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PubMed2006

An update on pharmacologic treatments for autism spectrum disorders.

Increasingly recognized over the past 20 years, autism spectrum disorders (ASD) are heterogeneous. Medication treatments remain fundamentally ameliorative, so prioritizing symptoms and matching medications to the patient's constellation of symptoms remains the psychopharmacologic approach to ASD. Atypical antipsychotic medications and glutamatergic agents are receiving increased attention, and antidepressants are being examined for specific symptoms and for younger patients who have autism. Large multisite networks (Research Units on Pediatric Psychopharmacology; Studies to Advance Autism Research and Treatment) have been constructed to expedite studies to elucidate effective treatments for ASD. Findings from these networks are coupled with those from recent independent trials.

Antidepressive Agents↗

PubMed2006

Use of the Mullen Scales of Early Learning for the assessment of young children with Autism Spectrum Disorders.

The psychological assessment is an important component of the diagnostic evaluation in young children suspected of having an Autism Spectrum Disorder but can be hampered by behavioral difficulties. Overt behaviors during administration of the Mullen Scales of Early Learning were coded in 22 preschoolers with an Autism Spectrum Disorder and 20 age-matched typically developing children. Children in the Autism Spectrum Disorder group required less time to complete the assessment but spent proportionally more time exhibiting off-task behaviors and less time engaged with the assessment. Scores obtained on the Mullen Scales were positively correlated with level of engagement and negatively correlated with off task behaviors.

Autistic Disorder↗

PubMed2005

Stepping Stones Triple P: a pilot study to evaluate acceptability of the program by parents of a child diagnosed with an Autism Spectrum Disorder.

The experience of parents of children with Autism Spectrum Disorder (ASD) in standard parenting programs has not been researched, although anecdotal evidence suggests that they do not find them acceptable. Forty-two parents of children with ASD were asked to view a DVD explaining individual parenting strategies from Stepping Stones, a new branch of the Triple P program targeted specifically at parents of children with disabilities. Parents were asked to rate each strategy for acceptability, usability and behavioural intention, i.e., their intention to use the strategy. Additionally, parental attributions and parental perceived control were explored as possible barriers to positive evaluations of Stepping Stones parenting strategies. A focus group of parents was used to gather more detailed parent response to the program. Parent responses to the program were generally positive and attribution of the child's behaviour to uncontrollable factors was found to predict higher ratings of usability. The results were interpreted within the context of Weiner's attributional theory and the theory of reasoned action. The limitations of this study and suggestions for future research are discussed.

Adolescent↗

PubMed2001

Predicting spoken language level in children with autism spectrum disorders.

Thirty-five children who received an autism spectrum diagnosis at the age of 2 years (24 with autism, 11 with PDD-NOS) were re-evaluated 2 years later to examine factors related to the development of spoken language. Child variables (play level, motor imitation ability and joint attention) and environmental variables (socioeconomic status and hours of speech/language therapy between ages 2 and 3) were used to predict an aggregate measure of language outcome at age 4. After controlling for age 2 language skills, the only significant predictors were motor imitation and number of hours of speech/language therapy. Implications of these results for understanding the early developmental course of autism spectrum disorders and the effects of intervention are discussed.

Autistic Disorder↗

PubMed2006

Development in infants with autism spectrum disorders: a prospective study.

BACKGROUND: Autism is rarely diagnosed before three years of age despite evidence suggesting prenatal abnormalities in neurobiological processes. Little is known about when or how development becomes disrupted in the first two years of life in autism. Such information is needed to facilitate early detection and early intervention. METHODS: This prospective study of autism spectrum disorders (ASD) examined development using the Mullen Scales of Early Learning (MSEL) in 87 infants tested at target ages 6, 14, and 24 months. Participants came from infants at high risk (siblings of children with autism) and low risk (no family history of autism) groups. Based on language test scores, Autism Diagnostic Observation Schedule, and clinical judgment at 24 months of age, participants were categorized as: unaffected, ASD, or language delayed (LD). Longitudinal linear regression and ANOVA models were applied to MSEL raw scores, and estimates were compared between the three diagnostic groups. RESULTS: No statistically significant group differences were detected at 6 months. By 14 months of age, the ASD group performed significantly worse than the unaffected group on all scales except Visual Reception. By 24 months of age, the ASD group performed significantly worse than the unaffected group in all domains, and worse than the language delayed group in Gross Motor, Fine Motor, and Receptive Language. The developmental trajectory of the ASD group was slower than the other groups', and showed a significant decrease in development between the first and second birthdays. CONCLUSIONS: Variations from typical and language delayed development are detectable in many children with ASD using a measure of general development by 24 months of age. Unusual slowing in performance occurred between 14 and 24 months of age in ASD.

Algorithms↗

PubMed2005

Incidence of autism spectrum disorders: changes over time and their meaning.

AIM: Several reviews have noted a huge increase in the rate of diagnosed autism spectrum disorders. The main aims of this paper are: 1) to use published empirical findings to consider whether the rise reflects a true increase in incidence, as distinct from the consequences of better ascertainment and a broadening of the diagnostic concept; and 2) to consider how epidemiological data may be used to test hypotheses about possible causal influences, using MMR and thimerosal as examples. METHODS: Search of the literature for studies with a large epidemiological base population, systematic standardized screening, a focus on an age group for which diagnostic assessments are reliable and valid, and diagnosis by trained professionals using high-quality research assessments. Also, search of a broader literature to consider the evidence from all epidemiological studies with respect to the hypothesized causal effect of MMR and thimerosal on autism spectrum disorders. RESULTS: The true incidence of autism spectrum disorders is likely to be within the range of 30-60 cases per 10 000, a huge increase over the original estimate 40 years ago of 4 per 10000. The increase is largely a consequence of improved ascertainment and a considerable broadening of the diagnostic concept. However, a true risk due to some, as yet to be identified, environmental risk factor cannot be ruled out. There is no support for the hypothesis for a role of either MMR or thimerosal in causation, but the evidence on the latter is more limited. CONCLUSION: Progress in testing environmental risk hypotheses will require the integration of epidemiological and biological studies.

Autistic Disorder↗

PubMed2001

Brief report: macrographia in high-functioning adults with autism spectrum disorder.

The initial description of Asperger syndrome commented on the poor handwriting and motor coordination difficulties of individuals with this condition. Early descriptions of autism do not remark upon such difficulties. Recent evidence, however, suggests that individuals with both conditions have a similar motor control impairment. Handwriting has not been formally assessed in this context. Our study compared handwriting size between individuals with autism spectrum disorder and age- and IQ-matched control subjects. Macrographia was observed among subjects with autism spectrum disorder which remained statistically significant when covaried with educational level. This finding may correlate with the anatomical abnormalities present in the cerebellum of individuals with autism spectrum disorder.

Adolescent↗

PubMed2006

Abnormalities of cholesterol metabolism in autism spectrum disorders.

Although Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al., 2001; Am J Med Genet 98:191-200.], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated (1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and (2) the type and incidence of other sterol disorders in the same group. Using gas chromatography/mass spectrometry, cholesterol, and its precursor sterols were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dl, which is below the 5th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD.

Autistic Disorder↗

PubMed2004

Molecular genetics of autism spectrum disorder.

We are on the brink of exciting discoveries into the molecular genetic underpinnings of autism spectrum disorder. Overwhelming evidence of genetic involvement coupled with increased societal attention to the disorder has drawn in more researchers and more research funding. Autism is a strongly genetic yet strikingly complex disorder, in which evidence from different cases supports chromosomal disorders, rare single gene mutations, and multiplicative effects of common gene variants. With more and more interesting yet sometimes divergent findings emerging every year, it is tempting to view these initial molecular studies as so much noise, but the data have also started to coalesce in certain areas. In particular, recent studies in families with autism spectrum disorder have identified uncommon occurrences of a novel genetic syndrome caused by disruptions of the NLGN4 gene on chromosome Xp22. Previous work had identified another uncommon syndrome that is caused by maternal duplications of the chromosome 15q11-13 region. We highlight other converging findings, point toward those areas most likely to yield results, and emphasize the contributions of multiple approaches to identifying the genes of interest.

Animals↗

PubMed1998

Gangliosides in cerebrospinal fluid in children with autism spectrum disorders.

Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.

Adolescent↗

PubMedDate not supplied

Screening for autism spectrum disorder in adult psychiatric outpatients in a clinic in Taiwan.

Patients with adult autism spectrum disorder (ASD) continue to suffer from impairment in socialization and communication skills, and a proportion of them may develop psychiatric symptoms. It is thus likely that physicians in adult psychiatric departments may see a number of patients with ASD. Identification of patients with ASD is helpful and important for rehabilitation. This study estimated the prevalence of ASD among adult psychiatric outpatients in a Taiwanese medical center. A total of 660 patients were screened with Nylander and Gillberg's "Autism Spectrum Disorder in Adult Screening Questionnaire." Patients with high scores then underwent a diagnostic clinical interview conducted by child psychiatrists. Four patients (0.6%) were found to have ASD.

Adolescent↗

PubMed1999

Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders.

BACKGROUND: One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. OBJECTIVE: To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. DESIGN: Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder-not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical EEG, when available. Multiple-dipole, spatiotemporal modeling was used to identify sites of origin and propagation for epileptiform transients. RESULTS: The MEG of all children with LKS showed primary or secondary epileptiform involvement of the left intra/perisylvian region, with all but 1 child showing additional involvement of the right sylvian region. In all cases of LKS, independent epileptiform activity beyond the sylvian region was absent, although propagation of activity to frontal or parietal regions was seen occasionally. MEG identified epileptiform activity in 41 of the 50 (82%) children with ASDs. In contrast, simultaneous EEG revealed epileptiform activity in only 68%. When epileptiform activity was present in the ASDs, the same intra/perisylvian regions seen to be epileptiform in LKS were active in 85% of the cases. Whereas primary activity outside of the sylvian regions was not seen for any of the children with LKS, 75% of the ASD children with epileptiform activity demonstrated additional nonsylvian zones of independent epileptiform activity. Despite the multifocal nature of the epileptiform activity in the ASDs, neurosurgical intervention aimed at control has lead to a reduction of autistic features and improvement in language skills in 12 of 18 cases. CONCLUSIONS: This study demonstrates that there is a subset of children with ASDs who demonstrate clinically relevant epileptiform activity during slow-wave sleep, and that this activity may be present even in the absence of a clinical seizure disorder. MEG showed significantly greater sensitivity to this epileptiform activity than simultaneous EEG, 1-hour clinical EEG, and 24-hour clinical EEG. The multifocal epileptiform pattern identified by MEG in the ASDs typically includes the same perisylvian brain regions identified as abnormal in LKS. When epileptiform activity is present in the ASDs, therapeutic strategies (antiepileptic drugs, steroids, and even neurosurgery) aimed at its control can lead to a significa

Autistic Disorder↗

PubMed2006

Attributing social and physical meaning to ambiguous visual displays in individuals with higher-functioning autism spectrum disorders.

The weak central coherence (WCC) account of autism characterizes the learning style of individuals with this condition as favoring localized and fragmented (to the detriment of global and integrative) processing of information. This pattern of learning is thought to lead to deficits in aspects of perception (e.g., face processing), cognition, and communication (e.g., focus on disjointed details rather than "gist" or context), ultimately leading to social impairments. This study was carried out to examine whether WCC applies to social and to non-social aspects of learning alike, or, alternatively, some areas of learning (e.g., physical reasoning) are spared in autism. classic social animation as quantified in the Social Attribution Task (SAT) () and a novel animation involving physical reasoning (the Physical Attribution Task; PAT) were used to test the domain specificity of the WCC hypothesis. A pilot study involving a reference group of typically developing young adults and a group of individuals with higher-functioning autism spectrum disorders (ASDs) revealed gender differences in the reference group in regards to performance on the PAT (males outperformed females). In a follow-up case-control comparison involving only males where the ASD group was matched on age and IQ to a typically developing (TD) group of children, adolescents, and adults, the ASD group showed lower SAT scores and comparable PAT scores relative to the TD group. The interaction of diagnostic group by task was highly significant, with little overlap between the groups in the distributions of SAT minus PAT scores. These results indicated preserved integrative skills in the area of physical attribution in the ASD group, thus failing to support the WCC account as a domain-independent (or more general) model of learning in autism, while highlighting the centrality of the social deficits in the characterization of learning style in the autism spectrum disorders.

Adolescent↗

PubMed2005

Systematic review of prevalence studies of autism spectrum disorders.

AIM: To quantitatively examine the influence of study methodology and population characteristics on prevalence estimates of autism spectrum disorders. METHODS: Electronic databases and bibliographies were searched and identified papers evaluated against inclusion criteria. Two groups of studies estimated the prevalence of typical autism and all autism spectrum disorders (ASD). The extent of variation among studies and overall prevalence were estimated using meta-analysis. The influence of methodological factors and population characteristics on estimated prevalence was investigated using meta-regression and summarised as odds ratios (OR). RESULTS: Forty studies met inclusion criteria, of which 37 estimated the prevalence of typical autism, and 23 the prevalence of all ASD. A high degree of heterogeneity among studies was observed. The overall random effects estimate of prevalence across studies of typical autism was 7.1 per 10,000 (95% CI 1.6 to 30.6) and of all ASD was 20.0 per 10,000 (95% CI 4.9 to 82.1). Diagnostic criteria used (ICD-10 or DSM-IV versus other; OR = 3.36, 95% CI 2.07 to 5.46), age of the children screened (OR = 0.91 per year, 95% CI 0.83 to 0.99), and study location (e.g. Japan versus North America; OR = 3.60, 95% CI 1.73 to 7.46) were all significantly associated with prevalence of typical autism. Diagnostic criteria, age of the sample, and urban or rural location were associated with estimated prevalence of all ASD. CONCLUSIONS: Sixty one per cent of the variation in prevalence estimates of typical autism was explained by these models. Diagnostic criteria used, age of children screened, and study location may be acting as proxies for other study characteristics and require further investigation.

Age Factors↗

PubMed2025

Systematic Review of Symptoms of Catatonia in Autism Spectrum Disorder.

Catatonia is a complex neuropsychiatric syndrome characterized by disturbances in mood, motor function, behavior and speech. It is increasingly recognized in individuals with autism spectrum disorder (ASD), although its identification remains challenging due to the overlapping clinical features of the two conditions. Shared characteristics, such as echophenomena, mannerisms, social indifference and repetitive behaviors can obscure accurate diagnosis. Although reports suggest a significant prevalence of catatonia among individuals with ASD, the condition remains poorly understood and frequently under recognized, leading to substantial diagnostic and treatment challenges. A systematic review was conducted to characterize the symptoms of catatonia in individuals with ASD. The literature search included peer-reviewed journal articles published in English from 1980 onward, focusing on studies examining co-occurring catatonia and ASD. A qualitative framework analysis was implemented to evaluate 45 peer-reviewed studies, with findings interpreted in relation to, and extending beyond, the diagnostic criteria for catatonia outlined in the International Classification of Diseases, 11th revision (ICD-11). The objective was to identify symptom patterns extending beyond current diagnostic frameworks and to support improved clinical recognition and diagnostic precision in ASD populations. The review identified six primary symptom clusters associated with catatonia in individuals with ASD: (1) psychomotor activity, (2) speech disturbances, (3) changes in behavior/skills/functions, (4) mental health symptoms, (5) physiological symptoms, and (6) symptoms related to arousal and awareness. Notably, several symptoms observed within these clusters are not currently included in the ICD-11 diagnostic criteria for catatonia. These additional symptoms include tics, motor compliance, incoherent speech, self-injury, impaired cognition, and appetite changes, suggesting a broader clinical presentation of catatonia in ASD populations than is presently captured in existing diagnostic frameworks. The findings of this review highlight the significance of enhancing clinicians' awareness and understanding of how catatonia manifests in individuals with ASD. Most notably, six symptom clusters, psychomotor changes, speech disturbances, behavioral and functional regression, affective and psychiatric symptoms, physiological symptoms, and arousal/awareness disturbances, were observed. Several symptoms identified in this review are not included in the current diagnostic criteria, and their recognition may facilitate in earlier identification and timely intervention, potentially preventing the severe consequences of untreated catatonia in this population.

Humans↗

PubMed2005

Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study.

OBJECTIVE: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. METHOD: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire. RESULTS: Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects. CONCLUSIONS: This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.

Adolescent↗

PubMed1998

A dimensional classification of autism spectrum disorder by social communication domains.

OBJECTIVE: To investigate whether "social communication" could be used to assess severity of symptoms in autism spectrum disorder. Social communication refers to the communication of cognitive and emotional information through facial expression, gesture, and prosody and through implicit understanding of pragmatics and of theory of mind. METHOD: Subjects were evaluated by raters using the Autism Diagnostic interview-Revised and either the Autism Diagnostic Observation Schedule or the Pre-Linguistic Autism Diagnostic Observation Schedule. Two investigators independently diagnosed autism, Asperger's disorder, or pervasive developmental disorder-not otherwise specified in 63 subjects. Items from the Autism Diagnostic Interview-Revised that were judged to represent social communication behaviors were factor-analyzed. RESULTS: Three factors were identified: affective reciprocity, joint attention, and theory of mind. Comparing this new classification approach to DSM-IV led to suggestions for possible changes in the latter: (1) Vocabulary and grammar deficiencies in autistic persons should be coded under developmental language disorder, (2) The diagnosis of Asperger's disorder may not be needed. (3) Requiring that all persons with autism spectrum disorder have a symptom from the "restrictive, repetitive, and stereotypic" list may need to be reconsidered. CONCLUSIONS: The DSM-IV category of pervasive developmental disorder may be ideal for diagnosing "classic" autism, but it may be inadequate for diagnosing less severe forms of the disorder.

Adolescent↗

PubMed2006

Autism spectrum disorder: seeing is not understanding.

Impairments in social and emotional skills are a defining feature of autism spectrum disorder. Recent research shows that structural and functional abnormalities within the neural system that matches observation and execution of actions--the mirror neuron system--may explain the social aspects of the pathophysiology of autism spectrum disorder.

Autistic Disorder↗