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Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data.

OBJECTIVE: The issue of thimerosal-containing vaccines as a possible cause of autistic spectrum disorders (ASD) and neurodevelopmental disorders (NDDs) has been a controversial topic since 1999. Although most practitioners are familiar with the controversy, many are not familiar with the type or quality of evidence in published articles that have addressed this issue. To assess the quality of evidence assessing a potential association between thimerosal-containing vaccines and autism and evaluate whether that evidence suggests accepting or rejecting the hypothesis, we systematically reviewed published articles that report original data pertinent to the potential association between thimerosal-containing vaccines and ASD/NDDs. METHODS: Articles for analysis were identified in the National Library of Medicine's Medline database using a PubMed search of the English-language literature for articles published between 1966 and 2004, using keywords thimerosal, thiomersal, mercury, methylmercury, or ethylmercury alone and combined with keywords autistic disorder, autistic spectrum disorder, and neurodevelopment. In addition, we used the "related links" option in PubMed and reviewed the reference sections in the identified articles. All original articles that evaluated an association between thimerosal-containing vaccines and ASD/NDDs or pharmacokinetics of ethylmercury in vaccines were included. RESULTS: Twelve publications that met the selection criteria were identified by the literature search: 10 epidemiologic studies and 2 pharmacokinetic studies of ethylmercury. The design and quality of the studies showed significant variation. The preponderance of epidemiologic evidence does not support an association between thimerosal-containing vaccines and ASD. Epidemiologic studies that support an association are of poor quality and cannot be interpreted. Pharmacokinetic studies suggest that the half-life of ethylmercury is significantly shorter when compared with methylmercury. CONCLUSIONS: Studies do not demonstrate a link between thimerosal-containing vaccines and ASD, and the pharmacokinetics of ethylmercury make such an association less likely. Epidemiologic studies that support a link demonstrated significant design flaws that invalidate their conclusions. Evidence does not support a change in the standard of practice with regard to administration of thimerosal-containing vaccines in areas of the world where they are used.

Autistic Disorder↗

The role of the medial temporal lobe in autistic spectrum disorders.

The neural basis of autistic spectrum disorders (ASDs) is poorly understood. Studies of mnemonic function in ASD suggest a profile of impaired episodic memory with relative preservation of semantic memory (at least in high-functioning individuals). Such a pattern is consistent with developmental hippocampal abnormality. However, imaging evidence for abnormality of the hippocampal formation in ASD is inconsistent. These inconsistencies led us to examine the memory profile of children with ASD and the relationship to structural abnormalities. A cohort of high-functioning individuals with ASD and matched controls completed a comprehensive neuropsychological memory battery and underwent magnetic resonance imaging for the purpose of voxel-based morphometric analyses. Correlations between cognitive/behavioural test scores and quantified results of brain scans were also carried out to further examine the role of the medial temporal lobe in ASD. A selective deficit in episodic memory with relative preservation of semantic memory was found. Voxel-based morphometry revealed bilateral abnormalities in several areas implicated in ASD including the hippocampal formation. A significant correlation was found between parental ratings reflecting autistic symptomatology and the measure of grey matter density in the junction area involving the amygdala, hippocampus and entorhinal cortex. The data reveal a pattern of impaired and relatively preserved mnemonic function that is consistent with a hippocampal abnormality of developmental origin. The structural imaging data highlight abnormalities in several brain regions previously implicated in ASD, including the medial temporal lobes.

Adolescent↗

[The neuropaediatric and pathogenic clinical bases of autistic spectrum disorder].

INTRODUCTION: The dimension of the autistic spectrum embraces a considerable degree of clinical complexity which is, in turn, an expression of the numerous systems involved in the functioning of the central nervous system. Every day different biological factors are revealed which put in doubt other factors that, in a more objective way, appear to be involved in a particular aetiology. DEVELOPMENT AND CONCLUSIONS: It is clear that exactly what causes autistic spectrum disorder is still unknown and it may be useful to analyse cases with a known aetiology and correlate them with other similar cases, as it is likely to be this association between findings and studies in the future that will probably enable us to better define the bases and the underlying causes of the complex and manifold origin of the autistic spectrum. This will enable a more efficient therapeutic approach to be developed, which, when all is said and done, is what is primarily sought in the management of children with autistic spectrum disorder.

Autistic Disorder↗

[Best practice guidelines for research in autistic spectrum disorders].

INTRODUCTION: Achieving a better knowledge of autism and other pervasive developmental disorders known as autistic spectrum disorders (ASD), poses a major scientific challenge. These disorders are some of the earliest and most severe psychopathological disorders in infancy; they include an heterogeneous group of conditions; its prevalence rate seems to be continually increasing and they generate a significant social impact. AIMS AND DEVELOPMENT: Nowadays, there is a current international agreement on the general requirements to be fulfilled by research projects and the priority areas to be considered when developing ASD high quality research. In Spain, although there are some established research groups with broad experience and expertise in these disorders, public funding opportunities and research development are still scarce. For this reason, the Study Group of the Instituto de Salud Carlos III has generated by consensus some Good Practice Guidelines for Research in ASD. CONCLUSIONS: After comparing priorities and recommendations from international reference documents with the results obtained after having carried out an exhaustive bibliographic revision of articles published in autism in the last 30 years by Spanish authors, methodological and ethical recommendations are established. Finally, structural deficiencies to be corrected and emerging research initiatives to be supported are identified.

Child Development Disorders, Pervasive↗

Adjustment, sibling problems and coping strategies of brothers and sisters of children with autistic spectrum disorder.

BACKGROUND: Siblings of children with autistic spectrum disorder (ASD) express more problem behaviours and experience more difficulties in their relationships than do children in families where all children are developing typically. We know little about what contributes to these difficulties. METHOD: Mothers of a child with ASD completed the Child Behavior Checklist (Achenbach, 1991) with respect to a non-disabled sibling. Siblings responded to a questionnaire tapping their knowledge about their brother or sister's disorder. They reported on problems they had experienced with their brother or sister with ASD and on the coping strategies they had used in response to these events. Problems were classified into 1 of 5 problem types. RESULTS: Aggressive behaviour was the most commonly reported interaction problem and anger was the usual response. Siblings did not generally choose blaming (either self or other) as a coping strategy when facing difficulties with their brother or sister with ASD. Neither coping strategies nor knowledge of ASD were associated with adjustment. Forty percent of non-disabled siblings had scores on the Child Behavior Checklist that placed them in the borderline or clinical range. CONCLUSIONS: The current study indicated that siblings of children with ASD are at increased risk of developing internalising behaviour problems. The contributing factors to this outcome are unknown at this point. It is important for research to focus on dynamic variables in the search for these contributors, as they are open to change.

Adaptation, Psychological↗

Intonation and emotion in autistic spectrum disorders.

The classic picture of an autistic individual includes an impoverished ability to interpret or express emotion. The prosody of spoken language in autistic children is thought to lack emotional content. In this study, the verbal intonation of children with autism was examined and compared to that of children with Asperger Syndrome (AS) and normal controls (ctrl). Utterances elicited by repetition and by spontaneous story completion were analyzed by quantifying phonetic features (pitch, amplitude, and length) and comparing them to subjective ratings of produced emotion (happy, sad or angry). Since the most consistent phonetic correlate of these emotional targets has been demonstrated to be pitch range, speakers with autistic spectrum disorders were expected to have decreased pitch range; however in the repetition task, autistic subjects actually had a larger pitch range than the other groups. Other measures of intonation including amplitude, duration, and location of pitch peak revealed defects that are more complex than predicted. In spontaneous speech, autistic subjects performed more poorly on both phonetic targets and subjective ratings than ctrls, and AS subjects fell between autistics and normals.

Adolescent↗

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↗

Autistic spectrum disorder: diagnostic difficulties.

Recognition of the autistic spectrum disorders is becoming more widespread amongst basic scientists, clinicians, and the general population. The term does not imply anything about pathology or aetiology, although it has proved to be a useful concept clinically. From Kanner's classical autism the concept has widened in scope to include milder and more subtle impairments. From a clinical perspective, there are many alternative diagnoses in an individual with autistic-like symptoms, and thorough investigation is necessary to exclude these.

Asperger Syndrome↗

Improved social and language skills after secretin administration in patients with autistic spectrum disorders.

We report three children with autistic spectrum disorders who underwent upper gastrointestinal endoscopy and intravenous administration of secretin to stimulate pancreaticobiliary secretion. All three had an increased pancreaticobiliary secretory response when compared with nonautistic patients (7.5 to 10 mL/min versus 1 to 2 mL/min). Within 5 weeks of the secretin infusion, a significant amelioration of the children's gastrointestinal symptoms was observed, as was a dramatic improvement in their behavior, manifested by improved eye contact, alertness, and expansion of expressive language. These clinical observations suggest an association between gastrointestinal and brain function in patients with autistic behavior.

Autistic Disorder↗

An audit of referrals of children with autistic spectrum disorder to the dietetic service.

UNLABELLED: Autistic spectrum disorder (ASD) is a developing area for dietetic referrals. There is little published data on current dietetic practice. Some children with ASD are referred for gluten/casein free diet. The theory is that abnormal metabolites in the urine may be a result of incomplete breakdown of gluten and casein in the gut. There are some published open studies that support the efficiency of such a diet [Knivsberg et al. (1995) Scand. J. Educ. Res.39: 223; Lucarelli et al. (1995) Panminerva Med.37: 137; Whiteley et al. (1999) Int. J. Res. Practice 3: 45] and also that there are many anecdotal reports that the diet helps some children. AIMS AND OBJECTIVES: This study aimed to audit the types of referral made to the dietetic service to identify key dietetic issues and to describe factors which may influence outcome/disease management. METHODS: Dietetic records were used to audit the referrals to the dietetic service over a 3-month period. Seven-day diet histories were assessed using computer food composition tables and topics of interest recorded against a draft protocol agreed within the profession. RESULTS: Requests for gluten-free and casein-free dietetic advice, and/or the management of food selectivity and dysfunctional feeding behaviour constituted the majority of referrals. In many cases, child's environment was rarely simple. CONCLUSIONS: Despite the limitations of this small study, the findings suggest that the management of these referrals is highly complex. A dietitian's input should ensure that the nutritional adequacy of the diet is maintained or restored.

Autistic Disorder↗

Trends in autism.

Leo Kanner described autism in 1943, and Hans Asperger described the syndrome in 1944. The term Pervasive Developmental Disorders (PDD) was first used in the 1980s to describe a class of disorders that include (1) Autistic disorder, (2) Rett disorder or syndrome, (3) Childhood Disintegrative Disorder, (4) Asperger's disorder or syndrome, and (5) Pervasive Developmental Disorder Not Otherwise Specified, or PDDNOS. Autism prevalence studies published before 1985 showed prevalence rates of 4 to 5 per 10,000 children for the broader autism spectrum, and about 2 per 10,000 for the classic autism definition. Since 1985 there have been higher rates of autism reported from several countries. From the UK a prevalence rate of 16.8 per 10,000 children for autistic disorder was reported, and 62.6 per 10,000 for the entire autistic spectrum disorders. Sweden reported a prevalence of 36 per 10,000 for Asperger and 35 per 10,000 for social impairment, or a total prevalence of 71 per 10,000 for suspected and possible cases. From the US, 40 per 10,000 in three to ten year old children for autistic disorder and 67 per 10,000 children for the entire autism spectrum was reported. From the north region in Israel for children born between 1989-93 in the Haifa area, an incidence rate of 10 per 10,000 was found for autism. In recent years concern has been shown about the possible increase in the prevalence of autistic spectrum disorders. Studies have shown an increase, but during these last twenty years diagnostic criteria and definition have also changed. Although many factors are at play, it is evident that there has been an increase.

Autistic Disorder↗

Music therapy for autistic spectrum disorder.

BACKGROUND: The central impairments of people with autistic spectrum disorder (ASD) include social interaction and communication. Music therapy uses music and its elements to enable communication and expression, thus attempting to address some of the core problems of people with ASD. OBJECTIVES: To review the effects of music therapy for individuals with autistic spectrum disorders. SEARCH STRATEGY: The following databases were searched: CENTRAL, 2005, (Issue 3); Medline, (1966 to July 2004); Embase, (1980 to July 2004); LILACS, (1982 to July 2004); PsycINFO, (1872 to July 2004); CINAHL, (1982 to July 2004); ERIC, (1966 to July 2004); ASSIA, (1987 to July 2004); Sociofile, (1963 to July 2004); Dissertation Abstracts International, (late 1960's to July 2004). These searches were supplemented by searching specific sources for music therapy literature and manual searches of reference lists. Personal contacts to some investigators were made. SELECTION CRITERIA: All randomised controlled trials or controlled clinical trials comparing music therapy or music therapy added to standard care to "placebo" therapy, no treatment or standard care. DATA COLLECTION AND ANALYSIS: Studies were independently selected, quality assessed and data extracted by two authors. Continuous outcomes were synthesised using a standardised mean difference (SMD) in order to enable a meta-analysis combining different scales, and to facilitate the interpretation of effect sizes. Heterogeneity was assessed using the I(2) statistic. MAIN RESULTS: Three small studies were included (total n = 24). These examined the short-term effect of brief music therapy interventions (daily sessions over one week) for autistic children. Music therapy was superior to "placebo" therapy with respect to verbal and gestural communicative skills (verbal: 2 RCTs, n = 20, SMD 0.36 CI 0.15 to 0.57; gestural: 2 RCTs, n = 20, SMD 0.50 CI 0.22 to 0.79). Effects on behavioural problems were not significant. AUTHORS' CONCLUSIONS: The included studies were of limited applicability to clinical practice. However, the findings indicate that music therapy may help children with autistic spectrum disorder to improve their communicative skills. More research is needed to examine whether the effects of music therapy are enduring, and to investigate the effects of music therapy in typical clinical practice.

Autistic Disorder↗

[The intelligence structure of autistic persons].

In a research project on the genetics of autistic disorders 115 subjects were examined. An autistic disorder was diagnosed in 102 of the subjects using the standardized Autism Diagnostic Interview (ADI; Le Couteur et al., 1989/ADI-R; Lord et al., 1994). The WAIS-R or WISC-R could be administered to 42 of the subjects. The mean full-scale IQ was 84.4, slightly below the range of normal intelligence. The mean verbal IQ (89.3) was considerably higher than the performance IQ (78.9). Analysis of the subtest patterns showed the highest scores to be in those subtests measuring knowledge of dates and facts and visuospatial abilities. The lowest scores were on subtests requiring an understanding of social relations and the ability to understand concrete social actions. This subtest pattern confirms results of other studies on the intelligence of individuals with autism and was independent of gender and level of intelligence. The subtest pattern appears to be specific for autistic disorder; it has been interpreted with reference to the theory of "weak central coherence" (Frith, 1989; Shah & Frith, 1993), which postulates that in autistic individuals stimulus perception and processing occurs independently of the general context. The results suggest that the differentiation between different types of autistic disorders should be abandoned in favor of a continuum of autistic disorders with differing degrees of severity.

Adolescent↗

Trend study of autistic spectrum disorders at Queen Sirikit National Institute of Child Health.

BACKGROUND: Increases in the incidence and prevalence of autistic spectrum disorders have been reported recently in the United States and Europe, but there are only a few reports on the trend of this problem in Thailand. OBJECTIVES: To study trend in autistic spectrum disorder patients and to find the factors that correlate with the incidence of this disorder at Queen Sirikit National Institute of Child Health. MATERIAL AND METHOD: A hospital-based prospective trend study was conducted in patients aged less than 12 years old, who attended the Child and Adolescent Department, Queen Sirikit National Institute of Child Health, Bangkok, form January 1998 to December 2002. Autistic spectrum disorders were defined as autistic disorder pervasive developmental disorder-not otherwise specified (PDD-NOS), and Asperger's disorder Related factors were recorded and analyzed Aged-adjusted incidence rate in both sexes and proportion rates of related factors were calculated by using the direct method Standard t-test and correlation coefficient were performed to test for statistically significant difference in the prevalence rate in each group. RESULTS: There were 610 new patients aged less than 12 years who displayed behavior consistent with autistic spectrum disorders. The increasing trend in the incidence of autistic spectrum disorder is observed (r = 0. 935, p = 0. 02). The incidence rate of autistic spectrum disorders among out patients less than 12 years has increased from 1.43 per 10, 000 in 1998 to 6.94 per 10, 000 in 2002. The correlation factors "an only one child in the family" is observed (r = 0.9, p = 0.038). CONCLUSION: During the 5 years of the study, a significant increase in the incidence of autistic spectrum disorders was observed at Queen Sirikit National Institute of Child Health. Increase in the incidence of ASD in this center cannot explain by any solid evidence from the present study.

Child↗