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PubMed1998

Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders.

Comprehensive data on the developmental history and current behaviours of a large sample of high-functioning individuals with diagnoses of autism, Asperger's syndrome, or other related disorder were collected via parent interviews. This provided the basis for a taxonomic analysis to search for subgroups. Most participants also completed theory of mind tasks. Three clusters or subgroups were obtained; these differed on theory of mind performance and on verbal abilities. Although subgroups were identified which bore some relationship to clinical differentiation of autistic, Asperger syndrome, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) cases, the nature of the differences between them appeared strongly related to ability variables. Examination of the kinds of behaviours that differentiated the groups suggested that a spectrum of autistic disorders on which children differ primarily in term of degrees of social and cognitive impairments could explain the findings.

Adolescent↗
PubMed2000

Reciprocal social behavior in children with and without pervasive developmental disorders.

An invariant feature of pervasive developmental disorders (PDDs) is a relative deficit in the capacity for reciprocal social behavior (RSB). The authors acquired teacher reports of RSB in 287 schoolchildren and parent reports of RSB in 158 child psychiatric patients using a new research instrument, the Social Reciprocity Scale. Total scores on this measure of RSB were continuously distributed in all groups of subjects; children with PDDs scored significantly higher for the degree of deficits in RSB than did clinical or nonclinical controls. Latent class analysis and factor analysis failed to demonstrate separate categories of deficiency for core autistic symptomatology and more general impairments in RSB, consistent with the notion of a "broader autism phenotype." Assessments of RSB on a continuous scale may be useful clinically for characterizing the behavior of children whose social deficits fall below the threshold for a full diagnosis of autism. They may also be useful in genetic-linkage studies of autistic spectrum disorders.

Adolescent↗
PubMed2005

Self injurious behavior in autism: clinical aspects and treatment with risperidone.

Self injurious behavior (SIB) is frequent in autistic spectrum disorders. The aim of this study was to investigate the phenomenology of SIB in a group of children with autistic disorder, and to test whether treatment with risperidone might reduce it. A group of eleven children diagnosed with autistic disorder according to the DSM-IV criteria (mean age 8.7+/-2.2 ys) and with severe SIB were recruited for an open study of six months of treatment with risperidone. The Yale-Paris Self-Injurious Behavior Scale was used to delineate the clinical characteristics and as an outcome measure. Head-hitting and hand biting were the most frequent forms of self aggression observed. Nine children presented a mild improvement in SIB and 2 did not show any variation. A decrease in Yale-Paris Self Injurious Behavior Scale score (from M 15.1+/-1.4 to 13.3+/-1.4) was noted mainly due to the reduction of frequency. Side effects of risperidone were not severe.

Antipsychotic Agents↗
PubMed2004

Essential fatty acids and phospholipase A2 in autistic spectrum disorders.

A health questionnaire based on parental observations of clinical signs of fatty acid deficiency (FAD) showed that patients with autism and Asperger's syndrome (ASP) had significantly higher FAD scores (6.34+/-4.37 and 7.64+/-6.20, respectively) compared to controls (1.78+/-1.68). Patients with regressive autism had significantly higher percentages of 18:0,18:2n-6 and total saturates in their RBC membranes compared to controls, while 24:0, 22:5n-6, 24:1 and the 20:4n-6/20:5n-3 ratio were significantly higher in both regressive autism and ASP groups compared to controls. By comparison, the 18:1n-9 and 20:4n-6 values were significantly lower in patients with regressive autism compared to controls while 22:5n-3, total n-3 and total dimethyl acetals were significantly lower in both regressive autism and ASP groups compared to controls. Storage of RBC at -20 degrees C for 6 weeks resulted in significant reductions in highly unsaturated fatty acid levels in polar lipids of patients with regressive autism, compared to patients with classical autism or ASP, or controls. Patients diagnosed with both autism and ASP showed significantly increased levels of EPA ( approximately 200%) and DHA ( approximately 40%), and significantly reduced levels of ARA ( approximately 20%), 20:3n-6 and ARA/EPA ratio in their RBC polar lipids, when supplemented with EPA-rich fish oils, compared to controls and non-supplemented patients with autism. Patients with both regressive autism and classical autism/Asperger's syndrome had significantly higher concentrations of RBC type IV phospholipase A2 compared to controls. However, patients with autism/ASP, who had taken EPA supplements, had significantly reduced PLA2 concentrations compared to unsupplemented patients with classical autism or ASP.

Asperger Syndrome↗
PubMed2005

Open-label risperidone for Asperger's disorder: negative symptom spectrum response.

OBJECTIVE: Asperger's disorder consists of negative symptoms similar to those seen in schizophrenia, autism, schizoid personality disorder, and schizotypal personality disorder. We investigated whether risperidone, which is effective in treating the negative symptoms of schizophrenia, would improve such symptoms observed in Asperger's disorder in a prospective, open-label trial. METHOD: Thirteen male patients aged 6 to 18 years who were diagnosed with Asperger's disorder by DSM-IV criteria were enrolled in a 12-week, prospective, open-label pilot study from March 13, 2002 to August 11, 2003. All subjects were started on risperidone 0.25 mg twice per day. Doses were increased based on clinical indication and tolerability. The primary efficacy variable was the Scale for the Assessment of Negative Symptoms (SANS). Each subject's baseline score served as his control. Secondary efficacy measures included the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Montgomery-Asberg Depression Rating Scale, Global Assessment Scale, and a modified Asperger Syndrome Diagnostic Scale. RESULTS: We found a statistically significant improvement from baseline for last-observation-carried-forward (LOCF) analyses as well as for analyses of 12-week completers (N = 9) in our primary outcome measure, SANS scores (F = 13.41, p < .0001 for 12-week completers; F = 9.64, p < .0001 for LOCF). We also found statistically significant improvement in all secondary efficacy measurements (F values range, 8.41 to 15.73, p values range, < .0001 to < .005 for 12-week completers; F values range, 6.53 to 7.75, all p < .0001 for LOCF). CONCLUSIONS: Subjects' symptoms significantly improved after risperidone. The open-label nature of this small pilot study suggests caution in interpreting these data, but the results suggest that placebo-controlled trials should follow.

Adolescent↗
PubMed2002

[Communication and language in the autistic spectrum: autism and dysphasia].

INTRODUCTION: The alterations of language and communication seen in children with autistic spectrum disorders (TEA) have some similar and some dissimilar features to those seen in children with specific language disorders (TEL). The basic disorder of TEA seems to be due to alterations in the social and mental use of codes of communication, both verbal and non verbal. Children with TEL however have better non verbal and practical abilities. OBJECTIVE: In view of this, we decided to determine the qualitative difference in function in communication and language between the two populations. PATIENTS AND METHODS: The great heterogeneity between persons with autistic spectrum disorders and even variation between individuals makes investigation of large groups difficult. It is therefore necessary to study individual cases or groups with small numbers. If we fix our attention on language and communication, it is important to define subtypes of function with the population affected by the autistic spectrum of disorders at an early age, in the fields of communication, receptive language and expressive language in our small sample of persons; taking the normal course of development in each field as the parameter for comparison. This is a pilot study within a long term research project. RESULTS: The results reported here are the preliminary findings of what will be a more extensive study with fuller analysis of the results. CONCLUSIONS: The preliminary findings suggest that there are different linguistic and communication function profiles in the different populations compared.

Aphasia↗
PubMed2004

Neurologic treatment strategies in autism: an overview of medical intervention strategies.

Child neurologists are likely to be caring for an increasing number of patients with autistic spectrum disorder (ASD). ASD may occur in as many as 1/100 to 1/200 births. It appears to be a multifactorial disease, with many phenotypes or subgroups. No simple treatment is currently approved for curing or managing core symptoms of autism. We rationally propose a symptom-based review of what treatments may offer relief to specific subtypes of clinical behaviors seen in autism. There is a lack of clinically based evidence on which to universally recommend a rational clinical algorithm for treatment; we suggest that rational pharmacotherapy may offer symptomatic relief to core areas of dysfunction in the autistic population. Future research into rational medical treatment options is desperately needed.

Aggression↗
PubMed2000

Pervasive developmental disorders: a 10-year review.

OBJECTIVE: To summarize recent advances about the nature, diagnosis, and treatment of pervasive developmental disorders. METHOD: Review of Medline databases, books, and book chapters published between July 1989 and November 1999. RESULTS: Clinical and genetic studies support expansion of the concept of autism to include a broader spectrum of social communication handicaps. The prevalence of autism is approximately 1 per 2,000; the prevalence of autism and Asperger's disorder together is 1 per 1,000. The Checklist for Autism in Toddlers is a useful screening instrument for 18-month-old children; the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule are instruments of choice for research. Although twin and family studies clearly support genetic factors as important in autism, linkage analysis studies indicate that many genes may be involved. There is no one treatment of choice. Social-pragmatic approaches, augmented by individualized strategies and social coaching, may be best for teaching social communication skills. Pharmacological interventions have a limited role in improving social communication, but selective serotonin reuptake inhibitors and atypical neuroleptic medications may help ameliorate aggression, hyperactivity, and other secondary problems. CONCLUSIONS: Private and government agencies must continue to support basic and applied research.

Autistic Disorder↗
PubMed2006

Frontal anatomy and reaction time in Autism.

Widespread frontal lobe abnormalities, encompassing anatomy and function, are known to be implicated in Autistic Spectrum Disorders (ASD). The correlation between neurobiology and behaviour, however, is poorly understood in ASD. The aim of this study was to investigate frontal lobe anatomy and cognitive function in individuals with ASD, compared to control subjects. Thus, we assessed whole brain and frontal lobe parenchymal volume, and grey and white matter density differences in ASD, compared to control subjects, using high resolution T1-weighted magnetic resonance imaging (MRI). Furthermore, all subjects underwent a computerized reaction time task (RTT) for cognitive assessment. No differences in total parenchymal brain volume were observed, however, autistic individuals showed significantly smaller frontal lobe parenchymal volume (FLPV) and decreased white matter density, compared to control subjects. Error rates did not differ significantly between groups during the RTT, but ASD individuals responded significantly slower to target stimuli. Furthermore, reduced FLPV correlated positively with increased reaction time in individual with ASD. Decreased FLPV could be an indicator for abnormal brain development resulting in reduced processing speed in ASD.

Adult↗
PubMed2005

Autism interventions: a critical update.

As yet, there is no aetiology-based intervention for autistic spectrum disorders (ASD); despite this, parents and professionals still need to make informed decisions regarding treatment options for children with ASD. This paper seeks to evaluate widely used interventions according to specific research criteria. Interventions presented are grouped into psychoeducational/behavioural approaches, psychopharmacological interventions, and the less traditional or complementary approaches. The conclusions are less than favourable: while some interventions do have empirical support, others have been proven to have no positive effects, and furthermore, there are no robust data favouring one approach over the others. Nevertheless, several criteria for choosing between treatment options are briefly discussed.

Autistic Disorder↗
PubMed2007

Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.

Adolescent↗
PubMed2000

Epilepsy and epileptiform EEG: association with autism and language disorders.

The relationship between epilepsy, language, behavior, and cognition is not well understood. Developmental and acquired disabilities such as autistic spectrum disorders, Landau-Kleffner Syndrome, electrical status epilepticus in sleep, and developmental dysphasias have been associated with epileptiform abnormalities. These disorders share many common features and raise important questions regarding this intricate relationship. This article reviews these disorders and discusses the proposed interaction between epileptiform abnormalities and cognitive dysfunction. Diagnostic and treatment issues will also be reviewed.

Autistic Disorder↗
PubMed1999

The screening and diagnosis of autistic spectrum disorders.

The Child Neurology Society and American Academy of Neurology recently proposed to formulate Practice Parameters for the Diagnosis and Evaluation of Autism for their memberships. This endeavor was expanded to include representatives from nine professional organizations and four parent organizations, with liaisons from the National Institutes of Health. This document was written by this multidisciplinary Consensus Panel after systematic analysis of over 2,500 relevant scientific articles in the literature. The Panel concluded that appropriate diagnosis of autism requires a dual-level approach: (a) routine developmental surveillance, and (b) diagnosis and evaluation of autism. Specific detailed recommendations for each level have been established in this document, which are intended to improve the rate of early suspicion and diagnosis of, and therefore early intervention for, autism.

Asperger Syndrome↗
PubMed2003

How well does early diagnosis of autism stand the test of time? Follow-up study of children assessed for autism at age 2 and development of an early diagnostic service.

Twenty children who presented with severe and communication difficulties at age 2 underwent a comprehensive assessment for autism, and were reassessed at age 4-5. In common with other recent studies, diagnosis of autistic spectrum disorders at age 2 was found to be reliable and stable. The communication and social skills of the children showed little change overall by the second assessment. However, children whose scores deteriorated in the social domain tended to have presented initially with more significant behaviour problems. Few repetitive behaviours were observed at age 2, whereas these were more apparent by age 4-5. The finding that early diagnosis of autism is reliable and stable has led to the development of an early diagnostic service in Southampton, which is described. The importance of early diagnosis is that it opens the door to early intervention programmes, which in turn prevent many problems from occurring in later life.

Age of Onset↗
PubMed1993

Fragile-X syndrome and autism: a prevalent association or a misinterpreted connection?

The present study surveys autistic behavioral characteristics of 58 mentally retarded male adults with fragile-X syndrome. Results were compared with a control group of 58 fragile-X negative mentally retarded men, matched on age, cognitive level, living conditions and length of institutionalisation. We demonstrate that this and other controlled studies have not given much evidence for a specific association between fra(X) syndrome and the global diagnosis of autism. A high proportion of fra(X) adults display a limited number of specific behavioral characteristics that belong to the spectrum of pervasive developmental disorders. Non-functional body movements, unacceptable vocal and speech habits, social avoidance reactions and eccentric peculiarities are significantly different between the two groups. We further propose that the core features of autism, namely social indifference and severely disturbed social relations, are in general not found in the fra(X) group. On the contrary, they had a more positive general mood, were more sensitive to social contact and attention from others and approached not only new physical environments but also other people with great openness and interest. Moreover, we found that fra(X) adults had average interpersonal and communicative skills. This peculiar combination of "autistic-like" behavior and social sensitivity or openness could probably be accounted for by feelings of social anxiety. Finally implications of this "social anxiety" hypothesis for research and treatment are discussed.

Activities of Daily Living↗
PubMed2006

The importance of catatonia and stereotypies in autistic spectrum disorders.

Motor disturbances are often observed in individuals with autistic spectrum disorders (ASDs) and recognized as diagnostic features of these disorders. The movement disorders characteristically associated with autism include stereotypies and self-injurious behavior. Yet, individuals with ASD may also be at the risk for catatonia. Although not as frequent as stereotypies, up to 17% of older adolescents and adults with autistic disorder may have severe catatonic-like symptoms. Catatonia may be a comorbid risk factor of autism that warrants further empirical and clinical evaluations. Clinicians may need to be attentive to more subtle signs of catatonic-like symptoms in individuals diagnosed with ASDs, especially as they enter adolescence and young adulthood. Stress has been implicated as a possible precursor for symptoms; however, its role has not been empirically proven as a potential risk factor. Clinicians might also need to assess for signs of significant declines in motor movements, as this appears to be a useful diagnostic indicator of catatonic-like symptoms. The literature on stereotypies and autism is more extensive than for catatonia and ASDs, probably because of the higher rate of stereotypies with autism. Explanations for the occurrence of stereotypies range from genetic to behavioral contingencies, with evidence for a multifactor explanation. Assessment measures often include items that assess for stereotypies to aid with diagnosing these symptoms in individuals with autism. Treatment for stereotypies is largely behavioral at the present time and requires consistent reinforcement of treatment gains to manage the symptoms successfully. An important area of future research in autism is the relation among different types of motor abnormalities, including stereotypies and catatonia.

Adolescent↗
PubMed2006

Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.

Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.

Animals↗