1. Adams C, Lockton E, Freed J, Gaile J, Earl G, McBean K, Nash M, Green J, Vail A, Law J. {{The Social Communication Intervention Project: a randomized controlled trial of the effectiveness of speech and language therapy for school-age children who have pragmatic and social communication problems with or without autism spectrum disorder}}. {Int J Lang Commun Disord}. 2012; 47(3): 233-44.
Background: Children who show disproportionate difficulty with the pragmatic as compared with the structural aspects of language are described as having pragmatic language impairment (PLI) or social communication disorder (SCD). Some children who have PLI also show mild social impairments associated with high-functioning autism or autism spectrum disorder (ASD). There is little robust evidence of effectiveness of speech-language interventions which target the language, pragmatic or social communication needs of these children. Aims: To evaluate the effectiveness of an intensive manualized social communication intervention (SCIP) for children who have PLI with or without features of ASD. Methods & Procedures: In a single-blind RCT design, 88 children with pragmatic and social communication needs aged 5;11-10;8, recruited from UK speech and language therapy services, were randomly assigned in a 2:1 ratio to SCIP or to treatment-as-usual. Children in the SCIP condition received up to 20 sessions of direct intervention from a specialist research speech and language therapist working with supervised assistants. All therapy content and methodology was derived from an intervention manual. A primary outcome measure of structural language and secondary outcome measures of narrative, parent-reported pragmatic functioning and social communication, blind-rated perceptions of conversational competence and teacher-reported ratings of classroom learning skills were taken pre-intervention, immediately post-intervention and at 6-month follow-up. Analysis was by intention to treat. Outcomes & Results: No significant treatment effect was found for the primary outcome measure of structural language ability or for a measure of narrative ability. Significant treatment effects were found for blind-rated perceptions of conversational competence, for parent-reported measures of pragmatic functioning and social communication, and for teacher-reported ratings of classroom learning skills. Conclusions & Implications: There is some evidence of an intervention effect on blind and parent/teacher-reported communication outcomes, but not standardized language assessment outcomes, for 6-11-year-old children who have pragmatic and social communication needs. These findings are discussed in the context of the increasingly central role of service user outcomes in providing evidence for an intervention. The substantial overlap between the presence of PLI and ASD (75%) across the whole cohort suggests that the intervention may also be applicable to some verbally able children with ASD who have pragmatic communication needs.
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2. Al-Farsi YM, Al-Sharbati MM, Waly MI, Al-Farsi OA, Al-Shafaee MA, Al-Khaduri MM, Trivedi MS, Deth RC. {{Effect of suboptimal breast-feeding on occurrence of autism: A case-control study}}. {Nutrition}. 2012.
OBJECTIVE: To evaluate the association between suboptimal breast-feeding practices and autism spectrum disorders (ASDs). METHODS: A case-control study was conducted in 102 ASD cases and 102 matched healthy controls. RESULTS: Based on adjusted odds ratios from logistic regression models, ASD was found to be associated with the late initiation of breast-feeding (odds ratio 1.48, 95% confidence interval 1.01-3.1), a non-intake of colostrum (odds ratio 1.7, 95% confidence interval 1.03-4.3), prelacteal feeding, and bottle-feeding. The risk of ASD was found to decrease in a dose-response fashion over increasing periods of exclusive breast-feeding (P for trend = 0.04) and continued breast-feeding (P for trend = 0.001). CONCLUSION: The study indicates that increased ASD risk is generally associated with suboptimal breast-feeding practices.
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3. Ballan MS. {{Parental Perspectives of Communication about Sexuality in Families of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2012; 42(5): 676-84.
To explore the content of communication about sexuality between parents and children with autism spectrum disorders, semi-structured interviews were conducted with 18 parents of children ages 6-13. Content analysis and ethnographic summary were used to interpret the data. Findings suggest that parent’s perceptions of a child’s behaviors and comprehension are associated with the likelihood that communication occurs. However, parents recognize the risks their children experience, with the greatest fears being sexual victimization and misperceptions related to the intent of their child’s behaviors. This study provides information on the nature of communication about sexuality in families of children with autism spectrum disorders and can help tailor interventions aimed at assisting parents to communicate sexuality information effectively.
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4. Barrett B, Byford S, Sharac J, Hudry K, Leadbitter K, Temple K, Aldred C, Slonims V, Green J. {{Service and Wider Societal Costs of Very Young Children with Autism in the UK}}. {J Autism Dev Disord}. 2012; 42(5): 797-804.
Autism spectrum disorders (ASD) are associated with a substantial economic burden, but there is little evidence of the costs in the early years; the period in which children are increasingly likely to be diagnosed. We describe the services used by 152 children aged 24-60 months with autism, report family out-of-pocket expenses and productivity losses, and explore the relationship between family characteristics and costs. Children received a wide range of hospital and community services including relatively high levels of contact with speech and language therapists and paediatricians. Total service costs varied greatly (mean pound430 per month; range pound53 to pound1,116), with some families receiving little statutory support. Higher costs were associated with increasing age and symptom severity.
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5. Benvenuto A, Battan B, Porfirio MC, Curatolo P. {{Pharmacotherapy of autism spectrum disorders}}. {Brain Dev}. 2012.
Although no pharmacological or behavioral therapy has currently proven effective for treating all core symptoms of autism, many dysfunctional behaviors may be treated pharmacologically. Drug treatments should always be part of a comprehensive management plan that includes behavioral and educational interventions, and should be focused on specific targets. Several classes of psychotropic medications have been used to decrease the wide range of « maladaptive » or « interfering » behaviors and associated medical problems that can interfere with relationships and physical health and hinder the implementation of various non-pharmacological interventions. Atypical neuroleptics have been shown to be useful in the treatment of behavioral symptoms in autism. Attention deficit and hyperactivity disorder medications may be effective for counteracting the additional features of hyperactivity and short attention span. Antiepileptic drugs and selective serotonin reuptake inhibitors have shown promising results, but there are no specific indications for them as of yet. With respect to potential drug targets, some clinical features are caused by a dysfunction in neurochemical signaling systems, and thus may improve with selective pharmacological interventions acting on specific abnormal neurobiological pathways. Recent animal studies can be useful models for understanding the common pathogenic pathways leading to autism spectrum disorders (ASDs), and have the potential to offer new biologically focused treatment options.
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6. Bolte S, Schlitt S, Gapp V, Hainz D, Schirman S, Poustka F, Weber B, Freitag C, Ciaramidaro A, Walter H. {{A close eye on the eagle-eyed visual acuity hypothesis of autism}}. {J Autism Dev Disord}. 2012; 42(5): 726-33.
Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD.
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7. Boucher J, Mayes A, Bigham S. {{Memory in autistic spectrum disorder}}. {Psychol Bull}. 2012; 138(3): 458-96.
Behavioral evidence concerning memory in forms of high-functioning autism (HFA) and in moderately low-functioning autism (M-LFA) is reviewed and compared. Findings on M-LFA are sparse. However, it is provisionally concluded that memory profiles in HFA and M-LFA (relative to ability-matched controls) are similar but that declarative memory impairments are more extensive in M-LFA than in HFA. Specifically, both groups have diminished memory for emotion- or person-related stimuli. Regarding memory for nonsocial stimuli, both groups probably have mental-age-appropriate nondeclarative memory, and within declarative memory, both groups have mental-age-appropriate immediate free recall of within-span or supraspan lists of unrelated items, as well as cued recall and paired associate learning. By contrast, recognition is largely unimpaired in HFA but moderately impaired in M-LFA, and free recall of meaningful or structured stimuli is moderately impaired in HFA but more severely impaired in M-LFA. Theoretical explanations of data on declarative memory in HFA identify problems in the integrative processing, or the consolidation and storage, of complex stimuli or a specific problem of recollection. Proposed neural substrates include the following: disconnectivity of primary sensory and association areas; dysfunctions of medial prefrontal cortex, hippocampus, or posterior parietal lobe; or combinations of these associated with neural disconnectivity. Hypothetically, perirhinal dysfunction might explain the more extensive declarative memory impairments in M-LFA. Foreseeable consequences of uneven memory abilities in HFA and M-LFA are outlined, including possible effects on language and learning in M-LFA. Finally, priorities for future research are identified, highlighting the urgent need for research on memory in lower functioning individuals. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
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8. Brandt T, Desai K, Grodberg D, Mehta L, Cohen N, Tryfon A, Kolevzon A, Soorya L, Buxbaum JD, Edelmann L. {{Complex autism spectrum disorder in a patient with a 17q12 microduplication}}. {Am J Med Genet A}. 2012; 158A(5): 1170-7.
Autism spectrum disorders (ASDs) are phenotypically complex developmental neuropsychiatric disorders affecting approximately 0.6% of the population. About 30-70% of affected children are also considered to have intellectual disability (ID). The underlying genetic causes of ASDs are diverse with a defined etiology in 16-20%. Array comparative genomic hybridization (aCGH) has proven useful in identifying sub-microscopic chromosome aberrations in a subset of patients, some of which have been shown to be recurrent. One such aberration is the 1.4 Mb microdeletion at chromosome 17q12, which has been reported to be associated with renal disease, growth restriction, diabetes, cognitive impairment, seizures, and in some cases an ASD. Patients with the reciprocal chromosome 17q12 microduplication typically have also been identified with ID and in some cases seizures and behavioral abnormalities. Here we report a patient with a de novo, 1.4 Mb microduplication diagnosed with significant ID involving complex deficits and autism. To our knowledge, this is the first report of a patient with the 17q12 microduplication and a complex ASD phenotype. (c) 2012 Wiley Periodicals, Inc.
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9. Brunelle F, Bargiacchi A, Chabane N, Saitovitch A, Grevent D, Zilbovicius M, Boddaert N. {{[Brain imaging of infantile autism]}}. {Arch Pediatr}. 2012; 19(5): 547-50.
Understanding of brain structural anomalies seen in children with autism has considerably progressed since the apparition of MRI and functional imaging. All the results are converging toward the description of anatomical and functional anomalies in the regions of the so-called « social brain ». Statistical analyses show diminution of gray matter in the region of the superior temporal sulcus (STS). Functional studies with PET shows a diminution of brain blood flow at rest in the same region. Brain activation studies show absence of activation of the specialized region in processing human voice and hypoactivation of « social brain » regions in complex tasks of social cognition. At last, abnormal connectivity between the frontal and temporal regions has been showed. Those regions are implicated in processing sensorial inputs necessary for normal social life. All those anomalies could be responsible of the abnormal social behaviour pattern of children with autism.
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10. Carrasco M, Volkmar FR, Bloch MH. {{Pharmacologic treatment of repetitive behaviors in autism spectrum disorders: evidence of publication bias}}. {Pediatrics}. 2012; 129(5): e1301-10.
OBJECTIVE: The goal of this study was to examine the efficacy of serotonin receptor inhibitors (SRIs) for the treatment of repetitive behaviors in autism spectrum disorders (ASD). METHODS: Two reviewers searched PubMed and Clinicaltrials.gov for randomized, double-blind, placebo-controlled trials evaluating the efficacy of SRIs for repetitive behaviors in ASD. Our primary outcome was mean improvement in ratings scales of repetitive behavior. Publication bias was assessed by using a funnel plot, the Egger’s test, and a meta-regression of sample size and effect size. RESULTS: Our search identified 5 published and 5 unpublished but completed trials eligible for meta-analysis. Meta-analysis of 5 published and 1 unpublished trial (which provided data) demonstrated a small but significant effect of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.22 [95% confidence interval: 0.07-0.37], z score = 2.87, P < .005). There was significant evidence of publication bias in all analyses. When Duval and Tweedie’s trim and fill method was used to adjust for the effect of publication bias, there was no longer a significant benefit of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.12 [95% confidence interval: -0.02 to 0.27]). Secondary analyses demonstrated no significant effect of type of medication, patient age, method of analysis, trial design, or trial duration on reported SRI efficacy. CONCLUSIONS: Meta-analysis of the published literature suggests a small but significant effect of SRI in the treatment of repetitive behaviors in ASD. This effect may be attributable to selective publication of trial results. Without timely, transparent, and complete disclosure of trial results, it remains difficult to determine the efficacy of available medications.
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11. Cebula KR. {{Applied behavior analysis programs for autism: sibling psychosocial adjustment during and following intervention use}}. {J Autism Dev Disord}. 2012; 42(5): 847-62.
Psychosocial adjustment in siblings of children with autism whose families were using a home-based, applied behavior analysis (ABA) program was compared to that of siblings in families who were not using any intensive autism intervention. Data gathered from parents, siblings and teachers indicated that siblings in ABA families experienced neither significant drawbacks nor benefits in terms of their behavioral adjustment, sibling relationship quality and self-concept compared to control group siblings, either during or following intervention use. Parents and siblings perceived improvements in sibling interaction since the outset of ABA, with parents somewhat more positive in their views than were siblings. Social support was associated with better sibling outcomes in all groups. Implications for supporting families using ABA are considered.
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12. Chadman KK, Guariglia SR, Yoo JH. {{New directions in the treatment of autism spectrum disorders from animal model research}}. {Expert Opin Drug Discov}. 2012; 7(5): 407-16.
Introduction: Currently, there is not an effective pharmacotherapy for the core symptoms of the autism spectrum disorders (ASD), which include aberrant social behavior, delayed communication and repetitive behavior and/or restricted interests. There are several drugs that treat the symptoms associated with autism including irritability, aggressiveness and hyperactivity. Current drug research is based on the ongoing genetic, animal model and neuropathologic research. Two areas in particular, the glutamate and oxytocin systems, provide exciting new avenues for drug discovery. Areas covered: This review examines what approaches have been used for the drugs that are currently being used to treat people with ASD. For the most part, drugs that treat other neuropsychiatric disorders have been examined to treat the people with ASD, unfortunately with little effect on the core symptoms. Expert Opinion: Until recently, there was not a plethora of knowledge about the neurobiological substrates of social behavior, pragmatic language usage and repetitive and/or restricted behaviors. Therefore, drug discovery has used the tools available for other neuropsychiatric disorders. Now that more biological information is available, there are many avenues for research for drug targets for ASD.
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13. Chiang HM, Cheung YK, Hickson L, Xiang R, Tsai LY. {{Predictive factors of participation in postsecondary education for high school leavers with autism}}. {J Autism Dev Disord}. 2012; 42(5): 685-96.
This exploratory study was designed to identify the factors predictive of participation in postsecondary education for high school leavers with autism. A secondary data analysis of the National Longitudinal Transition Study 2 (NLTS2) data was performed for this study. Potential predictors of participation in postsecondary education were assessed using a backward logistic regression analysis. This study found that the high school’s primary post-high school goal for the student, parental expectations, high school type, annual household income, and academic performance were significant predictors of participation in postsecondary education. The findings of this current study may provide critical information for parents of children with autism as well as educators and professionals who work with students with autism.
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14. Clopper CG, Rohrbeck KL, Wagner L. {{Perception of dialect variation by young adults with high-functioning autism}}. {J Autism Dev Disord}. 2012; 42(5): 740-54.
The linguistic profile of people with Autism spectrum disorders typically involves intact perceptual processing, accompanied by deficits in the social functions of language. In a series of three experiments, the impact of this profile on the perception of regional dialect was examined. Young adults with High-Functioning Autism exhibited similar performance to a typically developing comparison group in regional dialect classification and localness rating tasks, suggesting that they can use indexical information in speech to make judgments about the regional background of unfamiliar talkers. However, the participants with High-Functioning Autism were less able to differentiate among the dialects in a language attitudes task, suggesting that they do not share social stereotypes related to dialect variation with the typically developing comparison group.
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15. Cottenceau H, Roux S, Blanc R, Lenoir P, Bonnet-Brilhault F, Barthelemy C. {{Quality of life of adolescents with autism spectrum disorders: comparison to adolescents with diabetes}}. {Eur Child Adolesc Psychiatry}. 2012; 21(5): 289-96.
Relationships are of great importance during adolescence. Because of their social, communication and behavioral impairments, adolescents with Asperger’s syndrome (AS) or high functioning autism (HFA) probably suffer from considerable impairment of their quality of life when facing their peers in school. Nevertheless, only one recent study has been published on this subject, indicating a lower health-related quality of life in children and adolescents with autism spectrum disorders (ASD) than in healthy controls. The goals of our study were to clarify the consequences of autistic disorder without mental retardation on such adolescents’ daily lives, and to consider them in comparison with the impact of a chronic somatic disease (diabetes) and with the period of adolescence itself, using the VSP-A questionnaire. Adolescents with diabetes were chosen as a comparison group because of the encumbrance of having a constant need for insulin supplementation, to be assimilated to the constant need for communicative adjustments in teenagers with ASD, and the consequences in daily life. The effects of social skill training and social support on quality of life and the appropriateness of using the VSP-A in this population were also studied. Twenty-six adolescents with AS and HFA, 44 diabetic adolescents, and 250 controls completed a self-administered and validated questionnaire on quality of life, the VSP-A. Scores for adolescents with ASD were significantly lower than those of the control and the diabetic adolescents, especially for friendships, leisure time, and affective and sexual relationships. On the other hand, better scores were obtained for the relationships with parents and teachers and for self-image. Social parameters affected the quality of life of subjects with ASD, such as having friends, regularly participating in a sport, and having the support of a school carer. For subjects with autistic spectrum disorders and without mental retardation, impairment of quality of life is significant in adolescence and young adulthood. Such adolescents are dissatisfied with their relationships, although they often have real motivation to succeed with them. Relevance of VSP-A questionnaire in these special individuals is discussed.
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16. Courtemanche A, Schroeder S, Sheldon J, Sherman J, Fowler A. {{Observing signs of pain in relation to self-injurious behaviour among individuals with intellectual and developmental disabilities}}. {J Intellect Disabil Res}. 2012; 56(5): 501-15.
Background Self-injurious behaviour is a chronic condition among people with intellectual and developmental disabilities for which there is no known cure. The pain hypothesis suggests that individuals who engage in self-injury have altered or diminished pain perception. The purpose of the present study was to assess how frequently individuals diagnosed with an intellectual and developmental disability who engage in chronic self-injury displayed non-verbal signs of pain in relation to their self-injury. Methods We videotaped four participants (aged 28-50 years) in their homes during times when they were likely to engage in self-injury. Using continuous recording measures, we coded videotapes for the frequency and duration of self-injury and expressions of non-verbal pain-related behaviours. Sequential analyses were conducted to identify temporal relations between pain-related behaviours and self-injury. Results Our data suggest that the existing measures of pain may be systematically related to instances of self-injury. The relationships, however, appear to vary depending on the person who engages in self-injury, the environmental contexts in which the self-injury occurs, and perhaps, the type of self-injury in which the person engages. Conclusions These results support some of the findings of Symons et al. and they raise questions about the blunted nociception hypothesis of self-injury.
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17. Crittendon JA, Lee EB, Warren ZE. {{Sibling recurrence rate of autism spectrum disorders is 18.7%}}. {Evid Based Ment Health}. 2012; 15(2): 31.
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18. Dereu M, Raymaekers R, Warreyn P, Schietecatte I, Meirsschaut M, Roeyers H. {{Can child care workers contribute to the early detection of autism spectrum disorders? A comparison between screening instruments with child care workers versus parents as informants}}. {J Autism Dev Disord}. 2012; 42(5): 781-96.
Several screening instruments for ASD in young children were developed during the last decades. Only few studies compare the discriminative power of these instruments in the same sample. In particular comparisons of instruments that use different informants are scarce in young children. The current study compared the discriminant ability of the Checklist for Early Signs of Developmental Disorders (CESDD) filled out by child care workers with that of frequently used parent questionnaires in a sample of 357 children between 5.57 and 48.13 months old who showed signs of ASD or language delay. The discriminant power of the CESDD was as good as that of parent questionnaires. Therefore, inclusion of child care workers in the early detection of ASD seems promising.
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19. Elbe D, Lalani Z. {{Review of the pharmacotherapy of irritability of autism}}. {J Can Acad Child Adolesc Psychiatry}. 2012; 21(2): 130-46.
OBJECTIVE: To review the randomized controlled trial data regarding pharmacotherapy of irritability of autism. METHOD: A LITERATURE REVIEW WAS CONDUCTED USING THE MEDLINE SEARCH TERMS: ‘autism’ OR ‘autism spectrum disorder’ with the following limits: Randomized Controlled Trials (RCTs), human trials, English language. Additional articles were identified from reference information. Trials involving nutritional supplements, hormones or drugs not approved by either Health Canada or the US Food and Drug Administration (FDA) were excluded from analysis. RESULTS: Twenty-three RCTs that met criteria were identified. The greatest number of RCTs involved risperidone, with six of seven placebo-controlled risperidone trials reporting statistically significant improvements on the primary outcome measure. Two aripiprazole RCTs and one olanzapine RCT reported statistically significant improvement in primary outcome measures. Haloperidol was superior to both clomipramine and placebo in a head-to-head crossover trial, while risperidone was superior to haloperidol for treatment of behavioural symptoms in a separate head-to-head trial. Clonidine, methylphenidate, valproate and levocarnitine monotherapy were superior to placebo in single RCTs, while adjunctive treatments cyproheptadine, pentoxifylline and topiramate were superior to placebo in small studies when given in combination with an antipsychotic. Adverse events from RCTs were summarized, including weight gain and metabolic effects, if available. CONCLUSION: The bulk of positive RCT evidence for the pharmacotherapy of irritability of autism pertains to FDA approved antipsychotics risperidone and aripiprazole. RCTs supporting efficacy of several alternative and adjunctive agents may afford additional treatment options when optimal antipsychotic doses fail to control symptoms or cause intolerable adverse effects. Behavioural therapy should be employed where possible either before, or in addition to pharmacotherapy.
20. Eriksson MA, Westerlund J, Anderlid BM, Gillberg C, Fernell E. {{First-degree relatives of young children with autism spectrum disorders: Some gender aspects}}. {Res Dev Disabil}. 2012; 33(5): 1642-8.
Prenatal risk factors, with special focus on gender distribution of neurodevelopmental and psychiatric conditions were analysed in first-degree relatives in a population-based group of young children with autism spectrum disorders (ASD). Multiple information sources were combined. This group was contrasted with the general population regarding data from the Swedish Medical Birth register. In the ASD group, information was also obtained at parental interviews focusing on developmental and psychiatric disorders in the family. Compared to the general population, fathers of children with ASD were older and parents more often of non-European origin. Mothers of children with ASD had an increased rate of antidepressant and psychoactive medication use, and of scheduled caesarean sections. Fathers and brothers of children with ASD had high rates of ASD including the broader phenotype. Mothers of children with ASD had high rates of depression and other psychiatric disorders. These findings, hypothetically, could reflect a different ASD phenotype and difficulties diagnosing ASD in females or be an example of the close genetic relation between ASD and other psychiatric disorders. The results suggest that, in clinical and research settings, the familial background in ASD should be reviewed with a broader approach, and not be restricted to « looking out » only for diagnoses and symptoms traditionally accepted as being part of or typical of ASD. The high rate of parents of non-European origin has been noted in many Swedish studies of ASD, but the reason for this association, remains unclear.
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21. Fendri-Kriaa N, Rouissi A, Ghorbel R, Mkaouar-Rebai E, Belguith N, Gouider-Khouja N, Fakhfakh F. {{Novel Mutations in the C-Terminal Region of the MECP2 Gene in Tunisian Rett Syndrome Patients}}. {J Child Neurol}. 2012; 27(5): 564-8.
Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6 to 18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. In the present study, we performed a mutational analysis of the MECP2 gene in 2 typical Rett syndrome patients and in 1 atypical Rett syndrome girl. The results showed the presence of 3 de novo point mutations in the C-terminal region: 2 novel mutations: c.1065C>A (p.S355R) and c.1030C>G (p.R344G) in the 2 typical Rett syndrome girls, but also the c.996C>T (p.S332S) mutation first described in the atypical Rett syndrome patient.
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22. Fisch GS. {{Autism and epistemology III: Child development, behavioral stability, and reliability of measurement}}. {Am J Med Genet A}. 2012; 158A(5): 969-79.
Early diagnosis and treatment of autism increases the likelihood that symptoms associated with the disorder can be alleviated. However, the behaviors of both typically and atypically developing young infants and toddlers are quite variable and often change as these children age. Studies have shown that this is the case for same-aged children who are diagnosed with autistic disorder (AD) or other Pervasive Developmental Disabilities (PDDs). Therefore, an early accurate assessment of AD or PDD may be problematic. Moreover, instruments used to make the diagnosis may not be as reliable as desired. Statistics employed to evaluate diagnostic accuracy and behavioral stability of instruments’ or clinicians’ assessments suggest that their diagnoses have been only moderately successful. In addition, the statistics themselves have limitations that would suggest that the measures of diagnostic accuracy and behavioral stability implemented may not be as effective as they would seem. A resolution to these problems is proposed. (c) 2012 Wiley Periodicals, Inc.
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23. Fombonne E. {{Autism in adult life}}. {Can J Psychiatry}. 2012; 57(5): 273-4.
24. Fountain C, Winter AS, Bearman PS. {{Six developmental trajectories characterize children with autism}}. {Pediatrics}. 2012; 129(5): e1112-20.
OBJECTIVE: The goal of this study was to describe the typical longitudinal developmental trajectories of social and communication functioning in children with autism and to determine the correlates of these trajectories. METHODS: Children with autism who were born in California from 1992 through 2001 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations present in the database were excluded, resulting in a sample of 6975 children aged 2 to 14 years. Score sequences were constructed based on 9 evaluative items for social, communication, and repetitive behavior functioning. Typical trajectories were identified by using group-based latent trajectory modeling, and multinomial logistic regression models were used to determine the odds of classification within each trajectory varied by individual and family-level factors. RESULTS: Six typical patterns of social, communication, and repetitive behavior functioning were identified. These trajectories displayed significant heterogeneity in developmental pathways, and children whose symptoms were least severe at first diagnosis tended to improve more rapidly than those severely affected. One group of approximately 10% of children experienced rapid gains, moving from severely affected to high functioning. Socioeconomic factors were correlated with trajectory outcomes; children with non-Hispanic, white, well-educated mothers were more likely to be high functioning, and minority children with less-educated mothers or intellectual disabilities were very unlikely to experience rapid gains. CONCLUSIONS: Children with autism have heterogeneous developmental pathways. One group of children evidenced remarkable developmental change over time. Understanding what drives these outcomes is thus critical.
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25. Freitag CM. {{[Autistic disorders – the state of the art and recent findings: epidemiology, aetiology, diagnostic criteria, and therapeutic interventions]}}. {Z Kinder Jugendpsychiatr Psychother}. 2012; 40(3): 139-49.
This review article is based on a state-of-the-art lecture given at the 32nd meeting of the German Child Psychiatry Association in March 2011. It summarizes recent findings from epidemiological studies (comorbid disorders, risk factors), early diagnosis, classification, and evidence-based therapeutic interventions (psychopharmacology, early intervention, group-based behavioural interventions). Intensive research over the last years has led to a better understanding of, and improved therapeutic options for, autism spectrum disorders.
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26. Frustaci A, Neri M, Cesario A, Adams JB, Domenici E, Dalla Bernardina B, Bonassi S. {{Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses}}. {Free Radic Biol Med}. 2012.
Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.
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27. Geurts HM, Vissers ME. {{Elderly with autism: executive functions and memory}}. {J Autism Dev Disord}. 2012; 42(5): 665-75.
Cognitive autism research is mainly focusing on children and young adults even though we know that autism is a life-long disorder and that healthy aging already has a strong impact on cognitive functioning. We compared the neuropsychological profile of 23 individuals with autism and 23 healthy controls (age range 51-83 years). Deficits were observed in attention, working memory, and fluency. Aging had a smaller impact on fluency in the high functioning autism (HFA) group than in the control group, while aging had a more profound effect on visual memory performance in the HFA group. Hence, we provide novel evidence that elderly with HFA have subtle neuropsychological deficits and that the developmental trajectories differ between elderly with and without HFA in particular cognitive domains.
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28. Ghanizadeh A. {{Atomoxetine for Treating ADHD Symptoms in Autism: A Systematic Review}}. {J Atten Disord}. 2012.
Objective: This study systematically reviews the current literature on the administration of atomoxetine for treating children and adolescents with comorbidity on autism spectrum disorder (ASD) and ADHD. Method: PubMed/Medline and Google Scholar databases were electronically searched to find the published trials on atomoxetine and ASD. Results: Six articles reported the clinical trials of atomoxetine for treatment of ADHD symptoms in patients with autism or pervasive development disorders. Only one study that was placebo-controlled crossover pilot trial reported that it is effective. Atomoxetine may be effective in high-functioning patients with autism or patients with low severity. Those with high severity of ASD may be more vulnerable to the adverse effects of atomoxetine. Conclusion: There are not enough controlled clinical trials for showing the efficacy of atomoxetine for treatment of ADHD symptoms in autism. Although evidence suggests potential efficacy of atomoxetine, the current evidences are not conclusive. (J. of Att. Dis. 2012; XX(X) 1-XX).
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29. Ghanizadeh A. {{May GABA transaminase inhibitors improve stereotyped behaviors in Rett syndrome?}}. {Amino Acids}. 2012; 42(5): 2037-8.
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30. Gliga T, Elsabbagh M, Hudry K, Charman T, Johnson MH. {{Gaze Following, Gaze Reading, and Word Learning in Children at Risk for Autism}}. {Child Dev}. 2012; 83(3): 926-38.
This study investigated gaze-following abilities as a prerequisite for word learning, in a population expected to manifest a wide range of social and communicative skills-children with a family history of autism. Fifty-three 3-year-olds with or without a family history of autism took part in a televised word-learning task. Using an eye-tracker to monitor children’s gaze behavior, it was shown that the ability to follow gaze was necessary but not sufficient for successful word learning. Those children who had poor social and communicative skills followed gaze to the labeled object but did not then learn the associated word. These findings shed light on the conditions that lead to successful word learning in typical and atypical populations.
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31. Griswold AJ, Ma D, Cukier HN, Nations LD, Schmidt MA, Chung RH, Jaworski JM, Salyakina D, Konidari I, Whitehead PL, Wright HH, Abramson RK, Williams SM, Menon R, Martin ER, Haines JL, Gilbert JR, Cuccaro ML, Pericak-Vance MA. {{Evaluation of Copy Number Variations Reveals Novel Candidate Genes in Autism Spectrum Disorder Associated Pathways}}. {Hum Mol Genet}. 2012.
Autism spectrum disorders (ASDs) are highly heritable, yet relatively few associated genetic loci have been replicated. Copy number variations (CNVs) have been implicated in autism; however, the majority of loci contribute to less than 1% of the disease population. Therefore, independent studies are important to refine associated CNV regions and discover novel susceptibility genes. In this study, a genome-wide SNP array was utilized for CNV detection by two distinct algorithms in a European ancestry case-control dataset. We identify a significantly higher burden in the number and size of deletions, and disrupting more genes in ASD cases. Moreover, eighteen deletions larger than 1Mb were detected exclusively in cases, implicating novel regions at 2q22.1, 3p26.3, 4q12, and 14q23. Case-specific CNVs provided further evidence for pathways previously implicated in ASDs, revealing new candidate genes within the GABAergic signaling and neural development pathways. These include DBI, an allosteric binder of GABA receptors, GABARAPL1, the GABA receptor-associated protein, and SLC6A11, a postsynaptic GABA transporter. We also identified CNVs in COBL, deletions of which cause defects in neuronal cytoskeleton morphogenesis in model vertebrates, and DNER, a neuron specific Notch ligand required for cerebellar development. Moreover, we found evidence of genetic overlap between ASDs and other neurodevelopmental and neuropsychiatric diseases. These genes include glutamate receptors (GRID1, GRIK2 and GRIK4), synaptic regulators (NRXN3, SLC6A8, and SYN3), transcription factor (ZNF804A), and RNA binding protein FMR1. Taken together, these CNVs may be a few of the missing pieces of ASD heritability and lead to discovering novel etiological mechanisms.
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32. Harris JC. {{Autism risk factors: moving from epidemiology to translational epidemiology}}. {J Am Acad Child Adolesc Psychiatry}. 2012; 51(5): 461-3.
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33. Howlin P, Moss P. {{Adults with autism spectrum disorders}}. {Can J Psychiatry}. 2012; 57(5): 275-83.
In the decades since autism was first formally described in the 1940s, there have been major advances in research relating to diagnosis, causation, and treatment approaches for children with this condition. However, research into prognosis, outcomes, or effective interventions for adults with autism spectrum disorders (ASDs) is much more limited. In this paper, we review studies of outcome in adulthood. The findings indicate that, as adults, many people with ASD, including those of normal IQ, are significantly disadvantaged regarding employment, social relationships, physical and mental health, and quality of life. Support to facilitate integration within the wider society is frequently lacking, and there has been almost no research into ways of developing more effective intervention programs for adults. Moreover, most of the research on outcome has involved relatively young people in their 20s and 30s-much less is known about outcomes for people with ASD as they reach mid-late adulthood. Systematic follow-up studies from childhood through adulthood are needed if we are to gain a better understanding of trajectories of development over the lifespan, to identify the factors that influence prognosis, and to determine how these factors exert their effects and how they may be modified to ensure a better future.
34. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton LL, Fulton RS, Magrini VJ, Ye K, Darnell JC, Darnell RB, Mardis ER, Wilson RK, Schatz MC, McCombie WR, Wigler M. {{De novo gene disruptions in children on the autistic spectrum}}. {Neuron}. 2012; 74(2): 285-99.
Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.
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35. Jackson P, Skirrow P, Hare DJ. {{Asperger Through the Looking Glass: An Exploratory Study of Self-Understanding in People with Asperger’s Syndrome}}. {J Autism Dev Disord}. 2012; 42(5): 697-706.
Hobson (Autism and the development of mind. Lawrence Erlbaum, Hove, UK 1993) has proposed that the cognitive and linguistic disabilities that characterise autism result from abnormalities in inter-subjective engagement during infancy, which in turn results in impaired reflective self-awareness. The aim of the present study was to test Hobson’s hypothesis by examining self-understanding in Asperger’s syndrome (AS) using Damon and Hart’s (Self-understanding in childhood and adolescence. Cambridge University Press, Cambridge, 1988) model of self-concept. Ten participants with Asperger’s syndrome were compared with ten non AS controls using the Self-understanding Interview (Damon and Hart in Self-understanding in Childhood and Adolescence. Cambridge University Press, Cambridge, 1988). The study found that the Asperger’s group demonstrated impairment in the « self-as-object » and « self-as-subject » domains of the Self-understanding Interview, which supported Hobson’s concept of an impaired capacity for self-awareness and self-reflection in people with ASD. The results are discussed with reference to previous research regarding the development of self-understanding in people with ASD.
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36. Joosten AV, Bundy AC, Einfeld SL. {{Context Influences the Motivation for Stereotypic and Repetitive Behaviour in Children Diagnosed with Intellectual Disability with and without Autism}}. {J Appl Res Intellect Disabil}. 2012; 25(3): 262-71.
Background Children are motivated to engage in stereotypic and repetitive behaviours for a number of reasons. Their motivation seems to change according to context, but little empirical evidence supports that observation. Interventions designed to reduce the behaviours may be improved by an increased understanding of the interaction between motivation and context. Method Using Rasch analysis, we analysed data describing stereotypic behaviours from 279 Revised Motivation Assessment Scales (MAS:R). Data were gathered from two groups of children: Group 1 with intellectual disability (n = 37) and Group 2 with both intellectual disability and autism (n = 37). We examined behaviours in three contexts: free time, transition and while engaged in tasks. MAS:R distinguishes two intrinsic motivators: enhanced sensation and decreased anxiety and three extrinsic motivators: seeking attention or objects or escape. Results Significant differences in motivators were observed during free time and transition. No one motivator predominated while children were engaged in tasks. For both groups, sensory enhancement was a more likely motivator in free time and anxiety reduction was a more likely motivator during transition. Transition was the context most likely to influence extrinsic motivators, but there were significant differences between the groups. Conclusions Context influences the motivation for stereotyped and repetitive behaviours. Transition has a particularly powerful effect.
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37. Kanne SM, Wang J, Christ SE. {{The Subthreshold Autism Trait Questionnaire (SATQ): Development of a Brief Self-Report Measure of Subthreshold Autism Traits}}. {J Autism Dev Disord}. 2012; 42(5): 769-80.
The current study was motivated by a need for a self-report questionnaire that assesses a broad range of subthreshold autism traits, is brief and easily administered, and is relevant to the general population. An initial item pool was administered to 1,709 students. Structural validity analysis resulted in a 24-item questionnaire termed the Subthreshold Autism Trait Questionnaire (SATQ; Cronbach’s alpha coefficient = .73, test-retest reliability = .79). An exploratory factor analysis suggested 5 factors. Confirmatory factor analysis indicated the 5 factor solution was an adequate fit and outperformed two other models. The SATQ successfully differentiated between an ASD and student group and demonstrated convergent validity with other ASD measures. Thus, the current study introduces and provides initial psychometric support for the SATQ.
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38. Kasari C, Gulsrud A, Freeman S, Paparella T, Hellemann G. {{Longitudinal follow-up of children with autism receiving targeted interventions on joint attention and play}}. {J Am Acad Child Adolesc Psychiatry}. 2012; 51(5): 487-95.
OBJECTIVE: This study examines the cognitive and language outcomes of children with an autism spectrum disorder (ASD) over a 5-year period after receiving targeted early interventions that focused on joint attention and play skills. METHOD: Forty children from the original study (n = 58) had complete data at the 5-year follow-up. RESULTS: In all, 80% of children had achieved functional use of spoken language with baseline play level predicting spoken language at the 5-year follow-up. Of children who were using spoken language at age 8 years, several baseline behaviors predicted their later ability, including earlier age of entry into the study, initiating joint attention skill, play level, and assignment to either the joint attention or symbolic play intervention group. Only baseline play diversity predicted cognitive scores at age 8 years. CONCLUSIONS: This study is one of the only long-term follow-up studies of children who participated in preschool early interventions aimed at targeting core developmental difficulties. The study findings suggest that focusing on joint attention and play skills in comprehensive treatment models is important for long-term spoken language outcomes.
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39. Kim HJ, Kim SH, Kim HD, Lee JS, Lee YM, Koo KY, Kang HC. {{Genetic and epileptic features in rett syndrome}}. {Yonsei Med J}. 2012; 53(3): 495-500.
Purpose: Rett syndrome is a severe neurodevelopmental disorder in females. Most have mutations in the methyl-CpG-binding protein 2 (MECP2) gene (80-90%). Epilepsy is a significant commonly accompanied feature in Rett syndrome. Our study was aimed at comprehensive analysis of genetic and clinical features in Rett syndrome patients, especially in regards to epileptic features. Materials and Methods: We retrospectively reviewed 20 patients who were diagnosed with MECP2 mutations at Severance Children’s Hospital between January 1995 and July 2010. All patients met clinical criteria for Rett syndrome. Evaluations included clinical features, epilepsy classification, electroencephalography analysis, and treatment of seizures. Results: Ages ranged from 3.6 to 14.3 years (7.7+/-2.6). Fourteen different types of MECP2 mutations were found, including a novel in-frame mutation (1153-1188 del36). Fourteen of these patients (70.0%) had epilepsy, and the average age of seizure onset was 3.0+/-1.8 years. Epilepsy was diverse, including partial seizure in four patients (28.5%), secondarily generalized seizure in six (42.8%), generalized tonic seizure in two (14.3%), Lennox-Gastaut syndrome in one (7.1%), and myoclonic status in non-progressive encephalopathy in one (7.1%). Motor functions were delayed so that only 10 patients (50.0%) were able to walk independently: five (35.8%) in the epilepsy group and five (83.3%) in the non-epilepsy group. Average developmental scale was 33.5+/-32.8 in the epilepsy group and 44.4+/-21.2 in the non-epilepsy group. A clear genotype-phenotype correlation was not found. Conclusion: There is a tendency for more serious motor impairment and cognitive deterioration in Rett syndrome patients with epilepsy.
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40. Koolen S, Vissers CT, Hendriks AW, Egger JI, Verhoeven L. {{The Interplay Between Attentional Strategies and Language Processing in High-functioning Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2012; 42(5): 805-14.
This study examined the hypothesis of an atypical interaction between attention and language in ASD. A dual-task experiment with three conditions was designed, in which sentences were presented that contained errors requiring attentional focus either at (a) low level, or (b) high level, or (c) both levels of language. Speed and accuracy for error detection were measured from 16 high-functioning adults with ASD, and 16 matched controls. For controls, there was an attentional cost of dual level processing for low level performance but not for high level performance. For participants with ASD, there was an attentional cost both for low level and for high level performance. These results suggest a compensatory strategic use of attention during language processing in ASD.
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41. Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL, Hertz-Picciotto I. {{Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders}}. {Pediatrics}. 2012; 129(5): e1121-8.
OBJECTIVE: We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring. METHODS: Children aged 2 to 5 years (517 ASD, 172 DD, and 315 controls) were enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a population-based, case-control investigation between January 2003 and June 2010. Eligible children were born in California, had parents who spoke English or Spanish, and were living with a biological parent in selected regions of California. Children’s diagnoses were confirmed by using standardized assessments. Information regarding maternal conditions was ascertained from medical records or structured interview with the mother. RESULTS: All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10-2.37; odds ratio: 2.35 [95% confidence interval: 1.43-3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P < .01). Among children without ASD, those exposed to any MC scored lower on all MSEL and Vineland Adaptive Behavior Scales (VABS) subscales and composites by at least 0.4 SD (P < .01 for each subscale/composite). CONCLUSIONS: Maternal MCs may be broadly associated with neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns.
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42. Kuhn M, Grave S, Bransfield R, Harris S. {{Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and Autism Spectrum Disorder}}. {Med Hypotheses}. 2012; 78(5): 606-15.
Patients diagnosed with Lyme disease share many of the same physical manifestations as those diagnosed with an Autism Spectrum Disorder (ASD). In this study four male children (ages 26-55months) who have an ASD diagnosis and one male child (age 18months) who displayed behaviors consistent with an ASD, were assessed using the SCERTS Assessment Process Observation (SAP-O) form. The SAP-O meets state and federal requirements for providing a comprehensive, ongoing assessment of a child with an ASD [33]. The SAP-O form measures children’s abilities using observational, authentic assessment procedures in the domains of joint attention, symbol use, mutual regulation, and self regulation via observations of specific behaviors in familiar settings [33]. The five children tested positive for Lyme disease and their SAP-O score was evaluated before and after 6months of antibiotic therapy. Each child was prescribed 200mg of amoxicillin three times per day and three of the five children were prescribed an additional 50mg of Azithromycin once per day. All of the children’s scores on the SAP-O assessment improved after 6months of antibiotic therapy. The assessors also reported anecdotal data of improved speech, eye contact, sleep behaviors, and a reduction of repetitive behaviors.
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43. Lai DC, Tseng YC, Hou YM, Guo HR. {{Gender and geographic differences in the prevalence of autism spectrum disorders in children: analysis of data from the national disability registry of Taiwan}}. {Res Dev Disabil}. 2012; 33(3): 909-15.
The prevalence of autism spectrum disorders (ASD) in the world has increased dramatically in the recent decades. However, data at the national level are limited, and geographic differences are seldom evaluated. According to the law, the local governments in Taiwan began to certify disabled residents and provide various services in 1980, and the central government maintains a registry of certified cases. The registry started to enroll cases of ASD in 1990, providing a unique opportunity for studying ASD at the national level. Because the government discourages the certification under 3 years of age, we limited our analyses to those who were at least 3 years old. Using the registry data from 2004 to 2010, we calculated the prevalence of ASD by age, gender, and geographic area and assessed the changes over time. From 2004 to 2010, the registered cases between 3 and 17 years old increased from 3995 to 8072 annually, and the prevalence generally increased every year in all age groups (p<0.01). In each year there were more boy cases than girl cases, and the prevalence rate ratio ranged from 5.64:1 to 6.06:1 (p<0.01 in all years), with an increasing trend over time (p<
