive developmental disorder, not otherwise specified]] (commonly abbreviated as PDD-NOS), which is diagnosed when the full set of criteria for autism or Asperger syndrome are not met.<ref name=\"Johnson\" />\n\n"
"<!-- Treatment -->\n"
"Early speech or [[Early intensive behavioral intervention|behavioral interventions]] can help children with autism gain self-care, social, and communication skills.<ref name=CCD/> Although there is no known cure,<ref name=CCD/> there have been reported cases of children who recovered.<ref name=Helt/> Not many children with autism live independently after reaching adulthood, though some become successful.<ref name=\"Howlin\">{{cite journal | vauthors = Howlin P, Goode S, Hutton J, Rutter M | title = Adult outcome for children with autism | journal = J Child Psychol Psychiatry | volume = 45 | issue = 2 | pages = 212–29 | year = 2004 | pmid = 14982237 | doi = 10.1111/j.1469-7610.2004.00215.x }}</ref> An [[Sociological and cultural aspects of autism|autistic culture]] has developed, with some individuals seeking a cure and others believing autism should be [[Autism rights movement|accepted as a difference and not treated as a disorder]].<ref name=Silverman/>\n\n"
"<!-- Epidemiology -->\n"
"Globally, autism is estimated to affect 21.7 million people as of 2013.<ref name=\"Collab\">{{cite journal |author = Global Burden of Disease Study 2013 Collaborators |title=Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.|journal=Lancet|year = 2015|pmid=26063472 |doi=10.1016/S0140-6736(15)60692-4}}</ref> As of 2010, the number of people affected is estimated at about 1–2 per 1,000 worldwide. It occurs four to five times more often in boys than girls. About 1.5% of children in the United States (one in 68) are diagnosed with ASD {{as of|2014|lc=y}}, a 30% increase from one in 88 in 2012.<ref name=\"ASD Data and Statistics\">{{cite web |url = http://www.cdc.gov/ncbddd/autism/data.html |title = ASD Data and Statistics |website = CDC.gov |accessdate= 5 April 2014 |archiveurl = http://web.archive.org/web/20140418153648/http://www.cdc.gov/ncbddd/autism/data.html |archivedate = 18 April 2014 }}</ref><ref name=\"MMWR2012\">{{cite journal | vauthors = | title = Prevalence of autism spectrum disorders — autism and developmental disabilities monitoring network, 14 sites, United States, 2008 | journal = MMWR Surveill Summ | volume = 61 | issue = 3 | pages = 1–19 | year = 2012 | pmid = 22456193 | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm | archivedate = 25 March 2014 | archiveurl = http://web.archive.org/web/20140325235639/http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm }}</ref><ref name=\"NHSR65\">{{cite journal | vauthors = Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC | title = Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011–2012 | journal = Natl Health Stat Report | volume = | issue = 65 | pages = 1–11 | year = 2013 | pmid = 24988818 | url = http://www.cdc.gov/nchs/data/nhsr/nhsr065.pdf | archiveurl = http://www.webcitation.org/6JoG0uE7r|archivedate=21 September 2013 }}</ref> The rate of autism among adults aged 18 years and over in the United Kingdom is 1.1%.<ref name=NHSEstimating/> The number of people diagnosed has been increasing dramatically since the 1980s, partly due to changes in diagnostic practice and government-subsidized financial incentives for named diagnoses;<ref name=\"NHSR65\"/> the question of whether actual rates have increased is unresolved.<ref name=Newschaffer/>\n\n"
"==Characteristics==\n"
"Autism is a highly variable [[neurodevelopmental disorder]]<ref name=Geschwind/> that first appears during infancy or childhood, and generally follows a steady course without [[Remission (medicine)|remission]].<ref name=ICD-10-F84.0/> People with autism may be severely impaired in some respects but normal, or even superior, in others.<ref>{{vcite book|title = Biopsychology|author= Pinel JPG|publisher = Pearson|year = 2011|isbn = 978-0-205-03099-6|location = Boston, Massachusetts|page = 235}}</ref> Overt symptoms gradually begin after the age of six months, become established by age two or three years,<ref>{{cite journal | vauthors = Rogers SJ | title = What are infant siblings teaching us about autism in infancy? | journal = Autism Res | volume = 2 | issue = 3 | pages = 125–37 | year = 2009 | pmid = 19582867 | pmc = 2791538 | doi = 10.1002/aur.81 }}</ref> and tend to continue through adulthood, although often in more muted form.<ref name=Rapin/> It is distinguished not by a single symptom, but by a characteristic triad of symptoms: impairments in social interaction; impairments in communication; and restricted interests and repetitive behavior. Other aspects, such as atypical eating, are also common but are not essential for diagnosis.<ref name=Filipek/> Autism's individual symptoms occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits.<ref name=London/>\n\n"
"===Social development===\n"
"Social deficits distinguish autism and the related [[autism spectrum disorder]]s (ASD; see [[#Classification|Classification]]) from other developmental disorders.<ref name=Rapin/> People with autism have social impairments and often lack the intuition about others that many people take for granted. Noted autistic [[Temple Grandin]] described her inability to understand the [[social communication]] of [[neurotypical]]s, or people with normal [[neural development]], as leaving her feeling \"like an anthropologist on Mars\".<ref>{{vcite book |title=[[An Anthropologist on Mars]]: Seven Paradoxical Tales |author=[[Oliver Sacks|Sacks O]] |publisher=Knopf |year=1995 |isbn=978-0-679-43785-7 }}</ref>\n\n"
"Unusual social development becomes apparent early in childhood.<!-- ref name=Volkmar/ --> Autistic infants show less attention to social stimuli, smile and look at others less often, and respond less to their own name. Autistic toddlers differ more strikingly from [[social norms]]; for example, they have less [[eye contact]] and [[turn-taking]], and do not have the ability to use simple movements to express themselves, such as pointing at things.<ref name=Volkmar/> Three- to five-year-old children with autism are less likely to exhibit social understanding, approach others spontaneously, imitate and respond to emotions, communicate nonverbally, and take turns with others. However, they do form [[Attachment (psychology)|attachments]] to their primary caregivers.<ref>{{cite journal | vauthors = Sigman M, Dijamco A, Gratier M, Rozga A | title = Early detection of core deficits in autism | journal = Ment Retard Dev Disabil Res Rev | volume = 10 | issue = 4 | pages = 221–33 | year = 2004 | pmid = 15666338 | doi = 10.1002/mrdd.20046 }}</ref> Most childen with autism display moderately less [[Attachment in children#Secure attachment|attachment security]] than neurotypical children, although this difference disappears in children with higher mental development or less severe ASD.<ref>{{cite journal | vauthors = Rutgers AH, Bakermans-Kranenburg MJ, van Ijzendoorn MH, van Berckelaer-Onnes IA | title = Autism and attachment: a meta-analytic review | journal = J Child Psychol Psychiatry | volume = 45 | issue = 6 | pages = 1123–34 | year = 2004 | pmid = 15257669 | doi = 10.1111/j.1469-7610.2004.t01-1-00305.x }}</ref> Older children and adults with ASD [[Face perception#Face perception in individuals with autism|perform worse on tests of face and emotion recognition]].<ref name=\"Sigman\">{{cite journal | vauthors = Sigman M, Spence SJ, Wang AT | title = Autism from developmental and neuropsychological perspectives | journal = Annu Rev Clin Psychol | volume = 2 | pages = 327–55 | year = 2006 | pmid = 17716073 | doi = 10.1146/annurev.clinpsy.2.022305.095210 }}</ref>\n\n"
"Children with high-functioning autism suffer from more intense and frequent loneliness compared to non-autistic peers, despite the common belief that children with autism prefer to be alone. Making and maintaining friendships often proves to be difficult for those with autism. For them, the quality of friendships, not the number of friends, predicts how lonely they feel. Functional friendships, such as those resulting in invitations to parties, may affect the quality of life more deeply.<ref name=Burgess/>\n\n"
"There are many anecdotal reports, but few systematic studies, of aggression and violence in individuals with ASD. The limited data suggest that, in children with intellectual disability, autism is associated with aggression, destruction of property, and [[tantrum]]s.<ref>{{cite journal | vauthors = Matson JL, Nebel-Schwalm M | title = Assessing challenging behaviors in children with autism spectrum disorders: A review | journal = Research in Developmental Disabilities | volume = 28 | issue = 6 | pages = 567–79 | date = November 2007 | pmid = 16973329 | doi = 10.1016/j.ridd.2006.08.001 }}</ref>\n\n"
"===Communication===\n"
"About a third to a half of individuals with autism do not develop enough natural speech to meet their daily communication needs.<ref>{{cite journal | vauthors = Noens I, van Berckelaer-Onnes I, Verpoorten R, van Duijn G | title = The ComFor: an instrument for the indication of augmentative communication in people with autism and intellectual disability | journal = J Intellect Disabil Res | volume = 50 | issue = 9 | pages = 621–32 | year = 2006 | pmid = 16901289 | doi = 10.1111/j.1365-2788.2006.00807.x }}</ref> Differences in communication may be present from the first year of life, and may include delayed onset of [[babbling]], unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with the caregiver. In the second and third years, children with autism have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Children with autism are less likely to make requests or share experiences, and are more likely to simply repeat others' words ([[echolalia]])<ref name=Landa/><ref name=Tager-Flusberg/> or [[Pronoun reversal|reverse pronouns]].<ref name=Kanner1943/> [[Joint attention]] seems to be necessary for functional speech, and deficits in joint attention seem to distinguish infants with ASD:<ref name=\"Johnson\">{{cite journal | vauthors = Johnson CP, Myers SM | title = Identification and evaluation of children with autism spectrum disorders | journal = Pediatrics | volume = 120 | issue = 5 | pages = 1183–215 | year = 2007 | pmid = 17967920 | doi = 10.1542/peds.2007-2361 | url = http://pediatrics.aappublications.org/cgi/content/full/120/5/1183 | archiveurl = http://web.archive.org/web/20090208013449/http://pediatrics.aappublications.org:80/cgi/content/full/120/5/1183 | archivedate = 8 February 2009 }}</ref> for example, they may look at a pointing hand instead of the pointed-at object,<ref name=Volkmar/><ref name=Tager-Flusberg/> and they consistently fail to point at objects in order to comment on or share an experience.<ref name=Johnson/> Children with autism may have difficulty with imaginative play and with developing symbols into language.<ref name=\"Landa\">{{cite journal | vauthors = Landa R | title = Early communication development and intervention for children with autism | journal = Ment Retard Dev Disabil Res Rev | volume = 13 | issue = 1 | pages = 16–25 | year = 2007 | pmid = 17326115 | doi = 10.1002/mrdd.20134 }}</ref><ref name=\"Tager-Flusberg\">{{cite journal | vauthors = Tager-Flusberg H, Caronna E | title = Language disorders: autism and other pervasive developmental disorders | journal = Pediatr Clin North Am | volume = 54 | issue = 3 | pages = 469–81 | year = 2007 | pmid = 17543905 | doi = 10.1016/j.pcl.2007.02.011 }}</ref>\n\n"
"In a pair of studies, high-functioning children with autism aged 8–15 performed equally well as, and adults better than, individually matched controls at basic language tasks involving vocabulary and spelling. Both autistic groups performed worse than controls at complex language tasks such as figurative language, comprehension and inference. As people are often sized up initially from their basic language skills, these studies suggest that people speaking to autistic individuals are more likely to overestimate what their audience comprehends.<ref name=Williams/>\n\n"
"===Repetitive behavior===\n"
"Autistic individuals display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R)<ref name=Lam-Aman/> categorizes as follows.\n\n"
"[[File:Autistic-sweetiepie-boy-with-ducksinarow.jpg|thumb|alt=Young boy asleep on a bed, facing the camera, with only the head visible and the body off-camera. On the bed behind the boy's head is a dozen or so toys carefully arranged in a line.|A young boy with autism who has arranged his toys in a row]]\n"
"* '''[[Stereotypy]]''' is repetitive movement, such as hand flapping, head rolling, or body rocking.\n"
"* '''[[Compulsive behavior]]''' is intended and appears to follow rules, such as arranging objects in stacks or lines.\n"
"* '''Sameness''' is resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted.\n"
"* '''[[Ritual#Psychology|Ritualistic behavior]]''' involves an unvarying pattern of daily activities, such as an unchanging menu or a dressing ritual. This is closely associated with sameness and an independent validation has suggested combining the two factors.<ref name=\"Lam-Aman\">{{cite journal | vauthors = Lam KS, Aman MG | title = The Repetitive Behavior Scale-Revised: independent validation in individuals with autism spectrum disorders | journal = J Autism Dev Disord | volume = 37 | issue = 5 | pages = 855–66 | year = 2007 | pmid = 17048092 | doi = 10.1007/s10803-006-0213-z }}</ref>\n"
"* '''Restricted behavior''' is limited in focus, interest, or activity, such as preoccupation with a single television program, toy or game.\n"
"* '''[[Self-injury]]''' includes movements that injure or can injure the person, such as eye-poking, [[Dermatillomania|skin-picking]], hand-biting and head-banging.<ref name=Johnson/>\n"
"No single repetitive or self-injurious behavior seems to be specific to autism, but only autism appears to have an elevated pattern of occurrence and severity of these behaviors.<ref>{{cite journal | vauthors = Bodfish JW, Symons FJ, Parker DE, Lewis MH | title = Varieties of repetitive behavior in autism: comparisons to mental retardation | journal = J Autism Dev Disord | volume = 30 | issue = 3 | pages = 237–43 | year = 2000 | pmid = 11055459 | doi = 10.1023/A:1005596502855 }}</ref>\n\n"
"===Other symptoms===\n"
"Autistic individuals may have symptoms that are independent of the diagnosis, but that can affect the individual or the family.<ref name=\"Filipek\">{{cite journal | vauthors = Filipek PA, Accardo PJ, Baranek GT, Cook EH, Dawson G, Gordon B, Gravel JS, Johnson CP, Kallen RJ, Levy SE, Minshew NJ, Ozonoff S, Prizant BM, Rapin I, Rogers SJ, Stone WL, Teplin S, Tuchman RF, Volkmar FR | title = The screening and diagnosis of autistic spectrum disorders | journal = J Autism Dev Disord | volume = 29 | issue = 6 | pages = 439–84 | year = 1999 | pmid = 10638459 | doi = 10.1023/A:1021943802493 | author. = }} This paper represents a consensus of representatives from nine professional and four parent organizations in the US.</ref>\n"
"An estimated 0.5% to 10% of individuals with ASD show unusual abilities, ranging from [[splinter skill]]s such as the memorization of trivia to the extraordinarily rare talents of prodigious [[Savant syndrome|autistic savants]].<ref>{{cite journal | vauthors = Treffert DA | title = The savant syndrome: an extraordinary condition. A synopsis: past, present, future | journal = Philosophical Transactions of the Royal Society B | volume = 364 | issue = 1522 | pages = 1351–7 | year = 2009 | pmid = 19528017 | pmc = 2677584 | doi = 10.1098/rstb.2008.0326 | url = http://rstb.royalsocietypublishing.org/content/364/1522/1351.full | laysummary = https://www.wisconsinmedicalsociety.org/professional/savant-syndrome/savant-syndrome-overview/ | laysource = Wisconsin Medical Society }}</ref> Many individuals with ASD show superior skills in perception and attention, relative to the general population.<ref>{{cite journal | vauthors = Plaisted Grant K, Davis G | title = Perception and apperception in autism: rejecting the inverse assumption | journal = Philosophical Transactions of the Royal Society B | volume = 364 | issue = 1522 | pages = 1393–8 | year = 2009 | pmid = 19528022 | pmc = 2677593 | doi = 10.1098/rstb.2009.0001 | url = http://rstb.royalsocietypublishing.org/content/364/1522/1393.full }}</ref> [[Sensory system|Sensory]] abnormalities are found in over 90% of those with autism, and are considered core features by some,<ref name=\"Geschwind-2009\">{{cite journal | vauthors = Geschwind DH | title = Advances in autism | journal = Annu Rev Med | volume = 60 | pages = 367–80 | year = 2009 | pmid = 19630577 | pmc = 3645857 | doi = 10.1146/annurev.med.60.053107.121225 }}</ref> although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders.<ref>{{cite journal | vauthors = Rogers SJ, Ozonoff S | title = Annotation: what do we know about sensory dysfunction in autism? A critical review of the empirical evidence | journal = J Child Psychol Psychiatry | volume = 46 | issue = 12 | pages = 1255–68 | year = 2005 | pmid = 16313426 | doi = 10.1111/j.1469-7610.2005.01431.x }}</ref> Differences are greater for under-responsivity (for example, walking into things) than for over-responsivity (for example, distress from loud noises) or for sensation seeking (for example, rhythmic movements).<ref>{{cite journal | vauthors = Ben-Sasson A, Hen L, Fluss R, Cermak SA, Engel-Yeger B, Gal E | title = A meta-analysis of sensory modulation symptoms in individuals with autism spectrum disorders | journal = J Autism Dev Disord | volume = 39 | issue = 1 | pages = 1–11 | year = 2009 | pmid = 18512135 | doi = 10.1007/s10803-008-0593-3 }}</ref> An estimated 60%–80% of autistic people have motor signs that include [[poor muscle tone]], [[Apraxia|poor motor planning]], and [[toe walking]];<ref name=Geschwind-2009/> deficits in motor coordination are pervasive across ASD and are greater in autism proper.<ref>{{cite journal | vauthors = Fournier KA, Hass CJ, Naik SK, Lodha N, Cauraugh JH | title = Motor coordination in autism spectrum disorders: a synthesis and meta-analysis | journal = J Autism Dev Disord | volume = | issue = | year = 2010 | pmid = 20195737 | doi = 10.1007/s10803-010-0981-3 }}</ref>\n\n"
"Unusual eating behavior occurs in about three-quarters of children with ASD, to the extent that it was formerly a diagnostic indicator. Selectivity is the most common problem, although eating rituals and food refusal also occur;<ref name=\"Dominick\">{{cite journal | vauthors = Dominick KC, Davis NO, Lainhart J, Tager-Flusberg H, Folstein S | title = Atypical behaviors in children with autism and children with a history of language impairment | journal = Res Dev Disabil | volume = 28 | issue = 2 | pages = 145–62 | year = 2007 | pmid = 16581226 | doi = 10.1016/j.ridd.2006.02.003 }}</ref> this does not appear to result in [[malnutrition]]. Although some children with autism also have [[gastrointestinal]] symptoms, there is a lack of published rigorous data to support the theory that children with autism have more or different gastrointestinal symptoms than usual;<ref>{{cite journal | vauthors = Erickson CA, Stigler KA, Corkins MR, Posey DJ, Fitzgerald JF, McDougle CJ | title = Gastrointestinal factors in autistic disorder: a critical review | journal = J Autism Dev Disord | volume = 35 | issue = 6 | pages = 713–27 | year = 2005 | pmid = 16267642 | doi = 10.1007/s10803-005-0019-4 }}</ref> studies report conflicting results, and the relationship between gastrointestinal problems and ASD is unclear.<ref>{{cite journal | vauthors = Buie T, Campbell DB, Fuchs GJ, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H | title = Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report | journal = Pediatrics | volume = 125 | issue = Suppl 1 | pages = S1–18 | year = 2010 | pmid = 20048083 | doi = 10.1542/peds.2009-1878C | url = http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S1 | author. = | archiveurl = http://web.archive.org/web/20100706035348/http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S1 | archivedate = 6 July 2010 }}</ref>\n\n"
"Parents of children with ASD have higher levels of [[stress (psychological)|stress]].<ref name=\"Volkmar\">{{vcite book|authors=Volkmar FR, Paul R, Rogers SJ, Pelphrey KA|title=Handbook of Autism and Pervasive Developmental Disorders, Assessment, Interventions, and Policy|publisher=[[John Wiley & Sons]]|isbn=1-118-28220-5|year=2014|page=301|accessdate=24 December 2014|url=https://books.google.com/books?id=4yzqAgAAQBAJ&pg=PT301}}</ref> Siblings of children with ASD report greater admiration of and less conflict with the affected sibling than siblings of unaffected children and were similar to siblings of children with [[Down syndrome]] in these aspects of the sibling relationship. However, they reported lower levels of closeness and intimacy than siblings of children with [[Down syndrome]]; siblings of individuals with ASD have greater risk of negative well-being and poorer sibling relationships as adults.<ref>{{cite journal | vauthors = Orsmond GI, Seltzer MM | title = Siblings of individuals with autism spectrum disorders across the life course | journal = Ment Retard Dev Disabil Res Rev | volume = 13 | issue = 4 | pages = 313–20 | year = 2007 | pmid = 17979200 | doi = 10.1002/mrdd.20171 | url = http://www.waisman.wisc.edu/family/pubs/Autism/2007%20siblings_autism_life-course.pdf | format = PDF | archiveurl = http://web.archive.org/web/20130530100939/http://www.waisman.wisc.edu/family/pubs/Autism/2007%20siblings_autism_life-course.pdf | archivedate = 30 May 2013 }}</ref>\n\n"
"==Causes==\n"
"{{main|Causes of autism}}\n\n"
"It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism's characteristic triad of symptoms.<ref name=Fractionable/> However, there is increasing suspicion that autism is instead a complex disorder whose core aspects have distinct causes that often co-occur.<ref name=\"Fractionable\">{{cite journal | vauthors = Happé F, Ronald A | title = The 'fractionable autism triad': a review of evidence from behavioural, genetic, cognitive and neural research | journal = [[Neuropsychol Rev]] | volume = 18 | issue = 4 | pages = 287–304 | year = 2008 | pmid = 18956240 | doi = 10.1007/s11065-008-9076-8 }}</ref><ref name=HappeTime/>\n\n"
"[[File:Single Chromosome Mutations.svg|thumb|alt=Three diagrams of chromosome pairs A, B that are nearly identical. 1: B is missing a segment of A. 2: B has two adjacent copies of a segment of A. 3: B's copy of A's segment is in reverse order.|Deletion (1), duplication (2) and inversion (3) are all [[chromosome abnormalities]] that have been implicated in autism.<ref name=Beaudet/>]]\n"
"Autism has a strong genetic basis, although the [[Heritability of autism|genetics of autism]] are complex and it is unclear whether ASD is explained more by rare [[mutation]]s with major effects, or by rare multigene interactions of common genetic variants.<ref name=\"Abrahams\">{{cite journal | vauthors = Abrahams BS, Geschwind DH | title = Advances in autism genetics: on the threshold of a new neurobiology | journal = [[Nature Reviews Genetics]] | volume = 9 | issue = 5 | pages = 341–55 | year = 2008 | pmid = 18414403 | pmc = 2756414 | doi = 10.1038/nrg2346 }}</ref><ref>{{cite journal | vauthors = Buxbaum JD | title = Multiple rare variants in the etiology of autism spectrum disorders | journal = Dialogues Clin Neurosci | volume = 11 | issue = 1 | pages = 35–43 | year = 2009 | pmid = 19432386 | pmc = 3181906 }}</ref> Complexity arises due to interactions among multiple genes, the environment, and [[epigenetic]] factors which do not change [[DNA]] but are heritable and influence [[gene expression]].<ref name=\"Rapin\">{{cite journal | vauthors = Rapin I, Tuchman RF | title = Autism: definition, neurobiology, screening, diagnosis | journal = [[Pediatr Clin North Am]] | volume = 55 | issue = 5 | pages = 1129–46 | year = 2008 | pmid = 18929056 | doi = 10.1016/j.pcl.2008.07.005 }}</ref> Studies of twins suggest that [[heritability]] is 0.7 for autism and as high as 0.9 for ASD, and siblings of those with autism are about 25 times more likely to be autistic than the general population.<ref name=Geschwind-2009/> However, most of the mutations that increase autism risk have not been identified. Typically, autism cannot be traced to a [[Mendelian]] (single-gene) mutation or to a single [[chromosome abnormality]], and none of the genetic syndromes associated with ASDs have been shown to selectively cause ASD.<ref name=Abrahams/> Numerous candidate genes have been located, with only small effects attributable to any particular gene.<ref name=Abrahams/> The large number of autistic individuals with unaffected family members may result from [[copy number variation]]s—spontaneous [[Deletion (genetics)|deletions]] or [[Gene duplication|duplications]] in genetic material during [[meiosis]].<ref>{{cite journal | vauthors = Cook EH, Scherer SW | title = Copy-number variations associated with neuropsychiatric conditions | journal = Nature | volume = 455 | issue = 7215 | pages = 919–23 | year = 2008 | pmid = 18923514 | doi = 10.1038/nature07458 }}</ref> Hence, a substantial fraction of autism cases may be traceable to genetic causes that are highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome.<ref name=\"Beaudet\">{{cite journal | vauthors = Beaudet AL | title = Autism: highly heritable but not inherited | journal = Nat Med | volume = 13 | issue = 5 | pages = 534–6 | year = 2007 | pmid = 17479094 | doi = 10.1038/nm0507-534 }}</ref>\n\n"
"Several lines of evidence point to [[Synapse|synaptic]] dysfunction as a cause of autism.<ref name=Levy/> Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with [[cell adhesion]].<ref name=\"Betancur\">{{cite journal | vauthors = Betancur C, Sakurai T, Buxbaum JD | title = The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders | journal = [[Trends Neurosci]] | volume = 32 | issue = 7 | pages = 402–12 | year = 2009 | pmid = 19541375 | doi = 10.1016/j.tins.2009.04.003 }}</ref> Gene replacement studies in mice suggest that autistic symptoms are closely related to later developmental steps that depend on activity in synapses and on activity-dependent changes.<ref name=\"Walsh\">{{cite journal | vauthors = Walsh CA, Morrow EM, Rubenstein JL | title = Autism and brain development | journal = [[Cell (journal)|Cell]] | volume = 135 | issue = 3 | pages = 396–400 | year = 2008 | pmid = 18984148 | pmc = 2701104 | doi = 10.1016/j.cell.2008.10.015 }}</ref> All known [[teratogen]]s (agents that cause [[birth defect]]s) related to the risk of autism appear to act during the first eight weeks from [[Human fertilization|conception]], and though this does not exclude the possibility that autism can be initiated or affected later, there is strong evidence that autism arises very early in development.<ref name=\"Arndt\">{{cite journal | vauthors = Arndt TL, Stodgell CJ, Rodier PM | title = The teratology of autism | journal = [[Int J Dev Neurosci]] | volume = 23 | issue = 2–3 | pages = 189–99 | year = 2005 | pmid = 15749245 | doi = 10.1016/j.ijdevneu.2004.11.001 }}</ref>\n\n"
"Exposure to [[air pollution]] during pregnancy, especially [[heavy metal (chemistry)|heavy metals]] and particulates, may increase the risk of autism.<ref>{{cite journal |author=Lyall K, Schmidt RJ, Hertz-Picciotto I |title=Maternal lifestyle and environmental risk factors for autism spectrum disorders |journal=Int J Epidemiol |volume=43 |issue=2 |pages=443–64 |date=April 2014 |pmid=24518932 |doi=10.1093/ije/dyt282 }}</ref> [[Environmental factor]]s that have been claimed to contribute to or exacerbate autism, or may be important in future research, include certain foods, [[infectious disease]]s, [[solvent]]s, [[diesel exhaust]], [[PCBs]], [[phthalates]] and [[phenols]] used in plastic products, [[pesticide]]s, [[brominated flame retardant]]s, [[Ethanol|alcohol]], smoking, [[illicit drug]]s, [[vaccine]]s,<ref name=Newschaffer/> and [[prenatal stress]],<ref>{{cite journal | vauthors = Kinney DK, Munir KM, Crowley DJ, Miller AM | title = Prenatal stress and risk for autism | journal = [[Neurosci Biobehav Rev]] | volume = 32 | issue = 8 | pages = 1519–32 | year = 2008 | pmid = 18598714 | pmc = 2632594 | doi = 10.1016/j.neubiorev.2008.06.004 }}</ref> although no links have been found, and some have been completely disproven.\n\n"
"Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination. This has led to unsupported theories blaming [[Vaccine controversy#Vaccine overload|vaccine \"overload\"]], a [[Thiomersal controversy|vaccine preservative]], or the [[MMR vaccine controversy|MMR vaccine]] for causing autism.<ref name=\"GerberOffit2009\">{{cite journal | vauthors = Gerber JS, Offit PA | title = Vaccines and autism: a tale of shifting hypotheses | journal = Clin Infect Dis | volume = 48 | issue = 4 | pages = 456–61 | year = 2009 | pmid = 19128068 | pmc = 2908388 | doi = 10.1086/596476 | url = http://cid.oxfordjournals.org/content/48/4/456.full | archiveurl = http://web.archive.org/web/20131031043545/http://cid.oxfordjournals.org:80/content/48/4/456.full | archivedate = 31 October 2013 }}</ref> The latter theory was supported by a litigation-funded study that has since been shown to have been \"an elaborate fraud\".<ref name=\"WakefieldarticleBMJ\">{{cite journal | vauthors = Godlee F, Smith J, Marcovitch H | title = Wakefield's article linking MMR vaccine and autism was fraudulent | journal = [[BMJ]] | volume = 342:c7452 | pages = c7452 | year = 2011 | pmid = 21209060 | doi = 10.1136/bmj.c7452 | url = http://www.bmj.com/content/342/bmj.c7452.full | archiveurl = http://web.archive.org/web/20131111093448/http://www.bmj.com/content/342/bmj.c7452.full | archivedate = 11 November 2013 }}</ref> Although these theories lack convincing scientific evidence and are biologically implausible,<ref name=GerberOffit2009/> parental concern about a potential vaccine link with autism has led to lower rates of [[childhood immunizations]], [[MMR vaccine controversy#Disease outbreaks|outbreaks of previously controlled childhood diseases]] in some countries, and the preventable deaths of several children.<ref name=\"vaccines\">Vaccines and autism:\n"
"* {{cite journal | vauthors = Doja A, Roberts W | title = Immunizations and autism: a review of the literature | journal = [[Can J Neurol Sci]] | volume = 33 | issue = 4 | pages = 341–6 | year = 2006 | pmid = 17168158 | doi=10.1017/s031716710000528x}}\n"
"* {{cite journal | vauthors = Gerber JS, Offit PA | title = Vaccines and autism: a tale of shifting hypotheses | journal = [[Clin Infect Dis]] | volume = 48 | issue = 4 | pages = 456–61 | year = 2009 | pmid = 19128068 | pmc = 2908388 | doi = 10.1086/596476 | url = http://cid.oxfordjournals.org/content/48/4/456.full | archiveurl = http://web.archive.org/web/20131031043545/http://cid.oxfordjournals.org:80/content/48/4/456.full | archivedate = 31 October 2013 }}\n"
"* {{cite journal | vauthors = Gross L | title = A broken trust: lessons from the vaccine–autism wars | journal = PLoS Biol | volume = 7 | issue = 5 | pages = e1000114 | year = 2009 | pmid = 19478850 | pmc = 2682483 | doi = 10.1371/journal.pbio.1000114 }}\n"
"* {{cite journal | vauthors = Paul R | title = Parents ask: am I risking autism if I vaccinate my children? | journal = [[J Autism Dev Disord]] | volume = 39 | issue = 6 | pages = 962–3 | year = 2009 | pmid = 19363650 | doi = 10.1007/s10803-009-0739-y }}\n"
"* {{cite journal | vauthors = Poland GA, Jacobson RM | title = The Age-Old Struggle against the Antivaccinationists | journal = N Engl J Med | volume = 364 | pages = 97–9 | date = 13 January 2011 | pmid = 21226573 | doi = 10.1056/NEJMp1010594 | url = http://www.nejm.org/doi/full/10.1056/NEJMp1010594 | archiveurl = http://web.archive.org/web/20140423082318/http://www.nejm.org/doi/full/10.1056/NEJMp1010594 | archivedate = 23 April 2014 }}</ref><ref name=\"dublin\">{{cite journal | vauthors = McBrien J, Murphy J, Gill D, Cronin M, O'Donovan C, Cafferkey MT | title = Measles outbreak in Dublin, 2000 | journal = Pediatr. Infect. Dis. J. | volume = 22 | issue = 7 | pages = 580–4 | year = 2003 | pmid = 12867830 | doi = 10.1097/00006454-200307000-00002 }}</ref>\n\n"
"==Mechanism==\n"
"Autism's symptoms result from maturation-related changes in various systems of the brain.<!-- ref name=Penn/ --> How autism occurs is not well understood. Its mechanism can be divided into two areas: the [[pathophysiology]] of brain structures and processes associated with autism, and the [[neuropsychological]] linkages between brain structures and behaviors.<ref name=\"Penn\">{{cite journal | vauthors = Penn HE | title = Neurobiological correlates of autism: a review of recent research | journal = Child Neuropsychol | volume = 12 | issue = 1 | pages = 57–79 | year = 2006 | pmid = 16484102 | doi = 10.1080/09297040500253546 }}</ref> The behaviors appear to have multiple pathophysiologies.<ref name=London/>\n\n"
"===Pathophysiology===\n"
"[[File:Autismbrain.jpg|thumb|alt=Two diagrams of major brain structures implicated in autism. The upper diagram shows the cerebral cortex near the top and the basal ganglia in the center, just above the amygdala and hippocampus. The lower diagram shows the corpus callosum near the center, the cerebellum in the lower rear, and the brain stem in the lower center.|Autism affects the [[amygdala]], [[cerebellum]], and many other parts of the brain.<ref name=Amaral/>]]\n"
"Unlike many other brain disorders, such as [[Parkinson's]], autism does not have a clear unifying mechanism at either the molecular, cellular, or systems level; it is not known whether autism is a few disorders caused by mutations converging on a few common molecular pathways, or is (like intellectual disability) a large set of disorders with diverse mechanisms.<ref name=\"Geschwind\">{{cite journal | vauthors = Geschwind DH | title = Autism: many genes, common pathways? | journal = Cell | volume = 135 | issue = 3 | pages = 391–5 | year = 2008 | pmid = 18984147 | pmc = 2756410 | doi = 10.1016/j.cell.2008.10.016 | title. = }}</ref> Autism appears to result from developmental factors that affect many or all functional brain systems,<ref>{{cite journal | vauthors = Müller RA | title = The study of autism as a distributed disorder | journal = Ment Retard Dev Disabil Res Rev | volume = 13 | issue = 1 | pages = 85–95 | year = 2007 | pmid = 17326118 | pmc = 3315379 | doi = 10.1002/mrdd.20141 }}</ref> and to disturb the timing of brain development more than the final product.<ref name=\"Amaral\">{{cite journal | vauthors = Amaral DG, Schumann CM, Nordahl CW | title = Neuroanatomy of autism | journal = Trends Neurosci | volume = 31 | issue = 3 | pages = 137–45 | year = 2008 | pmid = 18258309 | doi = 10.1016/j.tins.2007.12.005 }}</ref> [[Neuroanatomical]] studies and the associations with [[teratogens]] strongly suggest that autism's mechanism includes alteration of brain development soon after conception.<ref name=Arndt/> This anomaly appears to start a cascade of pathological events in the brain that are significantly influenced by environmental factors.<ref>{{cite journal | vauthors = Casanova MF | title = The neuropathology of autism | journal = Brain Pathol | volume = 17 | issue = 4 | pages = 422–33 | year = 2007 | pmid = 17919128 | doi = 10.1111/j.1750-3639.2007.00100.x }}</ref> Just after birth, the brains of children with autism tend to grow faster than usual, followed by normal or relatively slower growth in childhood. It is not known whether early overgrowth occurs in all children with autism. It seems to be most prominent in brain areas underlying the development of higher cognitive specialization.<ref name=Geschwind-2009/> Hypotheses for the cellular and molecular bases of pathological early overgrowth include the following:\n"
"* An excess of [[neuron]]s that causes local overconnectivity in key brain regions.<ref>{{cite journal | vauthors = Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J | title = Mapping early brain development in autism | journal = Neuron | volume = 56 | issue = 2 | pages = 399–413 | year = 2007 | pmid = 17964254 | doi = 10.1016/j.neuron.2007.10.016 | author. = }}</ref>\n"
"* Disturbed [[neuronal migration]] during early [[gestation]].<ref name=\"Schmitz\">{{cite journal | vauthors = Schmitz C, Rezaie P | title = The neuropathology of autism: where do we stand? | journal = Neuropathol Appl Neurobiol | volume = 34 | issue = 1 | pages = 4–11 | year = 2008 | pmid = 17971078 | doi = 10.1111/j.1365-2990.2007.00872.x | title. = }}</ref><ref name=\"Persico\">{{cite journal | vauthors = Persico AM, Bourgeron T | title = Searching for ways out of the autism maze: genetic, epigenetic and environmental clues | journal = Trends Neurosci | volume = 29 | issue = 7 | pages = 349–58 | year = 2006 | pmid = 16808981 | doi = 10.1016/j.tins.2006.05.010 }}</ref>\n"
"* Unbalanced excitatory–inhibitory networks.<ref name=Persico/>\n"
"* Abnormal formation of [[synapse]]s and [[dendritic spine]]s,<ref name=Persico/> for example, by modulation of the [[neurexin]]–[[neuroligin]] [[Cell adhesion|cell-adhesion]] system,<ref>{{cite journal | vauthors = Südhof TC | title = Neuroligins and neurexins link synaptic function to cognitive disease | journal = Nature | volume = 455 | issue = 7215 | pages = 903–11 | year = 2008 | pmid = 18923512 | pmc = 2673233 | doi = 10.1038/nature07456 }}</ref> or by poorly regulated [[Protein synthesis|synthesis]] of synaptic proteins.<ref>{{cite journal | vauthors = Kelleher RJ, Bear MF | title = The autistic neuron: troubled translation? | journal = Cell | volume = 135 | issue = 3 | pages = 401–6 | year = 2008 | pmid = 18984149 | doi = 10.1016/j.cell.2008.10.017 | title. = }}</ref><ref>{{cite journal | vauthors = Bear MF, Dölen G, Osterweil E, Nagarajan N | title = Fragile X: translation in action. | journal = Neuropsychopharmacology | volume = 33 | issue = 1 | pages = 84–7 | year = 2008 | pmid = 17940551 | doi = 10.1038/sj.npp.1301610 | title. = }}</ref> Disrupted synaptic development may also contribute to [[epilepsy]], which may explain why the two conditions are associated.<ref>{{cite journal | vauthors = Tuchman R, Moshé SL, Rapin I | title = Convulsing toward the pathophysiology of autism | journal = Brain Dev | volume = 31 | issue = 2 | pages = 95–103 | year = 2009 | pmid = 19006654 | pmc = 2734903 | doi = 10.1016/j.braindev.2008.09.009 }}</ref>\n\n"
"The [[immune system]] is thought to play an important role in autism. Children with autism have been found by researchers to have [[inflammation]] of both the peripheral and central immune systems as indicated by increased levels of pro-inflammatory [[cytokines]] and significant activation of [[microglia]].<ref name=\"pmid24290389\">{{cite journal | vauthors = Hsiao EY | title = Immune dysregulation in autism spectrum disorder. | journal = International Review of Neurobiology | volume = 113 | pages = 269–302 | year = 2013 | pmid = 24290389 | doi = 10.1016/B978-0-12-418700-9.00009-5 }}</ref><ref name=\"pmid21906670\">{{cite journal | vauthors = Onore C, Careaga M, Ashwood P | title = The role of immune dysfunction in the pathophysiology of autism | journal = Brain, Behavior and Immunity | volume = 26 | issue = 3 | pages = 383–92 | date = August 2011 | pmid = 21906670 | doi = 10.1016/j.bbi.2011.08.007 }}</ref><ref name=\"pmid24795645\">{{cite journal | vauthors = Rossignol DA, Frye RE | title = Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. | journal = Frontiers in Physiology | volume = 5 | page = 150 | year = 2014 | pmid = 24795645 | doi = 10.1016/j.bbi.2011.08.007 }}</ref> Biomarkers of abnormal immune function have also been associated with increased impairments in behaviors that are characteristic of the core features of autism such as deficits in social interactions and communication.<ref name=\"pmid21906670\"/> Interactions between the [[immune system]] and the [[nervous system]] begin early during the [[Human embryogenesis|embryonic stage]] of life, and successful neurodevelopment depends on a balanced immune response. It is thought that activation of a pregnant mother's immune system such as from environmental toxicants or infection can contribute to causing autism through causing a disruption of brain development.<ref name=\"pmid21482187 \">{{cite journal | vauthors = Patterson PH | title = Maternal infection and immune involvement in autism. | journal = Trends in Molecular Medicine | volume = 17 | issue = 7 | pages = 389–94 | date = July 2011 | pmid = 21482187 | doi = 10.1016/j.molmed.2011.03.001 }}</ref><ref name=\"Chaste\">{{cite journal | vauthors = Chaste P, Leboyer M | title = Autism risk factors: genes, environment, and gene-environment interactions | journal = Dialogues Clin Neurosci | volume = 14 | issue = 3 | pages = 281–92 | year = 2012 | pmid = 23226953 | pmc = 3513682 }}</ref><ref>{{cite journal | vauthors = Ashwood P, Wills S, Van de Water J | title = The immune response in autism: a new frontier for autism research | journal = J Leukoc Biol | volume = 80 | issue = 1 | pages = 1–15 | year = 2006 | pmid = 16698940 | doi = 10.1189/jlb.1205707 | url = http://www.jleukbio.org/cgi/content/full/80/1/1 }}</ref> This is supported by recent studies that have found that infection during pregnancy is associated with an increased risk of autism.<ref name=\"pmid25218900\">{{cite journal | vauthors = Lee BK, Magnusson C, Gardner RM, Blomström S, Newschaffer CJ, Burstyn I, Karlsson H, Dalman C | title = Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. | journal = Brain, Behavior and Immunity | date = September 2014 | pmid = 25218900 | doi = 10.1016/j.bbi.2014.09.001 }}</ref><ref name=\"pmid20414802\">{{cite journal | vauthors = Atladóttir HO, Thorsen P, Østergaard L, Schendel DE, Lemcke S, Abdallah M, Parner ET | title = Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. | journal = Journal of Autism and Developmental Disorders | volume = 40 | issue = 12 | pages = 1423–30. | date = December 2010 | pmid = 20414802 | doi = 10.1007/s10803-010-1006-y }}</ref>\n\n"
"The relationship of [[neurochemical]]s to autism is not well understood; several have been investigated, with the most evidence for the role of [[serotonin]] and of genetic differences in its transport.<ref name=\"Levy\">{{cite journal | vauthors = Levy SE, Mandell DS, Schultz RT | title = Autism | journal = Lancet | volume = 374 | issue = 9701 | pages = 1627–38 | year = 2009 | pmid = 19819542 | pmc = 2863325 | doi = 10.1016/S0140-6736(09)61376-3 }}</ref> The role of group I [[metabotropic glutamate receptors]] (mGluR) in the pathogenesis of [[fragile X syndrome]], the most common identified genetic cause of autism, has led to interest in the possible implications for future autism research into this pathway.<ref name=\"pmid18093519\">{{cite journal | vauthors = Dölen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF | title = Correction of fragile X syndrome in mice | journal = Neuron | volume = 56 | issue = 6 | pages = 955–62 | year = 2007 | pmid = 18093519 | pmc = 2199268 | doi = 10.1016/j.neuron.2007.12.001 }}</ref> Some data suggests neuronal overgrowth potentially related to an increase in several [[growth hormone]]s<ref>{{cite journal | vauthors = Hughes JR | title = Update on autism: A review of 1300 reports published in 2008 | journal = Epilepsy Behav | volume = 16 | issue = 4 | pages = 569–589 | year = 2009 | pmid = 19896907 | doi = 10.1016/j.yebeh.2009.09.023 }}</ref> or to impaired regulation of [[growth factor receptor]]s. Also, some [[inborn errors of metabolism]] are associated with autism, but probably account for less than 5% of cases.<ref name=Manzi/>\n\n"
"The [[mirror neuron system]] (MNS) theory of autism hypothesizes that distortion in the development of the MNS interferes with imitation and leads to autism's core features of social impairment and communication difficulties. The MNS operates when an animal performs an action or observes another animal perform the same action. The MNS may contribute to an individual's understanding of other people by enabling the modeling of their behavior via embodied simulation of their actions, intentions, and emotions.<ref>MNS and autism:\n"
"* {{cite journal | vauthors = Williams JH | title = Self–other relations in social development and autism: multiple roles for mirror neurons and other brain bases | journal = Autism Res | volume = 1 | issue = 2 | pages = 73–90 | year = 2008 | pmid = 19360654 | doi = 10.1002/aur.15 }}\n"
"* {{cite journal | vauthors = Dinstein I, Thomas C, Behrmann M, Heeger DJ | title = A mirror up to nature | journal = Curr Biol | volume = 18 | issue = 1 | pages = R13–8 | year = 2008 | pmid = 18177704 | pmc = 2517574 | doi = 10.1016/j.cub.2007.11.004 }}</ref> Several studies have tested this hypothesis by demonstrating structural abnormalities in MNS regions of individuals with ASD, delay in the activation in the core circuit for imitation in individuals with Asperger syndrome, and a correlation between reduced MNS activity and severity of the syndrome in children with ASD.<ref name=\"Iacoboni\">{{cite journal | vauthors = Iacoboni M, Dapretto M | title = The mirror neuron system and the consequences of its dysfunction | journal = Nature Reviews Neuroscience | volume = 7 | issue = 12 | pages = 942–51 | year = 2006 | pmid = 17115076 | doi = 10.1038/nrn2024 }}</ref> However, individuals with autism also have abnormal brain activation in many circuits outside the MNS<ref>{{cite journal | vauthors = Frith U, Frith CD | title = Development and neurophysiology of mentalizing | journal = Philosophical Transactions of the Royal Society B | volume = 358 | issue = 1431 | pages = 459–73 | year = 2003 | pmid = 12689373 | pmc = 1693139 | doi = 10.1098/rstb.2002.1218 | url = http://rstb.royalsocietypublishing.org/content/358/1431/459.full.pdf | format = PDF }}</ref> and the MNS theory does not explain the normal performance of children with autism on imitation tasks that involve a goal or object.<ref>{{cite journal | vauthors = Hamilton AF | title = Emulation and mimicry for social interaction: a theoretical approach to imitation in autism | journal = Q J Exp Psychol | volume = 61 | issue = 1 | pages = 101–15 | year = 2008 | pmid = 18038342 | doi = 10.1080/17470210701508798 }}</ref>\n\n"
"[[File:Powell2004Fig1A.jpeg|thumb|upright|alt=A human brain viewed from above. About 10% is highlighted in yellow and 10% in blue. There is only a tiny (perhaps 0.5%) green region where they overlap.|Autistic individuals tend to use different areas of the brain (yellow) for a movement task compared to a control group (blue).<ref name=\"Powell\">{{cite journal | vauthors = Powell K | title=Opening a window to the autistic brain |journal=PLoS Biol |volume=2 |issue=8 |pages=E267 |year=2004 |pmid=15314667 |pmc=509312 |doi=10.1371/journal.pbio.0020267 |url=http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020267 |archiveurl=http://web.archive.org/web/20130526034145/http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020267 |archivedate=26 May 2013 }}</ref>]]\n"
"ASD-related patterns of low function and aberrant activation in the brain differ depending on whether the brain is doing social or nonsocial tasks.<ref>{{cite journal | vauthors = Di Martino A, Ross K, Uddin LQ, Sklar AB, Castellanos FX, Milham MP | title = Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis | journal = Biol Psychiatry | volume = 65 | issue = 1 | pages = 63–74 | year = 2009 | pmid = 18996505 | doi = 10.1016/j.biopsych.2008.09.022 }}</ref>\n"
"In autism there is evidence for reduced functional connectivity of the [[default network]], a large-scale brain network involved in social and emotional processing, with intact connectivity of the [[task-positive network]], used in sustained attention and goal-directed thinking. In people with autism the two networks are not negatively correlated in time, suggesting an imbalance in toggling between the two networks, possibly reflecting a disturbance of [[self-referential]] thought.<ref>{{cite journal | vauthors = Broyd SJ, Demanuele C, Debener S, Helps SK, James CJ, Sonuga-Barke EJ | title = Default-mode brain dysfunction in mental disorders: a systematic review | journal = Neurosci Biobehav Rev | volume = 33 | issue = 3 | pages = 279–96 | year = 2009 | pmid = 18824195 | doi = 10.1016/j.neubiorev.2008.09.002 }}</ref>\n\n"
"The underconnectivity theory of autism hypothesizes that autism is marked by underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.<ref>{{cite journal | vauthors = Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ | title = Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry | journal = Cereb Cortex | volume = 17 | issue = 4 | pages = 951–61 | year = 2007 | pmid = 16772313 | doi = 10.1093/cercor/bhl006 | url = http://cercor.oxfordjournals.org/cgi/content/full/17/4/951 | archiveurl = http://web.archive.org/web/20100707140313/http://cercor.oxfordjournals.org:80/cgi/content/full/17/4/951 | archivedate = 7 July 2010 }}</ref> Evidence for this theory has been found in [[functional neuroimaging]] studies on autistic individuals<ref name=\"Williams\">{{cite journal | vauthors = Williams DL, Goldstein G, Minshew NJ | title = Neuropsychologic functioning in children with autism: further evidence for disordered complex information-processing | journal = Child Neuropsychol | volume = 12 | issue = 4–5 | pages = 279–98 | year = 2006 | pmid = 16911973 | pmc = 1803025 | doi = 10.1080/09297040600681190 }}</ref> and by a [[Electroencephalography|brainwave]] study that suggested that adults with ASD have local overconnectivity in the [[Cerebral cortex|cortex]] and weak functional connections between the [[frontal lobe]] and the rest of the cortex.<ref>{{cite journal | vauthors = Murias M, Webb SJ, Greenson J, Dawson G | title = Resting state cortical connectivity reflected in EEG coherence in individuals with autism | journal = Biol Psychiatry | volume = 62 | issue = 3 | pages = 270–3 | year = 2007 | pmid = 17336944 | pmc = 2001237 | doi = 10.1016/j.biopsych.2006.11.012 }}</ref> Other evidence suggests the underconnectivity is mainly within each [[Cerebral hemisphere|hemisphere]] of the cortex and that autism is a disorder of the [[Association areas|association cortex]].<ref>{{cite journal | vauthors = Minshew NJ, Williams DL | title = The new neurobiology of autism: cortex, connectivity, and neuronal organization | journal = Arch Neurol | volume = 64 | issue = 7 | pages = 945–50 | year = 2007 | pmid = 17620483 | pmc = 2597785 | doi = 10.1001/archneur.64.7.945 }}</ref>\n\n"
"From studies based on [[event-related potential]]s, transient changes to the brain's electrical activity in response to stimuli, there is considerable evidence for differences in autistic individuals with respect to attention, orientation to auditory and visual stimuli, novelty detection, language and face processing, and information storage; several studies have found a preference for nonsocial stimuli.<ref>{{cite journal | vauthors = Jeste SS, Nelson CA | title = Event related potentials in the understanding of autism spectrum disorders: an analytical review | journal = J Autism Dev Disord | volume = 39 | issue = 3 | pages = 495–510 | year = 2009 | pmid = 18850262 | doi = 10.1007/s10803-008-0652-9 }}</ref> For example, [[magnetoencephalography]] studies have found evidence in children with autism of delayed responses in the brain's processing of auditory signals.<ref>{{cite journal | vauthors = Roberts TP, Schmidt GL, Egeth M, Blaskey L, Rey MM, Edgar JC, Levy SE | title = Electrophysiological signatures: magnetoencephalographic studies of the neural correlates of language impairment in autism spectrum disorders | journal = Int J Psychophysiol | volume = 68 | issue = 2 | pages = 149–60 | year = 2008 | pmid = 18336941 | pmc = 2397446 | doi = 10.1016/j.ijpsycho.2008.01.012 | author. = }}</ref>\n\n"
"In the genetic area, relations have been found between autism and [[schizophrenia]] based on duplications and deletions of chromosomes; research showed that schizophrenia and autism are significantly more common in combination with [[1q21.1 deletion syndrome]]. Research on autism/schizophrenia relations for chromosome 15 (15q13.3), chromosome 16 (16p13.1) and chromosome 17 (17p12) are inconclusive.<ref>{{cite journal | vauthors = Crespi B, Stead P, Elliot M | title = Evolution in health and medicine Sackler colloquium: Comparative genomics of autism and schizophrenia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = Suppl 1 | pages = 1736–41 | year = 2010 | pmid = 19955444 | pmc = 2868282 | doi = 10.1073/pnas.0906080106 }}</ref>\n\n"
"===Neuropsychology===\n"
"Two major categories of [[cognitive]] theories have been proposed about the links between autistic brains and behavior.\n\n"
"The first category focuses on deficits in [[social cognition]]. [[Simon Baron-Cohen]]'s [[empathizing–systemizing theory]] postulates that autistic individuals can systemize—that is, they can develop internal rules of operation to handle events inside the brain—but are less effective at empathizing by handling events generated by other agents. An extension, the extreme male brain theory, hypothesizes that autism is an extreme case of the male brain, defined psychometrically as individuals in whom systemizing is better than empathizing.<ref name=E-S-theory/> These theories are somewhat related to Baron-Cohen's earlier [[theory of mind]] approach, which hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others. The theory of mind hypothesis is supported by the atypical responses of children with autism to the [[Sally–Anne test]] for reasoning about others' motivations,<ref name=\"E-S-theory\">{{cite journal | vauthors = Baron-Cohen S | title = Autism: the empathizing–systemizing (E-S) theory | journal = Annals of the New York Academy of Sciences | volume = 1156 | pages = 68–80 | year = 2009 | pmid = 19338503 | doi = 10.1111/j.1749-6632.2009.04467.x | url = http://docs.autismresearchcentre.com/papers/2009_BC_nyas.pdf | format = PDF | archiveurl = http://web.archive.org/web/20131214134422/http://docs.autismresearchcentre.com/papers/2009_BC_nyas.pdf | archivedate = 14 December 2013 }}</ref> and the mirror neuron system theory of autism described in ''[[#Pathophysiology|Pathophysiology]]'' maps well to the hypothesis.<ref name=Iacoboni/> However, most studies have found no evidence of impairment in autistic individuals' ability to understand other people's basic intentions or goals; instead, data suggests that impairments are found in understanding more complex social emotions or in considering others' viewpoints.<ref>{{cite journal | vauthors = Hamilton AF | title = Goals, intentions and mental states: challenges for theories of autism | journal = J Child Psychol Psychiatry | volume = 50 | issue = 8 | pages = 881–92 | year = 2009 | pmid = 19508497 | doi = 10.1111/j.1469-7610.2009.02098.x }}</ref>\n\n"
"The second category focuses on nonsocial or general processing: the [[executive functions]] such as [[working memory]], planning, [[Inhibition Theory|inhibition]]. In his review, Kenworthy states that \"the claim of [[executive dysfunction]] as a causal factor in autism is controversial\", however, \"it is clear that executive dysfunction plays a role in the social and cognitive deficits observed in individuals with autism\".<ref name=Kenworthy/> Tests of core executive processes such as eye movement tasks indicate improvement from late childhood to adolescence, but performance never reaches typical adult levels.<ref>{{cite journal | vauthors = O'Hearn K, Asato M, Ordaz S, Luna B | title = Neurodevelopment and executive function in autism | journal = Dev Psychopathol | volume = 20 | issue = 4 | pages = 1103–32 | year = 2008 | pmid = 18838033 | doi = 10.1017/S0954579408000527 }}</ref> A strength of the theory is predicting stereotyped behavior and narrow interests;<ref>{{cite journal | vauthors = Hill EL | title = Executive dysfunction in autism | journal = Trends Cogn Sci | volume = 8 | issue = 1 | pages = 26–32 | year = 2004 | pmid = 14697400 | doi = 10.1016/j.dr.2004.01.001 }}</ref> two weaknesses are that executive function is hard to measure<ref name=\"Kenworthy\">{{cite journal | vauthors = Kenworthy L, Yerys BE, Anthony LG, Wallace GL | title = Understanding executive control in autism spectrum disorders in the lab and in the real world | journal = Neuropsychol Rev | volume = 18 | issue = 4 | pages = 320–38 | year = 2008 | pmid = 18956239 | pmc = 2856078 | doi = 10.1007/s11065-008-9077-7 }}</ref> and that executive function deficits have not been found in young children with autism.<ref name=Sigman/>\n\n"
"[[Weak central coherence theory]] hypothesizes that a limited ability to see the big picture underlies the central disturbance in autism. One strength of this theory is predicting special talents and peaks in performance in autistic people.<ref>{{cite journal | vauthors = Happé F, Frith U | title = The weak coherence account: detail-focused cognitive style in autism spectrum disorders | journal = J Autism Dev Disord | volume = 36 | issue = 1 | pages = 5–25 | year = 2006 | pmid = 16450045 | doi = 10.1007/s10803-005-0039-0 }}</ref> A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and [[perceptual]] operations in autistic individuals.<ref>{{cite journal | vauthors = Mottron L, Dawson M, Soulières I, Hubert B, Burack J | title = Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception | journal = J Autism Dev Disord | volume = 36 | issue = 1 | pages = 27–43 | year = 2006 | pmid = 16453071 | doi = 10.1007/s10803-005-0040-7 }}</ref> These theories map well from the underconnectivity theory of autism.\n\n"
"Neither category is satisfactory on its own; social cognition theories poorly address autism's rigid and repetitive behaviors, while the nonsocial theories have difficulty explaining social impairment and communication difficulties.<ref name=\"HappeTime\">{{cite journal | vauthors = Happé F, Ronald A, Plomin R | title = Time to give up on a single explanation for autism | journal = Nature Neuroscience | volume = 9 | issue = 10 | pages = 1218–20 | year = 2006 | pmid = 17001340 | doi = 10.1038/nn1770 }}</ref> A combined theory based on multiple deficits may prove to be more useful.<ref>{{cite journal | journal = Dev Rev | year = 2007 | volume = 27 | issue = 2 | pages = 224–60 | title = Cognitive theories of autism | vauthors = Rajendran G, Mitchell P | doi = 10.1016/j.dr.2007.02.001 }}</ref>\n\n"
"==Diagnosis==\n"
"[[Medical diagnosis|Diagnosis]] is based on behavior, not cause or mechanism.<ref name=\"London\">{{cite journal | vauthors = London E | title = The role of the neurobiologist in redefining the diagnosis of autism | journal = Brain Pathol | volume = 17 | issue = 4 | pages = 408–11 | year = 2007 | pmid = 17919126 | doi = 10.1111/j.1750-3639.2007.00103.x }}</ref><ref>{{cite journal | vauthors = Baird G, Cass H, Slonims V | title = Diagnosis of autism | journal = BMJ | volume = 327 | issue = 7413 | pages = 488–93 | year = 2003 | pmid = 12946972 | pmc = 188387 | doi = 10.1136/bmj.327.7413.488 | url = http://www.bmj.com/cgi/content/full/327/7413/488 | archiveurl = http://web.archive.org/web/20090306153446/http://www.bmj.com:80/cgi/content/full/327/7413/488 | archivedate = 6 March 2009 }}</ref> Under the [[DSM-5]], autism is characterized by persistent deficits in social communication and interaction across multiple contexts, as well as restricted, repetitive patterns of behavior, interests, or activities. These deficits are present in early childhood, typically before age three, and lead to clinically significant functional impairment. Sample symptoms include lack of social or emotional reciprocity, stereotyped and repetitive use of language or [[Idiosyncrasy#Psychiatry and psychology|idiosyncratic language]], and persistent preoccupation with unusual objects. The disturbance must not be better accounted for by [[Rett syndrome]], [[intellectual disability]] or global developmental delay.<ref name=DSM5/> [[ICD-10]] uses essentially the same definition.<ref name=\"ICD-10-F84.0\">{{cite web|url=http://apps.who.int/classifications/apps/icd/icd10online/?gf80.htm+f84 |year=2007 |accessdate=10 October 2009|work=ICD-10: International Statistical Classification of Diseases and Related Health Problems: Tenth Revision|publisher=World Health Organization |title=F84. Pervasive developmental disorders |archiveurl=http://web.archive.org/web/20130421042448/http://apps.who.int:80/classifications/apps/icd/icd10online/?gf80.htm+f84|archivedate=21 April 2013}}</ref>\n\n"
"Several diagnostic instruments are available. Two are commonly used in autism research: the [[Autism Diagnostic Interview-Revised]] (ADI-R) is a semistructured parent interview, and the [[Autism Diagnostic Observation Schedule]] (ADOS)<ref>{{cite journal | vauthors = Gotham K, Risi S, Dawson G, Tager-Flusberg H, Joseph R, Carter A, Hepburn S, McMahon W, Rodier P, Hyman SL, Sigman M, Rogers S, Landa R, Spence MA, Osann K, Flodman P, Volkmar F, Hollander E, Buxbaum J, Pickles A, Lord C | title = A replication of the Autism Diagnostic Observation Schedule (ADOS) revised algorithms | journal = J Am Acad Child Adolesc Psychiatry | volume = 47 | issue = 6 | pages = 642–51 | year = 2008 | pmid = 18434924 | pmc = 3057666 | doi = 10.1097/CHI.0b013e31816bffb7 }}</ref> uses observation and interaction with the child. The [[Childhood Autism Rating Scale]] (CARS) is used widely in clinical environments to assess severity of autism based on observation of children.<ref name=Volkmar/>\n\n"
"A [[pediatrician]] commonly performs a preliminary investigation by taking developmental history and physically examining the child. If warranted, diagnosis and evaluations are conducted with help from ASD specialists, observing and assessing cognitive, communication, family, and other factors using standardized tools, and taking into account any associated [[medical conditions]].<ref name=Dover/> A pediatric [[neuropsychologist]] is often asked to assess behavior and cognitive skills, both to aid diagnosis and to help recommend educational interventions.<ref name=\"Kanne\">{{cite journal | vauthors = Kanne SM, Randolph JK, Farmer JE | title = Diagnostic and assessment findings: a bridge to academic planning for children with autism spectrum disorders | journal = Neuropsychol Rev | volume = 18 | issue = 4 | pages = 367–84 | year = 2008 | pmid = 18855144 | doi = 10.1007/s11065-008-9072-z }}</ref> A [[differential diagnosis]] for ASD at this stage might also consider [[intellectual disability]], [[hearing impairment]], and a [[specific language impairment]]<ref name=Dover/> such as [[Landau–Kleffner syndrome]].<ref>{{cite journal | vauthors = Mantovani JF | title = Autistic regression and Landau–Kleffner syndrome: progress or confusion? | journal = Dev Med Child Neurol | volume = 42 | issue = 5 | pages = 349–53 | year = 2000 | pmid = 10855658 | doi = 10.1017/S0012162200210621 | title. = }}</ref> The presence of autism can make it harder to diagnose coexisting psychiatric disorders such as [[Major depressive disorder|depression]].<ref>{{cite journal | vauthors = Matson JL, Neal D | title = Cormorbidity: diagnosing comorbid psychiatric conditions | journal = Psychiatr Times | volume = 26 |issue=4 |year=2009|url=http://www.psychiatrictimes.com/display/article/10168/1403043 | archiveurl = http://web.archive.org/web/20130403062215/http://www.psychiatrictimes.com/display/article/10168/1403043 | archivedate = 3 April 2013 }}</ref>\n\n"
"[[Clinical genetics]] evaluations are often done once ASD is diagnosed, particularly when other symptoms already suggest a genetic cause.<ref name=Caronna/> Although genetic technology allows clinical geneticists to link an estimated 40% of cases to genetic causes,<ref>{{cite journal | vauthors = Schaefer GB, Mendelsohn NJ | title = Genetics evaluation for the etiologic diagnosis of autism spectrum disorders | journal = Genet Med | volume = 10 | issue = 1 | pages = 4–12 | year = 2008 | pmid = 18197051 | doi = 10.1097/GIM.0b013e31815efdd7 | laysummary = http://www.medicalnewstoday.com/articles/96448.php | laydate = 7 February 2008 | laysource = Medical News Today }} {{Wayback|df=yes|url=http://www.medicalnewstoday.com/articles/96448.php|date =20100901151333}}</ref> consensus guidelines in the US and UK are limited to high-resolution chromosome and [[fragile X]] testing.<ref name=Caronna/> A [[Genotype-first approach|genotype-first]] model of diagnosis has been proposed, which would routinely assess the genome's copy number variations.<ref>{{cite journal | vauthors = Ledbetter DH | title = Cytogenetic technology—genotype and phenotype | journal = N Engl J Med | volume = 359 | issue = 16 | pages = 1728–30 | year = 2008 | pmid = 18784093 | doi = 10.1056/NEJMe0806570 }}</ref> As new genetic tests are developed several ethical, legal, and social issues will emerge. Commercial availability of tests may precede adequate understanding of how to use test results, given the complexity of autism's genetics.<ref>{{cite journal | vauthors = McMahon WM, Baty BJ, Botkin J | title = Genetic counseling and ethical issues for autism | journal = American Journal of Medical Genetics | volume = 142C | issue = 1 | pages = 52–7 | year = 2006 | pmid = 16419100 | doi = 10.1002/ajmg.c.30082 }}</ref> [[Metabolic]] and [[neuroimaging]] tests are sometimes helpful, but are not routine.<ref name=Caronna/>\n\n"
"ASD can sometimes be diagnosed by age 14 months, although diagnosis becomes increasingly stable over the first three years of life: for example, a one-year-old who meets diagnostic criteria for ASD is less likely than a three-year-old to continue to do so a few years later.<ref name=\"Landa3\">{{cite journal | vauthors = Landa RJ | title = Diagnosis of autism spectrum disorders in the first 3 years of life | journal = Nat Clin Pract Neurol | volume = 4 | issue = 3 | pages = 138–47 | year = 2008 | pmid = 18253102 | doi = 10.1038/ncpneuro0731 }}</ref> In the UK the National Autism Plan for Children recommends at most 30 weeks from first concern to completed diagnosis and assessment, though few cases are handled that quickly in practice.<ref name=\"Dover\">{{cite journal | vauthors = Dover CJ, Le Couteur A | title = How to diagnose autism | journal = Arch Dis Child | volume = 92 | issue = 6 | pages = 540–5 | year = 2007 | pmid = 17515625 | doi = 10.1136/adc.2005.086280 }}</ref> Although the symptoms of autism and ASD begin early in childhood, they are sometimes missed; years later, adults may seek diagnoses to help them or their friends and family understand themselves, to help their employers make adjustments, or in some locations to claim disability living allowances or other benefits.\n\n"
"Underdiagnosis and overdiagnosis are problems in marginal cases, and much of the recent increase in the number of reported ASD cases is likely due to changes in diagnostic practices. The increasing popularity of drug treatment options and the expansion of benefits has given providers incentives to diagnose ASD, resulting in some overdiagnosis of children with uncertain symptoms. Conversely, the cost of screening and diagnosis and the challenge of obtaining payment can inhibit or delay diagnosis.<ref>{{cite journal | vauthors = Shattuck PT, Grosse SD | title = Issues related to the diagnosis and treatment of autism spectrum disorders | journal = Ment Retard Dev Disabil Res Rev | volume = 13 | issue = 2 | pages = 129–35 | year = 2007 | pmid = 17563895 | doi = 10.1002/mrdd.20143 }}</ref> It is particularly hard to diagnose autism among the [[visually impaired]], partly because some of its diagnostic criteria depend on vision, and partly because autistic symptoms overlap with those of common blindness syndromes or [[blindism]]s.<ref>{{cite journal | title = Visual impairment and autism: current questions and future research | vauthors = Cass H |journal=Autism |year=1998 |volume=2 |issue=2 |pages=117–38|doi=10.1177/1362361398022002 }}</ref>\n\n"
"===Classification===\n"
"Autism is one of the five [[pervasive developmental disorder]]s (PDD), which are characterized by widespread abnormalities of social interactions and communication, and severely restricted interests and highly repetitive behavior.<ref name=ICD-10-F84.0/> These symptoms do not imply sickness, fragility, or emotional disturbance.<ref name=Rapin/>\n\n"
"Of the five PDD forms, [[Asperger syndrome]] is closest to autism in signs and likely causes; [[Rett syndrome]] and [[childhood disintegrative disorder]] share several signs with autism, but may have unrelated causes; [[PDD not otherwise specified]] (PDD-NOS; also called ''atypical autism'') is diagnosed when the criteria are not met for a more specific disorder.<ref>{{cite journal | vauthors = Volkmar FR, State M, Klin A | title = Autism and autism spectrum disorders: diagnostic issues for the coming decade | journal = J Child Psychol Psychiatry | volume = 50 | issue = 1–2 | pages = 108–15 | year = 2009 | pmid = 19220594 | doi = 10.1111/j.1469-7610.2008.02010.x }}</ref> Unlike with autism, people with Asperger syndrome have no substantial delay in [[language development]].<ref name=\"DSM-IV-TR-299.00\">{{vcite book |author=American Psychiatric Association |title=Diagnostic and statistical manual of mental disorders: DSM-IV |chapter=Diagnostic criteria for 299.00 Autistic Disorder |publisher=American Psychiatric Association |edition=4 |location=Washington, DC|year=2000 |pages= |isbn=978-0-89042-025-6 |oclc=768475353 |url=http://cdc.gov/ncbddd/autism/hcp-dsm.html |accessdate=|archiveurl=http://web.archive.org/web/20131029080544/http://www.cdc.gov:80/ncbddd/autism/hcp-dsm.html |archivedate=29 October 2013 }}</ref> The terminology of autism can be bewildering, with autism, Asperger syndrome and PDD-NOS often called the ''autism spectrum disorders'' (ASD)<ref name=CCD/> or sometimes the ''autistic disorders'',<ref>{{cite journal | vauthors = Freitag CM | title = The genetics of autistic disorders and its clinical relevance: a review of the literature | journal = Mol Psychiatry | volume = 12 | issue = 1 | pages = 2–22 | year = 2007 | pmid = 17033636 | doi = 10.1038/sj.mp.4001896 }}</ref> whereas autism itself is often called ''autistic disorder'', ''childhood autism'', or ''infantile autism''. In this article, ''autism'' refers to the classic autistic disorder; in clinical practice, though, ''autism'', ''ASD'', and ''PDD'' are often used interchangeably.<ref name=\"Caronna\">{{cite journal | vauthors = Caronna EB, Milunsky JM, Tager-Flusberg H | title = Autism spectrum disorders: clinical and research frontiers | journal = Arch Dis Child | volume = 93 | issue = 6 | pages = 518–23 | year = 2008 | pmid = 18305076 | doi = 10.1136/adc.2006.115337 }}</ref> ASD, in turn, is a subset of the broader autism [[phenotype]], which describes individuals who may not have ASD but do have autistic-like [[Trait (biology)|traits]], such as avoiding eye contact.<ref>{{cite journal | vauthors = Piven J, Palmer P, Jacobi D, Childress D, Arndt S | title = Broader autism phenotype: evidence from a family history study of multiple-incidence autism families | journal = Am J Psychiatry | volume = 154 | issue = 2 | pages = 185–90 | year = 1997 | pmid = 9016266 | doi=10.1176/ajp.154.2.185}}</ref>\n\n"
"The manifestations of autism cover a wide [[Spectrum disorder|spectrum]], ranging from individuals with severe impairments—who may be silent, [[developmentally disabled]], and locked into hand flapping and rocking—to high functioning individuals who may have active but distinctly odd social approaches, narrowly focused interests, and verbose, [[pedantic]] communication.<ref>{{cite journal | vauthors = Happé F | title = Understanding assets and deficits in autism: why success is more interesting than failure | journal = Psychologist | volume = 12 | issue = 11 | pages = 540–7 | year = 1999 | url = http://www.thepsychologist.org.uk/archive/archive_home.cfm/volumeID_12-editionID_46-ArticleID_133-getfile_getPDF/thepsychologist/psy_11_99_p540-547_happe.pdf | format = PDF | archiveurl = http://web.archive.org/web/20120517162434/http://www.thepsychologist.org.uk/archive/archive_home.cfm/volumeID_12-editionID_46-ArticleID_133-getfile_getPDF/thepsychologist/psy_11_99_p540-547_happe.pdf |archivedate=17 May 2012 }}</ref> Because the behavior spectrum is continuous, boundaries between diagnostic categories are necessarily somewhat arbitrary.<ref name=Geschwind-2009/> Sometimes the syndrome is divided into low-, medium- or [[high-functioning autism]] (LFA, MFA, and HFA), based on [[IQ]] thresholds,<ref>{{cite journal | vauthors = Baron-Cohen S | title = The hyper-systemizing, assortative mating theory of autism | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 30 | issue = 5 | pages = 865–72 | year = 2006 | pmid = 16519981 | doi = 10.1016/j.pnpbp.2006.01.010 | url = http://autismresearchcentre.com/docs/papers/2006_BC_Neuropsychophamacology.pdf | format = PDF | archiveurl = http://web.archive.org/web/20120513020615/http://autismresearchcentre.com/docs/papers/2006_BC_Neuropsychophamacology.pdf | archivedate = 12 May 2012 }}</ref> or on how much support the individual requires in daily life; these subdivisions are not standardized and are controversial. Autism can also be divided into [[Syndrome|syndromal]] and non-syndromal autism; the syndromal autism is associated with severe or profound [[intellectual disability]] or a congenital syndrome with physical symptoms, such as [[tuberous sclerosis]].<ref>{{cite journal | vauthors = Cohen D, Pichard N, Tordjman S, Baumann C, Burglen L, Excoffier E, Lazar G, Mazet P, Pinquier C, Verloes A, Héron D | title = Specific genetic disorders and autism: clinical contribution towards their identification | journal = J Autism Dev Disord | volume = 35 | issue = 1 | pages = 103–16 | year = 2005 | pmid = 15796126 | doi = 10.1007/s10803-004-1038-2 | author. = }}</ref> Although individuals with Asperger syndrome tend to perform better cognitively than those with autism, the extent of the [[Diagnosis of Asperger syndrome#Differences from high-functioning autism|overlap between Asperger syndrome, HFA, and non-syndromal autism]] is unclear.<ref>Validity of ASD subtypes:\n"
"* {{cite journal | vauthors = Klin A | title = Autism and Asperger syndrome: an overview | journal = Rev Bras Psiquiatr | volume = 28 | issue = suppl 1 | pages = S3–S11 | year = 2006 | pmid = 16791390 | doi = 10.1590/S1516-44462006000500002 | url = http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006000500002&lng=en&nrm=iso&tlng=en | archiveurl = http://web.archive.org/web/20131029185542/http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006000500002&lng=en&nrm=iso&tlng=en | archivedate = 29 October 2013 }}\n"
"* {{cite journal | vauthors = Witwer AN, Lecavalier L | title = Examining the validity of autism spectrum disorder subtypes | journal = J Autism Dev Disord | volume = 38 | issue = 9 | pages = 1611–24 | year = 2008 | pmid = 18327636 | doi = 10.1007/s10803-008-0541-2 }}</ref>\n\n"
"Some studies have reported diagnoses of autism in children due to a loss of language or social skills, as opposed to a failure to make progress, typically from 15 to 30 months of age. The validity of this distinction remains controversial; it is possible that [[regressive autism]] is a specific subtype,<ref name=\"Stefanatos\">{{cite journal | vauthors = Stefanatos GA | title = Regression in autistic spectrum disorders | journal = Neuropsychol Rev | volume = 18 | issue = 4 | pages = 305–19 | year = 2008 | pmid = 18956241 | doi = 10.1007/s11065-008-9073-y }}</ref><ref name=\"Volkmar\">{{cite journal | vauthors = Volkmar F, Chawarska K, Klin A | title = Autism in infancy and early childhood | journal = Annu Rev Psychol | volume = 56 | pages = 315–36 | year = 2005 | pmid = 15709938 | doi = 10.1146/annurev.psych.56.091103.070159 }} A partial update is in: {{cite journal | vauthors = Volkmar FR, Chawarska K | title = Autism in infants: an update | journal = World Psychiatry | volume = 7 | issue = 1 | pages = 19–21 | year = 2008 | pmid = 18458791 | pmc = 2366821 }}</ref><ref name=Landa/><ref name=Landa3/> or that there is a continuum of behaviors between autism with and without regression.<ref>{{cite journal | vauthors = Ozonoff S, Heung K, Byrd R, Hansen R, Hertz-Picciotto I | title = The onset of autism: patterns of symptom emergence in the first years of life | journal = Autism Res | volume = 1 | issue = 6 | pages = 320–328 | year = 2008 | pmid = 19360687 | pmc = 2857525 | doi = 10.1002/aur.53 }}</ref>\n\n"
"Research into causes has been hampered by the inability to identify biologically meaningful subgroups within the autistic population<ref>{{cite journal | vauthors = Altevogt BM, Hanson SL, Leshner AI | title = Autism and the environment: challenges and opportunities for research | journal = Pediatrics | volume = 121 | issue = 6 | pages = 1225–9 | year = 2008 | pmid = 18519493 | doi = 10.1542/peds.2007-3000 | url = http://pediatrics.aappublications.org/cgi/content/full/121/6/1225 | archiveurl = http://web.archive.org/web/20100115140620/http://pediatrics.aappublications.org:80/cgi/content/full/121/6/1225 | archivedate = 15 January 2010 }}</ref> and by the traditional boundaries between the disciplines of [[psychiatry]], [[psychology]], [[neurology]] and [[pediatrics]].<ref>{{cite journal | vauthors = Reiss AL | title = Childhood developmental disorders: an academic and clinical convergence point for psychiatry, neurology, psychology and pediatrics | journal = J Child Psychol Psychiatry | volume = 50 | issue = 1–2 | pages = 87–98 | year = 2009 | pmid = 19220592 | doi = 10.1111/j.1469-7610.2008.02046.x }}</ref> Newer technologies such as [[fMRI]] and [[diffusion tensor imaging]] can help identify biologically relevant [[phenotype]]s (observable traits) that can be viewed on [[brain scan]]s, to help further [[neurogenetic]] studies of autism;<ref>{{cite journal | vauthors = Piggot J, Shirinyan D, Shemmassian S, Vazirian S, Alarcón M | title = Neural systems approaches to the neurogenetics of autism spectrum disorders | journal = Neuroscience | volume = 164 | issue = 1 | pages = 247–56 | year = 2009 | pmid = 19482063 | doi = 10.1016/j.neuroscience.2009.05.054 }}</ref> one example is lowered activity in the [[fusiform face area]] of the brain, which is associated with impaired perception of people versus objects.<ref name=Levy/> It has been proposed to classify autism using genetics as well as behavior.<ref>{{cite journal | vauthors = Stephan DA | title = Unraveling autism | journal = American Journal of Human Genetics | volume = 82 | issue = 1 | pages = 7–9 | year = 2008 | pmid = 18179879 | pmc = 2253980 | doi = 10.1016/j.ajhg.2007.12.003 }}</ref>\n\n"
"==Screening==\n"
"About half of parents of children with ASD notice their child's unusual behaviors by age 18 months, and about four-fifths notice by age 24 months.<ref name=Landa3/> According to an article in the ''Journal of Autism and Developmental Disorders'', failure to meet any of the following milestones \"is an absolute indication to proceed with further evaluations. Delay in referral for such testing may delay early diagnosis and treatment and affect the long-term outcome\".<ref name=Filipek/>\n"
"* No [[babbling]] by 12 months.\n"
"* No [[Gesture|gesturing]] (pointing, waving, etc.) by 12 months.\n"
"* No single words by 16 months.\n"
"* No two-word (spontaneous, not just [[echolalia|echolalic]]) phrases by 24 months.\n"
"* Any loss of any language or social skills, at any age.\n"
"US and Japanese practice is to [[Screening (medicine)|screen]] all children for ASD at 18 and 24 months, using autism-specific formal screening tests. In contrast, in the UK, children whose families or doctors recognize possible signs of autism are screened. It is not known which approach is more effective.<ref name=Levy/> Screening tools include the [[Modified Checklist for Autism in Toddlers]] (M-CHAT), the Early Screening of Autistic Traits Questionnaire, and the First Year Inventory; initial data on [[Modified Checklist for Autism in Toddlers|M-CHAT]] and its predecessor, the [[Checklist for Autism in Toddlers]] (CHAT), on children aged 18–30 months suggests that it is best used in a clinical setting and that it has low [[Sensitivity (tests)|sensitivity]] (many false-negatives) but good [[Specificity (tests)|specificity]] (few false-positives).<ref name=Landa3/> It may be more accurate to precede these tests with a broadband screener that does not distinguish ASD from other developmental disorders.<ref>{{cite journal | vauthors = Wetherby AM, Brosnan-Maddox S, Peace V, Newton L | title = Validation of the Infant–Toddler Checklist as a broadband screener for autism spectrum disorders from 9 to 24 months of age | journal = Autism | volume = 12 | issue = 5 | pages = 487–511 | year = 2008 | pmid = 18805944 | pmc = 2663025 | doi = 10.1177/1362361308094501 }}</ref> Screening tools designed for one culture's norms for behaviors like eye contact may be inappropriate for a different culture.<ref>{{cite journal | vauthors = Wallis KE, Pinto-Martin J | title = The challenge of screening for autism spectrum disorder in a culturally diverse society | journal = Acta Paediatr | volume = 97 | issue = 5 | pages = 539–40 | year = 2008 | pmid = 18373717 | doi = 10.1111/j.1651-2227.2008.00720.x }}</ref> Although [[genetic screening]] for autism is generally still impractical, it can be considered in some cases, such as children with neurological symptoms and [[dysmorphic feature]]s.<ref>{{cite journal | vauthors = Lintas C, Persico AM | title = Autistic phenotypes and genetic testing: state-of-the-art for the clinical geneticist | journal = Journal of Medical Genetics | volume = 46 | issue = 1 | pages = 1–8 | year = 2009 | pmid = 18728070 | pmc = 2603481 | doi = 10.1136/jmg.2008.060871 | url = http://jmg.bmj.com/content/46/1/1.long | archiveurl = http://web.archive.org/web/20131030000423/http://jmg.bmj.com/content/46/1/1.long | archivedate = 30 October 2013 }}</ref>\n\n"
"==Prevention==\n"
"Infection with [[rubella]] during [[pregnancy]] causes less than 1% of cases of autism;<ref name=Duchan/> [[rubella vaccine|vaccination against rubella]] can prevent many of those cases.<ref name=Lancet2015>{{cite journal|author=Lambert N, Strebel P, Orenstein W, Icenogle J, Poland GA|title=Rubella|journal=Lancet|date=7 January 2015|doi=10.1016/S0140-6736(14)60539-0|pmid=25576992}}</ref>\n\n"
"==Management==\n"
"{{main|Autism therapies}}\n"
"[[File:Opening a window to the autistic brain.jpg|thumb|alt=A young child points, in front of a woman who smiles and points in the same direction.|A three-year-old with autism points to fish in an aquarium, as part of an experiment on the effect of intensive shared-attention training on language development.<ref name=Powell/>]]\n"
"The main goals when treating children with autism are to lessen associated deficits and family distress, and to increase quality of life and functional independence. No single treatment is best and treatment is typically tailored to the child's needs.<ref name=CCD/> Families and the educational system are the main resources for treatment.<ref name=Levy/> Studies of interventions have methodological problems that prevent definitive conclusions about [[efficacy]].<ref>{{cite journal | vauthors = Ospina MB, Krebs Seida J, Clark B, Karkhaneh M, Hartling L, Tjosvold L, Vandermeer B, Smith V | title = Behavioural and developmental interventions for autism spectrum disorder: a clinical systematic review | journal = PLoS ONE | volume = 3 | issue = 11 | pages = e3755 | year = 2008 | pmid = 19015734 | pmc = 2582449 | doi = 10.1371/journal.pone.0003755 | url = http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003755 | author. = | archiveurl = http://web.archive.org/web/20131105071310/http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003755 | archivedate = 5 November 2013 }}</ref> Although many [[psychosocial]] interventions have some positive evidence, suggesting that some form of treatment is preferable to no treatment, the methodological quality of [[systematic review]]s of these studies has generally been poor, their clinical results are mostly tentative, and there is little evidence for the relative effectiveness of treatment options.<ref>{{cite journal | vauthors = Seida JK, Ospina MB, Karkhaneh M, Hartling L, Smith V, Clark B | title = Systematic reviews of psychosocial interventions for autism: an umbrella review | journal = Dev Med Child Neurol | volume = 51 | issue = 2 | pages = 95–104 | year = 2009 | pmid = 19191842 | doi = 10.1111/j.1469-8749.2008.03211.x }}</ref> Intensive, sustained [[special education]] programs and [[behavior therapy]] early in life can help children acquire self-care, social, and job skills,<ref name=\"CCD\">{{cite journal | vauthors = Myers SM, Johnson CP | title = Management of children with autism spectrum disorders | journal = Pediatrics | volume = 120 | issue = 5 | pages = 1162–82 | year = 2007 | pmid = 17967921 | doi = 10.1542/peds.2007-2362 }}</ref> and often improve functioning and decrease symptom severity and maladaptive behaviors;<ref name=\"Rogers\">{{cite journal | vauthors = Rogers SJ, Vismara LA | title = Evidence-based comprehensive treatments for early autism | journal = J Clin Child Adolesc Psychol | volume = 37 | issue = 1 | pages = 8–38 | year = 2008 | pmid = 18444052 | pmc = 2943764 | doi = 10.1080/15374410701817808 }}</ref> claims that intervention by around age three years is crucial are not substantiated.<ref name=\"HowlinCharman\">{{cite journal | vauthors = Howlin P, Magiati I, Charman T | title = Systematic review of early intensive behavioral interventions for children with autism | journal = Am J Intellect Dev Disabil | volume = 114 | issue = 1 | pages = 23–41 | year = 2009 | pmid = 19143460 | doi = 10.1352/2009.114:23-41 }}</ref> Available approaches include [[applied behavior analysis]] (ABA), developmental models, [[TEACCH|structured teaching]], [[speech and language therapy]], [[social skills]] therapy, and [[occupational therapy]].<ref name=CCD/> There is some evidence that early intensive behavioral intervention (EIBI), an early intervention model based on ABA for 20 to 40 hours a week for multiple years, is an effective treatment for some children with ASD.<ref>{{cite journal | vauthors = Reichow B, Barton EE, Boyd BA, Hume K | title = Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD) | journal = Cochrane Database of Systematic Reviews | volume = 10 | issue = | pages = CD009260 | year = 2012 | pmid = 23076956 | doi = 10.1002/14651858.CD009260.pub2 }}</ref>\n\n"
"Educational interventions can be effective to varying degrees in most children: [[Early intensive behavioral intervention|intensive ABA treatment]] has demonstrated effectiveness in enhancing global functioning in preschool children<ref name=\"Eikeseth\">{{cite journal | vauthors = Eikeseth S | title = Outcome of comprehensive psycho-educational interventions for young children with autism | journal = Res Dev Disabil | volume = 30 | issue = 1 | pages = 158–78 | year = 2009 | pmid = 18385012 | doi = 10.1016/j.ridd.2008.02.003 }}</ref> and is well-established for improving intellectual performance of young children.<ref name=Rogers/> Neuropsychological reports are often poorly communicated to educators, resulting in a gap between what a report recommends and what education is provided.<ref name=Kanne/> It is not known whether treatment programs for children lead to significant improvements after the children grow up,<ref name=Rogers/> and the limited research on the effectiveness of adult residential programs shows mixed results.<ref>{{cite journal | vauthors = Van Bourgondien ME, Reichle NC, Schopler E | title = Effects of a model treatment approach on adults with autism | journal = J Autism Dev Disord | volume = 33 | issue = 2 | pages = 131–40 | year = 2003 | pmid = 12757352 | doi = 10.1023/A:1022931224934 }}</ref> The appropriateness of including children with varying severity of autism spectrum disorders in the general education population is a subject of current debate among educators and researchers.<ref>{{cite journal |journal=Topics in Language Disorders |year=2003 |volume=23 |issue=2 |pages=116–133 |title=Inclusion of Learners with Autism Spectrum Disorders in General Education Settings | vauthors = Simpson RL, de Boer-Ott SR, Smith-Myles B|url=http://www.nursingcenter.com/pdf.asp?AID=520301 |doi=10.1097/00011363-200304000-00005}}</ref>\n\n"
"Many medications are used to treat ASD symptoms that interfere with integrating a child into home or school when behavioral treatment fails.<ref name=Rapin/><ref>{{cite journal | vauthors = Leskovec TJ, Rowles BM, Findling RL | title = Pharmacological treatment options for autism spectrum disorders in children and adolescents | journal = Harv Rev Psychiatry | volume = 16 | issue = 2 | pages = 97–112 | year = 2008 | pmid = 18415882 | doi = 10.1080/10673220802075852 }}</ref> More than half of US children diagnosed with ASD are prescribed [[psychoactive drug]]s or [[anticonvulsant]]s, with the most common drug classes being [[antidepressant]]s, [[stimulant]]s, and [[antipsychotic]]s.<ref>{{cite journal | vauthors = Oswald DP, Sonenklar NA | title = Medication use among children with autism spectrum disorders | journal = J Child Adolesc Psychopharmacol | volume = 17 | issue = 3 | pages = 348–55 | year = 2007 | pmid = 17630868 | doi = 10.1089/cap.2006.17303 }}</ref> Antipsychotics, such as [[risperidone]] and [[aripiprazole]], have been found to be useful for treating irritability, repetitive behavior, and sleeplessness that often occurs with autism.<ref>{{cite journal | vauthors = Posey DJ, Stigler KA, Erickson CA, McDougle CJ | title = Antipsychotics in the treatment of autism | journal = J Clin Invest | volume = 118 | issue = 1 | pages = 6–14 | year = 2008 | pmid = 18172517 | pmc = 2171144 | doi = 10.1172/JCI32483 | url = http://www.jci.org/articles/view/32483/version/1 | archiveurl = http://web.archive.org/web/20131220104731/http://www.jci.org/articles/view/32483/version/1 | archivedate = 20 December 2013 }}</ref> There is scant reliable research about the effectiveness or safety of drug treatments for adolescents and adults with ASD.<ref>Lack of research on drug treatments:\n"
"* {{cite journal | vauthors = Angley M, Young R, Ellis D, Chan W, McKinnon R | title = Children and autism—part 1—recognition and pharmacological management | journal = Aust Fam Physician | volume = 36 | issue = 9 | pages = 741–4 | year = 2007 | pmid = 17915375 | url = http://www.racgp.org.au/afp/200709/200709angley.pdf | format = PDF | archiveurl = http://web.archive.org/web/20130407205054/http://www.racgp.org.au/afp/200709/200709angley.pdf | archivedate = 7 April 2013 }}\n"
"* {{cite journal | vauthors = Broadstock M, Doughty C, Eggleston M | title = Systematic review of the effectiveness of pharmacological treatments for adolescents and adults with autism spectrum disorder | journal = Autism | volume = 11 | issue = 4 | pages = 335–48 | year = 2007 | pmid = 17656398 | doi = 10.1177/1362361307078132 }}</ref> A person with ASD may respond atypically to medications, the medications can have [[Adverse effect (medicine)|adverse effects]],<ref name=CCD/> and no known medication relieves autism's core symptoms of social and communication impairments.<ref>{{cite journal | vauthors = Buitelaar JK | title = Why have drug treatments been so disappointing? | journal = Novartis Found Symp | volume = 251 | pages = 235–44; discussion 245–9, 281–97 | year = 2003 | pmid = 14521196 | doi = 10.1002/0470869380.ch14 | title. = }}</ref> Experiments in mice have reversed or reduced some symptoms related to autism by replacing or modulating gene function,<ref name=Walsh/><ref name=\"pmid18093519\"/> suggesting the possibility of targeting therapies to specific rare mutations known to cause autism.<ref name=Betancur/><ref name=\"pmid20303363\">{{cite journal | vauthors = Dölen G, Carpenter RL, Ocain TD, Bear MF | title = Mechanism-based approaches to treating fragile X | journal = Pharmacol Ther | volume = 127 | issue = 1 | pages = 78–93 | year = 2010 | pmid = 20303363 | doi = 10.1016/j.pharmthera.2010.02.008 }}</ref>\n\n"
"Although many [[Alternative therapies for developmental and learning disabilities|alternative therapies and interventions]] are available, few are supported by scientific studies.<ref name=Sigman/><ref>Lack of support for interventions:\n"
"* {{cite journal | vauthors = Francis K | title = Autism interventions: a critical update | journal = Dev Med Child Neurol | volume = 47 | issue = 7 | pages = 493–9 | year = 2005 | pmid = 15991872 | doi = 10.1017/S0012162205000952 | url = http://journals.cambridge.org/production/action/cjoGetFulltext?fulltextid=313204 | format = PDF }}\n"
"* {{cite journal | vauthors = Levy SE, Hyman SL | title = Complementary and alternative medicine treatments for children with autism spectrum disorders | journal = Child Adolesc Psychiatr Clin N Am | volume = 17 | issue = 4 | pages = 803–20, ix | year = 2008 | pmid = 18775371 | pmc = 2597185 | doi = 10.1016/j.chc.2008.06.004 }}\n"
"* {{cite journal | vauthors = Rao PA, Beidel DC, Murray MJ | title = Social skills interventions for children with Asperger's syndrome or high-functioning autism: a review and recommendations | journal = J Autism Dev Disord | volume = 38 | issue = 2 | pages = 353–61 | year = 2008 | pmid = 17641962 | doi = 10.1007/s10803-007-0402-4 }}\n"
"</ref> Treatment approaches have little empirical support in [[Quality of life|quality-of-life]] contexts, and many programs focus on success measures that lack predictive validity and real-world relevance.<ref name=Burgess/> Scientific evidence appears to matter less to service providers than program marketing, training availability, and parent requests.<ref>{{cite journal | vauthors = Stahmer AC, Collings NM, Palinkas LA | title = Early intervention practices for children with autism: descriptions from community providers | journal = Focus Autism Other Dev Disabl | volume = 20 | issue = 2 | pages = 66–79 | year = 2005 | pmid = 16467905 | pmc = 1350798 | doi = 10.1177/10883576050200020301 }}</ref> Some alternative treatments may place the child at risk. A 2008 study found that compared to their peers, autistic boys have significantly thinner bones if on [[casein-free diet]]s;<ref>{{cite journal | vauthors = Hediger ML, England LJ, Molloy CA, Yu KF, Manning-Courtney P, Mills JL | title = Reduced bone cortical thickness in boys with autism or autism spectrum disorder | journal = J Autism Dev Disord | volume = 38 | issue = 5 | pages = 848–56 | year = 2008 | pmid = 17879151 | doi = 10.1007/s10803-007-0453-6 | laysummary = http://www.nih.gov/news/health/jan2008/nichd-29.htm | laydate = 29 January 2008 | laysource = NIH News }} {{Wayback|df=yes|url=http://www.nih.gov/news/health/jan2008/nichd-29.htm|date =20131001111904}}</ref> in 2005, botche")
matches = re.finditer(regex, test_str, re.VERBOSE | re.IGNORECASE | re.DOTALL | re.UNICODE)
for matchNum, match in enumerate(matches, start=1):
print ("Match {matchNum} was found at {start}-{end}: {match}".format(matchNum = matchNum, start = match.start(), end = match.end(), match = match.group()))
for groupNum in range(0, len(match.groups())):
groupNum = groupNum + 1
print ("Group {groupNum} found at {start}-{end}: {group}".format(groupNum = groupNum, start = match.start(groupNum), end = match.end(groupNum), group = match.group(groupNum)))
# Note: for Python 2.7 compatibility, use ur"" to prefix the regex and u"" to prefix the test string and substitution.
Please keep in mind that these code samples are automatically generated and are not guaranteed to work. If you find any syntax errors, feel free to submit a bug report. For a full regex reference for Python, please visit: https://docs.python.org/3/library/re.html