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PubMed2002

[Developmental amnesias].

OBJECTIVE: The literature on clinical and physiophatologic characteristics of the spectrum of memory disorders in childhood is reviewed in this article. DEVELOPMENT: There are only a few detailed reports of permanent specific memory disorders in children. Early anoxo ischaemic bihippocampal injuries can cause a selective permanent impairment of episodic daily life memory with preservation of semantic learning and general intelligence; this dissociation has been related to partial hippocampal damage whilst the entorhinal, parahippocampal and prefrontal cortices, which are critical to systematized memorizing and work memory, keep normal. Biological psychiatry research has shown that early childhood amnesias after psychological maltreatment or abuse could be related to damage in neuronal systems which support memory, caused by glutamatergic cascade. Both severe bilateral hippocampal sclerosis (also mediated by toxic neurotransmitters) in early malignant epilepsies, and massive bilateral damage of mesial temporal lobes due to herpex virus encephalitis or Reye's syndrome, cause severe amnesic deficits, frequently accompanied by absence of any language development and autism with features of Klüver-Bucy syndrome. There are also on record some examples of Korsakoff's syndrome in children with midfossa tumors. CONCLUSIONS: All types of classical amnesias described in adults have been observed in children. Developmental amnesias are probably more frequent than currently presumed. It must be paid special attention to selective autobiographical memory impairments in individuals who underwent a partial bihippocampal damage in perinatal or early postnatal periods; they are to be distinguished from, although it may coexist with, other clinical situations such as attention deficit disorder or semantic pragmatic disorder.

Adult↗

PubMed2005

Neurologic presentation of celiac disease.

Celiac disease (CD) long has been associated with neurologic and psychiatric disorders including cerebellar ataxia, peripheral neuropathy, epilepsy, dementia, and depression. Earlier reports mainly have documented the involvement of the nervous system as a complication of prediagnosed CD. However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology. These include migraine, encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex, Guillain-Barre-like syndrome, and neuropathy with positive antiganglioside antibodies. The association between most neurologic syndromes described and gluten sensitivity remains to be confirmed by larger epidemiologic studies. It further has been suggested that gluten sensitivity (as evidenced by high antigliadin antibodies) is a common cause of neurologic syndromes (notably cerebellar ataxia) of otherwise unknown cause. Additional studies showed high prevalence of gluten sensitivity in genetic neurodegenerative disorders such as hereditary spinocerebellar ataxia and Huntington's disease. It remains unclear whether gluten sensitivity contributes to the pathogenesis of these disorders or whether it represents an epiphenomenon. Studies of gluten-free diet in patients with gluten sensitivity and neurologic syndromes have shown variable results. Diet trials also have been inconclusive in autism and schizophrenia, 2 diseases in which sensitivity to dietary gluten has been implicated. Further studies clearly are needed to assess the efficacy of gluten-free diet and to address the underlying mechanisms of nervous system pathology in gluten sensitivity.

Autistic Disorder↗

PubMed1997

Reaction times to mental state and non-mental state questions in false belief tasks by high-functioning individuals with autism.

Nine people from the high functioning end of the autistic spectrum and eight non-handicapped controls matched on verbal IQ were given two tests of second-order false belief understanding. On the basis of previous research, it was hypothesised that the subjects with autism used different mechanisms to process mental state and non-mental state questions and that this difference would be reflected in a significant group by question type interaction in the reaction times to the two types of question. Although the results showed that the autistic subjects had longer reaction times to questions than controls, there was no evidence for differential reaction times for mental state and non mental state questions for either group.

Adult↗

PubMed2005

From complexity to category: responding to diagnostic uncertainties of autistic spectrum disorders.

OBJECTIVE: Recent data from Education Queensland has identified rising numbers of children receiving diagnoses of autistic spectrum disorder (ASD). Faced with funding diagnostic pressures, in clinical situations that are complex and inherently uncertain, it is possible that specialists err on the side of a positive diagnosis. This study examines the extent to which possible overinclusion of ASD diagnosis may exist in the presence of uncertainty and factors potentially related to this practice in Queensland. METHODS: Using anonymous self-report, all Queensland child psychiatrists and paediatricians who see paediatric patients with development/behavioural problems were surveyed and asked whether they had ever specified an ASD diagnosis in the presence of diagnostic uncertainty. Using logistic regression, elicited responses to the diagnostic uncertainty questions were related to other clinical- and practice-related characteristics. RESULTS: Overall, 58% of surveyed psychiatrists and paediatricians indicated that, in the face of diagnostic uncertainty, they had erred on the side of providing an ASD diagnosis for educational ascertainment and 36% of clinicians had provided an autism diagnosis for Carer's Allowance when Centrelink diagnostic specifications had not been met. CONCLUSION: In the absence of definitive biological markers, ASD remains a behavioural diagnosis that is often complex and uncertain. In response to systems that demand a categorical diagnostic response, specialists are providing ASD diagnoses, even when uncertain. The motivation for this practice appears to be a clinical risk/benefit analysis of what will achieve the best outcomes for children. It is likely that these practices will continue unless systems change eligibility to funding based on functional impairment rather than medical diagnostic categories.

Autistic Disorder↗

PubMed2005

Stimulus over-selectivity in rats.

The present study explored whether a similar phenomenon to stimulus over-selectivity occurred in rats, in the hope of establishing a non-human model for the autism. Rats were serially presented with two-15 seconds, two-element compound stimuli prior to the delivery of food, in an appetitive classical conditioning procedure. Each compound stimulus consisted of two lights. Once the rats had acquired a conditioned response (CR) to the stimuli, they were presented with each of the component elements separately in extinction. The rats demonstrated greater conditioning to components of the compound presented just prior to reinforcement than to the components of the temporally distant compound. However, there was a smaller difference between CRs to the components of the compound presented just prior to reinforcement (i.e. less overshadowing) than between the components of the temporally distant compound. It is suggested that rats demonstrated a form of stimulus over-selectivity, resulting in greater overshadowing of one cue by another. Such results may form the basis of a viable non-human model of this symptom of autistic spectrum disorder.

Animals↗

PubMedDate not supplied

[The communication of autistic spectrum children in group activities].

BACKGROUND: language is the most useful diagnostic feature in cases of infantile autism, and is many times connected with the prognosis. OBJECTIVE: to identify the communication profile of autistic spectrum children through the analysis of the functional use of language in two different communication situations. METHOD: five groups of recordings of 10 institutionalized children, during a period of 12 months, in two different communication situations: situation I (in a group with co-ordination) and situation II (in a group without co-ordination). RESULTS: in both situations of communication there was a significant change in the communication profile of these children. CONCLUSION: it can be observed that these children do perceive the differences present in situations of communication.

Adolescent↗

PubMed1996

A broader phenotype of autism: the clinical spectrum in twins.

The diagnostic boundaries of the behavioural phenotype for autism were examined in 28 MZ pairs and 20 DZ same-sex twin pairs, where one or both twins had autism. In the non-autistic cotwin (i.e. in twin pairs discordant for autism) it was common to find language impairments in childhood and social deficits persisting into adulthood. Concordance for this broader phenotype was much greater in MZ pairs than DZ pairs, indicating a strong genetic component. Behavioural and cognitive manifestations of autism were compared both within and between MZ twin pairs. The variation was as great within MZ twin pairs as between pairs, suggesting that it does not index genetic heterogeneity (although aetiological heterogeneity probably exists). Current diagnostic practices need re-evaluation.

Activities of Daily Living↗

PubMed2000

Autism--an evolving concept.

BACKGROUND: The rapid increase in research endeavour has not kept pace with the advent of well-publicized theories and treatments for autism. AIMS: To explore some of the newer developments in biological research into autism. METHOD: A review of recent publications and presentations. RESULTS: The concept is shifting from the narrow perception of aloof autism, described by Kanner, to a wider one that includes a spectrum extending to a broader, subclinical phenotype. The genetic basis has been established; now we need to discover the location and interaction of the relevant sites. There is considerable interest in the bowel as a pathogenetic agent, particularly in the effects of exogenous opioids and multiple viral infection (the latter posing a public health problem). Also of concern is the role of (potentially treatable) epilepsy, analogous to the Laudau-Kleffner syndrome. CONCLUSIONS: In the absence of a cure, the implementation of ideas will continue to outstrip factual evidence. Clinicians are challenged by the availability of information (and misinformation), particularly on the internet.

Autistic Disorder↗

PubMed2004

Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder.

OBJECTIVE: Determine the effect of a moderate dose multivitamin/mineral supplement on children with autistic spectrum disorder. DESIGN: Randomized, double-blind, placebo-controlled 3-month study. SUBJECTS: Twenty (20) children with autistic spectrum disorder, ages 3-8 years. RESULTS: A Global Impressions parental questionnaire found that the supplement group reported statistically significant improvements in sleep and gastrointestinal problems compared to the placebo group. An evaluation of vitamin B(6) levels prior to the study found that the autistic children had substantially elevated levels of B6 compared to a control group of typical children (75% higher, p < 0.0000001). Vitamin C levels were measured at the end of the study, and the placebo group had levels that were significantly below average for typical children, whereas the supplement group had near-average levels. DISCUSSION: The finding of high vitamin B(6) levels is consistent with recent reports of low levels of pyridoxal-5-phosphate and low activity of pyridoxal kinase (i.e., pyridoxal is only poorly converted to pyridoxal-5-phosphate, the enzymatically active form). This may explain the functional need for high-dose vitamin B(6) supplementation in many children and adults with autism.

Adult↗

PubMed2004

Not EEG abnormalities but epilepsy is associated with autistic regression and mental functioning in childhood autism.

The aim of the study was to investigate the potential association of epilepsy and EEG abnormalities with autistic regression and mental retardation. We examined a group of 77 autistic children (61 boys, 16 girls) with an average age of 9.1 +/- 5.3 years. Clinical interview, neurological examination focused on the evaluation of epilepsy, IQ testing, and 21-channel EEG (including night sleep EEG recording) were performed. Normal EEGs were observed in 44.4% of the patients, non-epileptiform abnormal EEGs in 17.5%, and abnormal EEGs with epileptiform discharges in 38.1% of the patients. Epilepsy was found in 22.1% of the subjects. A history of regression was reported in 25.8% of the patients, 54.8% of the sample had abnormal development during the first year of life, and 79.7% of the patients were mentally retarded. Autistic regression was significantly more frequent in patients with epilepsy than in non-epileptic patients (p = 0.003). Abnormal development during the first year of life was significantly associated with epileptiform EEG abnormalities (p = 0.014). Epilepsy correlated significantly with mental retardation (p = 0.001). Although the biological basis and possible causal relationships of these associations remain to be explained, they may point to different subgroups of patients with autistic spectrum disorders.

Adolescent↗

PubMed2006

The Autism-Spectrum Quotient (AQ) in Japan: A cross-cultural comparison.

The AQ (Autism-Spectrum Quotient) is a self-administered instrument for measuring the degree to which an adult with normal intelligence has the traits associated with the autistic spectrum. The AQ was administered in Japan to test whether the UK results would generalize to a very different culture. Three groups of subjects, adults with AS or HFA (n = 57), adult controls (n = 194), and University students (n = 1050) were assessed. The adults with AS/HFA had a mean AQ score which was significantly higher than both the controls and the University students. Among the controls, males scored significantly higher than females. The similarity of results in both the general population and the clinical group across the two cultures was remarkable.

Adolescent↗

PubMed2006

The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System.

Adult↗

PubMed2006

Attention to facial emotion expressions in children with autism.

High-functioning children in the autism spectrum are frequently noted for their impaired attention to facial expressions of emotions. In this study, we examined whether attention to emotion cues in others could be enhanced in children with autism, by varying the relevance of children's attention to emotion expressions. Twenty-eight high-functioning boys with autism and 31 boys from a control group were asked to sort photos depicting smiling or frowning faces of adults. As found in earlier studies, in neutral conditions children with autism were less attentive to emotion expressions than children from a control group. This difference disappeared when children were explicitly asked to make a socially relevant decision. These findings suggest that the attention of children with autism to emotion expressions in others is influenced by situational factors. Theoretical implications of these findings are discussed.

Affect↗

PubMed2006

Autism from 2 to 9 years of age.

CONTEXT: Autism represents an unusual pattern of development beginning in the infant and toddler years. OBJECTIVES: To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis. DESIGN: Prospective study of diagnostic classifications from standardized instruments including a parent interview (Autism Diagnostic Interview-Revised [ADI-R]), an observational scale (Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ADOS]), and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team's criterion standard diagnoses. SETTING: Three inception cohorts: consecutive referrals for autism assessment to (1) state-funded community autism centers, (2) a private university autism clinic, and (3) case controls with developmental delay from community clinics. PARTICIPANTS: At 2 years of age, 192 autism referrals and 22 developmentally delayed case controls; 172 children seen at 9 years of age. MAIN OUTCOME MEASURES: Consensus best-estimate diagnoses at 9 years of age. RESULTS: Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67, with a weighted kappa of 0.72. Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism. Each measure at age 2 years was strongly prognostic for autism at age 9 years, with odds ratios of 6.6 for parent interview, 6.8 for observation, and 12.8 for clinical judgment. Once verbal IQ (P = .001) was taken into account at age 2 years, the ADI-R repetitive domain (P = .02) and the ADOS social (P = .05) and repetitive domains (P = .005) significantly predicted autism at age 9 years. CONCLUSIONS: Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified. Judgment of experienced clinicians, trained on standard instruments, consistently added to information available from parent interview and standardized observation.

Adult↗

PubMed2006

Sleep electroencephalograms in young children with autism with and without regression.

A link has been postulated between regressive autism and the spectrum of epileptic encephalopathic conditions including Landau-Kleffner syndrome with the suggestion that subclinical epilepsy may be causative of regression in autism. This is an audit of investigation using sleep electroencephalograms (EEG) in 64 children (56 males, 8 females; mean age 35.6mo [SD 8.2mo]; range 18-48mo) with autism. No child had a history suggestive of epilepsy. Thirty-nine of the children presented with regressive autism and 20 of the participants showed some epileptiform abnormality. There was no significant difference in epileptiform activities in those who showed regression compared with those who did not. No child showed electrical status epilepticus with continuous spike-wave discharges in slow sleep. There was no evidence that these cases of autism with and without regression were associated with epileptic encephalopathy. The significance of epileptiform discharges without epilepsy in the sleep EEG in autism remains unknown.

Autistic Disorder↗

PubMed1997

A comparative study of Asperger syndrome with high-functioning atypical autism.

To test the validity of Asperger syndrome (AS) as defined in ICD-10, 26 patients (age range, 3.5 to 12 years) with AS and 16 patients (age range, 3 to 11.5 years) with high-functioning (IQ > 90) ICD-10 atypical autism (HAA) were compared on 64 clinical variables including obstetric risk factors, early developmental landmarks, IQ, autistic symptoms on the CARS-TV, epileptic EEG abnormalities and epilepsy. AS did not differ significantly from HAA on all but total and four item scores (i.e. imitation, visual responsiveness, auditory responsiveness and non-verbal communication) on the CARS-TV, in which AS scored significantly lower than HAA. A discriminant function based on imitation and auditory responsiveness predicted 76.2% of the 42 cases. The small difference from HAA indicates that AS is better to be regarded as the highest-functioning end of the PDD spectrum, rather than a valid subtype of PDD. However, the autistic symptom profile less distorted in AS than HAA may warrant a further study on its validity.

Autistic Disorder↗

PubMed2003

Supporting children on the autism spectrum in peer play at home and school: piloting the integrated play groups model in Taiwan.

The article focuses on integrated play groups (IPGs) as a model to support children with ASD in play with typically developing peers/siblings, and its recent adoption with children in a home and school setting in Taiwan. The first part provides a brief overview of the IPG model and its essential features. The second part reports on a pilot investigation that combined quantitative and qualitative methods to examine the effects of participation in IPGs on the symbolic and social play of two early elementary-aged children with autism. Preliminary findings suggest that each child made notable gains in reciprocal social interaction and symbolic/pretend play while participating in play groups. Implications are discussed in terms of play's role in enhancing socialization, imagination and peer cultural inclusion.

Autistic Disorder↗

PubMed2000

Short-term benefit from oral vancomycin treatment of regressive-onset autism.

In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology. To help test this hypothesis, 11 children with regressive-onset autism were recruited for an intervention trial using a minimally absorbed oral antibiotic. Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up. Although the protocol used is not suggested as useful therapy, these results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism.

Administration, Oral↗