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PubMed2003

Parent-mediated early intervention for young children with autism spectrum disorder.

BACKGROUND: Recent estimates concerning the prevalence of autistic spectrum disorder are much higher than those reported 30 years ago, with at least 1 in 400 children affected. This group of children and families have important service needs. The involvement of parents in implementing intervention strategies designed to help their autistic children has long been accepted as helpful. The potential benefits are increased skills and reduced stress for parents as well as children. OBJECTIVES: The objective of this review was to determine the extent to which parent-mediated early intervention has been shown to be effective in the treatment of children aged 1 year to 6 years 11 months with autistic spectrum disorder. In particular, it aimed to assess the effectiveness of such interventions in terms of the benefits for both children and their parents. SEARCH STRATEGY: A range of psychological, educational and biomedical databases were searched. Bibliographies and reference lists of key articles were searched, field experts were contacted and key journals were hand searched. SELECTION CRITERIA: Only randomised or quasi-randomised studies were included. Study interventions had a significant focus on parent-implemented early intervention, compared to a group of children who received no treatment, a waiting list group or a different form of intervention. There was at least one objective, child related outcome measure. DATA COLLECTION AND ANALYSIS: Appraisal of the methodological quality of included studies was carried out independently by two reviewers. Differences between the included studies in terms of the type of intervention, the comparison groups used and the outcome measures were too great to allow for direct comparison. MAIN RESULTS: The results of this review are based on data from two studies. Two significant results were found to favour parent training in one study: child language and maternal knowledge of autism. In the other, intensive intervention (involving parents, but primarily delivered by professionals) was associated with better child outcomes on direct measurement than were found for parent-mediated early intervention, but no differences were found in relation to measures of parent and teacher perceptions of skills and behaviours. REVIEWER'S CONCLUSIONS: This review has little to offer in the way of implications for practice: there were only two studies, the numbers of participants included were small, and the two studies could not be compared directly to one another. In terms of research, randomised controlled trials involving large samples need to be carried out, involving both short and long-term outcome information and full economic evaluations. Research in this area is hampered by barriers to randomisation, such as availability of equivalent services.

Autistic Disorder↗

PubMed2001

Antiepileptic drugs: affective use in autism spectrum disorders.

Antiepileptic drugs are widely administered to individuals with autistic spectrum disorders. There are several reasons for the use of antiepileptic drugs in autistic spectrum disorders, including the high incidence of epilepsy in these individuals, the anecdotal reports suggesting an improvement of communication and behavior in autistic subjects with epileptic discharges, and the increased awareness that some disruptive behaviors may be manifestations of an associated affective disorder. In this study, data on the current use of antiepileptic drugs in the treatment of autism, and on the association of affective disorders with epilepsy and autism, are reviewed. The evidence supporting the hypothesis that there may be a subgroup of autistic children with epilepsy and affective disorders that preferentially respond to antiepileptic drugs is still very preliminary, and further investigations with double-blind controlled studies are needed. Although the role of antiepileptic drugs at the present time is not established, there is evidence that autism, epilepsy, and affective disorders commonly co-occur, and that they may share a common neurochemical substrate, which is the common target of the psychotropic mechanism of action of different antiepileptic drugs.

Adolescent↗

PubMed2001

Does DSM-IV Asperger's disorder exist?

DSM-IV criteria for autistic and Asperger's disorders were applied to 157 children with clinical diagnoses of autism or Asperger's disorder. All children met the DSM-IV criteria for autistic disorder and none met criteria for Asperger's disorder, including those with normal intelligence and absence of early speech delay. The reason for this was that all children had social impairment and restricted and repetitive behavior and interests (required DSM-IV symptoms for both autistic and Asperger's disorders) and all had a DSM-IV communication impairment (which then qualified them for a diagnosis of autistic disorder and not Asperger's disorder). Communication problems exhibited by all children were impaired conversational speech or repetitive, stereotyped, or idiosyncratic speech (or both), which are DSM-IV criteria for autism. These findings are consistent with those of 5 other studies and indicate that a DSM-IV diagnosis of Asperger's disorder is unlikely or impossible.

Adolescent↗

PubMed2002

A systematic review of the use of atypical antipsychotics in autism.

Conventional antipsychotic medication is commonly prescribed to patients with autistic spectrum disorder. However, a high incidence of severe adverse reactions highlights the need to find more favourable treatments. Atypical antipsychotics may combine efficacy in ameliorating some autistic symptoms with a lower incidence of some adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder, with particular focus on behaviour, cognition and physical well-being. Thirteen studies using risperidone, three using olanzapine, one using clozapine, one using amisulpride and one using quetiapine were identified. Few firm conclusions can be drawn due to the limitations of the studies; however, there is an indication that risperidone may be effective in reducing hyperactivity, aggression and repetitive behaviours, often without inducing severe adverse reactions. Olanzapine and clozapine may also be effective; however, there is little evidence for using amisulpride or quetiapine in this population. Randomized trials are required to clarify the effectiveness of these agents.

Antipsychotic Agents↗

PubMed2005

Reflections on opening Pandora's box.

Publishing my paper on Asperger's syndrome in 1981, and suggesting that it is part of the autistic spectrum, has had various consequences. These include the growth of interest in the syndrome among the general public as well as professionals. Controversy over definitions of subgroups and prevalence of autistic spectrum disorders has increased. Adult psychiatrists are becoming aware that high functioning autistic disorders can underlie psychiatric conditions. Naming the condition has helped many with the syndrome to greater understanding of their skills and disabilities. It has highlighted the special contribution people with Asperger syndrome have made to the world. There has been a growth of specialist services but many more are needed. Describing and naming the syndrome has had mainly positive effects.

Asperger Syndrome↗

PubMed2004

A modified screening tool for autism (Checklist for Autism in Toddlers [CHAT-23]) for Chinese children.

BACKGROUND: There is a recent trend of a worldwide increase in the incidence of autistic spectrum disorder. Early identification and intervention have proved to be beneficial. The original version of the Checklist for Autism in Toddlers (CHAT) was a simple screening tool for identification of autistic children at 18 months of age in the United Kingdom. Children with an absence of joint attention (including protodeclarative pointing and gaze monitoring) and pretend play at 18 months were at high risk of autism. Section A of the CHAT was a self-administered questionnaire for parents, with 9 yes/no questions addressing the following areas of child development: rough and tumble play, social interest, motor development, social play, pretend play, protoimperative pointing (pointing to ask for something), protodeclarative pointing, functional play, and showing. Section B of the CHAT consisted of 5 items, which were recorded with observation of the children by general practitioners or health visitors. The 5 items addressed the child's eye contact, ability to follow a point (gaze monitoring), pretend (pretend play), produce a point (protodeclarative pointing), and make a tower of blocks. A 6-year follow-up study of >16,000 children screened with the CHAT at 18 months in the United Kingdom showed a sensitivity of only 0.40 and a specificity of 0.98, with a positive predictive value (PPV) of 0.26. Rescreening using the same instrument at 19 months for those who failed the 18-month screening yielded a higher PPV of 0.75. Therefore, children were likely to have autism if they failed the CHAT at 18 months and failed again at 19 months. It was estimated that consistent failure in 3 key questions (ie, protodeclarative pointing, gaze monitoring, and pretend play) at 18 months indicated an 83.3% risk of having autism. Because of the poor sensitivity of the original CHAT for autism, a Modified Checklist for Autism in Toddlers (M-CHAT), consisting of 23 questions, with 9 questions from the original CHAT and an additional 14 questions addressing core symptoms present among young autistic children, was designed in the United States. The original observational part (ie, section B) was omitted. The M-CHAT was designed as a simple, self-administered, parental questionnaire for use during regular pediatric visits. The more questions children failed, the higher their risk of having autism. Two criteria were used to measure the sensitivity and specificity of M-CHAT. Criterion 1 used any 3 of the 23 questions, and criterion 2 used 2 of the 6 best questions that could be used to discriminate autism from other groups. The sensitivity and specificity for criterion 1 were 0.97 and 0.95 and those for criterion 2 were 0.95 and 0.99, respectively. M-CHAT had a better sensitivity than the original CHAT, because children up to 24 months of age were screened, with the aim of identifying those who might regress between 18 and 24 months. The 6 best questions of the M-CHAT addressed areas of social relatedness (interest in other children and imitation), joint attention (protodeclarative pointing and gaze monitoring), bringing objects to show parents, and responses to calling. Joint attention was addressed in the original CHAT, whereas the other areas were addressed only in the M-CHAT. To date, there has been no study of the application of either the original CHAT or the M-CHAT for Chinese populations. OBJECTIVES: CHAT-23 is a new checklist translated into Chinese, combining the M-CHAT (23 questions) with graded scores and section B (observational section) of the CHAT. We aimed to determine whether CHAT-23 could discriminate autism at mental ages of 18 to 24 months for Chinese children and to determine the best combination of questions to identify autism. METHODS: A cross-sectional cohort study was performed with 212 children with mental ages of 18 to 24 months. The children were categorized into 2 groups, ie, group 1 (N = 87) (autistic disorder: N = 53; pervasive developmental disorder: N = 33) and group 2 (N = 125) (nonautistic). The checklist included self-ad25) (nonautistic). The checklist included self-administered questionnaires with 23 questions (part A) and direct observations of 5 items by trained investigators (part B). We performed discriminant function analysis to We found that 7 key questions, addressing areas of joint attention, pretend play, social relatedness, and social referencing, were identified as discriminative for autism. For part A, failing any 2 of 7 key questions, ie, question 13 (does your child imitate you? [eg, you make a face; will your child imitate it?]), question 5 (does your child ever pretend, for example, to talk on the phone or take care of dolls, or pretend other things?), question 7 (does your child ever use his/her index finger to point, to indicate interest in something?), question 23 (does your child look at your face to check your reaction when faced with something unfamiliar?), question 9 (does your child ever bring objects over to you [parent] to show you something?), question 15 (if you point at a toy across the room, does your child look at it?), and question 2 (does your child take an interest in other children?), yielded sensitivity of 0.931 and specificity of 0.768. Failing any 6 of all 23 questions produced sensitivity of 0.839 and specificity of 0.848. For part B, failing any 2 of 4 items produced sensitivity of 0.736, specificity of 0.912, and PPV of 0.853. The 4 observational items were as follows: item B1: during the appointment, has the child made eye contact with you? item B2: does the child look across to see what you are pointing at? item B3: does the child pretend to pour out tea, drink it, etc?; item B4: does the child point with his/her index finger at the light? CONCLUSION: We found that integrating the screening questions of the M-CHAT (from the United States) and observational section B of the original CHAT (from the United Kingdom) yielded high sensitivity and specificity in discriminating autism at 18 to 24 months of age for our Chinese cohort. This new screening instrument (CHAT-23) is simple to administer. We found that a 2-stage screening program for autism can offer a cost-effective method for early detection of autism at 18 to 24 months. For CHAT-23, use of both the parental questionnaire and direct observation and use of the criterion of failing any 2 of 7 key questions yielded the highest sensitivity but a relatively lower specificity, whereas use of part B yielded the highest specificity but a lower sensitivity. We recommend identifying the possible positive cases with part A (parental questionnaire) and then proceeding to part B (observation) with trained assessors. The proposed algorithm for screening for autism is as follows. 1) The parents or chief caretakers complete a 23-item questionnaire when their children are 18 to 24 months of age. 2) The parents mail, fax, or hand this 23-item questionnaire to the local child health agency. 3) Clerical staff members check for and score failure, with the criteria of failing any 2 of 7 key questions or failing any 6 of 23 questions; if either criterion is met, then the staff members highlight the medical records of the suspicious cases. 4) Trained child health care professionals observe the children who failed any 2 of 7 key questions or any 6 of 23 questions. These identified patients are observed for 5 minutes for part B of the CHAT-23. 5) Any child who fails any 2 of 4 items requires direct referral to a comprehensive autism evaluation team, for early diagnostic evaluation and early intervention. The high sensitivity and specificity of the criteria observed in our study suggested that CHAT-23 might be used to differentiate children with autism. Additional international collaboration with the use of the CHAT, M-CHAT, and CHAT-23 could provide more prospective epidemiologic data, to establish whether there is a genuine increase in the worldwide incidence of autism.

Attention↗

PubMed2003

Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment.

The clinical significance of an interstitial duplication of (15)(q11-q13) remains unclear and controversial. The reported phenotypes vary widely and appear to be influenced by the parent of origin of the duplication. Aside from cases of dup(15) reported with autism, the behavioral phenotype of individuals with dup(15) has not been described. We present three families, two with intrachromosomal duplication (15)(q11-q13) ascertained because of developmental delay in a relative. Two families show clear evidence of multigenerational maternal inheritance. The individuals discussed in this paper have minor anomalies and developmental delays. In addition, we describe a behavioral phenotype which often includes attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder. Responses to medications used to manage these behaviors are also described, including a positive response to methylphenidate and a poor response to fluoxetine. The duplication in each presenting individual, and available family members, was investigated utilizing cytogenetic and molecular techniques including high resolution cytogenetics, fluorescence in situ hybridization (FISH), DNA methylation studies, and quantitative fluorescence PCR. High resolution cytogenetic techniques alone missed some cases, demonstrating the need to confirm results with other methods.

Child↗

PubMedDate not supplied

Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism.

Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism.

Adolescent↗

PubMed2001

[Speech development and intelligence in autism. How uniform is Asperger syndrome?].

Since the introduction of a separate diagnosis for Asperger's syndrome in the ICD-10 and DSM-IV classification systems, a controversial debate has continued on whether Asperger's syndrome is a specific, clearly distinguishable disorder within the autistic spectrum or whether it represents a milder phenotypical variation of autism. The effect on the amount of autistic symptoms of the variables language delay and level of intelligence was analyzed within a sample of individuals exhibiting autism diagnosed by standardized methods. Both variables showed a significant effect on the degree of autistic symptoms in that impairments in social interaction were less noticeable. In addition, a subsample of individuals exhibited symptoms assumed to be characteristic for Asperger's syndrome. The findings support the assumption that autism and Asperger's syndrome represent "extreme points" on a scale of severity, which leads to the suggestion that the classification of different subtypes of autism could be abandoned in favor of a dimensional (multiaxial) approach.

Adolescent↗

PubMed2006

The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial.

This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12 weeks that they were on the diet. Group data indicated no statistically significant findings even though several parents reported improvement in their children. Although preliminary, this study demonstrates how a controlled clinical trial of the GFCF diet can be conducted, and suggests directions for future research.

Adolescent↗

PubMed1992

Domain specificity in conceptual development: neuropsychological evidence from autism.

To understand some aspects of conceptual development it is necessary to take cognitive architecture into account. For this purpose, the study of normal development is often not sufficient. Fortunately, one can also study neurodevelopmental disorders. For example, autistic children have severe difficulties developing certain kinds of concepts but not others. We find that whereas autistic children perform very poorly on tests of the concept, believes, they are at or near ceiling on comparable tasks that test understanding of pictorial representation. A similar pattern was found in a second study which looked at understanding of a false map or diagram: normal 4-year-olds showed a marked advantage in understanding a false belief over a false map, while the autistic subjects performed better on the map. These findings suggest that the concept, believes, develops as a domain-specific notion that is not equatable with "having a picture (map or diagram) in the head." This result supports the existence of a specialized cognitive mechanism, which subserves the development of folk psychological notions, and which is dissociably damaged in autism. We extend these ideas to outline a new model of the development of false belief performance.

Autistic Disorder↗

PubMed1988

Children with inadequate language development: management guidelines for otolaryngologists.

Otolaryngologists are in the front line of physicians asked to evaluate children whose language development is lagging. The 4 most prevalent conditions to consider in the differential diagnosis are impaired hearing, mental deficiency, developmental language disorder or dysphasia, and one of the disorders on the autistic spectrum. Guidelines on when to become concerned and what to do about such children are provided. Early diagnosis is essential in order to provide remedial education at the language learning age when intervention is likely to be most efficacious.

Autistic Disorder↗

PubMed1999

Appropriate investigations for clinical care versus research in children with autism.

As disorders on the autistic spectrum are behaviorally defined, there is no medical test to diagnose autism. The purpose of a medical evaluation is to detect particular etiologies, and manifestations like clinical or subclinical epilepsy or behavior problems that might mandate pharmacologic intervention. Defining a unique syndrome or genetic etiology may benefit other family members, although, currently, specific causes are detectable in only a small minority of individuals on the autistic spectrum. The paper lists elements of the history, examination, and laboratory testing most likely to be informative in clinical practice. Ordering large numbers of tests in the absence of a specific clinical indication is not recommended because it is invasive, wasteful and unlikely to generate useful data. This is not true, of course, in the context of a hypothesis-driven, approved research protocol where collecting standardized data and applying the most up-to-date research technologies is appropriate.

Autistic Disorder↗

PubMed1998

Proton magnetic resonance spectroscopy of the brain in three cases of Rett syndrome: comparison with autism and normal controls.

Rett syndrome (RS) is a clinically defined disorder characterized by autistic behavior, and cognitive and motor skill loss early in life. We performed 1H-MRS of the brain in 3 cases of RS in comparison with in autism and controls. The older patient with RS demonstrated decreased N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine (Cr) ratios when compared with the autism and control groups, whereas the younger patients did not demonstrate these decreased metabolite ratios. The Cho/Cr ratio did not differ among Rett syndrome, autism and controls. Since the clinical stage did not differ among the 3 cases of RS, it was suggested that NAA was decreased with increasing age and was not related with the clinical stage of RS. The NAA/Cho, NAA/Cr and Cho/Cr ratios did not differ between autism and controls. The present data suggest that there may be a secondary degenerative process of late onset in RS, which pathophysiologically differs from autism.

Adolescent↗

PubMed2004

Should autistic children be evaluated for mitochondrial disorders?

Autism is etiologically heterogeneous; medical conditions are implicated in only a minority of cases, whereas metabolic disorders are even less common. Recently, there have been articles describing the association of autism with mitochondrial abnormalities. We critically review the current literature and conclude that mitochondrial disorders are probably a rare and insignificant cause of pure autism; however, evidence is accumulating that both autosomal recessive and maternally inherited mitochondrial disorders can present with autistic features. Most patients will present with multisystem abnormalities associated with autistic behavior. Finding biochemical or structural mitochondrial abnormalities in an autistic child does not necessarily imply a primary mitochondrial disorder but can also be secondary to technical inaccuracies or another genetic disorder. Clinicians should be careful in diagnosing a mitochondrial disorder in an autistic child because it has important implications for accurate genetic counseling, prognosis, and therapy.

Autistic Disorder↗

PubMed2003

General practitioners' knowledge on childhood developmental and behavioural disorders.

INTRODUCTION: Childhood developmental and behavioural disorders are increasingly being recognised, with high demands for earlier diagnosis and intervention. In Singapore, referrals to the Child Development Unit, KK Women's and Children's Hospital, originate mainly from primary health care practitioners, who therefore should have adequate baseline knowledge of normal development as well as common developmental and behavioural disorders. METHODOLOGY: A pilot study, using a questionnaire survey, was conducted, with the aim of assessing existing knowledge in childhood developmental and behavioural paediatrics amongst a cohort of general practitioners (GPs) in Singapore. True/False questions on normal development as well as developmental disorders such as autistic spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD) and learning disability, were structured. These disorders were selected because of their relatively higher prevalence. RESULTS: A total of 48 GPs were surveyed, representing 2% of non-specialists practising in the private sector. The median total score (T-score) was 9 (range 6 to 13) of a possible 14. Only just over a-third of the group achieved the pass rate (defined arbitrarily as 75%) for T-score, with two-thirds replying correctly to all questions on normal development. Scores for factual ASD/ADHD questions were also not ideal, with some myths being believed as truths. CONCLUSION: The scores reflect knowledge and educational deficits in developmental paediatric medicine amongst the study cohort. Expected to provide holistic care and counselling, these GPs are currently insufficiently equipped with the necessary knowledge and skills to support families of special-needs children. Education and training programmes in this aspect of paediatric medicine are clearly needed, through the organisation of CME lectures and incorporation of various developmental topics into the training curriculum. This will enable early identification and diagnosis of childhood developmental and behavioural disorders, which will in turn allow greater optimisation of potential and functionality in these special-needs children.

Adult↗

PubMed2006

Asperger syndrome revisited.

Asperger syndrome (AS) is a disorder on the continuum of autistic spectrum disorders characterized by a lack of social reciprocity and empathy, and severe difficulties in social integration. Controversy remains as to what constitutes AS and whether it should be declared a separate disease or higher-functioning autism. This review discusses the contributions made by Hans Asperger and Leo Kanner in first delineating the condition, and examines the syndrome's incidence, prevalence, and etiologies. Recent studies using neuroimaging are described, along with current diagnostic and treatment options.

Affective Symptoms↗

PubMed2005

Measuring autistic traits: heritability, reliability and validity of the Social and Communication Disorders Checklist.

BACKGROUND: Autistic traits are widely distributed in the general population, but the boundaries of the autistic spectrum are unclear. Whole-population surveys of unselected samples of children are hampered by the lack of appropriate screening instruments. AIMS: To assess whether the Social and Communication Disorders Checklist (SCDC) fulfils the need for a sensitive measure of autistic traits, which can be completed in a few minutes and which measures heritable characteristics in both males and females. METHOD: A12-item scale, the SCDC, was completed by three independent samples drawn from a twin register, a group with Turner syndrome and children with a diagnosis of autistic-spectrum disorder attending clinics. The data were used to establish the heritability, reliability and validity of the checklist. RESULTS: Traits measured by the SCDC were highly heritable in both genders (0.74). Internal consistency was excellent (0.93) and test - retest reliability high (0.81). Discriminant validity between pervasive developmental disorder and other clinical groups was good, discrimination from non-clinical samples was better; sensitivity (0.90), specificity (0.69). CONCLUSIONS: The SCDC is a unique and efficient first-level screening questionnaire for autistic traits.

Adolescent↗