Refer to: Ornitz EM: Childhood aLtism-A revicw of the clinicaland experimental litcrattire (Medical Progress). CalifMed 118:21-47, Apr 1973

MEDICAL PROGRESS

Childhood AutismA Review of the Clinical and Experimental Literature

EDWARD M. ORNITZ, MD, Los Angeles

This review of the literature on childhood autism discusses theclinical characteristics, differential diagnosis, prognosis andtreatment of the autistic behavioral syndrome from a develop-mental perspective. It includes a discussion of the influence ofprenatal and perinatal antecedents, genetic and socio-familialfactors, and epidemiologic considerations. Neurologic, electro-encephalographic and experimental neurophysiologic, meta-bolic, biochemical and hematologic investigations are reviewed.Special emphasis has been given to the changing clinical mani-

festations which accompany maturation and to the problems ofrecognition of childhood autism in the very young child.

OF THE MANY TYPES OF UNUSUAL BEHAVIOR seenin young children, the behavior of the autisticchild has been the most difficult to understand. Thegreat variability of the abnormal behavior, thechanges concomitant with the maturation of thechild,' 2 the wide differences in degree of severityfrom case to case, the confusing and inconsistentterminology which has been used to describesuch children, and the lack of any physical signshave made diagnosis in the individual case a diffi-cult and often unreliable procedure. The behavioris often so bewildering to the parents that it ishard to obtain an adequate description of thechild's development. Often the parent can onlysay, "He is just different from other children";unless the physician suspects the diagnosis and

From the Department of Psychiatry, University of California,Los Angeles, Center tor the Health Sciences.

Reprint requests to E. M. Ornitz, MD, Department of Psychi-atry, University of California, Los Angeles, Center for the HealthSciences, Los Angeles, Ca. 90024.

knows which symptoms to elicit, the diagnosticprocess may be thwarted at the outset and thephysician may find himself saying, "Let's wait andsee if he grows out of it."

Parental concern about the child's behavior maybe communicated at any time. A mother may com-ment to her pediatrician that her newborn ormonth-old infant reacts very differently than herother babies. Neglected cases may not come tomedical attention until the patient is as much assix or seven years of age. Parents usually seekprofessional help when the child is about two yearsof age since a delay in speech development is mostlikely to alarm parents at that time. Earlier andmore subtle symptoms may have been ignored ordenied.What is the typical clinical appearance of the

two- to four-year-old autistic child? The present-ing problem may be delayed speech, and hearing

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loss may be suspected. In fact, many such childrenare first seen in speech and hearing clinics beforethe diagnosis of childhood autism is considered.On questioning, it may be found that although thechild uses no speech or has ceased to use a fewpreviously acquired words and does not respondto verbal commands, he does attend to certainsounds. In fact, he may seem to seek out auditorystimulation. For example, he may flick, rub orbang his ears, inducing quite intense auditoryinput, or he may scratch surfaces and put his earto the surface listening to the sound that he makes.He may occasionally startle to quiet sounds orcup his hands over his ears and become agitatedupon hearing a siren, a vacuum cleaner or perhapsjust the distant sound of an airplane overhead.The child's failure to communicate with speech isoften accompanied by a failure to communicatewith gesture or pointing. The parents often com-plain that their child seems to look through themand that eye-to-eye contact is actively avoided.The child relates poorly to people in many otherways. He often ignores the presence both of otherchildren and of adults. He may react to beingpicked up by struggling or becoming either com-pletely limp or rigid. The child may show no inter-est in games or toys. He may wiggle his fingers, flaphis hands, walk on his toes, rock, sway and whirl.This is the typical clinical appearance of a severelyimpaired two- to four-year-old autistic child. Inless severe cases, or when seen at a younger orolder age, only some of the symptoms may bepresent, the overall intensity of the symptoms maybe milder, the bizarre behavior may occur moreintermittently and the clinical picture will be lessclear.

TerminologyAt least six major diagnostic rubrics have been

used to describe young children with this set ofsymptoms. Although isolated cases were reportedearlier, the syndrome was first formally describedin a group of 11 children by Kanner in 1943 underthe heading "Autistic Disturbances of AffectiveContact."3 In 1944 Kanner adopted the term earlyinfantile autism, drawing attention to the fact thatthe autistic behavior develops in early infancy.4This term and its synonyms-childhood autism,infantile autism and autistic child-have becomethe most commonly accepted way of referring tothis condition. It is also occasionally referred toas Kanner's syndrome. A second diagnostic rubricis atypical development.5-8 This term has been

used to describe patients whose symptoms maybe less severe. The term symbiotic psychosis hasbeen used to describe children whose way of relat-ing appeared superficially to be the opposite ofan autistic way of relating.9"10 The children, ratherthan being aloof and remote, would cling tenaci-ously to the parent. Since such behavior can befound transiently or intermittently in autistic chil-dren who are otherwise completely emotionallydetached, this term does not describe an independ-ent disorder.The term pseudo-retarded or pseudo-defective"'

was used at a time when considerable emphasis wasplaced on the differential diagnosis between mentalretardation and childhood autism. Many of theautistic children functioned at a retarded level,failed to relate to normal task-oriented social sit-uations, and failed to use language. It was thoughtthat the retardation was only apparent-an arti-fact of their untestability and inability to commu-nicate.""2 Since more recent studies have dem-onstrated that the majority of autistic children arein fact permanently retarded, this term is no longerapplicable.'3"14 The more general but less welldefined term infantile psychosis and its synonyms-childhood psychosis and early onset psychosis-have been used extensively.8"322 When used todescribe children whose symptoms begin before36 months of age, these terms are acceptable syno-nyms for childhood autism.A final term which has received wide usage as

a diagnostic label for this same group of childrenis childhood schizophrenia."""1,2'23-30 The use ofthis term has created some semantic confusion andmuch diagnostic controversy in the literature con-cerned with autistic children, since many studentsof this illness feel that childhood autism is phe-nomenologically quite distinct from the schizo-phrenias of later life8' 20'21'3' while others describea continuum of symptoms relating the two syn-dromes.""17,32'33 Both the distinctions and the re-lationships between childhood autism and schizo-phrenia will be discussed in appropriate sectionsof this paper. The terms childhood schizophreniaand schizophrenic child will be used in this reviewas acceptable synonyms for childhood autism withthe understanding that the patients have the setof symptoms described in the following sectionsand that the illness is recognized at less than fiveyears of age and deviant development is presentbefore three years of age. Children who definitelywere free of autistic symptoms before they werefive years old and then began to have schizo-

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phrenic symptoms are not to be classified as au-tistic on phenomenologic grounds even though theunderlying pathophysiologic mechanisms mightbe similar in the two groups of children.34'35 Thechildren who first became schizophrenic in middlechildhood after a normal early development shouldnot be called aAtistic and their disorder has beenreferred to as late onset psychosis.'8

Clinical CourseChildhood autism begins at birth or early in

post-natal life although in many cases the firstsymptoms may not be recalled or recognized bythe parents. Two courses of development of theillness have been reported. In the first, the parentsdescribe deviant behavior from birth. In the sec-ond, there seems to be a period of relatively nor-mal development up to the age of 18 to 24 months,at which time the onset of symptoms occurs. Theonset of the disorder will almost invariably occurbefore 30 months of age and rarely occurs pastthe third birthday.'8'20 The subsequent clinicalpicture is the same regardless of the exact age atonset of the first symptoms. Very careful history-taking may elicit symptoms which did indeed occurduring the first year of life, but which were for-gotten, overlooked or denied by the parents dueto either anxiety about their child's developmentor unfamiliarity with normal development.

The neonatal periodThe mother may be convinced that the new-

born baby is different from her other babies butshe cannot articulate the subtle nature of thestrange behavior. The infant may cry infrequentlyor seem not to need companionship or stimulation.He may become limp or rigid when held. He isoften described as a "very good baby" who neverfusses, or as intensely irritable and over-reactiveto any form of stimulation. Muscle tone may seemflaccid.36

The first half yearDuring the first half year of life the child may

continue to be "undemanding" but it soon becomesapparent that he is failing to notice the comingand going of his mother. Responsive smiling doesnot occur or is delayed. At four or five months thenormal anticipatory response to being picked updoes not occur. Often a baby who is unresponsiveto toys such as a bird mobile, rattle or a crib gymmay be paradoxically over-reactive to sounds pro-duced by the vacuum cleaner, the washing machine

or the telephone. The earliest vocalization-coo-ing and babbling-may not appear or be consid-erably delayed.

The second half yearDuring the second six months, the baby often

shows an unusual response to the introduction ofsolid foods. The usually uneventful introductionof strained baby foods is often followed by refusalto accept, retain, chew or swallow foods withrough texture such as chopped meats. Withoutintervention some autistic children remain onpureed baby foods for several years. Toys whichwere ignored in the first half year of life are nowcast or flicked away or simply dropped out ofhand. The motor milestones such as sitting, crawl-ing, pulling to a stand and initiating walking occa-sionally are accelerated but are more likely to bedelayed. Developmental sequences may be irregu-lar; for example, late sitting without support maybe followed by precocious pulling to a stand andthen late walking.' If developmental testing isattempted at this time or during the second yearof life these spurts and lags in development areoften reflected in wide scatter on developmentalprofiles.36

The six- to twelve-month-old autistic baby isunaffectionate. When picked up he may becomeeither limp or stiff, and when put down notseem to care. He often fails to show the normaleighth month "stranger anxiety" and does not playpeek-a-boo and pat-a-cake at ten or eleven monthsof age.37 At 12 months, he does not wave bye-byeresponsively and syllables are not combined intopolysyllabic sounds and words. Occasionally thechild develops a few words and then a few monthslater ceases to use them. Along with the absenceof communicative speech there is no nonverbalcommunication. The child neither points nor lookstoward a desired object. Toward the end of thefirst year, peculiar reactions to sensory stimulidevelop and continue into the third year of life.At times the autistic baby may become agitated orpanicked by the same unexpected or loud soundsas those to which he is completely oblivious onother occasions. Changes in other sensory modali-ties-illumination, the feel of certain fabrics, andproprioceptive and vestibular sensations inducedby change in position-may also evoke distress.

The second and third years

During the second and third years, the childseeks stimulation in all sensory modalities and

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often engages in peculiar mannerisms which seemto provide such stimulation. For example, theremay be noisy and vigorous tooth grinding or thechild will scratch surfaces and listen intently tothe sounds that he creates. He will place his eyesvery close to the surface of an object such as amoving top and intently stare at the passing visualpatterns. He will rub his hands over the surfaceof different fabrics, responding to fine texturaldifferences. A number of unusual repetitive andstereotyped mannerisms involve the hands. Thetendency of the normal six month old to intentlyregard his own hand and finger movements oftenbecomes a permanent part of the autistic child'sbehavioral repertoire. He may either sustain thisinfantile mannerism or flap his hands or rapidlywiggle his fingers while regarding, often in theperiphery of his visual field, his own hand move-ments. Other unusual motility patterns occur. Thenormal transient toe walking which accompaniesthe early stages of learning to walk may becomea permanent behavior.38 The children engage inexcessive body rocking, swaying, and head bang-ing39 and often roll their head from side to side.They may whirl around and around for manyminutes without becoming dizzy. In states of ex-citement all of these behaviors may be seen tooccur together. Often in response to some stimulus,the child will suddenly run in circles on his toes,whirl, make staccato-like lunging and dartingmovements and vigorously flap his hands. Thetwo- and three-year-old autistic child shows littleor no interest in toys. Toy cars, dolls or puppetsare ignored or arranged in some idiosyncratic pat-tern without regard to function or meaning. Thereis little or no development of imagination, fantasyor role-taking in play.40 Preoccupation with spin-ning objects may preclude all other forms of play.A spinning top may elicit explosive yet organizedbouts of motor discharge including toe walking,darting and lunging toward the top and a staccatoflapping of the hands. The limited interest in toysis accompanied by indifference to human contact.The autistic child does not look at the adult whenhe wants something but moves the adult's handtoward the desired object much as if manipulatinga pair of pliers.

The fourth and fifth year

Most of this behavior continues into the fourthand fifth year, after which the severe reactions tosensory stimuli and the bizarre motility patternsmay abate. Then the focus of clinical attention

may be the unusual speech. The child may remainmute or speech may be limited to a few incon-sistently used words. When speech does occur, itis often limited to delayed echolalia. This is aparrot-like imitation of the speech of others occur-ring out of social context and having little or nocommunicative value. For example, the childmight say, "Do you want to take a walk?" whilebathing or eating, parroting word for word a ques-tion that was directed to him earlier in the day.Along with the echolalia there is misuse of thepersonal pronouns (the substitution of "you" or"he" for "I" or "me").

Middle childhood

After the fifth or sixth year, two types of pro-gression of the disorder occur. Some of the chil-dren may continue to manifest most of the symp-toms already described. In others, there may bea gradual change in the clinical picture; the symp-toms of childhood autism become less evident andnew features develop, suggesting either alternativeor secondary diagnostic considerations (see sectionon prognosis below). With increasing age, theunusual responses to sensory stimulation and thebizzare motility patterns become less apparent.The disturbed relating is more likely to continuebeyond the sixth year and its severity tends to bein proportion to its severity during the first fiveyears. The same is true of the language disturb-ances, and if language has not been used consist-ently for communication by age five years, thenit is extremely unlikely that more advanced speechdevelopment will ever occur. When this is thecase, intellectual development remains at a stand-still and if the extreme responses to sensory stim-ulation and the bizarre motility patterns abate,then the child begins to look less autistic and moreand more retarded. This is not the case if thechild develops communicative speech by his fifthbirthday. In this case, one observes a child whosecommunications are very literal and who showsa reduced capacity for abstract thinking, a deficitwhich appropriate evaluation may be able todemonstrate in the younger nonverbal autisticchild.41 Affect tends to be flat, and verbal com-munication does not lead to emotional involve-ment with others. The child remains an aloof,emotionally detached and often bizarre-appearingyoungster. In some cases the child's communica-tions appear to be characterized by loose, irrele-vant and tangential thinking, and if the child hasdeveloped any degree of fantasy life the expressed

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fantasies tend to be bizarre and are often confusedwith reality. Another type of behavior seen insome autistic children between the ages of fiveand ten years is impulsivity and lack of emotionalcontrol, coupled with restlessness, irritability andhyperactivity.

The Behavioral Syndrome ofChildhood Autism

The previous section of this paper has empha-sized the developmental aspect of this disorderand the changes in symptoms with the age of thechild. It is also helpful to think of several cate-gories or subclusters of symptoms when makingthe diagnosis of childhood autism. These symptomsubclusters include (1) disturbances of relating,(2) disturbances of speech and language, (3) dis-turbances of developmental rate, (4) disturbancesof motility and (5) disturbances of perception.

Disturbances of relatingThese symptoms involve relationships both with

people and with inanimate objects. Behaviors in-dicative of an early failure to develop interper-personal relationships include poor or deviant eyecontact,42-44 delayed or absent social smile, de-layed or absent anticipatory response to beingpicked Up,3'45 apparent aversion to physical con-tact, a tendency to react to another person's handor foot rather than to the person,45 disinterest inplaying games with others and a general preferencefor being alone.31'4fi The disturbed interpersonalrelationships may be more subtle and need notbe consistently observed. Experiments carried outunder well controlled laboratory conditions suggestthat the disturbed relationships may not be funda-mental to the disorder47'48 but may be secondaryto disturbances of perception.49 The use of inani-mate objects is limited to flicking, twirling or spin-ning them. There is a tendency to order and ar-range objects in a constant manner so that thechild seems to want to maintain an unvaryingsameness in his environment.3 40'45'50 With increas-ing age, these same tendencies are manifest in arigidity and inflexibility in the use of play ma-terial.51'52

Disturbanices of speech and languageSpeech development is usually characterized by

muteness or echolalia.3"2'53-55 Along with theecholalia there may be misuse or reversal of thepersonal pronouns.3'31'56'57 The tendency to echo

the speech of others without regard for the socialcontext or communicative value of the words maypervade tests of language function in autistic chil-dren. For example, while normal children alwaysrecall sentences better than non-sentences, autisticchildren remember "nonsense" as well as "sense";their recall process seems to depend on an "echobox type" memory store.47 Although attemptshave been made to understand the echolalia ofautistic children in a psychodynamic and psycho-analytic context,56'58 the echolalia in autistic chil-dren probably is related to the severe rigidity ofimitation observed in the speech of these chil-dren.59 When communicative speech does developit is atonal and arrhythmic, lacks inflection andfails to convey emotion.29 This poverty of the tonaland affective qualities of speech in young autisticchildren is paralleled in older autistic children bya restriction of spontaneity and originality of com-munication.52'60

Disturbances of development rate

Autistic children show great irregularity in theage at which the sequential motor and languagemilestones are passed." 36 While some autistic chil-dren show either a normal or precocious develop-mental progression, a greater number manifestearly developmental retardation. The most charac-teristic course, however, is to find discontinuitiesin the normal sequence of development.6' Forexample, an autistic child may sit without supportprecociously, and then there may be a long delaybefore he will pull to a stand. Thus a sequenceof spurts and lags is characteristic of the develop-ment of autistic children.' The unevenness of de-velopment is also manifest in the special abilitiesof some otherwise very retarded autistic children.62

Disturbances of motilityTo a great extent the strange and bizarre ap-

pearance of autistic children is due to their pecu-liar mannerisms and motility patterns. The deviantmotility may involve the hands, the lower extrem-ities, or the trunk and entire body. While the man-nerisms are often complex and ritualistic andclearly do not have the appearance of eitherinvoluntary movements or seizure discharge pat-terns, they are stereotyped, strikingly similar ingeneral pattern and form in most autistic children,and do not seem to be entirely voluntary. Theseverity of this aspect of the syndrome varies de-cidedly from one autistic child to another. Thedeviant motility may appear intermittently or in-

CALIFORNIA MEDICINE 25The Western Journal of Medicine

frequently in some autistic children and may occurcontinuously in others.63'64Some of the most characteristic and striking

motor behaviors involve the hands.2'83'5-68 Theautistic child may hold his hands in front of hiseyes and writhe or twist the fingers and palms.Activity of this type often merges into a repetitivestereotyped wiggling of the fingers or the entirehand. This "hand flapping" involves a rapid anduntiring alternating flexion and extension of thefingers or hand or an alternating pronation andsupination of the forearm. Similar "flapping"movements of the lower extremities may occurbut the most striking involvement of the lowerextremities is toe walking.38 This may occurtransiently during states of excitement or whilerunning in circles. However, it is often the onlymode of walking and may persist on occasion intoadolescence.

Disturbances involving the trunk or the entirebody include staccato lunging and darting move-ments, terminated by sudden stops. The childrenalso engage in an unusual amount of body rockingand swaying, often accompanied by head rollingor head banging. A history of severe infantilehead banging is often associated with the laterdevelopment of self-mutilation.39 The children alsowhirl themselves around the longitudinal bodyaxis. In spite of all this gross motor activity, au-tistic children are not necessarily hyperactive.These children are not constantly in motion noris there a restless, irritable quality to their activity.In fact, the various behaviors just described maybe interrupted by sudden brief episodes of immo-bility, often associated with bizarre posturing ofthe trunk or extremities. Very young autistic chil-dren tend to arch the back and hyperextend theneck, maintaining this uncomfortable position forbrief periods. Some or all of these motility pat-terns can at times be elicited by rapidly spinninga child's top in front of the patient.

Disturbances of perceptionThe disturbances of perception charactertistic

of autistic children do not necessarily involve theperceptual deficits seen in children who have mini-mal cerebral dysfunction. These latter deficits in-volve difficulty in perceiving the shape of objectsand their orientation in space, abilities which maybe intact in autistic children. When such deficitsdo occur in autistic children, they may be second-ary to a failure to sustain attention toward visualstimuli.47 The disturbances of perception in au-

tistic children involve a faulty modulation of sen-sory input,2'34 69 a distortion of the normal hierar-chy of receptor preferences,70 and an impairedability to use sensory input to make discrimina-tions in the absence of feedback from motorresponses.47

The inability to adequately modulate sensoryinput constitutes a striking aspect of autistic symp-toms.2 28 29'66'69 All sensory modalities are affectedand the faulty modulation of sensory input maybe manifest as either a lack of responsiveness oran exaggerated reaction to sensory stimuli.28'29Both types of abnormal reactivity to sensory stim-uli can occur in the same child.28

Hypo-reactivity to auditory stimuli is apparentin the disregard of both verbal commands andloud sounds. Sudden sounds which would elicitan impressive startle reaction in normal childrenmay elicit no response whatsoever in some autisticchildren.7' Visually the children may ignore newpersons or features in their environment and theymay walk into objects as if they did not see them.A similar response to tactile stimuli may occurduring the first two years of life; objects placedin the hand may be allowed to fall away as if theyhad no tactile representation. Painful stimuli areoften ignored; the children may not notice painfulbumps, bruises, cuts or injections.

Contrasting starkly to the hypo-reactivity tosensory stimuli are decidedly exaggerated reac-tions to the same stimuli. The children may showboth heightened awareness of sensory stimuli andheightened sensitivity to sensory stimuli.28 Alongwith the heightened awareness of sensation thereis often a tendency to seek it out and induce it.Some of the disturbances of motility seem to pro-vide intense sensory stimulation but may also bea way of mastering sensory stimuli.72 The childrentend to induce sounds by scratching surfaces andputting their ears down close to the surface. Theymay be distracted by background stimuli of mar-ginal intensity. They may rub, bang or flick attheir ears or grind their teeth-all activities thatinduce intense auditory input. Visually they regardtheir own writhing hand and finger movements ortheir more vigorous hand flapping, and they scru-tinize the fine detail of surfaces. There are alsobrief episodes of intense staring.- The children mayrub surfaces of furniture or fabric in response tofine textural differences. Many of the behaviors ofautistic children also suggest that they are activelyseeking out vestibular and proprioceptive stimu-lation.11"12 They whirl themselves around and

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around, repetitively rock and sway back and forth,or roll their heads from side to side. The repetitivehand flapping also provides proprioceptive input.

Contrasting with both the tendency to ignoreand to seek out sensory stimuli is the paradoxicaldistress induced by stimuli in all sensory modal-ities. The children may become agitated by thesound of sirens, vacuum cleaners, or barking dogsand they may cup their hands over their ears inan attempt to shut out both these intense soundsand also mild novel sounds such as the crinkleof paper.2869 Sudden changes in illumination orconfrontation with an unexpected object may elicitthe same fearful reactions to visual stimuli. In thetactile modality there may be severe intolerancefor certain fabrics; the children are often disturbedby wool blankets or clothing and seem to prefersmooth surfaces. During the first year of life theintroduction of the rough-textured table foodsoften evokes distress. The same child who mayseek out vestibular stimulation by whirling him-self can show a pronounced aversion to vestibularstimulation induced by roughhouse, anti-gravityplay or even riding in an elevator.

Autistic children do not show the same prefer-ence in the use of the various sensory modalitiesas do normal or non-autistic mentally retardedchildren. They have been described as preferringto use "proximal" receptors (touch, smell andtaste) rather than "distal" receptors (audition andvision).70,73 Both autistic and non-autistic childrentend to respond to light in preference to sound butnon-autistic children can readily be conditioned torespond preferentially to a sound source whereasthis is not possible with autistic children.74 Thisapparent dominance of visual over auditory stim-uli may actually be due to an inability to respondto two or more stimulus modalities in a complexstimulus presentation. Autistic children are over-selective in responding to only one component ofa stimulus complex consisting of, for example,auditory, visual and tactile components.75'76 Visualstimulation itself seems less meaningful to autisticthan to non-autistic children, in that autistic chil-dren show fewer eye movements in response toand spend less time regarding visual displays thando non-autistic children.47'74 While autistic chil-dren may have normal or even advanced formperception 7 they make poor use of visual discrim-ination in learning.74'77 They seem to be depend-ent on feedback from their own motor responsestoward sensory stimuli in order to make senseout of perceptions.47'78

Differential Diagnosis

Childhood autism is not necessarily mutuallyexclusive with a number of conditions from whichit must be differentiated. In particular childhoodautism may coexist with mental retardation, anumber of organic brain syndromes, and a varietyof seizure disorders. The problem of differentiat-ing childhood autism from these conditions withwhich it may also be associated will be returnedto after considering other conditions where a moresatisfactory differential diagnosis can be made.

Maternal deprivation

Since autistic children are described as havingbeen "extremely good babies" who "prefer to belet alone" a lack of adequate stimulation duringthe early years is often considered in the genesisof the illness.79 If the mothering of the infant hasbeen characterized by aloofness, indifference andminimal physical contact, can this induce autisticbehavior? Various degrees of environmental de-privation do indeed induce serious developmentaldisturbances in children. The immediate and long-term sequelae of environmental deprivation havebeen well documented both in infants raised ininstitutions80'81'82 and in infants raised at home.83Environmental deprivation of young infants is tobe understood to encompass at least three types ofdeprivation: (1) maternal deprivation involvingdeprivation of love, human contact, physicalwarmth and cuddling, and the give and take ofsocial interaction with a caring adult; (2) anabsence of novelty, resulting in an unrelieved con-dition of environmental monotony and boredom;and (3) an actual deficit of sensory input in allsensory modalities (auditory, visual, kinesthetic,tactile and vestibular). Infants reared in these cir-cumstances show disturbances of developmentalrate, motility, relating, language and perception.These are the same general aspects of developmentwhich are adversely affected in autistic children.The nature of the individual symptoms is quitedifferent, however, in the environmentally de-prived than in the autistic children.66

Environmentally deprived children suffer a uni-form retardation of the acquisition of motor skillsand speech as well as a delay in the adaptive useof toys. Autistic children show an uneven motorand speech development characterized by spurtsand lags. Environmentally deprived infants showcertain unusual motor patterns-for example,

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athetoid movements of the hands. These move-ments do not develop into the tenacious, stereo-typed hand flapping or finger wiggling of autisticchildren. Whirling, toe walking and darting andlunging movements of autistic children are notseen in environmentally deprived children. En-vironmentally deprived children do engage, how-ever, in a considerable amount of body rockingand some hand posturing, but these activities areeasier to interrupt than in autistic childrefi. Likeautistic children, environmentally deprived chil-dren show various disturbances of relating. Theyadapt poorly to holding but do not become limpor rigid as do autistic children. While the deprivedchildren may flick at toys or drop them as doyoung autistic children, their general interest intoys remains undeveloped. Autistic children, incontrast, tend to use. toys in bizarre ways, such asspinning them. Deprived children fail to seekadults out when given the opportunity, but unlikethe autistic children, who seem to avoid eye con-tact, they engage in intense visual regarding ofadults. While autistic children rarely develop activeinterest in playing games with others, the deprivedchildren do participate in games although suchinterest develops later than in normals. When seenin the second or third year of life, children whohave suffered from serious environmental depri-vation may show a delay in language acquisitionsimilar to that seen in autistic children. However,they do acquire lang-uage if the environmental de-privation is relieved, and once language is acquiredthe speech does not have the atonal, arrhythmic,hollow-sounding quality of the speech of autisticchildren, nor do echolalia and misuse of pro-nouns occur. The environmentally deprived chil-dren do not show the faulty modulation of sensoryinput seen in autistic children. In contrast to thetendency of autistic children to engage in excessivetactile exploration, the deprived children show adiminished tendency to touch themselves or to con-tact the environment through mouthing activity.When the conditions of environmental depriva-

tion are relieved, deprived children usually makesignificant gains. However, a number of sequelaehave been observed. There is a persistent faultyself-regulation of food intake. The previously de-prived children do not know when they are satiated,but they do not develop bizarre food preferences orexclude solid foods as do autistic children. Thereare residual mild deficits in coordination of bodymovement but the hand flapping and toe walkingseen in autistic children do not occur. Residual

lags in language development are not accompaniedby the delayed echolalia of the autistic child. In-stead of remaining emotionally detached fromadults as do autistic children, the children recov-ering from environmental deprivation show anindiscriminate friendliness to them. They fail todevelop strong emotional ties to any individualperson. Again, on follow-up, environmentally de-prived children do not show the sensory hyper-sensitivities and hyposensitivities or the preoccupa-tion with spinning objects seen in autistic children.When a mother has postpartum depression or

other serious emotional disorder during her child'sfirst year and adequate care of the child by amother surrogate has not been provided, the physi-cian should consider the following two possibili-ties. First, because of the mother's emotional stateshe may only be able to provide perfunctory careof her baby and the child may, in fact, developthe environmental deprivation syndrome due tomaternal deprivation and the accompanying pov-erty of sensory stimulation. Second, the primarycondition may be an insidiously developing autisticdisturbance in the child which has an adverseemotional influence on a sensitive mother. Thechild's failure to relate to the mother and to re-spond positively to her ministrations may resultin loss of self-esteem and a resultant maternaldepression.

Anaclitic depressionLike the environmental deprivation syndrome,

the anaclitic depression is accompanied by pro-found developmental retardation and severe dis-turbances of relating, and therefore it must bedistinguished from childhood autism. Unlike theenvironmental deprivation syndrome, anaclitic de-pression is associated with the interruption afterthe sixth month of life of a good mother-infantrelationship.84 The interruption may be due todeath, illness, depression or absence of the mother.The infant reacts by becoming weepy, demand-ing and clinging. If the mother does not returnwithin a few weeks, this weepy stage progressesinto a period of psychomotor and language re-tardation, weight loss and intense wailing. Aftertwo or three months, the child becomes lethargicand apathetic; the weeping and wailing are re-placed by quiet whimpering, and facial rigidity sug-gests a profound depression. The motor and per-ceptual symptoms accompanying the syndrome ofchildhood autism do not occur and the failure to

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relate to adults is characterized by apathy andwithdrawal rather than the the lack of involvementcharacteristic of the autistic child.

Other behavioral disturbances due toenvironmental influences

In addition to the absence or loss of adequatemothering in the first and second year of life,various types of disturbances of the mother-infantrelationship or disturbances within the family set-ting can induce unusual behavior accompanied bydevelopmental lags in the child. Body rocking andsome other unusual mannerisms, gestures andhabits may develop during the first and secondyear of life in response to chronic frustration ortraumatic emotional experiences. It is to be em-phasized that not all bizarre behavior seen inyoung children implies childhood autism. In thedifferential diagnosis of childhood autism theremust be a thorough assessment of family relation-ships and the mother-child relationship.

Since failure to use language is so prominent apart of the autistic syndrome during the first fewyears of life, the condition of elective mutismdeserves special emphasis. In elective mutism thechild is quite capable of the complete use ofspeech but voluntarily withholds it. These childrenhave usually been heard to speak fluently at sometime in the past or will speak fluently under cer-tain limited conditions. For example, some elec-tively mute children will only speak in the pres-ence of other children and never when an adultis present. Others will only speak within, neveroutside the family. At times the child will speakonly in a whisper. The voluntary withholding ofspeech is usually in response to a specific patho-logical family situation or mother-infant interac-tion. It occurs in response to premature attemptson the part of the parents to force speech develop-ment or in family settings where the need to keepa "family secret" has been unduly impressed uponthe child.

Major sensory deficitsDeafness and blindness in early childhood can

precipitate severe emotional reactions. The com-bination of such emotional disturbance with thelimitations imposed by the sensory deficit canresult in a clinical picture which may be confusedwith childhood autism.85 Since absence or delayof speech acquisition almost always accompaniesthe syndrome of childhood autism during the firsttwo years of life, hearing loss should always be

considered. Adequate otologic examination toevaluate possible causes of chronic or intermit-tent hearing loss should be carried out. Someautistic children are first seen in speech and hear-ing clinics since the diagnosis of deafness may besuspected before the possibility of childhood au-tism is considered. Childhood autism is usuallysuspected when attention is paid to symptoms ofthe disorder such as the disturbed motility pat-terns and the tendency to over-react as well asto under-react to both auditory and other typesof stimulation.

Complete or partial blindness can induce dis-turbed behavior often associated with mannerismsknown as "blindisms." These blindisms involvemanneristic gesturing with the hands in front ofthe face; they usually do not have the stereotypedquality of the hand flapping of autistic children.Furthermore, the blind children do show interestin their environment when their visual deficit isrecognized by others and an attempt made to re-late to them through non-visual means. The syn-drome of childhood autism has been described inassociation with retrolental fibroplasia but not withother types of visual impairment.86 Since retro-lental fibroplasia is often associated with organicbrain damage, there is reason to suspect that theautistic symptoms are associated with the lattercondition rather than with the visual deficit per se.

Developmental aphasia (congenitalauditory imperception)When the autistic child first comes for diag-

nostic consideration, often the presenting problemis delay in the acquisition and deficiency in theuse of speech. Therefore, a number of develop-mental disorders characterized by language dis-turbance must be considered. The effects of ma-ternal deprivation or loss, emotional disorders andhearing deficit on the acquisition and use ofspeech have already been discussed. Languageretardation as part of a general mental retardationwill be considered below. A relatively rare butdiagnostically troublesome developmental disorderwhich requires additional consideration is develop-mental receptive and expressive aphasia.31 In boththis disorder and in childhood autism there areabnormal responses to sounds, delay in the acqui-sition of speech, difficulty in its comprehensionand use, and difficulties in articulation.87'88 Asspeech is slowly acquired both aphasic and autisticchildren distort and invent words. Because of theirdifficulty in communicating and being understood,

CALIFORNIA MEDICINE 29The Western Journal of Medicine

aphasic children may develop secondary disturb-ances of relating and social responsiveness sugges-tive of the problems of autistic children. However,aphasic children do not develop the sensory hyper-and hypo-sensitivities characteristic of autistic chil-dren and they do show the capacity to relate bynonverbal gestures and expressions and they re-spond to the gestures and expressions of others.8"Young asphasic children usually point towarda desired object whereas autistic children willnot.7'90 9' As speech is acquired, aphasic childrenrarely show the lack of "communicative intent"and emotion92 and the delayed echolalia"0'9' char-acteristic of the speech of autistic children. Whenlinguistic operations are translated into visualforms, aphasic children demonstrate comprehen-sion whereas autistic children do not."4 A curiousand interesting finding is that there is a history oflanguage delay in the parents or siblings in aboutone-third of the cases of both aphasic and autisticchildren.90The differential diagnosis of childhood autism

must include consideration of three additional con-ditions. While mental retardation, several organicbrain syndromes, and certain types of seizure dis-orders may be distinguished from childhood au-tism, these three disease categories may also co-exist with childhood autism.

Mental retardationWhen childhood autism was first recognized as

a disease entity, an attempt was made to differen-tiate it from mental retardation.89 Terms such aspseudo-retardation were devised on the assump-tion that the retardation seen in autistic childrenwas only apparent and due to the child's unwill-ingness rather than inability to perform on devel-opmental or intellectual tests.""12 However, greaterclinical experience with autistic children and re-cent follow-up studies have demonstrated that lowscores on developmental tests or "untestability"in the early years of life may be predictive ofretarded functioning later in life.'3"4 Autistic chil-dren not only will not, but actually cannot, per-form many tasks.95 The notion that autistic chil-dren have a primary affective deficiency96 andgood cognitive potential45 has given way to therecognition that the cognitive deficiency in child-hood autism is every bit as real as in mental retar-dation90 97 and that approximately 75 percent ofautistic children can be expected to performthroughout life at a retarded level.98 Mental retar-dation and childhood autism can clearly coexist.99

Organic brain syndromesThe minority of autistic children who are not

retarded usually do not reveal evidence from his-tory or examination of definite central nervoussystem impairment. Of the majority of autisticchildren who are retarded, a number may showpresumptive or definite evidence of organic braindamage or of one of the specific organic brainsyndromes.'00 '0" It should be emphasized thatalthough attempts have been made to link au-tistic behavior with degenerative diseases such asHeller's syndrome,'02 childhood autism does notordinarily follow the clinical course of a degenera-tive organic process.8' Childhood autism does,however, occur in association with the sequelaeof prenatal and perinatal complications,' 03 neonatalconditions associated with brain damage such as ret-trolental fibroplasia,8'" infantile spasms,'6" 18,01104,105cerebral lipidosis,"' and metabolic conditions suchas phenylketonuria,"'63"' Addison's disease,'06 andceliac disease'07"l08 or infectious conditions suchas congenital rubella.87'109 Congenital rubella de-serves special mention in that 8 to 10 percentof the children affected by it may show autisticsymptoms"0 and in a number of classical cases ofchildhood autism the patients have been shown tohave had congenital rubella.'09

Seizure disordersThe alterations in consciousness associated with

seizure disorders must be distinguished from thebehavior of young autistic children. In some youngchildren, momentary posturing and staring maysimulate petit mal epilepsy, and electroencepha-lography is required to rule out a seizure disorder.In other young children, autism and a seizure dis-order may coexist.16"18 Seizure disorders are morelikely to occur as autistic children become older.Twenty-five percent of a well-followed series beganto have seizures between 11 and 19 years of age.Most of these children had normal electroence-phalograms and neurologic assessment earlier inlife.'3'90 Both grand mal18'90 and psychomotor sei-zures have been described in autistic children.104"1

Prenatal and Perinatal FactorsThe maternal age at the time of birth of autistic

children does not differ from that of the generalpopulation.'04"1'2"'13 While an excess of first-bornautistic children in two-child families has beenreported,22"'4 there is no relationship to birth orderwhen families with three or more children aretaken into account. 8,30,3'0412'113 Early reports of

30 APRIL 1973 * 118 * 4

a highly significant excess of male over femaleautistic children (4:1)114 have been confirmed insome studies18'22"113"115"'16 but not in other series,where male to female ratios of 2.8:1,30,112 2.6:1,1031.7: 1,"17 and 1.6:1104 have been reported. Itshould be remembered that equivalent excesses ofmale over female will be found in general childpsychiatric populations.30

Childhood autism does not seem to be asso-ciated with prematurity.'8"104"'12"117"18 There havebeen a number of studies of the incidence of otherprenatal and perinatal complications in childhoodautism. 8"103,"04,"12,"'5"'7"119"120 The findings fromthese several investigations are difficult to comparein that in some investigations siblings of the pa-tients were used as controls,'03"12'119 while in otherstudies non-autistic "handicapped" children,"12normal children'03"'17 or so-called late onset psy-chosis patients'8 were used as controls. While sev-eral of these investigations have found a greaterincidence of prenatal complications in the autisticthan in the control group,' 1803"112"'17 only one studyreported a significant increase in prenatal compli-cations in the autistic children."17 The overall find-ings in respect to perinatal complications weresimilar. Again while several investigations found ahigher incidence of perinatal complications in theautistic children18,'103,112,119 in only one series wasthe increase in perinatal complications in the au-tistic children significantly greater than in the con-trols, and in this study unfortunately the diagnosticcriteria for the patient group were vague and non-specific."19 When all prenatal and perinatal compli-cations were lumped together there is a suggestionfrom four studies that there may be a significantassociation of such complications with childhoodautism.18'103115"20 These findings must be viewedwith caution because of the lack of uniformity ofboth diagnostic criteria for the children and assess-ment of importance of the prenatal and perinatalcomplications. Pollack and Woerner have dis-cussed the methodologic problems in some ofthese studies.'21

Family BackgroundConstitutional and genetic factors

With the exception of two studies," 3"122 neitheran increased incidence of schizophrenia nor a his-tory of childhood autism has been reported in theparents or non-twin siblings of autistic chil-dren.'8'0'2289"'4 Creak and Inil found four prob-ably psychotic siblings in 79 families and twoschizophrenic parents out of 120 studied. Meyers

and Goldfarb'22 found 8 percent of the siblingsand 21 percent of the parents examined to beschizophrenic.

Studies of twins in whom one or both membersof the pair are autistic are of interest for a genetichypothesis for childhood autism. Vaillant reviewedthe literature to 1963 adding two sets of twins,'23and additional cases were considered by Rimlandin 1964.124 The most recent review of the literatureon autistic twins included the cases considered byboth Vaillant and Rimland and critically examinedthe evidence both for monozygosity and the diag-nosis of childhood autism.20 Satisfactory evidencefor both the clinical diagnosis of childhood autismand the criteria for monozygosity was provided foronly four out of 20 reported twin pairs. Of thesefour, one pair of monozygotic twins was con-cordant'25 and one was discordant for childhoodautism.'26 One dizygotic pair was concordant'27and one was discordant.'23 Allowing less stringentrequirements for the clinical descriptions and theevidence for monozygosity, and excluding two twinpairs because of evidence of organic brain impair-ment and three other pairs where the literaturereference was limited to a "personal communica-tion to the author," the remaining 15 of the 20twin pairs cited by Rutter20 break down as follows:Out of ten presumably monozygotic pairs, eightwere concordantl25"128-134 and two discordant'23"126for childhood autism. Of five presumably dizygoticpairs, only one was concordant'27 and four werediscordant for childhood autism."13"123"135"136 It canbe concluded that the available evidence from twinstudies, though in a majority of cases technicallyimperfect, is suggestive of the possibility of a ge-netic determinant in at least some cases of child-hood autism.

It is of interest to note that childhood autismhas been described in diverse racial stocks includ-ing, for example, children in Finnish'37 and Japa-nese'38 populations.

Attempts to find chromosomal abnormalities inautistic children have been unsuccessful.'368"39Studies reporting unusual dermatoglyphic pat-terns'40 and hand morphology'4'- in some psychoticchildren with autistic features have yet to bereplicated.

Family characteristicsSince the first description of autistic children in

1943,3 the parents of the children have come underintense psychiatric scrutiny.'42 The original clinicaldescription of the parents as being persons strongly

CALIFORNIA MEDICINE 31The Western Journal ot Medicine

preoccupied with abstractions, limited in geniuineinterest in people and emotionally cold so thatthe children experience a mechanization of humanrelationships,89 has died hard.50"143-'45 Unconsciousmaternal hostility toward and rejection of the childwho becomes autistic or schizophrenic has alsobeen postulated.'46"47 More balanced appraisalshave described the parents as being unusually "per-plexed" and thus thwarted or ineffective in dealingwith their psychotic child.'48 Such mothers havealso been described as lacking in clarity of com-munication.'49 However, parental perplexity orunclarity may be secondary to the intense andoften insoluble problems of raising a child withthis kind of disturbance. A number of carefulstudies of parental emotional characteristics andchild rearing attitudes have not confirmed asser-tions that the parents of autistic children are eitherunusually cold or aloof or have any other emotionalor personality characteristics which would in anyway predispose the autistic child to his dis-order.'8,90'97"150"'51 Other studies have also indicatedthat the extreme emotional stress of having anautistic child in the family may induce or precipi-tate emotional disorders in some susceptible par-ents"3 and that the professional assumption thatthere must be something wrong with the parentsin order to have such a seriously disturbed childmay also cause iatrogenic emotional disorder inthe parents.'52

Investigations which have utilized psychologicaltest results to demonstrate psychopathogenic per-sonality traits in the parents of autistic children153have frequently failed to consider the emotionalcontext in which the tests are administered. Forexample, in a well-designed study Schopler andLoftin recently showed that out of anxiety parentsof autistic chilren may appear to have a thoughtdisorder on psychological testing if the testing isdone in the context of their relationship with theirpsychotic child but not in the context of theirrelationship with the normal sibling of the psy-chotic child.'54 As accumulating clinical evidencehas indicated that as a group the parents of au-tistic children are emotionally no different thanthe parents of normal or neurotic children, anattempt has been made to sustain the notion thatnevertheless adverse environmental influencesmust have contributed to the development of theautistic symptoms. Thus, while the parents indi-vidually may be accepted as "normal," the possi-bility of family turmoil or some other disturbancein the family dynamics or parent-infant relation-

ship at an early critical period of a child's devel-opment has been invoked.7'8 However, no sufficientevidence has been presented and other studieshave suggested a normal family structure.30

Since the first group of cases was described in1943,3 several references to the unusual intelli-gence of the parents of these children have ap-peared.31,50,112,114 It should be noted, however, thatintelligence may be tied to socio-economic statusand that studies which have found increased in-telligence in the parents of autistic children havealso found the socio-economic status of the par-ents to be skewed toward higher levels.20 Lotter"12found, however, that the intellectual superiorityof the mothers though not of the fathers was inde-pendent of social class and level of education. Tworecent studies 'comparing the verbal intelligenceof both the mothers and fathers of autistic childrenwith that of parents of normal children where bothgroups were matched for socio-economic statusfound no difference in intelligence between thetwo groups.'55" 56 Thus there is now some doubtabout the earlier assertions that the parents ofautistic children are unusually intelligent.

Considerable attention has been given to pos-sible differences in the socio-economic status perse of the families of autistic children. Nine reportssuggesting that autistic children are found in fam-ilies whose socio-economic status is higher thanthat of the general population or of matched con-troIS3,18,22,30,112114, 151,157 were not confirmed bythree studies, one of which studied the distribu-tion of autistic and non-autistic psychotic childrenamong five social classes,'58 one of which com-pared the families of autistic patients with matchednon-autistic patients'59 and one of which com-pared the families of autistic patients withmatched normal controls.'55 The finding that thesocio-economic level of the fathers of autisticchildren is somewhat higher than that of fathersof brain-damaged children but not of the fathersof normal childrenl'5 may very well be due tothe fact that perinatal morbidity is likely to begreater in lower socio-economic levels.

In general it can be said that there is no com-pelling evidence suggesting that there are any sig-nificant or important differences in the parentalcharacteristics or the family structure of the fam-ilies of autistic children. The possibility that thereis an overall increased incidence of autistic chil-dren in families of higher socio-economic statusassociated with higher parental intelligence is in-teresting though of no special clinical relevance

32 APRIL 1973 * 118 * 4

at present. Certainly this reviewer and others"'5have seen autistic children in families of all socio-economic, ocupational, educational, intellectual,religious and racial backgrounds.

Epidemiologic Considerations

The comprehensive epidemiologic study ofchildhood autism by Lotter demonstrated a preva-lence rate of 4.5 autistic children per 10,000 eight-to ten-year-old children resident in the Countyof Middlesex, England.1'; A smaller prevalencerate (0.7 per 10,000) was reported by Treffert(using different epidemiologic techniques andpossibly different diagnostic criteria) in a popu-lation-based survey of three- to eleven-year-oldchildren in Wisconsin. I7 Both figures can be con-sidered minimal since autistic children youngerthan four years old and older than six years oldare often misdiagnosed. At all events, childhoodautism does not seem to be as rare a conditionas is often popularly stated. Lotter pointed outthat, based on his own survey of school-age chil-dren, there were as many educable autistic chil-dren as there were blind children in special schoolsin the surveyed population area.'60 Thus the au-tistic child represents a significant epidemiologicproblem.

Prognosis

In approximately 7 percent'6 to 28 percent98of autistic children who had not been epileptic inearly childhood a seizure disorder develops later.Approximately 75 percent of the autistic childrenare and remain mentally retarded.'7'98 Many ofthese may be "untestable" when seen in the pre-school period95 but repeated developmental test-ing with increasing age has demonstrated that "un-testability" in early childhood is actually a prog-nostic sign of low intellectual functioning in theautistic child.'4 Those autistic children who haveseizures or other indications of organic braindamage tend to be in the more retarded group ofautistic children.98""5 They also tend to be chil-dren whose language function remains severelyundeveloped or impaired. It has long been recog-nized that failure to use language for communica-tion by the age of five years implies a very poorprognosis for further intellectual and personalitydevelopment. 137,27,50,161 Failure to use toys ap-propriately also signifies poor prognosis."6 Thus,the autistic child who is close to his fifth birthday,is not using communicative speech (the speech

may be limited to echolalia), does not play appro-priately with toys, and who appears intellectuallyretarded or is untestable during the course of de-velopmental evaluation has a poor prognosis in-deed and is likely to require lifelong institutionalcare.'62

For the minority of autistic children who aretestable and show relatively normal intellectualfunction on developmental tests and who developcommunicative speech before the age of five years.the outlook is somewhat different. In the majorityof these cases, a clearly defined schizophrenicpsychosis with delusions and hallucinations doesnot develop.98'63 Most of the children, however,do become extremely shy, introverted, passive,withdrawn, and schizoid.3' Although not havingdelusions or hallucinations, some of these childrendo develop severe disturbances of reality testingsuch as is seen in the more covert forms of schizo-phrenia referred to as pseudo-neurotic or border-line states."" 17'24 One series of cases15'33 and sev-eral individual case reports documenting a transi-tion from early infantile autism to a frank schizo-phrenia in late childhood,2 adolescence34 or adult-hood'64 are of interest and suggest that furtherresearch on possible relationships between the twodiagnostic conditions deserves consideration.34 Al-though some of those autistic children who arenot retarded and who do develop useful lan-guage before five years of age are able to live insociety and to obtain employment,'65 it is to beemphasized that they represent a minority of theautistic population seen in early childhood andthat even those children with a relatively goodprognosis will usually have significant residualpersonality and cognitive impairments.'5

Problems in Early Recognition

Several factors have complicated the recognitionand diagnosis of childhood autism in the earlyyears of life. First, pediatricians and practitionersof family medicine have not known what to lookfor since many descriptions of the illness havebeen couched in terms of psychoanalytic ego psy-chology'0 instead of providing clear-cut descrip-tions of behavior. While the former may be usefulin the context of developmental ego psychologyand even in the treatment of selected cases,'66 onlyan accurate description of the specific behaviorswhich constitute the syndrome of childhood autismpermits accurate early diagnosis. The second prob-lem confronting the physician is that many of the

CALIFORNIA MEDICINE 33The Western Journal of Medicine

symptoms of the autistic child are behaviors whichare seen as part of normal development in normalinfants and toddlers.66 This "maturational lag"'has contributed to the serious difficulties in recog-nizing childhood autism during the first and secondyear of life.

In current practice many cases of suspectedchildhood autism are not referred for psychiatricevaluation until the fourth or fifth year becausesymptoms such as toe walking, hand flapping dur-ing states of excitation, hypersensitivity to sensorystimuli and idosyncratic play activities are eitheroverlooked or passed off as immaturity. Until re-cently, psychiatric referral often has not been par-ticularly helpful since many psychiatrists trainedin adult psychiatry, and even many child psychia-trists trained in institutions where the emphasishas been upon the treatment of the older child,have not seen young autistic children.A third problem in early recognition is that

both psychiatrists and other physicians have fo-cussed primarily on the disturbances of relatingseen in autistic children. There has been a failureto appreciate the fact that the disturbances ofrelating represent only a part of the syndrome ofchildhood autism and that at least equal attentionmust be given to both the disturbances of motilityand perception. Both the disturbances of relatingand language may, in fact, not be seen during thefirst two years of life and failure to look forunusual motility patterns and sensory hyper-and hyposensitivities may result in missing thediagnosis.A fourth problem is that childhood autism has

frequently been viewed in an all or nothing con-text. Physicians have not been prepared for thefact that childhood autism may occur with degreesof severity which vary from case to case and thatthe autistic behavior may occur inconsistently inthe individual patient. Thus as with most medicalconditions childhood autism can be seen in verymild or in very severe forms. An autistic childmay have adequate eye to eye contact and maydesire to be held by his mother some of the timeand yet show severe sensory hypersensitivities,hand flapping, whirling and echolalic speech. Anautistic child may spend long hours in stereotypedperseverative play limited primarily to spinningobjects and yet may come when called and berelatively responsive to the parent on occasion.A fifth factor complicating early diagnosis is

that the condition is often so bewildering to theparents that it is often impossible for the mother

of a young child beginning to show autistic symp-toms to articulate her concerns to her pediatricianor family doctor. She often feels guilty or ashamedof her child's behavior and it may be very difficultfor the average mother to acknowledge the factthat her infant does not seem to be dependentupon her or that he has no desire to be with her.The autistic infant's preoccupation with sensorystimuli or his own body movements to the exclu-sion of his interest in his mother or his apparentaversion to being cuddled and loved frequentlyinduces a profound loss of self-esteem in a youngmother. She may then deny as long as possible herconcerns about her infant's deviant developmentand when she does bring the infant to her physi-cian's attention she may articulate these concernsin so guarded and confusing a way as to throwthe physician off the track of accurate diagnosis.In other cases the mother's tendency to deny themore subtle aspects of deviant behavior in herinfant may occur due to her lack of knowledge ofnormal child development.'67 Many young mothersare not aware at what age a baby should firstindicate its desire to be picked up and held, whenan infant should establish and maintain eye con-tact, and when an infant should begin to show adifferential response to the mother or to a stranger.

With these considerations in mind, physiciansresponsible for the care of children during infancymay utilize the following approaches to the problemof deviant development. First, it is extremely im-portant that the physician be thoroughly groundedin a knowledge of normal development in earlychildhood. The usual knowledge of the normalmotor and language milestones must be supple-mented by a thorough understanding of the normalsequence of development of the infant-mother re-lationship and social awareness. Second, as withany medical condition, there must be a high indexof suspicion in the physician's mind. Many caseshave been missed in the early years of life pri-marily because childhood autism has been con-sidered a rare condition and has not been includedin the differential diagnosis.

O nce autism is suspected, it is necessary to bearin mind that the various symptoms of the disordermay only occur intermittently and, therefore, maynot be present on any one examination. Henceit is necessary to spend considerable time withthe young child showing deviant behavior and to

34 APRIL 1973 * 118 * 4

examine him under different conditions. The in-fant must be engaged in social play appropriate tohis age in order to bring out the deviant ways ofrelating characteristic of the autistic child. How-ever, if one sees the child only in circumstancesof active involvement in social interaction withan adult, then the disturbances of motility andresponse to sensory stimuli may be missed. Fre-quently it is only when the autistic child is leftalone that symptoms such as hand flapping, per-severative regarding of hand movements and bi-zarre tactile and visual exploration of the environ-ment become apparent. Presentation of certainsensory stimuli can be helpful. A rapidly spinningchild's top may induce hand flapping and bizarrestates of excitation which would otherwise bemissed on examination. The child should be testedwvith a loud sound capable of illiciting a vigorousstartle response in a normal infant; the failure ofthe autistic child to respond to such a sound withmore than an eyeblink is often impressive. Para-doxically, severe adversive reactions characterizedby withdrawal, agitation or fear can often be eli-cited by vibration of a tuning fork (256 hz.).

It is not only necessary to examine the child onseveral occasions and under several different con-ditions, but it is also necessary that he be in arelaxed but alert state. If the child is sleepy andit is near nap-time, all symptoms of the disordermay be missed. As many young autistic childrenare extremely disturbed and frightened in new orstrange settings, the physician may be confrontedin his office with a screaming child whose greatagitation precludes observation of any other be-havior. It may be necessary to familiarize thechild with the office over a period of time or tosee the child at home.

Examination of the child is only part of thediagnostic process. A thorough history of theprevious development must be obtained. It is mostimportant that the mother be asked the properquestions and that she be asked them in the propercontext. The physician must have a good relation-ship with the parent and must help her to feel thathe is on her side in trying to understand what thereis about her child's behavior that has troubled herand has created difficulties for her. It has beenan unfortunate aspect of both psychiatric and pedi-atric practice to tacitly assume and to unwittinglyconvey to the parent that if a child has an emo-tional or behavioral disturbance, then it mustsomehow be the parent's fault. Such a communi-cation to the parent, whether overt or covert, na-

tuarally increases the parent's difficulty in articu-lating her concerns about the child and increasesher tendency to deny significant behavior disorderin the child.Once the proper relationship with the parent

has been developed, the physician must then takethe initiative in eliciting relevant information-for example, how the child responded to the intro-duction of solid foods, or when he began showingan anticipatory response to being picked up, orresponded actively to pattycake or peek-a-boo.Many mothers will not spontaneously volunteersuch information either because they do not rea-lize that it would be of interest to the physicianin his assessment or because they are not awarethat the child has deviated from the norm.

Finally, the tendency of the physician to adopta "wait and see" attitude when confronted witha problem of deviant behavior in early infancydeserves comment. Many mothers of autistic chil-dren have commented that they were preplexed,confused and disturbed by their infant's behavioras early as the neonatal period. Their attemptsto draw the physician's attention to the child'sdeviant behavior in the early months of life wereessentially rebuffed by the physician's reply that"it is to early to be concerned" or "he'll probablygrow out of it" or "infants vary greatly in theirbehavior." The mothers continue to be worriedwhile the "wait and see" period extends well intothe third or fourth year of life. The physician'stendency to "wait and see" is frequently motivatedby excellent intentions: much unusual behaviorand temporary developmental lags in early infancydo indeed disappear with increasing age and thephysician is reluctant to alarm the mother undulyby expressing his concern or by responding activelyto hers when there is indeed a chance that thedisturbing behavior may "go away." Unfortu-nately, the result of such practice is often toleave the mother with a sense of isolation andalienation. She finds herself alone with her con-cerns and she must come to conclusions of herown device about what is wrong with her child.These are often erroneous and lead her to deny aprogressive developmental problem rather thanreturn to her physician for adequate evaluation.In general, parents are relieved rather than dis-turbed by adequate consultation and diagnosticstudy of their child.

CALIFORNIA MEDICINE 35The Western Journal ot Medicine

Neurologic andElectroencephalographic Examination

Neurologic examination of some autistic chil-dren is unremarkable'68 but "soft" neurologic signssuch as poor muscle tone, poor coordination,clumsiness, hyperactive knee jerks, hypotonia,generalized hyper-reflexia, drooling, short attentionspan, hyperkinesis, hypokinesis, ankle clonus andstrabismus have been reported in 40 to 75 percentof several series.29"3"'7320

Electroencephalographic findings are quite var-iable. Two reports of unusually low voltage EEG'Ssuggestive of hyperarousal'8'64 were not confirmedin two other studies'69"170 when stimulus conditionswere controlled. While some studies have reported50 to 80 percent of the patients to have abnormalEEG's characterized by either focal or diffusedspike, slow wave or paroxysmal spike and wavepatterns,'17'169"7' other studies have reported lessfrequent EEG abnormalities.'1845'120"168 In most ofthese investigations, the ages of the autistic chil-dren have varied widely at the time that the EEG'Swere recorded. In reports of the results, age wasoften not specified and it is quite possible that thehigher percentages of abnormal EEG's are asso-ciated with older patients. This would be com-patible with the increasing incidence of seizureswith increasing age.98 The clinical experience ofthis reviewer with autistic children under five yearsof age suggests that EEG abnormalities in youngautistic children are very rare indeed unless therehave been associated infantile spasms.

Neurophysiologic StudiesBecause of the extreme lack of cooperation of

autistic children, neurophysiologic studies havebeen quite limited in scope and number. Autisticchildren have a normal sleep cycle with nor-mal amounts of rapid eye movement (REM)sleep. 134172"173 However, the rapid eye movementactivity of REM sleep is reduced in autistic chil-dren'74 and is similar to that found in normal in-fants,'7' suggesting a maturational defect.'76 Whilethe transcephalic direct current potential is similarin autistic and normal children, an unusually highpercentage of "DC bursts" are found in six- tothirteen-year-old autistic children and one- to five-year-old normal children.'08 Unfortunately, ade-quate controls for eye movement activity were notreported so that this apparently interesting ma-turational finding may only reflect the tendency ofolder autistic and younger normal children to havemore vertical eye movements. The contingent

negative variation (CNV) is intact in autistic chil-dren when two stimuli are paired together but theautistic children, unlike normal controls, do notshow a differential response to slides of familiarand strange faces.'77 This does not seem to repre-sent a neurophysiologic abnormality, since thebasic ability to establish a CNV iS intact, but ratherreflects the ordinary clinical experience that au-tistic children do not show adequate differentialresponses to strangers and do not participate insocial interaction.178

Studies of auditorily evoked responses duringsleep have revealed only marginal differences be-tween autistic children and controls and have beencharacterized by great variability from subject tosubject.' 79-'8 One study of evoked responses toflashes and clicks in waking autistic children is in-conclusive since no statistical analysis of the datawas presented.'82 An inadequate galvanic skin re-sponse to both auditory and visual stimuli has beendemonstrated in autistic children.'83 This finding isconsistent with the clinical observation that autisticchildren do not show an adequate startle response.It was not possible, however, to replicate thefinding by using change in heart rate as the experi-mental measure.'84 Increased variability in theheart rate has been reported but adequate controlof activity level and stimulus conditions underwhich autistic and normal children were observedwas not documented.'85 Thus the assertion thatevidence was found for brain stem dysfunction issomewhat tenuous. However, other evidence im-plicating a brain stem disturbance has been found.Three separate investigations have demonstrateda consistent suppression of vestibular nystagmusin autistic children.'86-'88 It should be emphasizedthat the suppression of vestibularly induced nys-tagmus has only been demonstrated under con-ditions where visual fixation is possible.'88 Thus atheory of vestibular dysfunction in childhoodautism35 may require modification to take intoaccount a neurophysiologic defect involving thevestibulocerebellar axis since the strong proclivityof autistic children to suppress vestibular nystag-mus through ocular fixation might be explained bythe role of the cerebellar roof nuclei in the sup-pression of nystagmus through fixation.189 Thefinding of primitive neck and labyrinthine rightingresponses in eight- to twelve-year-old schizo-phrenic children is also suggestive of vestibulo-cerebellar dysfunction.'"" However, a history ofearly autistic development was not documentedfor the children in the latter study.

36 APRIL 1973 * 118 * 4

Metabolic, Biochemical andHematologic Studies

Indoleamine metabolism has received consid-erable attention in studies of autistic children. Theresults, while of a preliminary and often incon-sistent nature, suggest that this field of investiga-tion requires further serious study. One report ofdecreased urinary excretion of 5-hydroxyindolea-cetic acid in response to a tryptophan load'9' wasnot replicated in a later study.'92 Heeley and Rob-erts studied the ratio of urinary 3-hydroxy-kynure-nine to 3-hydroxyanthranilic acid in response totryptophan load and reported results suggestingdecreased availability of pyridoxine.'93 Sankar etal'94 reported an excessive amount of indolic sub-stances in the urine of five- to sixteen-year-oldhospitalized schizophrenic children. However, notenough clinical information is provided to deter-mine whether these children would be consideredautistic as described in this review. In contrast toSankar's findings, Jorgensen et al found a signifi-cant reduction in urinary excretion of tryptophanin three- to six-year-old psychotic children.'95Bufotenin (N,N-dimethylserotonin) has beenfound in the urine of some but not all autisticchildren.'96

Another group of studies has focused on theamount of serotonin in the peripheral blood andits relation to blood platelets. Schain and Freed-man found that 25 percent of a group of 23 chil-dren diagnosed as autistic had elevated bloodserotonin levels.'97 Ritvo et all98 found a signifi-cantly greater amount of whole blood serotonin infive autistic children 36 to 47 months of age thanin seven age-matched normals; there were no sig-nificant differences between older autistic childrenand age-matched controls. The platelet countshowed a slight decrease in normal children be-tween two and eight years of age while it increasedin autistic children through that age range, but thedifferences did not reach significance.'98 Therewere no differences in circadian rhythmicity foreither blood serotonin or platelets which mightinfluence these results.'99 Prolonged administra-tion of L-dopa decreased the blood serotonin con-centration in three out of four autistic childrenand there was a tendency toward an associatedincrease in platelet counts. However, there was nocorresponding change in the clinical course of thedisorder200 or in the sleep patterns of the chil-dren.20' Chronic oral ingestion of the serotoninprecursor 5-hydroxytryptophan had no effect on

behavior in two autistic children and caused someincrease in REM sleep time and also in the rapideye movements in REM sleep,202 an effect that alsooccurs in normal persons.203A related group of investigations has been con-

cerned with the concentration of serotonin withinblood platelets. Sankar et al found that the uptakeof serotonin by platelets was less in schizophrenicchildren than in control hospitalized children.'94Boullin et al204'205 reported an increased efflux ofserotonin from the platelets of autistic children.The same group did not find any unusual differ-ences in uptake or loss of dopamine from plateletsof autistic children.206A number of other miscellaneous studies have

been made. The plasma cortisol level, eosinophilecount, and histamine wheal test are not remark-able in autistic children.'08 Plasma and erythro-cyte cholinesterase activity,207 and serum mag-nesium,208 copper ceruloplasmin and ascorbic acidlevels209 are within normal limits. Baseline freefatty acid levels and the plasma free fatty acidresponse to glucose ingestion are within normallimits except for increased variability in the base-line plasma free fatty acid level210 which may beassociated with greater variability of daily caloricintake.21' In one study, both plasma and red bloodcell inorganic phosphate were reported to be ele-vated.212 One report of pituitary hypofunction (re-duced secretion of gonadotropins, ACTH and TSH)in children with the onset of illness in the firstthree years and behavior suggesting autistic devel-opment deserves an attempt at replication.213 Inone study of peripheral blood smears in schizo-phrenic children, an atypical leukocyte patternwas described.214 The types of abnormalities re-ported were similar to those associated with anti-body production or with response to viral infec-tions and allergic sensitivity and could not be dis-tinguished from those found in blood smears ofchildren with colds or asthma. The results maytherefore merely reflect an increased susceptibilityof schizophrenic children to infectious disorders.Studies from one laboratory reporting a serumfactor which increases the susceptibility of miceto seizures215'216 deserve further investigation inview of the increased incidence of seizures inautistic children.'3""

TreatmentAt the beginning of any discussion of the treat-

ment of autistic children it should be emphasizedthat there is no specific treatment for this disorder

CALIFORNIA MEDICINE 37The Western Journal of Medicine

and that in spite of strong claims by partisans ofparticular treatment approaches and a tremendousamount of dedicated effort which has gone intothese approaches, no single treatment has stoodthe test of time.217 The many different approacheswhich have been attempted have included familytherapy, psychotherapy and counseling for theparents of the autistic child, psychotherapy forthe autistic child himself, behavior modification,speech therapy, various forms of special education,the day treatment center approach, residentialtreatment, medication with a number of differentpsychotropic drugs, vitamins, electroconvulsivetherapy, sensory stimulation, and sensory isolation.

Since autistic children vary greatly in their in-tellectual capacity, use and understanding ofspeech, general developmental level, age at timeof treatment, level of personality development,general severity of the illness, and family circum-stances, it is not surprising that some of the abovetreatment approaches have been helpful in certaincases of childhood autism but not in others.27218The response to treatment is determined primarilyby the degree of impairment and only secondarilyby the type of treatment in the individual case.'1"At best, any one of the various types of treatmenthas been able to ameliorate but usually not elim-inate certain specific symptoms or deficits in someautistic children; the children, though improvedin a specific respect remain definitely autistic.'62

The best approach to treatment is a flexible onethat can be constantly adapted to the changes indevelopmental level, symptoms and capacity tocommunicate and learn which take place over aperiod of years.219 The parents and the patientsboth benefit most from an approach that provideslong-term management and guidance220 and recog-nizes that spontaneous improvements and regres-sions are likely to outweigh the influence of themost optimistically presented treatment plan.'7

With these reservations, some of the approachesto treatment will be discussed.

Therapeutic work with the parentsAttempts to treat the autistic child through

either treatment of his parents'45 or isolation fromhis parents146 were based on hypotheses that child-hood autism was entirely of psychogenic causa-tion, the ultimate cause being the psychopathologyof the parents. Such notions are no longer acceptedby the majority of serious investigators of this ill-ness and are now only of historical interest. How-ever, they should serve as a warning of the ease

with which the parents of ill children can bescapegoated by well-meaning professionals."12 Asthe psychogenic hypothesis of causation has givenway to mounting evidence that childhood autismis an innate condition with which the child is bornand involves some yet poorly understood centralnervous system dysfunction which interferes withthe child's capacity to correctly perceive his en-vironment, attempts to engage the parents in psy-chotherapeutic work have given way to morehelpful parental counseling.220 Such counseling isuseful when directed both at the very difficultmanagement problems presented by the autisticchild and at helping the parents with the guilt andloss of self-esteem engendered by having a childwho does not participate in ordinary parent-childrelationships.221'222 Earlier attempts to view andtreat the parent as the cause of the child's ill-ness7"45' 223.224 have given way to modern treatmentapproaches which have actually found the parent,when given proper counseling and support, to bea major asset in the treatment and managementof the autistic child.221'225'226

PsychotherapyConsiderable attention has been given to indi-

vidual psychotherapy with the autistic child.6'7"138'218,224.227.-230 With the passage of time such effortshave become confined to isolated treatment cen-ters166 due to the fact that either extravagantclaims that psychotherapy is the treatment ofchoice for all such children or that it is com-pletely useless have been made. The commonerror made by both those who have advocated andthose who have disparaged the effectiveness ofpsychotherapy for these children is that they havefailed to emphasize the important and strikingclinical differences between one autistic child andanother and the effect that these differences haveupon the outcome of psychotherapy. For example,a study purporting to demonstrate that operantconditioning is more effective than play therapywas carried out on a group of autistic childrensuffering from profound developmental retarda-tion.23' Naturally, expressive play therapy wouldbe doomed to failure in such a group. Likewise,extravagant claims that psychoanalytically basedpsychotherapy could be effective with the pro-foundly retarded type of autistic child have beenuniversally disappointing.

There is, however, a minority of autistic chil-dren who develop communicative speech relativelyearly in life and who do not suffer from a profound

38 APRIL 1973 * 118 * 4

developmental arrest. These children do developan organized and complex personality structureand have an active fantasy life; they have a psychicstructure which can be treated effectively by psy-chonalytically or dynamically oriented psycho-therapy.232 Even with this particular type of au-tistic child there must be modifications of classicaldynamic expressive psychotherapy.228 For exam-ple, it has been shown that these children requirea great amount of structure, predictability andlimits in the treatment situation as they do in theirlife in general and that the effectiveness of treat-ment depends in part upon the clarity of the struc-ture provided.233

In general, it is important to evaluate the de-gree of retardation, current developmental level,and availability or unavailability of speech forcommunication before recommending the treat-ment of choice for any particular autistic child.In some cases the treatment of choice is clearlypsychotherapy. It should be emphasized, however,that this form of treatment is useful in only a mi-nority of cases and may improve the child's abilityto relate while laying bare his basic cognitive andlanguage deficits.234

Behavior modificationPartly because psychotherapy can be applied

to only a small minority of autistic children, therehave been numerous attempts at using behaviormodification as a treatment. Behavior modificationutilizes operant conditioning techniques with eitherpositive (food, praise) or negative (pain, punish-ment) 235'236 reinforcement. While both greater231'237-242 and lesser degrees243'244 of success in carry-ing out this type of treatment have been claimed,the data from most of the studies indicate thatany positive response to treatment is limited tothe period of time during which the treatment ismaintained and does not generalize readily beyondthe specific experimental conditions44'218'245-247 un-less the treated child has already shown greaterpromise before the beginning of the treatment.A recent follow-up study by the group most

highly identified with behavior modification ofautistic children248 actually shows that relativelyminor changes in autistic self-stimulatory be-haviors and echolalic speech occurred during thecourse of therapy and that while there were in-creases in appropriate verbal behavior, socialbehavior and play, the best performance in theseareas was at such a low level that the childrenwould still be considered severely autistic by any

clinical standards. Furthermore, on long termfollow-up examination it was found that thosegains made during the treatment were not wellsustained. It has also been demonstrated that be-havior modification can reveal the very limitedcapacity to respond in an adaptive and appro-priate way even when the conditioning inducesa high degree of motivation in autistic chil-dren. 243,249As with psychotherapy, behavior modification

is appropriate for those autistic children withspecific symptoms at a specific developmentallevel. In certain cases it can make an unman-ageable autistic child more manageable250-253 andhas been used to reduce the amount of self-de-structive behavior in certain individual autisticchildren. 133,235,236,254 It must be emphasized, how-ever, that behavior modification is in no sense atreatment of the child's autism but is merely a wayof reducing temporarily the amount of certain un-desirable behaviors. The conditioning proceduresinvolved in behavior modification can make anautistic child more manageable, and at times this isa worthwhile goal. However, it must be emphasizedthat the more manageable child is no less autistic.

Speech therapyConsidering the severe deficit in the acquisition

of useful speech in most autistic children, the pos-sibilities of speech therapy have received scantattention.20 Most clinicians working with autisticchildren agree, however, that while some autisticchildren may have a primary language prob-lem,90'255 the failure or delay in speech acquisi-tion cannot be treated as an isolated deficit.222Attempts to develop useful speech through tech-niques of operant conditioning have often beenunrewarding. Even though the child may be con-ditioned to emit words in response to reward, thisprocedure only occasionally facilitates the use ofspeech for communication in these children.222Other workers are attempting to develop treat-ment plans which do emphasize meaningful com-municative speech; "speech therapy," therefore,is practiced in the context of a total assessment ofthe child's perceptual,256 communicative and cog-nitive,52'257 and developmental handicaps.258'259

The therapeutic milieu and special education

Special education, often referred to as milieutherapy, is perhaps the most widely practiced ap-proach to the treatment of autistic children. Theparticular procedures and treatment philosophies

CALIFORNIA MEDICINE 39The Western Journal of Medicine

vary from center to center260 and generally tendto draw upon techniques used in psychotherapy,behavior modification244'246'252'261 and speech ther-apy262 with autistic children. Many centers for thespecial education of autistic children add parentcounseling to comprehensive treatment programsand may involve the parents directly in the treat-ment of their children. Thus the milieu therapy orspecial education approach tends to be eclecticand pragmatic.The advantages of this approach are that it does

not attempt to fit all autistic children into theProcrustean bed of one or another particulartreatment approach. Rather the emphasis in spe-cial education has been to recognize the pro-nounced inter-individual variability of autisticchildren and to adapt a particular educational andtherapeutic program to the needs of the individualautistic child.263 One important aspect of variabil-ity within groups of autistic children is intellectualpotential.264 Even in those settings with the mostintensive treatment programs, autistic childrenwith very low intelligence quotient do not dowell.244264 However, special education does im-prove those autistic children with higher IQ's.98'264Hence a most important aspect of the initial as-sessment of an autistic child is that of his devel-opmental level at the time of assessment.

Special education programs for autistic chil-dren may be carried out in schools,252 in day treat-ment centers265'266 or in residential treatment set-tings.267 There is no evidence that residential treat-ment which involves separation of the child fromhis parents and family is any more effective thanday treatment approaches which are less expensiveand may produce better results.234 However, thereis a need for both types of programs; the decisionto place the child in residential treatment as op-posed to day treatment requires detailed consid-eration of the needs of the individual autistic childand his family. For example, if the child's difficultbehavior is causing a depression in the mother sosevere that she is unable to function well withthe child or with his normal siblings, then it mightbe well that he be treated out of the home situa-tion. If the child's self-destructive behavior is tax-ing the family's endurance then he might betterbe treated in a residential setting. On the otherhand, if the parents are coping well with theirautistic child's deviant behavior or if during thecourse of the diagnostic evaluation they show thecapacity to respond effectively to counseling di-rected at better management of the child, then

there is no reason to remove him from thehome.268'269 Adequate and complete assessment ofthe results of the special education approach tothe treatment of autistic children is yet to be com-pleted but several studies are in progress and someof the preliminary findings suggest that, while farfrom being a treatment of choice, special educa-tion is worthy of trial.260The special education of the autistic child can-

not be separated from the severe problems thesechildren have in relating both to their peers inwhose company they must learn and to theirteachers who would educate them. Thus effectivespecial education depends upon corrective sociali-zation, a process which is carried out both in daytreatment centers and in residential treatment. Asensitive and understandable account of correctivesocialization in a residential setting can be foundin the work of Goldfarb and his colleagues.267

Medication

Almost every conceivable psychotropic medica-tion has been used with autistic children. Theclasses of medication have included sedatives, anti-histamines, stimulants, major and minor tranquil-izers, anti-depressants, psychomimetics and anti-Parkinsonism drugs.As with psychotherapy, behavior modification,

special education and speech therapy, no singlemedication or class of medication has made au-tistic children any less autistic. Nor has any medi-cation or class of medication proven successful inremoving any particular symptom of the autisticsyndrome. Some drugs, however, have shownpromise in ameliorating or partially controllingnonspecific behavior complicating the autistic de-velopmental process. In particular some autisticchildren tend to be hyperactive, intractably rest-less, irritable, and over-responsive to all forms ofenvironmental stimuli. In these cases and also withthe sleep disturbances that sometimes complicatethe management of these children, some of themajor tranquilizers can be of help.270 Other autisticchildren are characterized by a torporous lethargyand underactivity, and a few attempts at treatmentwith psychoactivating drugs have been reported.Before considering individual drugs, it should benoted that, just as with psychotherapy or behaviormodification, the less impaired children respondbest to drug therapy.27'

The use of barbiturates for sedation in autisticchildren is generally not advisable. As is often truein young children in general, the barbiturates tend

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to have a paradoxical stimulating effect. The anti-histamine diphenhydramine often provides a moreeffective sedation. The minor tranquilizers deanol,hydroxyzine and meprobamate have been triedextensively with autistic children and generally areof little value. The phenothiazines prochlorpera-zine,2 chlorpromazine,270 and (in my personalexperience) thioridazine can be useful in control-ling excessive degrees of agitation and irritability.Reserpine has also been used for tranquilization132but offers no advantage over the phenothiazines.

For the withdrawn anergic type of autistic child,neither methylphenidate nor amphetamine deriva-tives have proved useful (personal experience).The piperazine phenothiazine, trifluoperazine, hasbeen reported to reduce withdrawal and affectiveblunting and to increase motor initiative in somevery young mute, retarded and anergic autisticchildren.271 The butyrophenone derivative triflu-peridol,273 the thioxanthene derivative thiothix-ene,274 a member of a class of drugs with actionssimilar to the piperazine type of phenothiazines,and the indol derivative molindone275 have all beenreported to have a similar combination of anti-psychotic and "stimulant" effects. It should beemphasized that none of these medications hasbeen shown to have any lasting effect and that atbest they take the edge off difficult behavior whenused as an adjunct to attempts at corrective so-cialization and special education.A number of other drugs have been tried. The

tricyclic anti-depressants imipramine276 and nor-triptyline277 do not appear to be useful. L-dopa,which reduces the tremor in Parkinson's disease,has no effect on the motility disturbances nor onthe general clinical course of childhood autism.200The behavior of autistic children is not affectedby 5-hydroxytryptophan, a serotonin precursor.202Methysergide is a methylated derivative of LSD,which is used in the prophylactic treatment ofmigraine headaches. Its effect on 11 very youngretarded schizophrenic children was a complexmixture of stimulation, disorganization and seda-tion; the sum total of drug effect could be con-sidered therapeutic in only two cases.278 Curiously,the psychotomimetic drug LSD-25 has also beenused to treat autistic children.279 Two reports sug-gesting that the drug increased social responsive-ness280,281 contrast with one study which empha-sized the rapid mood swings from elation todepression, the anxiety, the flattening of affect andthe auditory and visual hallucinations and de-creased alertness which were induced in most of

the children.282 A recently completed study indi-cates that while positive changes in affect occur,they are of a highly variable and transient natureand are accompanied by diminished responsive-ness.283 The evidence to date throws doubt onthe usefulness of this psychotomimetic agent as atherapeutic adjunct in the treatment of childhoodautism.

Recent claims that high dosages of single ormultiple vitamins-so-called megavitamin therapy-have a therapeutic effect on autistic childrendeserve special mention. As of the time of thiswriting it must be emphatically stated that no sci-entifically conducted, adequately controlled studiesof the effect of multiple vitamins or any single vita-min have appeared which have in any way sup-ported the claims of therapeutic effectiveness ofmedication of this type. The only well controlledscientific study yet published in this general areademonstrated that niacinamide had no therapueticeffect in a group of children four to twelve yearsold with the symptoms of childhood autism.284

Other treatment attemptsFinally, several miscellaneous treatment at-

tempts deserve mention if only to point out howthe intractability of this illness has driven cliniciansto extremes of therapeutic ingenuity and tenacity.Perhaps influenced by the severe sensory hyper-sensitivities and hyposensitivities of the autisticchild, experimental approaches to treatment havebeen based on both sensory stimulation in theform of intense human contact,79 vestibular andproprioceptive play285 or bodily contact and mas-sage,286'287 and sensory isolation.288 The thera-peutic effect of these divergent treatment attemptshas been minimal considering the great invest-ment of treatment time and effort involved, andsufficient replication has not yet been done. Fi-nally, it should be mentioned that electroconvul-sive therapy has been attempted289 without signi-cant or lasting benefit.20

Theoretical ConsiderationsChildhood autism is characterized by a pro-

found failure of sensorimotor integration66 com-plicated by serious disturbances of language andcognition90 and human relationships. This disorderhas its onset early in the first three years of life'and usually results in lifelong crippling distor-tions of the personality and intellectual develop-ment.'5'98"163 Earlier descriptions of this child-hood illness stressed the disturbances of relating,3

CALIFORNIA MEDICINE 41The Western Journal of Medicine

whereas accumulating clinical evidence has em-phasized the importance of the motor,'1,12 per-ceptual,344749290 and cognitive and languageimpairments.9029' The unique defect of sensori-motor integration found in this behavioral syn-drome is characterized by a faulty modulation ofsensory input and motor output.35 The former ismanifest in both hypo- and hypersensitivity tosensory stimuli and the latter in a number of bi-zarre motility patterns. These patterns are charac-terized by both brief states of catatonic inhibitionand by repetitive stereotyped motor patterns thatoften occur as part of general states of excitationinduced by internal and external sensory stimuli.While many of these strange motor acts appearto provide the child with a considerable measureof self-stimulation,68"9'2 the impaired ability ofautistic children to use sensory input to makeperceptual discriminations in the absence of feed-back from their own motor responses47 suggeststhat the bizarre and repetitive motor output mayactually be a compensatory activity which helpsthe autistic child to make sense out of sensation.Some clinical studies have stressed the primacyof the sensorimotor dysfunction66 while othershave focused on the language impairment andcognitive aspects of the disorder.90'97 It should benoted, however, that the onset of the disorder mayoccur at birth and that the earliest symptomsnecessarily reflect deviant responses to sensorystimuli and deviant motility at a time when thecognitive and language impairments have not yetbecome manifest.'

The cause of this illness is unknown.97 How-ever, since so many of the symptoms representdistortions or lags in the normal maturational se-quence,' an impairment in the basic mechanismscontrolling the timing and sequencing of the de-veloping control of motor output in relation tosensory input is implied.66'293 There is meager evi-dence (from twin studies) that in some cases thisdisturbed maturational mechanism may be on anhereditary or an early congenital basis but manycases are associated with other conditions repre-senting a variety of insults to central nervous sys-tem function. In all events, childhood autism isclearly a behavioral and emotional disorder basedon some type of organic brain impairment and isnot of psychogenic origin."

This is not to say, however, that treatment di-rected at improving the capacity of the child tofunction emotionally in a human environment can-not be helpful both to the child and his family.

Such an approach is not specific and should beconsidered only as one of several possible modesof treatment. There is in fact no specific treatmentand it is of the greatest importance that treatmentplanning be directed at the specific deficits andthe developmental limitations of the individualcase. Particular attention should be given to thechild's capacity to use language and to the child'sactual intellectual potential. Repeated develop-mental examinations over a period of time areoften helpful in establishing the child's true basalintelligence.

Finally, the relationship of childhood autism toadult psychiatric disorders deserves considera-tion.'} Childhood autism is the earliest develop-mental manifestation of psychosis, and a numberof students of this disorder have used the terminfantile or childhood psychosis as an appropriateepithet for this condition-""16'18"22 Assertions thatchildhood autism may also be the earliest mani-festation of schizophrenia"'45'89 are not incom-patible with the recognition that childhood autismis phenomnenologically distinct from schizophreniaof later childhood and adult life. 18"63'294 Althoughthe phenomenologic features of infantile autismand of schizophrenia are distinct, symptoms sug-gesting underlying perceptual disturbances in re-lation to motility in both conditions34"3566 andreports indicating the possibility of progressionfrom an early infantile autism to a later schizo-phrenia32'33"164 suggest the importance of furtherresearch on this aspect.

ACKNOWLEDGEMENTS

The preparation of this review was facilitated by thesupport given by The Benevolent Foundation of ScottishRite Freemasonry, Northern Jurisdiction, U.S.A., to theauthor's research program on childhood autism.

Mrs. Bernice Heyert and Mrs. Harriet Striker pro-vided invaluable assistance in assembling the references.

REFERENCES

This review of childhood autism is neither exhaustivenor complete. An annotated bibliography covering theliterature on early childhood psychosis between 1964 and1969 contains over 400 references.' The comprehensivereview of childhood schizophrenia and allied conditionsby Ekstein and his colleagues" covers the literature from1946 through 1956 and contains over 500 bibliographiccitations. In addition to the constraint imposed by thesheer magnitude of the literature, the following limita-tions have been placed on this review. An attempt hasbeen made to reduce the redundancy that necessarilyaccrues from multiple and repeated presentation of thesame work of a given author, research laboratory ortreatment center by limiting citations to those whicheither represent unique findings or hypotheses or elsecomprehensive reviews of a particular investigator's

42 APRIL 1973 * 118 * 4

earlier work. An attempt has also been made to limitthe citations to those in which the authors are dealingwith childhood autism in the sense that this behavioralsyndrome has been defined and described in this review.A brief perusal of the bibliography will quickly demon-strate that perhaps more of the titles refer to "childhoodschizophrenia," "childhood psychosis" or "infantile psy-chosis" than to childhood or infantile autism. The prob-lems of terminology have been considered in the bodyof this review. Articles could not simply be omitted onthe basis of the terminology employed without omittingvaluable material that is actually pertinent to the subjectof childhood autism. Unfortunately many authors havefailed to give a complete description of their patients.Therefore an attempt was made to include those articlesin which those who wrote them indicated in one of thefollowing ways that the subject matter related to autisticchildren: (1) a sufficient description of the patients wasgiven to indicate that a reasonable amount of autisticsymptoms was present; (2) the onset of the psychoticillness occurred before the child was five years of ageand there was some indication that autistic symptoms ordeviant development were present before three years ofage; or (3) the literature references cited indicated thatthe authors were cognizant of the clinical syndrome ofchildhood autism. In a few instances where these criteriawere not met but the article nevertheless merited inclu-sion, a relevant qualification was made in the text.The reader's attention is called to several earlier re-

views. An older, very comprehensive review written froma psychoanalytic and psychodynamic point of view byEkstein and his colleagues" is very useful. A more recentand shorter review by Reiser' also emphasizes the psycho-analytic and psychodynamic point of view. An excellentreview by Rutteri0 and a recent review by Hingtgen andBryson297 deal with all aspects of childhood autism froma more descriptive phenomenologic and pragmatic pointof view. Rutter has provided shorter reviews of researcheand follow-up studies.9" Two reviews limited to thera-peutic considerations are also helpful.2"8'247Two symposia on childhood autism, one held in In-

diana in 1968008 and the other in London in 1970 dealwith diagnostic, etiologic, phenomenologic and treatmentaspects of childhood autism. Several books on childhoodautism also merit the reader's attention. The book editedby Wing300 provides useful information on the clinical,educational and social aspects of childhood autism. Themonograph by O'Gorman30" provides helpful clinical ma-terial. Hermelin and O'Connor47 have written an excellentbook summarizing their own psychologic research as wellas the general field of psychological experimentation withautistic children. Goldfarb's monograph on childhoodschizophrenia is a sensitive clinical study of childrenwho are essentially autistic and is also a good introduc-tion to the earlier literature concerning the relativeimportance of organic and psychogenic factors.A recent thoughtful and sensitive book by Dr. Lorna

Wing302 has been written specifically as a guide to parentsof autistic children; it will also be of considerable use tophysicians and other professionals concerned with themanagement of autistic children.

1. Bender L, Freedman AM: A study of the first three years inthe maturation of schizophrenic children Q J Child Behav 4:245-272, 1952

2. Ornitz EM, Ritvo ER: Perceptual inconstancy in early infan-tile autism. Arch Gen Psychiat 18:76-98, 1968

3. Kanner L: Autistic disturbances of affective contact. NervChild 2:217-250, 1943

4. Kanner L: Early infantile autism. J Pediatr 25:211-217, 19445. Putnam MC, Rank B, Pavenstedt E, et al: Case study of an

atypical two-and-a-half year old. Amer J Orthopsychiat 18:1-30,1948

6. Rank B: Adaptation of the psychoanalytic technique for thetreatment of young children with atypical development. Amer JOrthopsychiat 19:130-139, 1949

7. Rank B: Intensive study and treatment of preschool childrenwho show marked personality deviations, or 'atypical development,'and their parents. In Caplan G (Ed): Emotional Problems of EarlyChildhood, New York, Basic Books, 1955

8. Reiser DE: Psychosis of infancy and early childhood asmanifested by children with atypical development. N Engl J ied269:790-798, 844-850, 1963

9. Mahler MS: On child psychosis and schizophrenia: autisticand symbiotic infantile psychosis. Psychoanal Study Child 7:286-305, 1952

10. Mahler MS: On early infantile psychosis. The symbiotic andautistic syndromes. J Am Acad Child Psychiat 4:554-568, 1965

11. Bender L: Schizophrenia in childhood-its recognition, de-scription and treatment. Am J Orthopsychiat 26:499-506, 1956

12. Bender L: Childhood schizophrenia. Clinical study of onehundred schizophrenic children. AM J Orthopsychiat 17:40-56, 1947

13. Rutter M, Greenfeld D, Lockyer L: A five- to fifteen-yearfollow-up study of infantile psychosis-II. Social and behavioraloutcome. Br J Psychiat 113:1183-1200, 1967

14. Lockyer L, Rutter M: A five- to fifteen-year follow-up studyof infantile psychosis-III. Psychological aspects. Br J Psychiat115:865-882, 1969

15. Brown JL: Adolescent development of children with infantilepsychosis. Semin Psychiat 1:79-89, 1969

16. Creak EM: Childhood psychosis. Br J Psychiat 109:84-89,1963

17. Havelkova M: Follow-up study of 71 children diagnosed aspsychotic in preschool age. Am J Orthopsychiat 38:846-857, 1968

18. Kolvin I, Ounsted C, Humphrey M, McNay A, RichardsonLM, Garside RF, Kidd JSH, Roth M: Six studies in the childhoodpsychoses. Br J Psychiat 118:381-419, 1971

19. Kolvin I: Psychoses in childhood-A comparative study. InRutter M (Ed): Infantile Autism-Concepts, Characteristics andTreatment, London, 1971

20. Rutter M: Psychotic disorders in early childhood. In CoppenAJ, Walk A (Eds): Recent Developments in Schizophrenia-Asymposium. RMPA, London, 1967, pp 133-158

21. Rutter M: The influence of organic and emotional factorson the origins, nature and outcome of childhood psychosis. DevMed Child Neurol 7:518-528, 1965

22. Rutter M, Lockyer L: A five- to fifteen-year follow-up studyof infantile psychosis-I. Description of sample. Br J Psychiat113:1169-1182, 1967

23. Alderton HR: A review of schizophrenia in childhood. CanPsychiat 11:276-285, 1966

24: Bender L, Freedman A, Grugett AE Jr, Helme W: Schizo-phrenia in childhood: a confirmation of the diagnosis. Trans AmNeurol Assoc 77:67-73, 1952

25. Creak M: Schizophrenic syndrome in childhood-Progressreport of a working party. Cerbr Palsy Bull 3:501-503, 1961

26. DeMyer MK, Churchill DW, Pontius W, Gilkey KM: Acomparison of five diagnostic systems for childhood schizophreniaand infantile autism. J Autism Child Schizo 1:175-189, 1971

27. Fish B, Shapiro T, Campbell M, Wile R: A classification ofschizophrenic children under five years. Am J Psychiat 124:109-117,1968

28. Goldfarb W: Self-awareness in schizophrenic children. ArchGen Psychiat 8:47-60, 1963

29. Goldfarb W: Childhood schizophrenia. Harvard Univ Press,1961

30. Lowe LH: Families of children with early childhood schizo-phrenia. Arch Gen Psychiat 14:26-30, 1966

31. Wing JK: Diagnosis, epidemiology, aetiology. In Wing JK(Ed): Early Childhood Autism, Oxford, Pergamon Press, 1966,pp 3-49

32. Bender L: Alpha and omega of childhood schizophrenia.J Autism Child Schizo 1:115-118, 1971

33. Brown JL, Reiser DE: Follow-up study of preschool childrenof atypical development (infantile psychosis)-Later personalitypatterns in adaptation to maturational stress. Am J Orthopsychiat33:336-338, 1963

34. Omitz EM: Disorders of perception common to early in-fantile autism and schizophrenia. Compr Psychiat 10:259-274, 1969

35. Ornitz EM: Vestibular dysfunction in schizophrenia andchildhood autism. Compr Psychiat 11:159-173, 1970

36. Fish B: Longitudinal observations of biological deviationsin a schizophrenic infant. Am J Psychiat 116:25-31, 1959

37. Ritvo S, Provence S: Form perception and imitation in someautistic children: Diagnostic findings and their contextual interpre-tation. Psychoanal Study Child 8:155-161, 1953

38. Colbert E, Koegler R: Toe walking in childhood schizo-phrenia. J Pediatr 53:219-220, 1958

39. Green AH: Self-mutilation in schizophrenic children. ArchGen Psychiat 17:234-244, 1967

40. DeMyer MK, Mann NA, Tilton JR, et al: Toy-play behaviorand use of body by autistic and normal children as reported bymothers. Psychol Rep 21:973-981, 1967

41. Davis BJ: A clinical method of appraisal of the languageand learning behavior of young autistic children. J Commun Dis1:277-296, 1967

CALIFORNIA MEDICINE 43The Western Journal of Medicine

42. Hutt C, Ounsted C: The biological significance of gazeaversion with particular reference to the syndrome of infantileautism. Behav Sci 11:346-356, 1966

43. Wolff S, Chess S: A behavioral study of schizophrenicchildren. Acta Psychiat Scand 40:438-466, 1964

44. McConnell OL: Control of eye contact in an autistic child.J Child Psychiat 8:249-255, 1967

45. Kanner L, Lesser LI: Early infantile autism. Pediatr ClinNorth Am 5:711-730, 1958

46. Wolf EG, Wenar C, Ruttenberg BA: A comparison of per-sonality variables in autistic and mentally retarded children. JAutism Child Schizo 2:92-108, 1972

47. Hermelin B, O'Connor N: Psychological Experiments withAutistic Children. Oxford, Pergamon Press, 1970

48. Churchill DW: Looking and approach behavior of psychoticand normal children as a function of adult attention or preoccu-pation. Compr Psychiat 13:171-177, 1972

49. Reichler RJ, Schopler E: Observations on the nature ofhuman relatedness. J Autism Child Schizo 1:283-296, 1971

50. Eisenberg L, Kanner L: Early infantile autism. 1943-1955.Am J Orthopsychiat 26:556-566, 1956

51. Frith U: Cognitive mechanisms in autism-Experiments withcolor and tone sequence production. J Autism Child Schizo2:160-173, 1972

52. Frith U: Spontaneous patterns produced by autistic, normaland subnormal children. In Rutter M (Ed): Infantile Autism-Concepts, Characteristics and Treatment. London, 1971, pp 113-133

53. Shapiro T, Fish B, Ginsberg GL: The speech of a schizo-phrenic child from two to six. Am J Psychiat 128:92-98, 1972

54. Cunningham DA, Dixon C: A study of the language of anautistic child. J Child Psychol Psychiat 2:193-202, 1961

55. Wolff S, Chess S: An analysis of the language of fourteenschizophrenic children. J Child Psychol Psychiat 6:29-41, 1965

56. Ekstein R: On the acquisition of speech in the autistic child.Reiss-Davis Clin Bull 1:63-80, 1964

57. Wing L: The syndrome of early childhood autism. Br JHosp Med 381-392, Sept 1970

58. Greenbaum GHC: An evaluation of niacinamide in thetreatment of childhood schizophrenia. Am J Psychiat 127:129-132,1970

59. Shapiro T, Roberts A, Fish B: Imitation and echoing inyoung schizophrenic children. J Am Acad Child Psychiat 9:548-567,1970

60. Cunningham MA: A five-year study of the language of anautistic child. J Child Psychol Psychiat 7:143-154, 1966

61.. Fish B: Involvement of the central nervous system in infantswith schizophrenia. Arch Neurol 2:115-121, 1960

62. Cain AC: Special "isolated" abilities in severely psychoticyoung children. Psychiatry 32:137-149, 1969

63. Sorosky AD, Ornitz EM, Brown MB, Ritvo ER: Systematicobservations of autistic behavior. Arch Gen Psychiat 18:439-449,1968

64. Hutt C, Hutt SJ, Lee D, Ounsted C: A behavioral andelectroencephalographic study of autistic children. J Psychiatr Res3:181-197, 1965

65. Aug RG, Ables BS: A clinician's guide to childhood psy-chois. Pediatrics 47:327-338, 1971

66. Ornitz EM: Childhood autism-A disorder of sensorimotorintegration. In Rutter M (Ed): Infantile Autism: Concepts, Char-acteristics and Treatment, London, 1971, pp 50-68

67. Ritvo ER, Ornitz EM, LaFranchi S: Frequency of repetitivebehaviors in early infantile autism and its variants. Arch GenPsychiat 19:341-347, 1968

68. Ornitz EM, Brown MB, Sorosky AD, et al: Environmentalmodification of autistic behavior. Arch Gen Psychiat 22:560-565,1970

69. Bergman P, Escalona SK: Unusual sensitivities in very youngchildren. Psychoanal Study Child 3-4:333-353, 1949

70. Receptor preferences in schizophrenic children. AMA ArchNeurol Psychiat 76:643-652, 1956

71. Anthony J: An experimental approach to the psychopathol-ogy of childhood autism. Br J Med Psychol 31:211-225, 1958

72. Stroh G, Buick D: Perceptual development and childhoodpsychosis. Br J Med Psychol 34:291-299, 1964

73. Schopler E: Early infantile autism and receptor processes.Arch Gen Psychiat 13:327-335, 1965

74. O'Connor N: Visual perception in autistic children. InRutter M (Ed): Infantile Autism: Concepts, Characteristics andTreatment, London, 1971, pp 69-80

75. Lovaas 01, Schreibman L, Koegel R, et al: Selective re-sponding by autistic children to multiple sensory input. J AbnormPsychol 77:211-222, 1971

76. Lovaas 01, Schreibman L: Stimulus overselectivity of autisticchildren in a two stimulus situation. Behav Res Ther 9:305-310,1971

77. Ottinger DR, Sweeny N, Loew LH: Visual discriminationlearning in schizophrenic and normal children. J Clin Psychol21:251-253, 1965

78. Frith U, Hermelin B: The role of visual and motor cuesfor normal, subnormal and autistic children. J Child Psychol Psy-chiat 10:153-163, 1969

79. DesLauriers AM, Carlson CF: Your Child is Asleep-EarlyInfantile Autism. Etiology, Treatment, Parental Influences. Home-wood, Illinois, The Dorsey Press, 1969

80: Spitz RA: Hospitalism-An inquiry into the genesis ofpsychiatric conditions in early childhood. Psychoanal Study Child1:53-74, 1945

81. Spitz RA: Hospitalism-A follow-up report. PsychoanalStudy Child 2:113-117, 1946

82. Provence S, Lipton RC: Infants in Institutions. New York,Inter Univ Press, 1962

83. Coleman RW, Provence S: Environmental retardation (hos-pitalism) in infants living in families. Pediatrics 19:285-292, 1957

84. Spitz RA: Anaclitic depression-An inquiry into the genesisof psychiatric conditions in early childhood-Il. Psychoanal StudyChild 2:313-342, 1946

85. Easson WM: Symptomatic autism in childhood and adoles-cence. Pediatrics 47:717-722, 1971

86. Keeler WR: Autistic patterns and defective communicationin blind children with retrolental fibroplasia. In Hoch PH, Zubin J(Eds): Psychopathology of Communication, New York, Grune andStratton, 1958, pp 64-83

87. Wing L: The handicaps of autistic children-A comparativestudy. J Child Psychol Psychiat 10:1-40, 1969

88. Churchill DW: The relation of infantile autism and earlychildhood schizophrenia to developmental language disorders ofchildhood. J Autism Child Schizo 2:182-197, 1972

89. Kanner L: Problems of nosology and psychodynamics ofearly infantile autism. Am J Orthopsychiat 19:416-426, 1949

90. Rutter M, Bartak L, Newman S: Autism-A central dis-order of cognition and language? In Rutter M (Ed): InfantileAutism: Concepts, Characteristics and Treatment, London, 1971,pp 148-172

91. Wing L, Wing JK: Multiple impairments in early childhoodautism. J Autism Child Schizo 1:256-266, 1971

92. de Hirsch K: Differential diagnosis between aphasic andschizophrenic language in children. J Speech Hear Disord 32:3-10,1967

93. Fay WH: On the basis of autistic echolalia. J CommunDisord 2:38-47, 1969

94. O'Connor N, Hermelin B: Visual analogies of verbal opera-tions. Lang Speech 8:197-207, 1965

95. Alpern GD: Measurement of "untestable" autistic children.J Abnorm Psychol 72:478-486, 1967

96. Anthony EJ: Low-grade psychosis in childhood. In RichardsBW (Ed): Proc Lond Conf Scient Study Ment Def 2: 398410,London, May and Baker, 1962

97. Rutter M, Bartak L: Causes of infantile autism-Some con-siderations from recent research. J Autism Child Schizo 1:20-32,1971

98. Rutter M: Autistic children-Infancy to adulthood. SeminPsychiat 2:435-450, 1970

99. Goldberg B, Soper HH: Childhood psychosis or mentalretardation-A diagnostic dilemma-l. Psychiatric and psycho-logical aspects. Can Med Assoc J 89:1015-1019, 1963

100. Eaton L, Menolascino FJ: Psychotic reactions of childhood-A follow-up study. Am J Orthopsychiat 37:521-529, 1967

101. Menolascino FJ: Autistic reactions in early childhood:Differential diagnosis consideration. J Child Psychol Psychiat6:203-218, 1965

102. Yakovlev PI, Weinberger M, Chipman CE: Heller's Syn-drome as a pattern of schizophrenic behavior disturbance in earlychildhood. Am J Ment Defic 53:318-337, 1948

103. Taft L, Goldfarb W: Prenatal and perinatal factors inchildhood schizophrenia. Dev Med Child Neurol 6:32-43, 1964

104. Schain RJ, Yannet H: Infantile autism. J Pediatr 57:560-567, 1960

105. Taft LT, Cohen HJ: Hypsarrhythmia and infantile autism:A clinical report. J Autism Child Schizo 1:327-336, 1971

106. Money J, Borrow NA, Clarke FC: Autism and autoimmunedisease-A family study. J Autism Child Schizo 1:146-160, 1971

107. Goodwin MS, Goodwin TC: In a dark mirror. Ment Hyg53:550-563, 1969

108. Goodwin MS, Cowen MA, Goodwin TC: Malabsorptionand cerebral dysfunction: A multivariate and comparative studyof autistic children. J Autism Child Schizo 1:48-62, 1971

109. Chess S: Autism in children with congenital rubella. JAutism Child Schizo 1:33-47, 1971

110. Desmond MM, Montgomery JR, Melnick JL, et al: Con-genital rubella encephalitis. Am J Dis Child 118:30-31, 1969

111. Sarvis MA, Garcia B: Etiological variables in autism.Psychiatry: J Stud Interpersonal Processes 24:307-317, 1961

112. Lotter V: Epidemiology of autistic conditions in youngchildren-Il. Some characteristics of the parents and children. SocPsychiat 1:163-173, 1967

113. Creak M, Ini S: Families of psychotic children. J ChildPsychol Psychiat 1:156-175, 1960

114. Kanner L: To what extent is early infantile autism de-termined by constitutional inadequacies. Proc Asscc Res Nerv MentDis 33:378-385, 1954

115. Gittelman M, Birch HG: Childhood schizophrenia. ArchGen Psychiat 17:16-25, 1967

44 APRIL 1973 * 118 * 4

116. Brown J: Prognosis from presenting symptoms of preschoolchildren with atypical development. Am J Orthopsychiat 30:382-390, 1960

117. Hinton GG: Childhood psychosis or mental retardaticn-A diagnostic dilemma-lI. Pediatric and neurological aspects. CanMed Assoc J 89:1020-1024, 1963

118. Terris M, LaPouse R, Monk M: The relation of prematurityand previous fetal loss to childhood schizophrenia. Am J Psychiat121:476-481, 1964

119. Rutt CN, Offord DR: Prenatal and perinatal complicationsin childhood schizophrenics and their siblings. J Nerv Ment Dis152:324-331, 1971

120. Ward TF, Hoddinott BA: A study of childhood schizo-phrenia and early infantile auitism. Can Psychiat Assoc J 10:377-386, 1965

121. Pollack M, Woerner MG: Pre- and peri-natal complicationsand "childhood schizophrenia"-A comparison of five controlledstudies. J Child Psychol Psychiat 7:235-242, 1966

122. Meyers D, Goldfarb W: Psychiatric appraisals of parentsand siblings of schizophrenic children. Am J Psychiat 118:902-915,1962

123. Vaillant GE: Twins discordant for early infantile autism.Arch Gen Psychiat 9:163-167, 1963

124. Rimland B: Infantile Autism, the Syndrome and Its Impli-cations for a Neural Theory of Behavior. New York, Appleton-Century-Crofts, 1964, pp 1-275

125. Bakwin H: Early infantile autism. J Pediatr 45:492-4971954

126. Kamp LNJ: Autistic syndrome in one of a pair of monozy-gotic twins. Psychiatr Neurol Neurochir 67:143-147, 1964

127. Ward TF, Hoddinott BA: Early infantile autism in fra-ternal twins. Can Psychiat Assoc J 7:191-195, 1962

128. Bruch H. Studies in schizophrenia. Acta Psychiat NeurolScand Suppl. 130, 1959

129. Chapman AH: Early infantile autism in identical twins.Arch Neurol Psychiat 78:621-623, 1957

130. Polan CG, Spencer MA: A check list of symptoms ofautism of early life. W Va Med J 55:198-204, 1959

131. Sherwin AC: Reactions to music of autistic (schizophrenic)children. Am J Psychiat 109:823-831, 1953

132. Lehman E, Haber J, Lesser SR: The use of reserpine inautistic children. J Nerv Ment Dis 125:351-356, 1957

133. Lovaas OI, Freitag G, Gold VJ, Kassorla IC: Experimentalstudies in childhood schizophrenia: Analysis of self-destructivebehavior. J Exp Child Psychol 2:67-84, 1965

134. Ornitz EM, Ritvo ER, Walter RD: Dreaming sleep inautistic twins. Arch Gen Psychiat 12:77-79, 1965

135. Keeler WR: Discussion of paper presented by Leo Kanner,MD (APA Psychiat Res Rep 7:66-76. Stress, Experimental Psy-chology, Child Psychiat, 1957)

136. Book JA, Nichtern S, Gruenberg E: Cytogenetical investi-gations in chidhood schizophrenia. Acta Psychiat Scand 39:309-323,1963

137. Arajarvi T, Alanen YO: 1. Psychosis in childhood-Aclinical, family and follow-up study. Acta Psychiat Scand Suppl174:7-32, 1964

138. Nakane A: The treatment of autistic children. A considera-tion of the therapeutic relationship. Jap J Child Psychiat 10:222-237, 1969

139. Judd LL, Mandell AJ: Chromosome studies in early in-fantile autism. Arch Gen Psychiat 18:450457, 1968

140. Hilbun WB: Dermatoglyphic findings on a group of psy-chotic children. J Nerv Ment Dis 151:352-358, 1970

141. Shapiro T: Hand morphology in some severely impairedschizophrenic children. Am J Psychiat 122:432435, 1965

142. Taft LT: Parents of autistic children. Dev Med ChildNeurol 11:104-106, 1969

143. Call JD: Interlocking affective freeze between an autisticchild and his "as-if" mother. J Am Acad Child Psychiat 2:2-15,1963

144. Despert JL: Some considerations relating to the genesis ofautistic behavior in children. Am J Orthopsychiat 21:335-347, 1951

145. Szurek SA, Berlin IN: Elements of psychotherapeutics withthe schizophrenic child and his parents. Psychiatry 19:1-9, 1956

146. Bettelheim B: The Empty Fortress-infantile Autism andthe Birth of the Self. New York, Free Press, 1967

147. Osterkamp A, Sands DJ: Early feeding and birth difficultiesin childhood schizophrenia-A brief study. J Genet Psychol101:363-366, 1962

148: Meyers D, Goldfarb W: Studies of perplexity in mothersof schizophrenic children. Am J Orthopsychiat 3:551-564, 1961

149. Goldfarb W, Levy DM, Meyers DI: The mother speaks toher schizophrenic child: Language in childhood schizophrenia.Psychiatry 35:217-226, 1972

150. DeMyer MK, Pontius W, Norton JA, et al: Parental prac-tices and innate activity in normal, autistic and brain damagedinfants. J Autism Child Schizo 2:49-66, 1972

151. Pitfield M, Oppenheim AM: Child rearing attitudes ofmothers of psychotic children. J Child Psychol Psychiat 5:51-57,1964

152. Schopler E: Parents of psychotic children as scapegoats.J Contemp Psychother 4:17-22, 1971

153. Singer MT, Wynne LC: Differentiating characteristics ofparents of childhood schizophrenics, childhood neurotics, andyoung adult schizophrenics. Am J Psychiat 120:234-243, 1963

154. Schopler E, Loftin J: Thought disorders in parents ofpsychotic children-A function of test anxiety. Arch Gen Psychiat20:174-181, 1969

155. Allen J, DeMyer MK, Norton JA, et al: Intellectuality inparents of psychotic, subnormal, and normal children. J AutismChild Schizo 1:311-326, 1971

156. Levine .M, Olson RP: Intelligence of 'parents of autisticchildren. J Abnorm Psychol 73:215-217, 1968

157. Treffert DA: Epidemiology of infantile autism. Arch GenPsychiat 22:431-438, 1970

158. McDermott JF, Harrison Si, Schrager J, et al: Social classand mental illness in children-The question of childhood psychosis.Am J Orthopsychiat 37:548-557, 1967

159. Ritvo ER, Cantwell D, Johnson E, et al: Social class factorsin autism. J Autism Child Schizo 1:297-310, 1971

160. Lotter V: Epidemiology of autistic conditions in youngchildren-I. Prevalence. Soc Psychiat 1:124-137, 1966

161. Eisenberg L: Autistic children in adolescence. Am JPsychiat 112:607-612, 1956

162. Eisenberg L: The course of childhood schizophrenia. ArchNeurol Psychiat 78:69-83, 1957

163. Kanner L: Follow-up study of eleven autistic childrenoriginally reported in 1943. J Autism Child Schizo 1:119-145, 1971

164. Darr GC, Worden FG: Case report twenty-eight years afteran infantile autistic disorder. Am J Orthopsychiat 21:559-570, 1951

165. Kanner L, Rodriguez A, Aashenden B: How far can autisticchildren go in matters of social adaptation? J Autism Child Schizo2:9-33, 1972

166. Ekstein R: Identity formation in the treatment of an autisticchild. In The Challenge: Despair and Hope in the Conquest ofInner Space. Further Studies of the Psychoanalytic Treatment ofSeverely Disturbed Children, New York, Brunner/Mazel, 1971,pp 98-120

167. Lewis SR, Van Ferney S: Early recognition of infantileautism. J Pediatr 56:510-512, 1960

168. Ritvo ER, Ornitz EM, Walter RD, et al: Correlation ofpsychiatric diagnoses and EEG findings-A double-blind study of184 hospitalized children. Am J Psychiat 126:988-996, 1970

169. Creak M, Pampiglione G: Clinical and EEG studies on agroup of 35 psychotic children. Dev Med Child Neurol 11:218-227,1969

170..Hermelin B, O'Connor N: Measures of the occipital alpharhythm in normal, subnormal and autistic children. Br J Psychiat114:603-610, 1968

171. White PT, DeMyer W, DeMyer M: EEG abnormalities inearly childhood schizophrenia: A double-blind study of psychiatric-ally disturbed --and normal children during Promazine sedation.Am J Psychiat 120:950-958, 1964

172. Ornitz EM, Ritvo ER, Walter RD: Dreaming sleep in au-tistic and schizophrenic children. Am J Psychiat 122:419-424, 1965

173. Onheiber P, White PT, DeMyer MK, et al: Sleep anddream patterns of child schizophrenics. Arch Gen Psychiat 12:568-571, 1965 -

174. Ornitz EM, Ritvo ER, Brown MB, et al: The EEG andrapid eye movements during REM sleep in normal and autisticchildrep. Electroenceph clin Neurophysiol 26:167-175, 1969

175. Ornitz EM, Wechter V, Hartman D, et al: The EEG andrapid eye movements during REM sleep in babies. Electroencephclin Neurophysiol 30:350-353, 1971

176. Ornitz EM: Development of sleep patterns in autistic chil-dren. In Clemente CD, Purpura D Mayer F (Eds): Sleep and theMaturing Nervous System, New York, Academic Press, 1972

177. Small JG, DeMyer MK, Milstein V: CNV responses ofautistic and normal children. J Autism Child Schizo 1:215-231,1971

178. Walter WG, Alridge VJ, Cooper R, et al: Neurophysio-logical correlates of apparent defects of sensorimotor integrationin autistic children. In Churchill, DW, Alpern GD, DeMyer M(Eds): Infantile Autism. Proceedings of the Indiana UniversityColloquium, Springfield, Charles C Thomas, 1971, pp 265-276

179. Ornitz EM, Ritvo ER, Panman LM, et al: The auditoryevoked response in normal and autistic children during sleep. Elec-troenceph clin Neurophysiol 25:221-230, 1968

180. Ornitz EM, Tanguay PE, Lee JCM, et al: The effect ofstimulus interval on the auditory evoked response during sleep inautistic children. J Autism Child Schizo 2:140-150, 1972

181. Ornitz EM, Ritvo ER, Lee YH, et al: The auditory evokedresponse in babies during REM sleep. Electroenceph clin Neuro-physiol 27:195-198, 1969

182. Small JG: Sensory evoked responses of autistic children.In Churchill DW, Alpern GD, DeMyer M (Eds): Infantile Au-tism: Proceedings of the Indiana University Colloquium, Spring-field, Charles C Thomas, 1971, pp 224-242.

183. Bernal ME, Miller WH: Electrodermal and cardiac re-sponses of schizophrenic children to sensory stimuli. Psychophysi-ology 7:155-168, 1970

184. Miller WH, Bernal ME: Measurement of the cardiac re-sponse in schizophrenic and normal children. Psychophysiology8:533-537, 1971

185. MacCulloch MJ, Williams C: On the nature of infantileautism. Acta Psychiat Scand 47:295-314, 1971

CALIFORNIA MEDICINE 45The Western Journal of Medicine

186. Pollack M, Krieger HP: Oculomotor and postural patternsin schizophrenic children. Arch Neurol Psychiat 79:720-726, 1958

187. Colbert EG, Koegler RR, Markham CH: Vestibular dys-function in childhood schizophrenia. Arch Gen Psychiat 1:600-617,1959

188. Ritvo ER, Ornitz EM, Eviatar A, Markham CH, BrownMB, Mason A: Decreased post-rotatory nystagmus in early infan-tile autism. Neurology 19:653-658, 1969

189. Wolfe JW: Mesodiencephalic and cerebellar influences onoptokinetic and vestibular nystagmus. Exp Neurol 25:24-34, 1969

190. Silver AA, Gabriel HP: The association of schizophreniain childhood with primitive postural responses and decreased muscletone. Dev Med Child Neurol 6:495-497, 1964

191. Sutton HE, Read JH: Abnormal amino acid metabolismin a case suggesting autism. AMA J Dis Child 96:23-28, 1958

192. Shaw CR, Lucas J, Rabinovitch RD: Metabolic studies inchildhood schizophrenia. AMA Arch Gen Psychiat 1:366-371, 1959

193. Heeley AF, Roberts GE: Tryptophan metabolism in psy-chotic children. Dev Med Child Neurol 7:46-49, 1965

194. Sankar DV Gold E, Phipps E, et al: General metabolicstudies on schizophrenic children. Ann NY Acad Sci 96:392-397,1962

195. Jorgensen OS, Mellerup ET, Rafelsen OJ: Amino acidexcretion in urine of children with various psychiatric diseases-A thin layer chromatrographic study. Dan Med Bull 17:166-170,1970

196. Himwich HE, Jenkins RL, Fujimori M, et al: A biochemi-cal study of early infantile autism. J Autism Child Schizo 2:114-126, 1972

197. Schain RJ, Freedman DX: Studies on 5-hydroxyindole me-tabolism in autistic and other mentally retarded children. JPediatr 58:315-320, 1961

198. Ritvo ER, Yuwiler A, Geller E, et al: Increased bloodserotonin and platelets in early infantile autism. Arch GenPsychiat 23:566-572, 1970

199. Yuwiler A, Ritvo ER, Bald D, et al: Examination ofcircadian rhythmicity of blood serotonin and platelets in autisticand non-autistic children. J Autism Child Schizo 1:421-435, 1971

200. Ritvo ER, Yuwiler A, Geller E, et al: Effects of L-dopain autism. J Autism Child Schizo 1:190-205, 1971

201. Kales A, Ritvo ER, Preston TA, et al: Effects of prolongedadmiinstration of L-dopa on the sleep patterns of autistic children.Psychophysiology 9:89-90, 1972

202. Zarcone V, Kales A, Scharf M, et al: The effects of chronicoral ingestion of 5-hydroxytryptophan (5-HTP) on physiology andblood levels of 5-hydroxytryptamine (5-HT) in two schizophrenicchildren. Psychophysiology 7:319, 1971

203. Wyatt RJ, Zarcone V, Engelman K, et al: Effects of5-hydroxytryptophan on the sleep of normal human subjects. Elec-troenceph clin Neurophysiol 30:505-509, 1971

204. Boullin DJ, Coleman M, O'Brien RA: Abnormalities inplatelet 5-hydroxytryptamine efflux in patients with infantile autism.Nature 226:371-372, 1970

205. Boullin DJ, Coleman M, O'Brien RA, et al: Laboratorypredictions of infantile autism based on 5-hydroxytryptamine effluxfrom blood platelets and their correlation with the Rimland E-2score. J Autism Child Schizo 1:63-71, 1971

206. Boullin DJ, O'Brien RA: Uptake and loss of C-dopamineby platelets from children with infantile autism. J Autism ChildSchizo 2:67-74, 1972

207. Lucas AR, Krause RR, Domino EF: Biological studies inchildhood schizophrenia: Plasma and RBC cholinesterase activity.J Autism Child Schizo 1:72-81, 1971

208. Gittelman M, Cleeman J: Serum magnesium level in psy-chotic and normal children. Behav Neuropsychiat 1:51-52, 1969

209. Koegler RR, Colbert EG, Eiduson S: Wanted-A chemicaltest for schizophrenia. Calif Med 94:26-29, 1961

210. DeMyer MK, Schwier H, Bryson CQ, et al: Free fatty acidresponse to insulin and glucose stimulation in schizophrenic, au-tistic and emotionally disturbed children. J Autism Child Schizo1:436-452, 1971

211. DeMyer MK, Ward SD, Lintzenich J: Comparison ofmacronutrients in the diets of psychotic and normal children. ArchGen Psychiat 18:584-590, 1968

212. Sankar DVS, Cates BA, Broer BA, et al: Biochemicalparameters of childhood schizophrenia (autism) and growth. InWortis J (Ed): Recent Advances in Biological Psychiatry, NewYork, Plenum Press, 1963, pp 76-82

213. Brambilla F, Viani F, Rossotti V: Endocrine aspects ofchild psychoses. Dis Nerv Syst 30:627-632, 1969

214. Fowle AM: Atypical leukocyte pattern of schizophrenicchildren. Arch Gen Psychiat 18:666-680, 1968

215. Gold S, Seller MJ: An epileptic factor in the serum ofpsychotic children. Med J Aust 2:876-877, 1965

216. Gold S: Further investigation of a possible epileptogenicfactor in the serum of psychotic children. Aust NZ J Psychiat1:153-156, 1967

217. Ward AJ: Early infantile autism-Diagnosis, etiology, andtreatment. Psychol Bull 73:350-362, 1970

218. Wenar C, Ruttenberg BA: Therapies for autistic children.In Masserman JH (Ed): Current Psychiatric Therapies, NewYork-London, Grune and Stratton 9:3242, 1969

219. Garcia B, Sarvis MA: Evaluation and treatment planningfor autistic children. Psychiatry 10:530-541, 1964

220. Wing L: Counselling and the principles of management.In Wing JK (Ed): Early Childhood Autism. Clinical, Educationaland Social Aspects, London, Pergamon Press, 1966, pp 257-277

221. Schulman JL: Management of the child with early infantileautism. Am J Psychiat 120:250-254, 1963

222. Rutter M, Sussenwein F: A developmental and behavioralapproach to the treatment of preschool autistic children. J AutismChild Schizo 1:376-397, 1971

223. Call JD: Prevention of autism in a young infant in a well-child conference. J Child Psychiat 2:451-459, 1963

224. Kaufman I, Rosenblum E, Heims L, Willer L: Childhoodpsychosis-I. Childhood schizophrenia-Treatment of children andparents. Am J Orthopsychiat 27:683-690, 1957

225. Schopler E, Reichler RJ: Parents as cotherapists in thetreatment of psychotic children. J Autism Child Schizo 1:87-102,1971

226. Schopler E, Reichler RJ: Developmental therapy by parentswith their own autistic child. In Rutter M (Ed): Infantile Autism:Concepts, Characteristics and Treatment, Edinburgh & London,Churchill Livingstone, 1971

227. Alpert A, Pfeiffer MS: Treatment of an autistic child.J Am Acad Child Psychiat 3:591-616, 1964

228. Escalona S: Some considerations regarding psychotherapywith psychotic children. Bull Menninger Clin 1Z: 126-134, 1948

229. Holter FR, Ruttenberg BA: Initial interventions in psycho-therapeutic treatment of autistic children. J Autism Child Schizo1:206-214, 1971

230. Eveloff HH: The autistic child. Arch Gen Psychiat 3:66-81,1960

231. Ney PG, Palvesky AE, Markely J: Relative effectivenessof operant conditioning and play therapy in childhood schizo-phrenia. J Autism Child Schizo 1:337-349, 1971

232. Ekstein R, Friedman SW: Do you have faith that I'llmake it? Reiss-Davis Clin Bull 8:94-105, 1971

233. Schopler E, Brehm SS, Kinsbourne M, et al: Effect oftreatment structure on development in autistic children. Arch GenPsychiat 24:415-421, 1971

234. Wenar C, Ruttenberg BA, Dratman ML, et al: Changingautistic behavior-The effectiveness of three milieus. Arch GenPsychiat 17:26-35, 1967

235. Simmons JQ, Reed BJ: Therapeutic punishment in severelydisturbed children. Curr Psychiat Ther 9:11-18, 1969

236. Simmons JQ, Lovaas 01: Use of pain and punishment astreatment techniques with childhood schizophrenics. Am J Psycho-ther 23:23-36, 1969

237. Hingtgen JN, Coulter SK, Churchill DW: Intensive rein-forcement of imitative behavior in mute autistic children. ArchGen Psychiat 17:36-43, 1967

238. Brawley ER, Harris FR, Allen KE, et al: Behavior Modi-fication of an autistic child. Behav Sci 14:87-97, 1969

239. Hewett FM: Teaching speech to an autistic child throughoperant conditioning. Am J Orthopsychiat 35:927-936, 1965

240. Lovaas 01, Schaeffer B, Simmons JQ: Building socialbehavior in autistic children by use of electric shock. Exp ResPersonal 1:99-109, 1965

241. Metz JR: Conditioning generalized imitation in autisticchildren. J Exp Child Psychol 2:389-399, 1965

242. Lovaas 01: Considerations in the development of a be-havioral treatment program for psychotic children. In ChurchillDW, Alpern GD, DeMyer M (Eds). Infantile Autism. Proceed-ings of the Indiana University Colloquium, Springfield, CharlesC Thomas, 1971, pp 124-144

243. Churchill DW: Psychotic children and behavior modifica-tion. Am J Psychiat 125:1585-1590, 1969

244. Fischer I, Glanville WK: Programmed teaching of autisticchildren. Arch Gen Psychiat 23: 90-94, 1970

245. Breger L: Comments on "building social behavior in autisticchildren by use of electric shock." J Exp Res Pers 1:110-113, 1965

246. Hudson E, DeMyer MK: Food as a reinforcer in educa-tional therapy of autistic children. Behav Res Ther 6:37-43, 1968

247. Leff R: Behavior modification and psychoses of childhood:A review. Psychol Bull 69:396-409, 1968

248. Lovaas 01, Koegel R, Simmons JQ, et al: Some generaliza-tion and follow-up measures on autistic children in behavior ther-apy. J Appl Behav Anal (in press)

249. Hingtgen JN, Churchill DW: Differential effects of behaviormodification in four mute autistic boys. In Churchill DW, AlpernGD, DeMyer M (Eds): Infantile Autism. Prcceedings of theIndiana University Colloquium, Springfield, Charles C Thomas,1971, pp 185-199

250. Wolf M, Risley T, Mees H: Application of operant con-ditioning procedures to the behavior problems of an autistic child.Behav Res Ther 1:305-312, 1964

251. Marshall GR: Toilet training of an autistic eight-year-oldthrough conditioning therapy-A case report. Behav Res Ther4:242-245, 1966

252. Martin GL, England G, Kaprowy E, et al: Operant ccn-ditioning of kindergarten-class behavior in autistic children. BehavRes Ther 6:281-294, 1968

253. Davison GC: A social learning therapy programme withan autistic child. Behav Res Ther 2:149-159, 1964

254. Lovaas OI, Simmons JQ: Manipulation of self-destructionin three retarded children. J Appl Behav Anal 2:143-157, 1969

46 APRIL 1973 * 118 * 4

255. Ruttenberg BA, Wolf EG: Evaluating the communicationof the autistic child. J Speech Hear Disord 32:314-324, 1965

256. Martin JAM: Sensory disorders in the autistic child andimplications for treatment. In Rutter M (Ed): Infantile Autism-Concepts, Characteristics and Treatment, Edinburgh and London,Churchill Livingstone, 1971, pp 286-296

257. Hermelin B: Rules and language. In Rutter M (Ed): In-fantile Autism-Concepts, Characteristics and Treatment, Edinburghand London, Churchill Livingstone, 1971, pp 98-112

258. Savage VA: An approach to treatment in the young autisticchild. In Rutter M (Ed): Infantile Autism-Concepts, Character-istics and Treatment, Edinburgh and London, Churchill Living-stone, 1971, pp 297-307

259. Wolf EG, Ruttenberg BA: Communication therapy for theautistic child. J Speech Hear Disord 32:331-335, 1967

260. Bartak L, Rutter M: Educational treatment of autisticchildren. In Rutter M (Ed): Infantile Autism-Concepts, Char-acteristics and Treatment, Edinburgh and London, Churchill Living-stone, 1971, pp 258-280

261. DeMyer MK, Ferster CB: Teaching new social behavior toschizophrenic children. J Am Acad Child Psychiat 1:443-461, 1962

262. Halpern WI: The schooling of autistic children-Prelimi-nary findings. Am J Orthopsychiat 40:665-671, 1970

263. Elgar S: Teaching autistic children. In Wing JK (Ed):Early Childhood Autism, Clinical, Educational and Social Aspects,London, Pergamon Press, 1966, pp 205-237

264. Goldfarb W, Goldfarb N, Pollack RC: Changes in IQ ofschizophrenic children during residential treatment. Arch GenPsychiat 21:673-691, 1969

265. Dubnoff B: The habilitation and education of the austiticchild in a therapeutic day school. Am J Orthopsychiat 35:385-386, 1965

266. Ruttenberg BA: A psychoanalytic understanding of in-fantile autism and its treatment. In Churchill DW, Alpern GD,DeMyer M (Eds): Infantile Autism. Proceedings of the IndianaUniversity Colloquium, Springfield, Charles C Thomas, 1971, pp145-184

267. Goldfarb W, Mintz I, Strook KW: A Time to Heal-Cor-rective Socialization-A Treatment Approach to Childhood Schizo-phrenia. New York, International Universities Press, Inc, 1969,pp 1-148

268. Wing L, Wing JK: The prescription of services. In WingJK (Ed): Early Childhood Autism-Clinical, Educational andSocial Aspects, London, Pergamon Press, 1966, pp 279-298

269. Goldfarb W, Goldfarb N, Pollack RC: Treatment of child-hood schizophrenia. A three-year comparison of day and residentialtreament. Arch Gen Psychiat 14:119-128, 1966

270. Connell PH: Medical treatment. In Wing JK (Ed): EarlyChildhood Autism. Clinical, Educational and Social Aspects,London, Pergamon Press. 1966, pp 101-111

271. Fish B, Shapiro T, Campbell M: Long-term prognosis andthe response of schizophrenic children to drug therapy-A con-trolled study of trifluoperazine. Am J Psychiat 123:32-39, 1966

272. Ferster CB, DeMyer MK: Increased performances of anautistic child with prochlorperazine administration. J Exp AnalBehav 4:84-86, 1961

273. Fish B, Campbell M, Shapiro T, Floyd A: Comparison oftrifluoperidol, trifluoperazine and chlorpromazine in preschoolschizophrenic children-The value of less sedative anti-psychoticagents. Curr Ther Res 11:589-595, 1969

274. Campbell M, Fish B, Shapiro T, Floyd A: Thiothixene inyoung disturbed children. Arch Gen Psychiat 23:70-72, 1970

275. Campbell M, Fish B, Shapiro T, et al: Study of molindonein disturbed preschool children. Curr Ther Res 13:28-33, 1971

276. Campbell M, Fish B, Shapiro T, et al: Imipramine inpreschool autistic and schizophrenic children. J Autism ChildSchizo 1:267-282, 1971

277. Kurtis LB: Clinical study of the response to nortriptylineon autistic children. Int J Neuropsychiat 2:298, 1966

278. Fish B, Campbell M, Shapiro T, et al: Schizophrenicchildren treated with methysergide. Dis Nerv Syst 30:534-540, 1969

279. Mogar RE, Aldrich MA: The use of psychedelic agentswith autistic schizophrenic children. Behav Neuropsychiat 1:44-52,1969

280. Bender L, Goldschmidt L, Sankar DVS: Treatment ofautistic schizophrenic children with LSD-25 and UML491. RecAdv Biol Psychiat 4:170-176, 1962

281. Simmons JQ, Leiken SJ, Lovaas 01, et al: Modification ofautistic behavior with LSD-25. Am J Psychiat 122:1201-1211, 1966

282. Freedman AM, Ebin EV, Wilson EA: Autistic schizo-phrenic children. An experiment in the use of D-lysergic aciddiethylamide (LSD-25). Arch Gen Psychiat 6:203-213, 1962

283. Simmons JQ, Benor D, Daniel D: The variable effects ofLSD-25 on the behavior of a heterogeneous group of childhoodschizophrenics. Behav Neuropsychiat 4:10-17, 1972

284. Greenbaum GHC: An evaluation of niacinamide in thetreatment of childhood schizophrenia. Am J Psychiat 127:129-132,1970

285. Ayres AJ, Heskett WM: Sensory integrative dysfunctionin a young schizophrenic girl. J Autism Child Schizo 2:174-181,1972286: Waal N: A special technique of psychotherapy with an

autistic child. In Caplan G (Ed): Emotional Problems of EarlyChildhood, New York, Basic Books, 1955

287. Schopler E: The development of body image and symbolformation through bodily contact with an autistic child. J ChildPsychol Psychiat 3:191-202, 1962

288. Schechter MD, Shurley JT Toussieng PW, et al: Sensoryisolation therapy of autistic chiidren-A preliminary report. JPediatr 74:564-569, 1969

289. Bender L: One hundred cases of childhood schizophreniatreated with electric shock. Trans Am Neurol Assoc 72:165-169,1947

290. Hingtgen JN, Churchill DW: Identification of perceptuallimitations in mute autistic children. Arch Gen Psychiat 21:68-71,1969

291. Rutter M: Concepts of autism: A review of research.J Child Psychol Psychiat 9:1-25, 1968

292. Lovaas 01, Litrownik A, Mann R: Response latencies toauditory stimuli in autistic children engaged in self-stimulatorybehavior. Behav Res Ther 9:39-49, 1971.

293. Bender L: Childhood schizophrenia-A review. J HillsideHosp 16:211-220, 1967

294. Rutter M: Relationships between child and adult psychiatricdisorders. Acta Psychiat Scand 48:3-21, 1972

295. Bryson CQ, Hingtgen JN: Early Childhood Psychosis-In-fantile Autism, Childhood Schizophrenia and Related Disorders.An Annotated Bibliography 1964-69. NIMH, Rockville, Md, DHEWPublication No (HSM)71-9062, 1971

296. Ekstein R, Bryant K, Friedman SW: Childhood schizo-phrenia and allied conditions. In Bellak L (Ed): Schizophrenia-A Review of the Syndrome, New York, Logos Press, 1958

297. Hingtgen JN, Bryson CQ: Recent developments in thestudy of early childhood psychoses; infantile autism, childhoodschizophrenia, and related disorders. Schizo Bull 5:8-54, 1972

298. Churchill DW, Alpern GD, DeMyer M (Eds): InfantileAutism. Proceedings of the Indiana University Colloquium, CharlesC Thomas, Springfield, 1971

299. Rutter M (Ed): Infantile Autism-Concepts, Characteristicsand Treatment, Edinburgh and London, Churchill Livingstone,1971

300. Wing JK (Ed): Early Childhood Autism. Clinical, Educa-tional and Social Aspects, London, Pergamon Press, 1966

301. O'Gorman G: The Nature of Childhood Autism, London,Butterworths, 1967

302. Wing L: Autistic Children-A Guide for Parents andProfessionals. New York, Brunner/Mazel, 1972

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