the early origins of autism

56 Scientific American February 2000

The Early Origins of

Autism

utism has been mystifying scientists for more than

half a century. The complex behavioral disorder

encompasses a wide variety of symptoms, most of

which usually appear before a child turns three. Children

with autism are unable to interpret the emotional states of others, failing

to recognize anger, sorrow or manipulative intent. Their language skills

are often limited, and they find it difficult to initiate or sustain conversa-

tions. They also frequently exhibit an intense preoccupation with a single

subject, activity or gesture.

These behaviors can be incredibly debilitating. How can you be included

in a typical classroom if you can’t be dissuaded from banging your head on

your desk? How can you make friends if your overriding interest is in cal-

endars? When children with autism also suffer from mental retardation—as

most of them do—the prognosis is even worse. Intensive behavioral therapy

improves the outcome for many patients, but their

symptoms can make it impossible for them to live in-

dependently, even if they have normal IQs.

New research into the causes of this baffling disorder is focusing

on genes that control the development of the brain

by Patricia M. Rodier

A

SEVEN-YEAR-OLD WITH AUTISMreaches for a soap bubble during play-time at the Eden Institute, a school forchildren with autism in Princeton, N.J.

Copyright 2000 Scientific American, Inc.

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I became involved in the search forautism’s causes relatively recently—andalmost by accident. As an embryologist, Ipreviously focused on various birth de-fects of the brain. In 1994 I attended a re-markable presentation at a scientific con-ference on research into birth defects.Two pediatric ophthalmologists, MarilynT. Miller of the University ofIllinois at Chicago and Ker-stin Strömland of GöteborgUniversity in Sweden, de-scribed a surprising outcomefrom a study investigatingeye motility problems in vic-tims of thalidomide, themorning-sickness drug thatcaused an epidemic of birthdefects in the 1960s. Thestudy’s subjects were adults who hadbeen exposed to the drug while still in thewomb. After examining these people,Miller and Strömland made an observa-tion that had somehow eluded previousresearchers: about 5 percent of thethalidomide victims had autism, which isabout 30 times higher than the rateamong the general population.

When I heard these results, I felt ashock of recognition, a feeling so pow-erful that I actually became dizzy andbegan to hyperventilate. In the effort toidentify autism’s causes, researchers had

long sought to pinpoint exactly whenthe disorder begins. Previous speculationhad focused on late gestation or earlypostnatal life as the time of origin, butthere was no evidence to back up eitherhypothesis. The connection with tha-lidomide suddenly threw a brilliant newlight on the subject. It suggested that

autism originates in the early weeks ofpregnancy, when the embryo’s brain andthe rest of its nervous system are just be-ginning to develop. Indeed, Miller andStrömland’s work convinced me that themystery of autism could soon be solved.

Genetic Factors

At least 16 of every 10,000 babiesis born with autism or one of its

related disorders [see box on page60]. Since autism was first identified in1943, scientists have made great strides

in describing its symptoms. The biologi-cal basis for autism, however, has beenelusive—an unfortunate circumstance,because such an understanding could en-able researchers to identify the leadingrisk factors for autism and possibly todesign new treatments for the condition.

By examining the inheritance of thedisorder, researchers have shown thatautism runs in families, though not in aclear-cut way. Siblings of people withautism have a 3 to 8 percent chance ofbeing diagnosed with the same disor-der. This is much greater than the 0.16percent risk in the general populationbut much less than the 50 percentchance that would characterize a genet-ic disease caused by a single dominantmutation (in which one faulty gene in-herited from one parent is sufficient tocause the disorder) or the 25 percentchance that would characterize a singlerecessive mutation (in which a copy ofthe faulty gene must be inherited fromeach parent). The results fit best withmodels in which variants of severalgenes contribute to the outcome. Tocomplicate matters further, relatives ofpeople with autism may fail to meet allthe criteria for the disorder but stillhave some of its symptoms. Althoughthese relatives may have some of thegene variants linked to autism—what-

58 Scientific American February 2000 The Early Origins of Autism

AUTISM’S EFFECTS include changes to the brain stem, the re-

gion just above the spinal cord (left). The brain stem of a per-

son with autism is shorter than a normal brain stem (be-low): the structures at the junction of the pons and the

medulla (such as the facial nucleus and the trapezoid

body) are closer to the structures of the lower medulla

(the hypoglossal nucleus and the inferior olive). It is

as though a band of tissue were missing. The brain

stem of a person with autism also lacks the superior

olive and has a smaller-than-normal facial nucleus.

Such changes could occur only in early gestation.

At least 16 of every 10,000 babies are born

with autism or one of itsrelated disorders.

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ever they may be—for some reason thegenetic factors are not fully expressedin these individuals.

Studies of twins in the U.K. confirmthat autism has a heritable componentbut suggest that environmental influ-ences play a role as well. For example,if genetic factors alone were involved,monozygotic (identical) twins, whoshare the same genes, should have a100 percent chance of sharing the samediagnosis. Instead, when one twin hasautism, the second twin has only a 60percent chance of being diagnosed withthe same disorder. That twin also hasan 86 percent chance of having some ofautism’s symptoms. These figures indi-cate that other factors must modify thegenetic predisposition to the disorder.

The Embryology of Autism

S everal environmental risk factorsare already known. In utero expo-

sure to rubella (German measles) or tobirth defect–causing substances such asethanol and valproic acid increases thechances that autism will develop. Peo-ple with certain genetic diseases, suchas phenylketonuria and tuberous scle-rosis, also have a greater chance of de-veloping autism. None of these factors,however, is present frequently enoughto be responsible for many cases. Fur-thermore, most exposures to diseasesor hazardous substances would be like-ly to affect both members of a pair oftwins rather than just one. Some of theenvironmental influences must be moresubtle than those identified so far. Re-searchers do not know how the multi-ple factors combine to make some peo-ple display symptoms while allowingothers to escape them. This variationmakes the search for autism’s causes es-pecially difficult.

In their 1994 study Miller and Ström-land added another environmental con-tributor to autism: thalidomide expo-

sure in utero. All their subjects—

Swedish adults born in the late 1950sand early 1960s—exhibited some of themalformations for which thalidomideis infamous: stunted arms and legs, mis-shapen or missing ears and thumbs,and neurological dysfunctions of theeye and facial muscles. Because scien-tists know which organs of the embryoare developing at each stage of preg-nancy, they can pinpoint the exact dayswhen a malformation can be induced:the thumb is affected as early as day 22after conception, the ears from days 20to 33, and the arms and legs from days25 to 35. What made the new study soexciting for me was Miller and Ström-land’s discovery that most of thethalidomide victims with autism hadanomalies in the external part of theirears but no malformations of the armsor legs. This pattern indicated that thesubjects had been injured very early ingestation—20 to 24 days after concep-tion—before many women even knowthey are pregnant.

For embryologists, nothing tells us somuch about what happened to an em-

bryo as knowing when it happened. Inthe case of thalidomide-induced autism,the critical period is much earlier thanmany investigators would have guessed.Very few neurons form as early as thefourth week of gestation, and most aremotor neurons of the cranial nerves, theones that operate the muscles of the eyes,ears, face, jaw, throat and tongue. Thecell bodies of these neurons are locatedin the brain stem, the region between thespinal cord and the rest of the brain. Be-cause these motor neurons develop atthe same time as the external ears, onemight predict that the thalidomide vic-tims with autism would also suffer fromdysfunctions of the cranial nerves. Millerand Strömland confirmed this predic-tion—they found that all the subjectswith autism had abnormalities of eyemovement or facial expression, or both.

CHILD WITH AUTISM is normal in appearance, at least to the untrained eye. But he

has a few physical anomalies characteristic of the disorder. The corners of his mouth are

low compared with the center of his upper lip, and the tops of his ears flop over (left).His ears are a bit lower than normal and have an almost square shape (right).

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Scientific American February 2000 59

Thalidomide Timeline

BIRTH DEFECTS caused by thalidomide vary depending on when the mother was ex-

posed to the drug (above). A 1994 study showed that thalidomide victims with autism

had ear anomalies and normal limbs, suggesting that the drug triggered the disorder 20 to

24 days after conception, when the embryo’s nervous system is starting to form (right).

The Early Origins of Autism

Age of embryo (days) 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

Damage causedby thalidomide

exposure atthis time

MISSING EARS SMALL EARS AND OTHER EAR MALFORMATIONS

MISSING OR SMALL THUMBS THUMBS WITH AN EXTRA JOINT

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The next logical question was, “Arethe cases of autism after thalidomideexposure similar to cases of unknowncause, or are they different?” Asidefrom their behavioral symptoms, peo-ple with autism have often been de-scribed not only as normal in appear-ance but as unusually attractive. Theyare certainly normal in stature, withnormal-to-large heads. The few studiesthat have tested nonbehavioral featuresof people with autism, however, haveconcluded that there are indeed minorphysical and neurological anomalies inmany cases, and they are the same onesnoted in thalidomide-induced autism.For example, minor malformations ofthe external ears—notably posterior ro-tation, in which the top of the ear is tilt-

ed backward more than 15 degrees—

are more common in children withautism than in typically developingchildren, children with mental retarda-tion or siblings of children with autism.Dysfunctions of eye movement hadbeen associated with autism before thethalidomide study, and lack of facialexpression is one of the behaviors usedto diagnose the condition.

The Neurobiology of Autism

Is it possible that all the symptomsof autism arise from changes in the

function of the cranial nerves? Probablynot. It is more likely that the nerve dys-functions in people with autism reflectan early brain injury that not only af-

fects the cranial nerves but also has sec-ondary effects on later brain develop-ment. That is, the injury to the brainstem might somehow interfere with theproper development or wiring of otherbrain regions, including those involvedin higher-level functions such as speech,resulting in the behavioral symptoms ofautism. Or perhaps the ear malforma-tions and cranial nerve dysfunctions areonly side effects of an injury that wedon’t understand. Whatever the truesituation may be, the anomalies in pa-tients with autism of unknown causewere much the same as the anomaliesin the thalidomide victims with autism.The conclusion was clear: many casesof autism, if not all, are initiated veryearly in gestation.


The Spectrum of Autism Disorders

Adiagnosis of autism requires that the patient exhibit abnor-mal behaviors in three categories [see list at right] and

have especially notable deficits in the category of social interac-tion. In addition, clinicians have identified several related disor-ders that share some of the behavioral features of autism buthave different emphases or additional symptoms.For example,Pervasive Development Disorder, Not Otherwise Specified(PDD-NOS) denotes patients who miss fulfilling the autism cri-teria in one of the three categories. As is true of autism, PDD-NOS includes patients with the whole range of IQs. Aspergersyndrome is used to describe patients with normal IQs and noevidence of language delay. Two much rarer diagnoses areChildhood Disintegrative Disorder, in which normal early devel-

opment is followed by regression to severe disability, and Rettsyndrome,a progressive neurological disorder that occurs onlyin females.

Although many scientists have long known that autism is aninherited disease, recent family studies by Peter Szatmari’sgroup at McMaster University in Ontario suggest that it is thespectrum of symptoms that runs in families rather than a sin-gle diagnosis. For example, a child with autism may have abrother with Asperger syndrome,or a woman with autism mayhave a nephew with PDD-NOS. These family studies stronglysuggest that at least three of the diagnoses—autism,PDD-NOSand Asperger syndrome—arise from some of the same inherit-ed factors. —P.M.R.

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The region of the brain implicatedby the thalidomide study—the brainstem—is one that has rarely been con-sidered in studies of autism or in studiesof other kinds of congenital brain dam-age, for that matter. On a simplistic lev-el, neurobiologists associate the brainstem with the most basic functions:breathing, eating, balance, motor coor-dination and so forth. Many of the be-haviors disturbed in autism, such as lan-guage, planning and interpretation ofsocial cues, are believed to be controlledby higher-level regions of the brain, suchas the cerebral cortex and the hip-pocampus in the forebrain.

Yet some symptoms common inautism—lack of facial expression, hyper-sensitivity to touch and sound, and sleep

disturbances—do sound like ones morelikely to originate in the brain regions as-sociated with basic functions. Further-more, the most consistently observed ab-normality in the brains of people withautism is not a change in the forebrainbut a reduction in the number of neu-rons in the cerebellum, a large process-ing center of the hindbrain that has longbeen known to have critical functions inthe control of muscle movement.

One reason for scientists’ confusionabout the brain regions involved inautism may be that our assumptionsabout where functions are controlledare shaky. For example, the laboratorygroup led by Eric Courchesne of theUniversity of California at San Diegohas shown that parts of the cerebellumare activated during certain tasks re-quiring high-level cognitive processing.Another difficulty is thatthe symptoms of autismare so complex. If simplerbehavioral abnormalitiescould be shown to be di-agnostic of the disorder,researchers might have abetter chance of identify-ing their source in the ner-vous system [see box onnext page].

In 1995 our research team had theopportunity to follow up on thethalidomide study by examining thebrain stem of a person with autism. Thetissue samples came from the autopsyof a young woman who had sufferedfrom autism of unknown cause; shehad died in the 1970s, but fortunatelythe samples of her brain tissue had beenpreserved. When we examined thewoman’s brain stem, we were struck bythe near absence of two structures: thefacial nucleus, which controls the mus-cles of facial expression, and the superi-or olive, which is a relay station for au-ditory information. Both structuresarise from the same segment of the em-bryo’s neural tube, the organ that devel-ops into the central nervous system.Counts of the facial neurons in thewoman’s brain showed only about 400cells, whereas counts of facial neuronsin a control brain showed 9,000.

Overall, the woman’s brain was nor-mal in size; in fact, it was slightly heav-ier than the average brain. I hypothe-sized that the brain stem was lackingonly the specific neurons already identi-fied—those in the facial nucleus and thesuperior olive—and to test that idea Idecided to measure the distances be-

tween a number of neuroanatomicallandmarks. I was surprised to discoverthat my hypothesis was absolutelywrong. Although the side-to-side mea-sures were indeed normal, the front-to-back measures were astonishingly re-duced in the brain stem of the womanwith autism. It was as though a band oftissue had been cut out of the brainstem, and the two remaining pieces hadbeen knit back together with no seamwhere the tissue was missing.

For the second time in my life, I felt apowerful shock of recognition. I heard aroaring in my ears, my vision dimmed,and I felt as though my head might ex-plode. The shock was not generated bythe unexpected result but by the realiza-tion that I had seen this pattern of short-ening before, in a paper that showedpictures of abnormal mouse brains.

When I retrieved the article from thestacks of papers on my office floor, Ifound that the correspondence betweenthe brain I had been studying and themouse brains described in the articlewas even more striking than I had re-membered. Both cases exhibited short-ening of the brain stem, a smaller-than-normal facial nucleus and the absenceof a superior olive. Additional featuresof the mice were clearly related to otheranomalies associated with autism: theyhad ear malformations and lacked oneof the brain structures controlling eyemovement.

What had altered the brains of thesemice? It was not exposure to thalidomideor any of the other environmental factorsassociated with autism but the elimina-tion of the function of a gene. These weretransgenic “knockout” mice, engineeredto lack the expression of the gene knownas Hoxa1 so that researchers could studythe gene’s role in early development. Theobvious question was, “Could this beone of the genes involved in autism?”

The literature supported the idea thatHoxa1 was an excellent candidate forautism research. The studies of knock-out mice showed that Hoxa1 plays acentral role in development of the brainstem. Groups in Salt Lake City and

The Early Origins of Autism Scientific American February 2000 61

Diagnostic Categories

Impairment of Social Interaction: Failureto use eye contact, facial expression orgestures to regulate social interaction;failure to seek comfort; failure to developrelationships with peers.

Impairment of Communication: Failure touse spoken language,without compensat-ing by gesture; deficit in initiating or sus-taining a conversation, despite adequatespeech; aberrant language (for example,repeating a question instead of replying).

Restricted and Repetitive Inter-ests and Behaviors: Abnormallyintense preoccupation with onesubject or activity; distress overchange; insistence on routines orrituals with no purpose; repetitivemovements,such as hand flapping. Many cases of autism,

if not all,are initiated veryearly in gestation.BEHAVIORAL THERAPY for chil-

dren with autism can help themlead happier lives as adults. Instruc-tors at the Eden Institute schoolcarefully evaluate the symptoms ofeach child to draw up an appropri-ate intervention plan. They oftenengage the children in stimulatingplay activities (far left). The insti-tute also provides supervised hous-ing for adults with autism (left).The 37-year-old man pictured hereused videocassette spools to makethe curtain behind his bed; his in-tense interest in these objects is acharacteristic behavior of autism.


London had studied different knockoutstrains with similar results. They foundthat the gene is active in the brain stemwhen the first neurons are forming—thesame period that Miller and Strömlandhad identified as the time when thalido-mide caused autism. Hoxa1 produces atype of protein called a transcriptionfactor, which modulates the activity ofother genes. What is more, Hoxa1 isnot active in any tissue after early em-bryogenesis. If a gene is active through-out life, as many are, altered function ofthat gene usually leads to problems thatincrease with age. A gene active onlyduring development is a better candi-date to explain a congenital disabilitylike autism, which seems to be stable af-ter childhood.

Hoxa1 is what geneticists call a “high-ly conserved” gene, meaning that the se-quence of nucleotides that make up itsDNA has changed little over the courseof evolution. We assume that this is acharacteristic of genes that are critical tosurvival: they suffer mutations as other

genes do, but most changes are likely tobe fatal, so they are rarely passed on tosubsequent generations. Although manyother genes appear in several forms—forexample, the genes that encode eye col-or or blood type—highly conserved genesare not commonly found in multipleversions (also known as polymorphicalleles, or allelic variants). The fact thatno one had ever discovered a variant ofHoxa1 in any mammalian species sug-gested that my colleagues and I mighthave trouble finding one in cases ofautism. On the other hand, it seemedlikely that if a variant allele could befound, it might well be one of the trig-gers for the development of the disorder.

Zeroing in on HOXA1

T he human version of the gene,labeled as HOXA1, resides on

chromosome 7 and is relatively small. Itcontains just two protein-coding re-gions, or exons, along with regions thatregulate the level of protein production

or do nothing at all. Deviations fromthe normal sequence in any part of agene can affect its performance, but thevast majority of disease-causing varia-tions are in the protein-coding regions.Thus, we began the search for variantalleles by focusing on the exons ofHOXA1. Using blood samples frompeople with autism and from subjects ina control group, we extracted the DNAand looked for deviations from the nor-mal sequence of nucleotides.

The good news is that we have identi-fied two variant alleles of HOXA1. Onehas a minor deviation in the sequence ofone of the gene’s exons, meaning thatthe protein encoded by the variant geneis slightly different from the protein en-coded by the normal gene. We have stud-ied this newly discovered allele in detail,measuring its prevalence among variousgroups of people to determine if it playsa role in causing autism. (The othervariant allele is more difficult to investi-gate because it involves a change in thephysical structure of the gene’s DNA.)


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NORMAL CHILDRENAND CHILDREN WITH AUTISM

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Scientists at York University and the Hospital for Sick Childrenin Toronto have recently identified an autism-related behav-

ior that is much simpler than the array of behaviors that have tradi-tionally been used to diagnose the condition.Susan Bryson and herdoctoral student Reginald Landry have found that children withautism respond abnormally to a task involving their reactions to vi-sual stimuli.Because this mental activity is probably mediated by aprimitive part of the brain—most likely the brain stem or the cere-bellum, or both—the discovery has important implications for theneurobiology of autism. Bryson and Landry’s work could also helpclinicians develop a simpler way to test children for the disorder.

In their study Bryson and Landry observed the reactions of twogroups of children, those with autism and those without it, as they

watched lights flashing on video screens [see illustration below].The children ranged in age from four to seven. In the first test,eachchild was placed in front of a three-screen panel, and a flashinglight appeared on the middle screen. This stimulus prompted allthe children to focus their eyes on the flashes (a).Then the middlescreen went blank,and a flashing light appeared on the far-right orfar-left screen of the panel. Both groups of children shifted theireyes to that screen (b). In the second test, however, the lights onthe middle screen kept flashing while the lights appeared on theother screen.The children without autism shifted their eyes to fo-cus on the new stimulus (c),but the children with autism remained“stuck”on the first stimulus and failed to turn their eyes to the newone (d).The two tests were repeated many times for each child.

A Simpler Symptom of Autism


We found that the rate of the variant al-lele among people with autism was sig-nificantly higher than the rate amongtheir family members who do not havethe disorder and the rate among unre-lated individuals without the disorder.The differences were much greater thanwould be expected by chance.

The bad news is that, just as the fami-ly studies had predicted, HOXA1 isonly one of many genes involved in the

spectrum of autism disorders. Further-more, the allele that we have studied indetail is variably expressed—its pres-ence does not guarantee that autism willarise. Preliminary data indicate that thevariant allele occurs in about 20 percentof the people who do not have autismand in about 40 percent of those whodo. The allele approximately doublesthe risk of developing the condition. Butin about 60 percent of people withautism, the allele is not present, mean-ing that other genetic factors must becontributing to the disorder.

To pin down those factors, we mustcontinue searching for other variants inHOXA1, because most genetic disor-ders result from many different deviantalleles of the same gene. Variations inother genes involved in early develop-ment may also predispose their carriersto autism. We have already discovered avariant allele of HOXB1, a gene onchromosome 17 that is derived from thesame ancestral source as HOXA1 andhas similar functions in the develop-ment of the brain stem, but its effect inautism appears to be minor. Other in-vestigators are scrutinizing candidate re-gions on chromosome 15 and on anoth-er part of chromosome 7. Although re-searchers are focusing on alleles thatincrease the risk of autism, other allelesmay decrease the risk. These could helpexplain the variable expression of thespectrum of autism-related disorders.

Even a minimal understanding of thegenetic basis of autism would be ofgreat value. For example, researcherscould transfer the alleles associated withautism from humans to mice, engineer-ing them to be genetically susceptible tothe disorder. By exposing these mice tosubstances suspected of increasing therisk of autism, we would be able tostudy the interaction of environmentalfactors with genetic background andperhaps compile an expanded list of

substances that women need to avoidduring early pregnancy. What is more,by examining the development of thesegenetically engineered mice, we couldlearn more about the brain damage thatunderlies autism. If researchers can de-termine exactly what is wrong with thebrains of people with autism, they maybe able to suggest drug therapies or oth-er treatments that could ameliorate theeffects of the damage.

Devising a genetic test for autism—

similar to the current tests for cystic fi-brosis, sickle cell anemia and other dis-eases—would be a much more difficulttask. Because so many genes appear tobe involved in the disorder, one cannotaccurately predict the odds of having achild with autism by simply testing forone or two variant alleles in the parents.Tests might be developed, however, forthe siblings of people with autism, whooften fear that their own children willinherit the disorder. Clinicians couldlook for a set of well-established geneticrisk factors in both the family memberwith autism and the unaffected sibling.If the person with autism has severalhigh-risk alleles, whereas the siblingdoes not, the sibling would at least bereassured that his or her offspringwould not be subject to the known riskswithin his or her family.

Nothing will make the search forautism’s causes simple. But every risk fac-tor that we are able to identify takesaway some of the mystery. More impor-tant, new data spawn new hypotheses.Just as the thalidomide results drew at-tention to the brain stem and to theHOXA1 gene, new data from develop-mental genetics, behavioral studies, brainimaging and many other sources can beexpected to produce more welcomeshocks of recognition for investigators ofautism. In time, their work may help al-leviate the terrible suffering caused bythe disorder.

The Early Origins of Autism Scientific American February 2000 63

The Author

PATRICIA M. RODIER is professor of obstetricsand gynecology at the University of Rochester. Shehas studied injuries to the developing nervous sys-tem since she was a postdoctoral fellow in embryol-ogy at the University of Virginia, but she began toinvestigate autism only after hearing the results ofthe thalidomide study. Rodier has assembled agroup of scientists from many disciplines at six in-stitutions to study the genetic and environmentalcauses of the disorder and says that working withexperts from other fields is rejuvenating.

Further Information

Autism in Thalidomide Embryopathy: A Population Study. K. Strömland, V.Nordin, M. Miller, B. Åkerström and C. Gillberg in Developmental Medicine andChild Neurology, Vol. 36, No. 4, pages 351–356; April 1994.

Embryological Origin for Autism: Developmental Anomalies of the Cra-nial Nerve Motor Nuclei. P. M. Rodier, J. L. Ingram, B. Tisdale, S. Nelson andJ. Romano in Journal of Comparative Neurology, Vol. 370, No. 2, pages 247–261;June 24, 1996.

Thinking in Pictures: and Other Reports from My Life with Autism. TempleGrandin. Vintage Books, 1996.

More information on autism is available at the Web page of the National Alliancefor Autism Research at www.naar.org

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Bryson and Landry found that children withother kinds of brain damage are perfectlynormal in their ability to disengage from onestimulus and focus on another. Children withautism, however, repeatedly fail to disengagefrom the first stimulus, even if they are highlyintelligent.Researchers suspect that this abili-ty is a low-level brain function because it typi-cally appears in infants—as early as three tofour months after birth—and in children withlow IQs. Animals also orient themselves to-ward new stimuli, so scientists could conceiv-ably use a similar test in animal studies to ver-ify whether genetic manipulations or toxico-logic exposures have produced this symptomof autism. —P.M.R.

CHILDRENWITH AUTISM


the early origins of autism

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