Autismo Autism and Asperger Syndrome Coexistence With Other Clinical Disorders

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Review article

Autism and Asperger syndrome: coexistencewith other clinical disorders

Gillberg C, Billstedt E. Autism and Asperger syndrome: coexistence withother clinical disorders.Acta Psychiatr Scand 2000: 102: 321330. # Munksgaard 2000.

Objective: To provide a clinically useful analysis of the extent to whichautism and Asperger syndrome coexist with other disorders.Method: Selective review of the literature detailing data pertaining tosymptoms and disorders sometimes encountered in connection withautism or Asperger syndrome.

Results: A large number of medical conditions, psychiatric disorders andbehavioural and motor dyscontrol symptoms are associated with autismand Asperger syndrome.Conclusion: Comorbidity is to be expected in autism spectrum disorders directly or indirectly. Comorbid conditions may be markers forunderlying pathophysiology and suggest a more varied treatmentapproach. There is a great need for in-depth research into this area,meaning that the exclusion criteria of current diagnostic manuals, i.e.those that rule out a diagnosis of autism in some disorders, and adiagnosis of certain other disorders in autism may have to be revised.

C. Gillberg, E. Billstedt

Department of Child and Adolescent Psychiatry,

University of Goteborg, Sweden

Key words: Asperger syndrome;

childhood autism; comorbidity

Christopher Gillberg, Department of Child and

Adolescent Psychiatry, Goteborg University, Annedals

Clinics, S-413 45 Goteborg, Sweden

Accepted for publication April 17, 2000

Introduction

Childhood autism (`Kanner syndrome') is a neuro-developmental disorder, which is dened on beha-vioural criteria reecting abnormal development ofsocial interaction, communication and imagination(13). It is part of a wider spectrum of disorders,which includes autistic psychopathy (Àspergersyndrome') (4, 5); childhood disintegrative disorder(`Heller syndrome') (2, 6), and autistic-like condi-tions (àtypical autism', `pervasive developmentaldisorder not otherwise specied') (2, 7, 8).

Once believed to be an extremely rare disorder

affecting 24 in 10000 children (9), it is nowbecoming generally agreed that the autism spectrumdisorders (Kanner syndrome included) affect at leasthalf a per cent of the general population of children(10). There is growing acceptance that autism is notsuch a rare condition with precise and indisputableboundaries. It has also become clear that, in childrenand adults diagnosed in the autism spectrum, thereare often other symptoms and disorders, notaccounted for by the autism spectrum diagnosisitself. Thus, there are (1) a number of specic andunspecic `medical' diagnoses that are often made

alongside the diagnosis of autism, (2) a number ofoverlapping/comorbid behavioural syndromes thatoften occur both in classic autism/Kanner syndromeand in more high-functioning conditions includingAsperger syndrome and, nally, (3) a number ofoverlapping/comorbid symptoms that do not bythemselves amount to the status of `disorderdiagnosis'.

The issue of `comorbidity' is slightly contentiousin that it is not always obvious what is inferred by theterm. Problems/disorders `comorbid' with a givencondition could be (i) coincidental, (b) causally

directly related, one condition leading to the other,or (c) causally indirectly related, another underlyingcondition/impairment leading both to the coreproblem and the comorbid disorder (s). The termòverlapping conditions' may be more neutral in thatit only infers that there may be overlap at thesupercial level with no links to hypotheticaletiology.

The present paper deals with this issue byselectively reviewing the types and scope of clinicallyimportant coexisting problems in autism andAsperger syndrome. A section towards the end of

Acta Psychiatr Scand 2000: 102: 321330Printed in UK. All rights reserved

Copyright # Munksgaard 2000

ACTA PSYCHIATRICASCANDINAVICAISSN 0001-690X

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the paper attempts to address the issue of themeaning of the ndings, both in terms of how autismshould be theoretically conceptualized and whatthey suggest in the way of clinical diagnosis, work-up and interventions.

Brief overview of coexistence with other disorders

The `medical diagnoses' that are often associatedwith autism can be subdivided into those that areunspecic and those that are rather more specic. Inthe former subgroup, mental retardation, epilepsy,speech and language disorders, hearing decits andvisual impairments are the most common in Kannersyndrome. Motor disorders (DCD/DevelopmentalCoordination Disorder, clumsiness, abnormal gaitpatterns, catatonic features) are also relativelycommon in Asperger syndrome, but otherwise theother `unspecic medical diagnoses' are rarely

encountered in typical cases of Asperger syndrome.The specic medical diagnoses include some 50different conditions, e.g. tuberous sclerosis,Angelman syndrome and Moebius syndrome, allof which have been shown by several differentstudies to be sometimes comorbid with autism orAsperger syndrome, and which have relatively largesubgroups with associated autism/Asperger syn-drome or other variants of severe autistic sympto-matology. These more specic diagnoses are often,although by no means always, genetically deter-mined disorders, many of which have identiableaetiologies.

The behavioural and motor dyscontrol syn-dromes that are often overlapping or comorbidwith autism also appear to be very common inAsperger syndrome, even though, for some condi-tions, the available evidence is less compelling for thelatter syndrome, due mainly to the fact that lessresearch has been published in respect of thissyndrome than with regard to Kanner syndrome.Common overlapping syndromes include attention-decit/hyperactivity disorder (ADHD), decits inattention, motor control and perception (DAMP),DCD, and Tourette syndrome.

The behavioural and emotional symptoms com-monly encountered in autism spectrum disorders,but which are currently not considered part of the setof diagnostic criteria, comprise sleep problems,abnormal sensory responses and attention decitsand symptoms of abnormal activity levels.

Coexistence of autism and medical diagnoses

Unspecic medical diagnoses

Mental retardation occurs in 80% of all childrenwith classic autism/Kanner syndrome (3, 11). This is

a fairly non-controversial statement, but one whichwould have to be revised were Asperger syndrome tobe accepted as the most high-functioning variant ofautism. Several recent studies have shown that casesclinically perceived as having Asperger syndrome(even Hans Asperger's own original cases) would bediagnosed as autistic disorder/childhood autism

under the DSM-IV/ICD-10 (12, 13). Given thatAsperger syndrome is much more common thanautism and since there is usually no asscociatedmental retardation many more cases of `non-retarded autism' would be identied, and hence therelative proportion of mental retardation in autismreduced drastically, perhaps even to under 20% (14).

Epilepsy occurs in about 30% of all children withKanner syndrome (5), and at much lower rates although possibly raised compared to the generalpopulation in Asperger syndrome.

Speech and language and motor control peculia-rities are common in Asperger syndrome, eventhough they are not highlighted as diagnostic criteriain the ICD or DSM. They are, however, included inone of the most often-used diagnostic manuals in theeld (15). Motor problems are also probably verycommon in autism (16), but the stereotype of theagile and beautiful individual with autism haspossibly precluded systematic research in the eld.There has been considerable debate as to theseparation of `semantic-pragmatic disorder' and`non-verbal learning disability' from high-function-ing autism spectrum disorders (17, 18). Low-functioning individuals with autism are often mute

(9). However, in the vast majority of cases, this is notcaused by dysphasia (17), but is due probably to theunderlying lack of an understanding of the meaningof communication (9, 11).

Hearing impairment is much more common inautism than in the general population (19). About1020% of all classic cases have moderatesevere orprofound hearing decits.

Severe visual impairment, including blindness,probably occurs at a rate well above that expected inthe general population. Retinopathy of prematurity(ROP) is almost denitely over-represented inpopulations suffering from autism, and ROP carries

an extremely high risk of autistic disorder (about onein every two cases) (20).

Specic medical diagnoses

More well-dened eponymous conditions affectabout one in four of all children with autism ingeneral population samples (21), and about one ineight in children referred to autism clinics (22).

Tuberous sclerosis complex. One to three to one inve of all children with tuberous sclerosis meet

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full criteria for autism (2325). Those with earlysymptomatic tuberous sclerosis, i.e. those withsymptoms of the disorder before 3 years of age,may meet criteria for autistic disorder even moreoften, at a rate of 5060% (26). Extrapolatingfrom general population prevalence data ontuberous sclerosis and autism these ndings

indicate that 29% of all autism cases areassociated with tuberous sclerosis. Thisproportion would be higher if autism cases withmental retardation only were considered, andmuch higher still if a sample of individuals withthe combination of autism, mental retardationand early onset epilepsy was being worked-up.

It appears that the location of the tubers(temporofrontal in particular) are linked to autisticsymptomatology in tuberous sclerosis (27).

Tuberous sclerois exists in at least two variantsTSC2 and TSC1. TCS2 is located on chromosome16p13.3 (encoding for the tuberin protein whichappears to have growth regulating properties) andchromosome 9q34 (which encodes hamartin, whosecellular functions are still unknown). It is of interestthat one of the autism susceptibility genes identiedby several different research groups is in the TSC2region (28).

Other neurocutaneous syndromes. Both neurobro-matosis type 1 (NF1) and hypomelanosis of Itohave been suggested to be associated with autism.In the case of NF1, a population study found 6%

of cases with autism/atypical autism also metcriteria for this diagnosis (29). NF1 is located onchromosome 17. NF2, leading to vestibularschwannomas and other tumours, has not yet beensuggested to be associated with autism. NF2 islocated on chromosme 22.

Hypomelanosis of Ito has been reported in aconsiderable number of cases with autism spectrumdisorders (30, 31), mainly Asperger syndrome andatypical autism. In a series of 76 patients withhypomelanosis of Ito, 10% had marked autisticfeatures (32). The aetiology of hypomelanosis of Itoremains obscure.

Fragile X syndrome. About one in three of allmales with the full fragile X mutation showmarked autistic features, and many of these meetfull criteria for autism early in life (33). Con-versely, 210% of all autism cases are associatedwith the fragile X syndrome (21, 34). The fragile Xsyndrome has been shown to be associated withexecutive function decits suggesting frontal lobedysfunction (35). The frontal lobes have beenimplicated in the pathogenesis of autism in many

recent reports, including a PET-scan study ofAsperger syndrome (36).

Partial tetrasomy 15q11.13. There is growingagreement that abnormality on chromosome 15q,particularly the condition now known as partialtetrasomy 15q11.13, is associated with autisticsymptomatology (37). This area on chromosome15 is abnormal in two behavioural phenotypesyndromes, namely PraderWilli syndrome andAngelman syndrome. The former of these is notassociated with autism, whereas the other isstrongly linked to autistic symptomatology.Interestingly, both these syndromes comprise rigid,stereotyped and repetitive behaviour patterns,which are also hallmarks of disorders in theautism spectrum.

Other chromosomal disorders. Most of the human

chromosomes have been implicated in the patho-genesis of autism. However, a recent review of allchromosomal studies in autism (38) suggests thatsusceptibility genes for autism would be mostlikely to be found on chromosome 15 and on theX chromosome, the two chromosomes that havebeen most consistently reported to show abnorm-ality in the eld of autism spectrum disorders.

Rett syndrome complex. For obscure reasons, Rettsyndrome has become listed as a particular formof an autism spectrum disorder in the ICD-10 and

DSM-IV. It is categorized there as one of thepervasive developmental disorders (PDDs). Rettsyndrome is conceptually similar to other neuro-logical disorders/syndromes in that it has arelatively large subgroup with severe autisticsymptomatology. However, not all individualswith Rett syndrome have any autistic symptomsat all, and tuberous sclerosis, with a possiblystronger link to autistic symptoms, is not groupedas a PDD.

Nevertheless, it is important to make note of thefact that young girls developing autistic symptomsshould be suspected of suffering from Rett syn-

drome. It is also important to be aware that thereare preserved speech cases in the Rett syndromecomplex (39), making differential diagnosis vis-a-visautism sometimes very difcult.

Rett syndrome has recently been shown to bestrongly associated with a gene coding for theprotein MECp2, which is located on chromosomeXq28. Because of the considerable overlap ofautism and Rett syndrome in terms of symptoma-tology at some stages of development, this discoverymight provide a clue to one of the locations forautism susceptibility genes.

Autism and Asperger syndrome comorbidity

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Moebius syndrome. Several different studies haveshown a considerable subgroup of patients withMoebius syndrome (congenital, bilateral facialnerve palsies usually due to abnormalities in thebrainstem) has an associated autistic disorder(40). The connection with Moebius syndromesuggests brain stem pathology in some cases of

autism.

Thalidomide syndrome. In a study of all 100Swedish victims of the thalidomide disaster, atleast 4% met full criteria for autistic disorder (41).This nding is also suggestive of early rsttrimester brain stem lesions as one possiblepathogenetic mechanism in autism.

Other medical conditions. Many other conditionsthan those listed in the foregoing have beenreported to be associated with autism. They

include fetal alcohol syndrome (42), rubellaembryopathy (43) and metabolic disorders, andhave been reviewed in detail by Gillberg andColeman (21).

Behavioural and motor control problems that often

coexist with autism and Asperger syndrome

Many individuals with syndromes dened on thebasis of deviant behaviour or motor dyscontrol alsomeet all or most of the symptom criteria fordiagnosing autistic disorder or Asperger syndrome.

The most common of these appear to be ADHDand Tourette syndrome, but many other more orless well-dened behavioural and motor dyscontrolsyndromes also have subgroups that meet most orall of the criteria for Kanner syndrome or Aspergersyndrome. Some individuals with autism spectrumdisorders have symptoms of specic behaviouralsyndromes that do not amount to the level of cut-offfor diagnosis. There is also a host of non-coresymtpoms associated with autism, problems thatmay be very marked and handicapping but that arenot included among the diagnostic criteria forautism spectrum disorders.

ADHD

Very few studies have looked systematically at theevidence linking autism and attention decits(including ADHD). Some of the failure to addressthis important comorbidity issue can probably beattributed to the specication in the diagnosticmanuals that autism and ADHD should not bediagnosed conjointly in any individual patient.

Mohammad Ghaziuddin and co-workers havereported on the comorbidity of autism and

Asperger syndrome in several different publications(44, 45). In a preliminary report they described theoccurrence of psychiatric disorders in a series of 35patients with Asperger syndrome diagnosed accor-ding to the ICD-10/DSM-IV criteria. Two-thirds ofthe patients had an additional psychiatric disorder.Children were most likely to suffer from ADHD,

while depression was the most common diagnosisin adolescents and adults (see further underDepression).

Recent neuropsychological studies (46, 47) havedemonstrated that high-functioning autism andAsperger syndrome are characterized by similartypes and degrees of attention decits that are seenmost clearly in children with ADHD. Even thoughthese studies did not formally diagnose the childrenwith autism or Asperger syndrome as havingADHD, it is clear that attention decits are verycommon, if not universal, in disorders in the autismspectrum.

Children with autism can be hyperactive orhypoactive. Only relatively few are normallyactive in infancy and the preschool period. Thereis often a characteristic trajectory of development inthis respect with hyperactivity in the preschool yearsfollowed by more normoactive behaviour in theearly school years and a tendency to hypoactivityfrom early adolescence.

Extreme degrees of hyperactivity are often en-countered in individuals with autism and autistic-like conditions who suffer from the fragile-Xsyndrome (33). This is also true in many cases of

autism spectrum disorders combined with tuberoussclerosis (23, 25). The hyperactivity is usually mostpronounced in the rst 10 years of life, and may belinked to severe bouts of aggression and destructivebehaviours. These ndings suggest that there maybe meaningful subgroups within the autism spec-trum that are better characterized by their comor-bidity than their diagnostic status within the autismspectrum.

DAMP

The Scandinavian concept of DAMP, while not

generally accepted outside Northern Europe, hasbeen the subject of many empirical studies. DAMPis conceptualized as the combination of ADHD andmotor-perceptual dysfunctions (now often referredto as developmental coordination disorder, or`DCD'). A relationship between DAMP andautistic-type behaviours was already noted in therst longitudinal study of Swedish 7-year-olds withand without DAMP (48). In that study 1.2% of thegeneral population had `severe DAMP' (comprisingADHD plus DCD plus perceptual problems plusspeechlanguage problems). Slightly more than half


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of the children with severe DAMP also had somemarked autistic features, i.e. they had the autismtriad, but symptoms were less severe than in classicautism in at least one of the three relevant domains(social interaction, communication, imagination).Almost half of this proportion (of children withsevere DAMP with autistic features) met full criteria

for Asperger syndrome (15). Two other populationstudies of Swedish 7-year-olds have demonstrated asimilar degree of comorbidity of DAMP withautistic features (49, 50).

DCD

The type of motor co-ordination problems con-sidered typical of Asperger syndrome (4) are alsothose that are typical of DCD (and hence ofDAMP).

Highly sophisticated analysis of home videotapesof the motor behaviours of infants who are later

diagnosed as having the syndrome of autism hasrevealed consistent motor abnormalities, includingabnormal turning-around behaviours and a`Moebius-like' facial motor performance (51).This provides another piece of evidence suggestingthat brain stem dysfunction is important in thepathogenesis of autism.

Tics and Tourette syndrome

It is only quite recently that the prevalence of tics inautism has become the subject of empirical study.The relationship of Asperger syndrome and tics, on

the other hand, has been noted for quite some time,and has been interpreted either as a spurious ndingor a marker for better outcome, both of which nowappear to be mistaken.

In a study of young people with autism, 8% werefound to have comorbid Tourette syndrome (52).

Several reports (5355) have documented the co-occurrence of Tourette syndrome and Aspergersyndrome. Some authors have taken this type ofcomorbidity as a predictor of better outcome inautism, but the evidence is not yet sufcient towarrant such a conclusion. In a Swedish populationstudy, 20% of all school-age children with deniteAsperger syndrome also met full criteria forTourette syndrome, and a full 80% had tics ofone kind or another (55). In another Swedishpopulation study, 10% of children with Tourettesyndrome also met full criteria for Aspergersyndrome (56).

Catatonia movement disorder

Lorna Wing has long argued that some relativelyhigh-functioning individuals with autism developcatatonia in late childhoodearly adult life (57).

Several other authors have noted a similar associa-tion (58, 59), and the present authors have comeacross several young individuals with autism/Asperger syndrome and catatonia developing inadolescence.

Obsessive-compulsive behaviour problemsThere are many similarities between the obsessiveand compulsive phenomena of obsessive compul-sive disorder (ÒCD') and obsessive compulsivepersonality disorder (ÒCPD') and the ritualisticand repetitive behaviours typical of both Kannerand Asperger syndromes (60). The symptomatologyof OCPD, as outlined in the DSM-IV, is strikinglysimilar to that of autistic psycopathy as portrayedby Asperger (4).

Depression

Links between affective disorders and autism havebeen suggested for decades (3). Depression is over-represented in close relatives of individuals sufferingfrom autism (61). It is common in children andadolescents with autism (44), and it has beenreported to be very common in Asperger syndrome(45, 62, 63).

Eating disorders

Autism was reported in a case of anorexia nervosa20 years ago (64). Several cases of anorexia nervosa

and autism occurring in the same families weredescribed by Gillberg (65) and later by Comings(66). In a controlled follow-up study of representa-tive cases of anorexia nervosa, 18% had an autismspectrum disorder (4% autistic disorder, 6%Asperger syndrome and 8% atypical autism) bothat the time of onset of the eating disorder (around15 years of age) and 5 and 10 years later (67). AGerman study showed the rate of underweight andeating disorders to be much increased in Aspergersyndrome/schizoid personality disorder (68).

Problems with eating including particular foodrefusal, food fads, pica, hoarding, overeating and

various degrees of anorectic behaviours, includingcomplete food refusal and compulsive ordering offood on the plate are extremely common inautism.

Some children with autism appear to prefer onlysoft foods and may have difculty chewing (orrather knowing that they are expected to chew).Others prefer only solid foods and appear nauseatedwhen expected to eat certain minced foods. It is verycommon for children with autism to accept onlypasta and French-fries. Low-functioning indivi-duals may èat' anything within reach, including


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pieces of papers, cigarettes, owers and even needlesand pins.

Selective mutism

Case reports of autism/Asperger syndrome/schizoidpersonality disorder in children have drawn atten-

tion to the possible comorbidity and familial linksof autism spectrum disorders and selective mutism(5, 69, 70). In a population study of selectivemutism, Kopp and Gillberg (71) found that one (agirl) out of ve school age children with selectivemutism also met full diagnostic criteria for Aspergersyndrome.

Childhood schizophrenia

Originally believed to be childhood schizophrenia,autism has long been separated from schizophrenia,and is considered by most authorities in the eld to

have little, if anything, to do with this disorder.Nevertheless, there is suggestive evidence thatchildren diagnosed with schizophrenia often havean early history indicating an autism spectrumdisorder (72).

Adolescent onset psychosis

Among 61 individuals presenting with `psychotic'symptoms (hallucinations, delusions, thought dis-order, mania, confusion) in adolescence (1319years), 5% had a prior diagnosis of Kannersyndrome (infantile autism) or Heller syndrome

(disintegrative psychosis) (73). These were casesoriginally believed to have a relatively goodprognosis. The autism spectrum diagnoses hadbeen made prior to age 5 years, and by age 10years, the children were doing remarkably wellgiven the original diagnostic categorization.However, in teenage, they suddenly, an unexpec-tedly developed orid psychotic symptoms.

Personality disorders and psychiatric disorders usually rst

diagnosed in adolescence or adult life

Judging from the diagnostic criteria for many of the

personality disorders in the DSM-IV, particularlythose grouped as clusters A and C, there should be aconsiderable degree of overlap between Aspergersyndrome and such conditions. No study haslooked specically at this type of overlap, butindirect data from a follow-up study of eatingdisorders (67) suggest that the overlap betweenAsperger syndrome and OCPD may be verymarked. Other personality disorder criteria likelyto be met by many individuals with Aspergersyndrome include those of paranoid, schizoid (67)and schizotypal personality disorder (74).

Fluctuating activity levels are common through-out the lifespan of some individuals with autism,and there is sometimes concern that the individualmight be suffering from manic-depressive typemood swings or outright bipolar disorder. Inhighfunctioning patients with autism it has beenwell documented that there is an increased risk of

bipolar disorder, both in the patients themselvesand their close relatives (75).

Asperger syndrome and other high-functioningautism spectrum disorders are sometimes found inyoung adult forensic psychiatric patients, if work-up is performed with a particular view to ndingpsychiatric and developmental disorders with onsetin childhood (76). There is also some limitedevidence that Asperger syndrome may be over-represented among mentally ill convicted violentoffenders (77).

Abnormal responses to sensory stimuli

In a prospective study of children with autism seenbefore their third birthday, àbnormal responses tosensory stimuli' was the class of symptoms, whichmost clearly distinguished autism from mentalretardation (78). Ornitz (79) reported similarndings.

Of these symptoms, an abnormal response tosound may be thought of as the most characteristicof all. The child who àcts deaf' and does not reactat all when an explosion is unexpectedly heardnearby may moments later turn at the sound of a

paper being removed from a chocolate (78). Manychildren with autism cover their ears to shut outeven òrdinary' noise levels (11, 80).

Abnormal responses to visual stimuli are presentin a subgroup of young children with autism, whooften give the impression of having difcultyrecognizing the things they see. Every now andthen autism is mistaken for blindness. Somechildren with delayed visual maturation showmany or all of the symptoms of autism (81). It ispossible that some aspects of the abnormal gazebehaviour characteristic of so many cases withautism and Asperger syndrome reect underlying

visual perceptual abnormalities (82).Abnormal reactions to touch, pain, heat or cold is

often encountered in autism (3).Children with autism often want to smell people

and objects (3). Clinical experience suggests thatperceptions relating to auditory and tactile stimulimay be more impaired in autism than are percep-tions of visual and, especially, olfactory stimuli. Thetwo latter functions make their rst intracranialnerve connections at a higher level in the nervoussystem. A preference for proximal stimuli has alsobeen experimentally evidenced in autism (83).


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Although abnormal sensory responses in autismare regarded by many as `primary' and in their viewshould therefore be included among the diagnosticcriteria, the most inuential diagnostic manuals donot do this. Nevertheless, most authorities agreethat for instance `undue sensitivity to sound' is anextremely common feature in autism and that it

differentiates autism from, for instance, dysphasia(11, 80).

Abnormal sleep patterns

Sleep patterns are abnormal in autism in a majorityof all cases (84). They may be most striking ininfancy and the rst few years of life, when the childmay keep the whole family awake by crying,but may sometimes continue right through toadulthood.

It is not uncommon for major sleep problems tobe the rst obvious outward sign that something is

seriously amiss in an infant who receive a diagnosisof autism only years later.

Aggression

Aggressive behaviours are common in autism at allages, but perhaps particularly in the adolescent andyoung adult group (85). It is possibly over-represented in Asperger syndrome also (86). Theaggressive acts can take on frightening proportionsand can lead to the requirement for heavy medi-cation or treatment in high-security wards. Never-theless, it is important to note that the majority of

individuals with autism spectrum disorders are notaggressive and that it is rare for really dangeroussituations to develop, even in the group that exhibitsseverely aggressive behaviours.

Self-injury

Self-injurious behaviours (SIBs) are said to aboundparticularly in children with the combination ofautism and mental retardation (87). However, SIBis common also in individuals with high-functioningautism. Some of the most common manifestationsof SIB are head-banging, wrist- or knuckle-biting,

chin-knocking, cheek-smacking, eye-poking, hair-tearing and clawing.

Concluding remarks

Implications for clinical practice in the everyday care of

individuals in the autism spectrum

It is already clear that comorbidity is common,indeed the rule, in autism and, albeit less welldocumented, in Asperger syndrome. Mental retar-dation occurs in about three-quarters of classical

cases of autism. An associated medical disorder,such as tuberous sclerosis, a metabolic or chromo-somal disorder, is present in 1025% of casesdepending on whether specialized clinic or commu-nity samples are being studied. In addition, epilepsy,hearing and visual impairments are very common.Such problems are relatively rare in Asperger

syndrome. However, with regard to additionalneuropsychiatric problems, such as ADHD,Tourette syndrome and other tic disorders, bothautism and Asperger syndrome show very high ratesof comorbidity. This may have important conse-quences for treatment. There is little, if any,evidence that individuals with autism spectrumdisorders respond less well to treatments for thesecomorbid problems than do those without adiagnosis in the autism spectrum.

The implications are that: (a) comorbidity is to beexpected whenever a diagnosis of autism or

Asperger syndrome is made, and (b) the exclusioncriteria of the DSM and ICD, i.e. those that rule outa diagnosis of autism in another disorder and adiagnosis of another disorder in autism, may haveto be disregarded.

There is a risk that children who do not receivediagnoses of all their various types of problems maybe withdrawn both from general services, such asproper schooling, if ADHD is the only diagnosismade in a case with both ADHD and autism andspecic treatments such as stimulant medication ifautism is the only diagnosis made in a case withboth autism and ADHD. The DSM and ICD

criteria are based on diagnostic algorithms accord-ing to relatively strict hierarchical rules. Theunderlying assumption has often been that certaindisorders are more `severe', `basic' or `pure' thanothers. This has clearly been the case in the eld ofautism, which has long been hailed as the `bestdened' of all child psychiatric disorders (9, 11, 22).The algorithms have been historically important,and provided a framework for studying `purer'forms of disorders, allowing the beginning of anunderstanding of the underpinnings of at least someclinical syndromes. However, adhering rigidly to

the strict exclusion criteria, in the face of mountingclinical evidence that they do not reect the problemproles shown by real-life patients, presents majorclinical problems for affected individuals and theirfamilies (52). It has sometimes precluded thedevelopment both of realistic clinical services andmore meaningful pathogenetic research.

The problems associated with insistence on rulingout certain diagnostic possibilities are clearlyreected in the ICD-10 section on autism.According to the strict operational rules, childhoodautism should be diagnosed in cases showing the


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typical autism triad before age 36 months.However, other childhood disintegrative disorderscan equally be diagnosed if the child shows thissymptom triad from the age of 25 months. For bothdisorders there is a criterion stating that symptomsshould not be `attributable to the other varieties ofpervasive developmental disorder'. So how is one to

diagnose children with symptom onset between 25and 36 months? A case in point of the absurdsituation that sometimes arises because of strictexclusion criteria in the DSM-IV is the category ofAsperger's disorder in that manual. None ofAsperger's own cases meet the diagnostic criteriafor Asperger's disorder (12)! These examples high-light the need for more extensive participation ofclinical researchers and clinicians (including aschairs) of the task forces of the DSM and ICD.

Implications for research on underlying mechanisms in autismand Asperger syndrome

The overlap/comorbidity encountered in disorderson the autism spectrum has several implications forthe understanding of pathogenesis in autism.

First, the extent and pattern of overlap with otherdisorders and symptoms suggest that it would beunlikely that a unique (and pathognomonic) set ofaetiological factors will be identied that pertain toautism and autism only.

Secondly, the overlap with symptoms anddisorders involving attention decits and tics

implicate dysfunction of the dopamine system inthe brain in autism spectrum disorders. There issome evidence that genes involved in the regulationof dopamine functioning may be abnormal inADHD (8891), and it has long been suggested,e.g. on the basis of the positive symptomatic effectsof central stimulants, that dopamine dysfunctionmight be at the root of ADHD. Several lines ofevidence, e.g. the reduction of tics by dopamineblockers, implicate the dopamine system also inTourette's and other tic disorders (92, 93). There arealso many other indirect leads linking autism withdopamine dysfunction. These include abnormal

cerebrospinal uid levels of dopamine breakdownproducts, rigid and catatonic motor behaviours,and the abundance of motor stereotypies usuallyencountered in classic variants of childhood autism(14).

Thirdly, the overlap with symptoms and syn-dromes involving obsessions and compulsions (60)suggest that the serotonin system may also bedysfunctional in disorders in the autism spectrum.Again, there are other indirect links between autismand serotonin dysfunction, most notably the robustnding of serotonin hyperfunction in about a third

of individuals diagnosed as having childhoodautism (14).

Fourthly, there may be lessons to be learnt frommore intense study of some of the specic medicaldisorders. For instance, in tuberous sclerosis, itappears that autistic symptoms are much morelikely to arise when there is temporal lobe (and

temporofrontal) afiction as compared with whenthese brain areas are unscathed (27). However, thereis also the possibility that tuberous sclerosis, with atleast two different gene locations on chromo-somes 9 and 16 increases the risk of autismspecically through gene effects. Two recentgenome scan studies of sib-pairs with autism haveimplicated the tuberous sclerosis chromosome 16area as a possible location for one of the autismsusceptibility genes.

The connection between thalidomide embryo-pathy and Moebius syndrome on one hand andautism on the other hand has implicated early rsttrimester brain stem insult as one possible mechan-ism. The studies of these syndromes (40) have alsoimplicated precise developmental timing windowsand specic brain stem areas in the pathogenesis ofat least some autism cases. The discovery of infantmotor control abnormalities in autism (51), and thesuggestion that the typical `Moebius mouth' may bepresent in infancy in autism, provide furthersupport for the notion of specic brain stemabnormalities in the pathogenetic chain of events.

Finally, the realization that autism is not a oftenencountered in the shape of a `pure' disorder, which

one can easily separate out from all other condi-tions, should make obvious the need of newapproaches in research. Studies of large generalpopulation samples where comorbidity patterns canbe analysed without bias should receive highpriority. Patterns of referral and atypical individualcharacteristics need to be addressed in all studies ofselected clinical samples. Small-scale `high-tech'studies (e.g. neuroimaging studies) should include`pure' cases (if such cases exist at all) andcases withvarious patterns of comorbidity. Also, as in theclinical setting, the exclusion criteria of the DSMand ICD, may need to be disregarded or dealt with

in other ways.

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Autismo Autism and Asperger Syndrome Coexistence With Other Clinical Disorders