Olanzapine in the treatment of pervasive developmental disorders: a case series analysis.
(9/993)
Controlling the symptoms that are characteristic of patients with pervasive developmental disorders is often challenging. We report on the safety and efficacy of olanzapine in the treatment of 7 patients with pervasive developmental disorders. The patients were all male and ranged in age from 8 to 52 years. They received olanzapine doses of 5-10 mg/d along with their various other drug regimens. Patients were monitored and evaluated for a mean duration of 17.7 (range 12-26) months while on olanzapine therapy. Very few side effects were observed during treatment. All patients showed clinically significant improvement on the Clinical Global Impressions scale, as well as an improved score as measured by the Global Assessment of Functioning scale. Our observations support the use of long-term olanzapine therapy for symptom control in patients with pervasive developmental disorders. (+info)
Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders.
(10/993)
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). Although MECP2 is ubiquitously transcribed, MeCP2 expression is developmentally regulated and heterogeneous in neuronal subpopulations, defined as MeCP2(lo) and MeCP2(hi). To test the hypothesis that pathways affecting MeCP2 expression changes may be defective in RTT, autism and other neurodevelopmental disorders without MECP2 mutations, a high-throughput quantitation of MeCP2 expression was performed on a tissue microarray containing frontal cortex samples from 28 different patients with neurodevelopmental disorders and age-matched controls. Combined quantitative analyses of MeCP2 protein and alternatively polyadenylated transcript levels were performed by laser scanning cytometry and tested for significant differences from age-matched controls. Normal cerebral samples showed an increase in total MeCP2 expression and the percentage of MeCP2(hi) cells with age that could be explained by increased MECP2 transcription within the MeCP2(hi) population. A significant decrease in the relative usage of the long transcript in the MeCP2(lo) population was observed in postnatal compared to fetal brain, but alternate polyadenylation did not correlate with MeCP2 expression changes at the single cell level. Brain samples from several related neurodevelopmental disorders, including autism, pervasive developmental disorder, Prader-Willi and Angelman syndromes showed significant differences in MeCP2 expression from age-matched controls by apparently different transcriptional and post-transcriptional mechanisms. These results suggest that multiple pathways regulate the complex developmental expression of MeCP2 and are defective in autism-spectrum disorders in addition to RTT. (+info)
Does routine child health surveillance contribute to the early detection of children with pervasive developmental disorders? An epidemiological study in Kent, U.K.
(11/993)
BACKGROUND: Recently changed guidelines for child health surveillance in the United Kingdom (U.K.) suggest targeted checks only, instead of the previously conducted routine or universal screening at 2 years and 3.5 years. There are concerns that these changes could lead to a delay in the detection of children with autism and other pervasive developmental disorders (PDD). Recent U.K. studies have suggested that the prevalence of PDD is much higher than previously estimated. This study establishes to which extent the routine checks contributed to the early detection and assessment of cases of PDD. Simultaneously we have evaluated the process involved and estimate the prevalence of PDD in our district. METHODS: Retrospective study design utilising community medical files. Headteachers of schools (n = 75) within Maidstone district (Kent) were asked to report all children with an established diagnosis of autism or PDD attending year 4 (born '91 and '92 / n = 2536) in October 2000 based on educational records. RESULTS: 59 schools (78.7%) took part in the study. A total of 33 children were reported. 21 fulfilled the inclusion criteria (12 falsely reported). The prevalences were (per 10,000): PDD 82.8 (male to female ratio 6:1), childhood autism 23.7, Asperger's syndrome 11.8 and autistic spectrum disorder 47.3. Co-existing medical conditions were noted in 14.3%; 52.4% were attending mainstream schools. In 63.2% of cases concerns--mainly in the area of speech and language development (SLD)--had been documented at the 2 year check. At the 3.5 year check concerns were noted in 94.1%--the main area was again SLD (76.5%), although behavioural abnormalities were becoming more frequent (47.1%). A total of 13 children (68.4%) were referred for further assessment as a direct result of the checks. CONCLUSIONS: The prevalences for different types of PDD were similar to figures published recently, but much higher than reported a few years ago. Analysis of our data suggests that routine surveillance is a valuable contributing factor for the early detection of PDD and thereby facilitates early intervention. Thus, if routine surveillance ceases, then an alternative method of early detection should be put in place. (+info)
The Brief Infant-Toddler Social and Emotional Assessment: screening for social-emotional problems and delays in competence.
(12/993)
OBJECTIVE: To examine the reliability and validity of the 42-item Brief Infant-Toddler Social and Emotional Assessment (BITSEA), a screener for social-emotional/behavioral problems and delays in competence. METHOD: Parents in a representative healthy birth cohort of 1,237 infants aged 12 to 36 months completed the Infant-Toddler Social and Emotional Assessment (ITSEA)/BITSEA, the Child Behavior Checklist (CBCL)/1.5-5, the MacArthur Communication Developmental Inventory vocabulary checklist, and worry questions. In a subsample, independent evaluators rated infant-toddler behavior. RESULTS: Test-retest reliability was excellent and interrater agreement (mother/father and parent/child-care provider) was good. Supporting validity, BITSEA problems correlated with concurrent evaluator problem ratings and CBCL/1.5-5 scores and also predicted CBCL/1.5-5 and ITSEA problem scores one year later. BITSEA measures of competence correlated with concurrent observed competence and predicted later ITSEA competence measures. Supporting discriminant validity, only 23% of high BITSEA problem scorers had delayed vocabulary. Moreover, the combined BITSEA problem/competence cutpoints identified 85% of subclinical/clinical CBCL/1.5-5 scores, while maintaining acceptable specificity (75%). CONCLUSIONS: Findings support the BITSEA as a screener for social-emotional/behavioral problems and delays in social-emotional competence. (+info)
Validation of the diagnosis of autism in general practitioner records.
(13/993)
BACKGROUND: We report on the validity of the computerized diagnoses of autism in a large case-control study investigating the possible association between autism and the measles, mumps and rubella vaccine in the UK using the General Practitioner Research Database (GPRD). We examined anonymized copies of all relevant available clinical reports, including general practitioners' (GP) notes, consultant, speech therapy and educational psychologists reports, on 318 subjects born between 1973 and 1997 with a diagnosis of autism or a related disorder recorded in their electronic general practice record. METHODS: Data were abstracted to a case validation form allowing for the identification of developmental symptoms relevant to the diagnosis of pervasive developmental disorders (PDDs). Information on other background clinical and familial features was also abstracted. A subset of 50 notes was coded independently by 2 raters to derive reliability estimates for key clinical characteristics. RESULTS: For 294 subjects (92.5%) the diagnosis of PDD was confirmed after review of the records. Of these, 180 subjects (61.2%) fulfilled criteria for autistic disorder. The mean age at first recording of a PDD diagnosis in the GPRD database was 6.3 years (SD = 4.6). Consistent with previous estimates, the proportion of subjects experiencing regression in the course of their development was 19%. Inter-rater reliability for the presence of a PDD diagnosis was good (kappa =.73), and agreement on clinical features such as regression, age of parental recognition of first symptoms, language delay and presence of epilepsy was also good (kappas ranging from.56 to 1.0). CONCLUSIONS: This study provides evidence that the positive predictive value of a diagnosis of autism recorded in the GPRD is high. (+info)
Are patients with social developmental disorders prosopagnosic? Perceptual heterogeneity in the Asperger and socio-emotional processing disorders.
(14/993)
It has been hypothesized that social developmental disorders (SDD) like autism, Asperger's disorder and the social-emotional processing disorder may be associated with prosopagnosic-like deficits in face recognition. We studied the ability to recognize famous faces in 24 adults with a variety of SDD diagnoses. We also measured their ability to discriminate changes in internal facial configuration, a perceptual function that is important in face recognition, and their imagery for famous faces, an index of their facial memory stores. We contrasted their performance with both healthy subjects and prosopagnosic patients. We also performed a cluster analysis of the SDD patients. One group of eight SDD subjects performed normally on all tests of face perception and recognition. The other 16 subjects were impaired in recognition, though most were better than prosopagnosic patients. One impaired SDD subgroup had poor perception of facial structure but relatively preserved imagery, resembling prosopagnosic patients with medial occipitotemporal lesions. Another subgroup had better perception than imagery, resembling one prosopagnosic with bilateral anterior temporal lesions. Overall, SDD subgroup membership by face recognition did not correlate with a particular SDD diagnosis or subjective ratings of social impairment. We conclude that the social disturbance in SDD does not invariably lead to impaired face recognition. Abnormal face recognition in some SDD subjects is related to impaired perception of facial structure in a manner suggestive of occipitotemporal dysfunction. Heterogeneity in the perceptual processing of faces may imply pathogenetic heterogeneity, with important implications for genetic and rehabilitative studies of SDD. (+info)
Rate of first recorded diagnosis of autism and other pervasive developmental disorders in United Kingdom general practice, 1988 to 2001.
(15/993)
BACKGROUND: There has been concern that the incidence of autism and other pervasive developmental disorders (PDDs) is increasing. Previous studies have been smaller, restricted to autism (excluding other pervasive developmental disorders such as Asperger's syndrome), included boys only, or have not been based on a national sample. We investigated time trends in the rates of diagnosis of pervasive developmental disorders. METHODS: We analysed the rates of first diagnosis of pervasive developmental disorders among people registered with a practice contributing to the United Kingdom General Practice Research Database during the period 1988 to 2001. We included 1410 cases from over 14 million person-years of observation. The main outcome measures were rates of diagnosis of pervasive developmental disorders by year of diagnosis, year of birth, gender and geographical region. RESULTS: The rate increased progressively from 0.40/10,000 person-years (95% CI 0.30 to 0.54) in 1991 to 2.98/10,000 (95% CI 2.56 to 3.47) in 2001. A similar change occurred in the age standardised incidence ratios, from 35 (95% CI: 26-47) in 1991 to 365 (95% CI: 314-425) in 2001. The temporal increase was not limited to children born during specific years nor to children diagnosed in a specific time period. The rate of diagnosis of PDDs other than autism rose from zero for the period 1988-1992 to 1.06/10,000 person-years in 2001. The rate of diagnosis of autism also increased but to a lesser extent. There was marked geographical variation in rates, with standardised incidence ratios varying from 66 for Wales to 141 for the South East of England. CONCLUSIONS: Better ascertainment of diagnosis is likely to have contributed to the observed temporal increase in rates of diagnosis of PDD, but we cannot exclude a real increase. (+info)
Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations.
(16/993)
BACKGROUND: The prevalence of pervasive developmental disorders has increased in recent years. Links with the measles component of the measles-mumps-rubella vaccine and the cumulative exposure to thimerosal through other vaccines have been postulated. OBJECTIVES: The purpose of this work was to estimate the pervasive developmental disorder prevalence in Montreal, Canada, in cohorts born from 1987 to 1998 and evaluate the relationship of trends in pervasive developmental disorder rates with: (1) changes in cumulative exposure to ethylmercury (thimerosal) occurring through modifications in the immunization schedule of young children and (2) trends in measles-mumps-rubella vaccination use rates and the introduction of a 2-measles-mumps-rubella dosing schedule during the study period. METHODS: We surveyed 27749 children born from 1987 to 1998 attending 55 schools from the largest Anglophone school board. Children with pervasive developmental disorders were identified by a special needs team. The cumulative exposure by age 2 years to thimerosal was calculated for 1987-1998 birth cohorts. Ethylmercury exposure ranged from medium (100-125 microg) from 1987 to 1991 to high (200-225 microg) from 1992 to 1995 to nil from 1996 onwards when thimerosal was entirely discontinued. Measles-mumps-rubella coverage for each birth cohort was estimated through surveys of vaccination rates. The immunization schedule included a measles-mumps-rubella single dose at 12 months of age up to 1995, and a second measles-mumps-rubella dose at 18 months of age was added on after 1996. RESULTS: We found 180 children (82.8% males) with a pervasive developmental disorder diagnosis who attended the surveyed schools, yielding a prevalence for pervasive developmental disorder of 64.9 per 10000. The prevalence for specific pervasive developmental disorder subtypes were, for autistic disorder: 21.6 of 10000; for pervasive developmental disorder not otherwise specified: 32.8 of 10000; and for Asperger syndrome: 10.1 of 10000. A statistically significant linear increase in pervasive developmental disorder prevalence was noted during the study period. The prevalence of pervasive developmental disorder in thimerosal-free birth cohorts was significantly higher than that in thimerosal-exposed cohorts (82.7 of 10000 vs 59.5 of 10000). Using logistic regression models of the prevalence data, we found no significant effect of thimerosal exposure used either as a continuous or a categorical variable. Thus, thimerosal exposure was unrelated to the increasing trend in pervasive developmental disorder prevalence. These results were robust when additional analyses were performed to address possible limitations because of the ecological nature of the data and to evaluate potential effects of misclassification on exposure or diagnosis. Measles-mumps-rubella vaccination coverage averaged 93% during the study interval with a statistically significant decreasing trend from 96.1% in the older birth cohorts (1988-89) to approximately 92.4% in younger birth cohorts (1996-1998). Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased. In addition, pervasive developmental disorder prevalence increased at the same rate before and after the introduction in 1996 of the second measles-mumps-rubella dose, suggesting no increased risk of pervasive developmental disorder associated with a 2-measles-mumps-rubella dosing schedule before age 2 years. Results held true when additional analyses were performed to test for the potential effects of misclassification on exposure or diagnostic status. Thus, no relationship was found between pervasive developmental disorder rates and 1- or 2-dose measles-mumps-rubella immunization schedule. CONCLUSIONS: The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations. (+info)