1. Barnett R. {{Autism}}. {Lancet}. 2016; 387(10033): 2082.
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2. Bekhet AK, Matel-Anderson D. {{Risk and Protective Factors in the Lives of Caregivers of Persons With Autism: Caregivers’ Perspectives}}. {Perspect Psychiatr Care}. 2016.
PURPOSE: The purpose of this descriptive exploratory study is to understand the experience of being a caregiver of a person with autism spectrum disorder (ASD) in the light of the resilience theory. METHODS: Qualitative data were collected as a part of a larger quantitative study. Ninety-three caregivers completed this qualitative study and responded to the two open-ended questions. In the parent study, subjects were recruited by convenience sampling from the Interactive ASD Network (IAN). FINDINGS: The identified categories appeared to reflect three distinct categories consistent with the resilience theory, labeled as follows: risk factors, protective factors, and overlapping factors. PRACTICE IMPLICATIONS: These findings help to inform the planning of tailored interventions to enhance caregivers’ resilience.
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3. Brown HK, Cobigo V, Lunsky Y, Dennis CL, Vigod S. {{Perinatal Health of Women with Intellectual and Developmental Disabilities and Comorbid Mental Illness}}. {Can J Psychiatry}. 2016.
OBJECTIVE: Women with intellectual and developmental disabilities (IDD) have high rates of adverse perinatal outcomes. However, the perinatal health of women with co-occurring IDD and mental illness (dual diagnosis) is largely unknown. Our objectives were to 1) describe a cohort of women with dual diagnosis in terms of their social and health characteristics and 2) compare their risks for adverse maternal and neonatal outcomes to those of women with IDD only. METHOD: We conducted a population-based study using linked Ontario (Canada) health and social services administrative data to identify singleton obstetric deliveries to women with dual diagnosis (n = 2080) and women with IDD only (n = 1852; 2002-2012). Primary maternal outcomes were gestational diabetes, gestational hypertension, preeclampsia/eclampsia, and venous thromboembolism. Primary neonatal outcomes were preterm birth, small for gestational age, and large for gestational age. We also examined several secondary outcomes. RESULTS: Women with dual diagnosis were more likely than women with IDD only to live in poor neighborhoods and to have prepregnancy health conditions; however, they had more frequent prenatal care. Infants born to women with dual diagnosis had increased risks for preterm birth (adjusted relative risk [aRR] 1.31, 95% confidence interval [CI] 1.08 to 1.59) and neonatal morbidity (aRR 1.35, 95% CI 1.03 to 1.76) compared with infants born to women with IDD only. All other primary and secondary outcomes were nonsignificant. CONCLUSIONS: Comorbid mental illness contributes little additional risk for adverse perinatal outcomes among women with IDD. Women with dual diagnosis and women with IDD alone require increased surveillance for maternal and neonatal complications.
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4. Cashin A. {{Autism Spectrum Disorder and Psychosis: A Case Study}}. {J Child Adolesc Psychiatr Nurs}. 2016.
PROBLEM: While apparently relatively common, there is often little clinician awareness of the risk of psychosis for people with autism. METHODS: A comprehensive review of the peer-reviewed literature and a presentation of a case study. FINDINGS: There is a paucity of research available to determine the prevalence of the experience of psychosis in people with autism. CONCLUSION: There is significant boundary overlap between autism spectrum disorder and schizophrenia spectrum disorder. This article provides a comprehensive review of the research and a case study of a 16-year-old male with autism who experienced a brief reactive psychosis.
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5. Chen C, Hung AY, Fan YT, Tan S, Hong H, Cheng Y. {{Linkage between pain sensitivity and empathic response in adolescents with autism spectrum conditions and conduct disorder symptoms}}. {Autism Res}. 2016.
Lack of empathy is one of the behavioral hallmarks in individuals with autism spectrum conditions (ASC) as well as youth with conduct disorder symptoms (CDS). Previous research has reliably documented considerable overlap between the perception of others’ pain and first-hand experience of pain. However, the linkage between empathy for pain and sensitivity to physical pain needs to be empirically determined, particularly in individuals with empathy deficits. This study measured the pressure pain threshold, which indexes sensitization of peripheral nociceptors, and assessed subjective ratings of unpleasantness and pain intensity in response to empathy-eliciting stimuli depicting physical bodily injuries in three age- and sex-matched participant groups: ASC, CDS, and typically developing controls (TDC). The results indicated that the pain threshold was lowest in the ASC group and highest in the CDS group. The ASC group displayed lower ratings of unpleasantness and pain intensity than did the TDC and CDS groups. Within the ASC and CDS, pain intensity ratings were significantly correlated with unpleasantness ratings to others’ pain. Moreover, the ASC significantly differed from the TDC in the correlation between pain threshold values and unpleasantness ratings. These findings may cast some light on the linkage between atypical low-level sensory functioning, for instance altered pain sensitivity, and high-level empathic processing. Autism Res 2016, (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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6. Dean OM, Gray KM, Villagonzalo KA, Dodd S, Mohebbi M, Vick T, Tonge BJ, Berk M. {{A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder}}. {Aust N Z J Psychiatry}. 2016.
OBJECTIVE: Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. METHOD: This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children’s Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. RESULTS: A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. CONCLUSION: This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.
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7. Diebo BG, Gammal I, Ha Y, Yoon SH, Chang JW, Kim B, Matsumoto M, Yamato Y, Takeuchi D, Hosogane N, Yagi M, Taneichi H, Schwab F, Lafage V, Ames C. {{Role of Ethnicity in Alignment Compensation: Propensity Matched Analysis of Differential Compensatory Mechanism Recruitment Patterns for Sagittal Malalignment in 288 ASD Patients from Japan, Korea and United States}}. {Spine (Phila Pa 1976)}. 2016.
STUDY DESIGN: Retrospective review of ASD patients in a multi-ethnic database OBJECTIVE.: To investigate the role of ethnicity on recruitment of compensatory mechanisms for sagittal spinal deformity. SUMMARY OF BACKGROUND DATA: While the impacts of age, gender and pelvic morphology on the ability to compensate for sagittal malalignment have been investigated, the role of ethnicity in compensatory mechanism recruitment is poorly understood. METHODS: Patients from USA (85% Caucasian) > 25 y/o were propensity matched by age, gender, and pelvic incidence with patients from Korea and Japan. Only primary patients or those with existing fusion below T12 were retained for analysis. Groups were sub-classified by deformity severity (aligned: sagittal vertical axis (SVA) < 50 mm; moderate malalignment: SVA 50-100 mm; severe malalignment: SVA >100 mm). Radiographic measurements including pelvic retroversion, thoracic kyphosis, loss of lumbar lordosis (PI minus LL), cervical lordosis and cervical SVA were compared between the groups. RESULTS: There were 288 patients (96 each in USA, KOR, JPN), with similar age (64-67yrs) and PI (49-53 degrees ). USA had smaller PI-LL in every alignment group (p < 0.05). In moderate malalignment, JPN had more pelvic retroversion than USA (30 degrees vs. 20 degrees ), and KOR had more thoracic hypokyphosis than USA (15 vs. 31 degrees ). In severe malalignment, JPN had more pelvic retroversion than USA (39 degrees vs. 27 degrees ), and KOR had more thoracic hypokyphosis than USA (15 degrees vs. 31 degrees ). KOR had smaller cSVA than USA in both aligned (11 vs. 27 mm) and moderate (19 vs. 31 mm) malalignment. In severe malalignment, KOR had less cervical lordosis (13 degrees KOR vs. 15 degrees USA vs. 27 degrees JPN). All differences with P < 0.05. CONCLUSIONS: Compensation for sagittal is ethnicity dependent. Korean patients favor thoracic compensation via hypokyphosis, and Japanese patients favor pelvic compensation via retroversion. Patient ethnicity should be considered when evaluating the sagittal plane and surgical correction strategies. LEVEL OF EVIDENCE: 3. Lien vers le texte intégral (Open Access ou abonnement)
8. Elagoz Yuksel M, Yuceturk B, Karatas OF, Ozen M, Dogangun B. {{The Altered Promoter Methylation Of Oxytocin Receptor Gene In Autism}}. {J Neurogenet}. 2016: 1-15.
Autism spectrum disorders (ASDs) are one of the life long existing disorders. Abnormal methylation status of gene promoters of oxytonergic system has been implicated as among the etiologic factors of ASDs. We, therefore, investigated the methylation frequency of oxytocin receptor gene (OXTR) promoter from peripheral blood samples of children with autistic features. Our sample includes 66 children in total (22-94 months); 27 children with ASDs according to the DSM-IV-TR and the Childhood Autism Rating Scale and 39 children who don’t have any autistic like symptoms as the healthy control group. We investigated the DNA methylation status of OXTR promoter by methylation specific enzymatic digestion of genomic DNA and polymerase chain reaction. A significant relationship has been found between ASDs and healthy controls for the reduction of methylation frequency of the regions MT1 and MT3 of OXTR. We could not find any association in the methylation frequency of MT2 and MT4 regions of OXTR. Although our findings indicate high frequency of OXTR promoter hypomethylation in ASDs, there is need for independent replication of the results in a bigger sample set. We expect that future studies with the inclusion of larger, more homogeneous samples will attempt to disentangle the causes of ASDs.
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9. Gabis LV, Gruber N, Berkenstadt M, Shefer S, Attia OL, Mula D, Cohen Y, Elizur SE. {{Fragile X Premutation Carrier Epidemiology and Symptomatology in Israel-Results from a Tertiary Child Developmental Center}}. {Cerebellum}. 2016.
Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as « carrier » were proven to be actually full mutation. The mean years of education were 14 (+/-1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.
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10. Kazdoba TM, Leach PT, Yang M, Silverman JL, Solomon M, Crawley JN. {{Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics}}. {Curr Top Behav Neurosci}. 2016.
Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism.
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11. Kim SH, Kim YS, Koh YJ, Lim EC, Kim SJ, Leventhal BL. {{Often Asked but Rarely Answered: Can Asians Meet DSM-5/ICD-10 Autism Spectrum Disorder Criteria?}}. {J Child Adolesc Psychopharmacol}. 2016.
OBJECTIVES: To evaluate whether Asian (Korean children) populations can be validly diagnosed with autism spectrum disorder (ASD) using Western-based diagnostic instruments and criteria based on Diagnostic and Statistical Manual on Mental Disorders, 5th edition (DSM-5; American Psychiatric Association 2013 ). METHODS: Participants included an epidemiologically ascertained 7-14-year-old (N = 292) South Korean cohort from a larger prevalence study (N = 55,266). Main outcomes were based on Western-based diagnostic methods for Korean children using gold standard instruments, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. Factor analysis and ANOVAs were performed to examine factor structure of autism symptoms and identify phenotypic differences between Korean children with ASD and non-ASD diagnoses. RESULTS: Using Western-based diagnostic methods, Korean children with ASD were successfully identified with moderate-to-high diagnostic validity (sensitivities/specificities ranging 64%-93%), strong internal consistency, and convergent/concurrent validity. The patterns of autism phenotypes in a Korean population were similar to those observed in a Western population with two symptom domains (social communication and restricted and repetitive behavior factors). Statistically significant differences in the use of socially acceptable communicative behaviors (e.g., direct gaze, range of facial expressions) emerged between ASD versus non-ASD cases (mostly p < 0.001), ensuring that these can be a similarly valid part of the ASD phenotype in both Asian and Western populations. CONCLUSIONS: Despite myths, biases, and stereotypes about Asian social behavior, Asians (at least Korean children) typically use elements of reciprocal social interactions similar to those in the West. Therefore, standardized diagnostic methods widely used for ASD in Western culture can be validly used as part of the assessment process and research with Koreans and, possibly, other Asians. Lien vers le texte intégral (Open Access ou abonnement)
12. Krakowiak P, Walker CK, Tancredi D, Hertz-Picciotto I, Van de Water J. {{Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions}}. {Autism Res}. 2016.
Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD-specific maternal autoantibodies are poorly understood. We sought to determine whether ASD-specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation. Participants were 227 mothers of 2-5 year old children with confirmed ASD, enrolled in CHARGE (Childhood Autism Risk from Genetics and the Environment) between January 2003 and April 2008, and from whom blood samples were collected and analyzed for anti-fetal brain autoantibodies (Ab+). MCs included diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews. Log-linear regression models were performed to estimate prevalence ratios and 95% confidence intervals (CI) based on robust standard errors. Fifty-six (25%) mothers were Ab+. Ab+ prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant. In a subset of 145 mothers whose children exhibited severe ASD (31 Ab+), those diagnosed with type 2 or gestational diabetes were 2.7-fold more likely to be Ab+ (95% CI 1.1, 6.6), controlling for delivery payer and smoking. Gestational diabetes specifically was associated with a 3.2-fold increased Ab+ prevalence (95% CI 1.2, 8.6). In this exploratory study, mothers whose children had severe ASD and who experienced diabetes were more likely to have anti-fetal brain autoantibodies 2-5 years later. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Macizo P, Soriano MF, Paredes N. {{Phonological and Visuospatial Working Memory in Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2016.
We evaluated phonological and visuospatial working memory (WM) in autism spectrum disorders. Autistic children and typically developing children were compared. We used WM tasks that measured phonological and visuospatial WM up to the capacity limit of each children. Overall measures of WM did not show differences between autistic children and control children. However, when the recall of children was examined in detail, autistic children showed reduced phonological WM compared with control children. Moreover, phonological and visuospatial WM did not increase with the age of autistic children while a development of phonological and visuospatial WM with age was found in control children. The pattern of results is discussed in terms of previous studies about WM and autism.
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14. Martinez-Cayuelas E, Ibanez-Mico S, Cean-Cabrera L, Domingo-Jimenez R, Alarcon-Martinez H, Martinez-Salcedo E. {{[Level of training in autistic spectrum disorders among hospital paediatricians]}}. {An Pediatr (Barc)}. 2016.
BACKGROUND: Training in autistic spectrum disorders is crucial in order to achieve an early diagnosis. However, the number of papers describing this training is limited. This study describes this level of knowledge among paediatricians from tertiary care hospitals in different regions of Spain and detects areas that need improvement. MATERIAL AND METHOD: A total of one hundred and fifty-seven (157) paediatricians working in tertiary healthcare hospitals located in three different regions in Spain consented to complete an online questionnaire divided in three sections (socio-demographic, knowledge about childhood autism, and opinion). Data were analysed using SPSS version 15. RESULTS: The total mean score of participating paediatricians in the questionnaire was 20.34 (+/- 2.43 SD) out of a total possible score of 23. Approximately two-thirds (65%) of paediatricians scored more or equal to the mean score. The knowledge gap was found to be higher with symptoms of repetitive behaviour patterns, concept of autism, and comorbidity, with no statistical significance. There were no differences in paediatrician scores within different socio-demographic groups. Just under two-thirds (64%) of paediatricians subscribed to the opinion that their own knowledge about autism is limited, and there is a significant lack of knowledge about facilities in every region. CONCLUSIONS: There is a sufficient level of knowledge about autism among paediatricians in tertiary healthcare, although a lack of awareness about the management of these patients, with poor coordination between the different specialists that are involved in their treatment. Efforts should focus on achieving a better coordination between these specialists, and update the knowledge gaps identified.
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15. McMahon AC, Rosbash M. {{Promiscuous or discriminating: Has the favored mRNA target of Fragile X Mental Retardation Protein been overlooked?}}. {Proc Natl Acad Sci U S A}. 2016.
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16. Mussap M, Noto A, Fanos V. {{Metabolomics of autism spectrum disorders: early insights regarding mammalian-microbial cometabolites}}. {Expert Rev Mol Diagn}. 2016.
INTRODUCTION: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders consisting of delayed or impaired language development and difficulties in social interactions. The very high degree of phenotypic heterogeneity in ASD originates from the interaction between environmental risk factors and susceptible genetic loci, leading to epigenetic DNA methylation. Advances in system biology are becoming strategic for implementing knowledge on the ASD aetiology and for the early diagnosis of the disease after birth. AREAS COVERED: We overhauled the value of either targeted or untargeted metabolomics studies in autism for identifying the most relevant metabolic pathways and key metabolites implicated in the disease, with special emphasis to mammalian-microbial metabolites. The most discriminant metabolites in ASD belong to amino acid metabolism, antioxidant status, nicotinic acid metabolism, and mitochondrial metabolism. Expert commentary: Most published studies point out the role of metabolites derived from the gut microbiota: they can modulate the behavioral phenotype of the autistic children, greatly influencing host metabolic pathways and the immune system, shaping the individual susceptibility to the disease. Pitfalls and caveats in metabolomics results across studies have been additionally recognized and discussed leading to the conclusion that metabolomics studies in ASD are far to be definitive and univocal.
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17. Noroozi R, Taheri M, Movafagh A, Mirfakhraie R, Solgi G, Sayad A, Mazdeh M, Darvish H. {{Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case-control study}}. {Autism Res}. 2016.
Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7), a receptor coding gene of this pathway, is a new candidate gene for autism. The aim of this study was to examine if there is a relationship between genetic variants rs779867 and rs6782011 of GRM7 with ASD. The present research was designed as a population-based, case-control study including 518 ASD patients versus 472 control individuals. The results showed that the frequency of rs779867 G/G genotype was significantly higher in ASD patients compared to healthy controls (P = 0.0001). Also, the G allele of this SNP was found to be significantly more frequent in the patients than control group (P = 0.0001). Haplotype analysis exhibited significant association of two estimated block of rs6782011/rs779867 in ASD patients versus control group. We found higher significant frequency of GT haplotype and lower frequencies of AT and AC haplotypes in the patients group compared to healthy controls (P = 0.001, P = 0.006, and P = 0.05, respectively). Our study indicated that the rs779867 polymorphism is associated with ASD; thus, results of this study provide supportive evidence of association of the GRM7 gene with ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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18. Ryan C, Furley P, Mulhall K. {{Judgments of Nonverbal Behaviour by Children with High-Functioning Autism Spectrum Disorder: Can they Detect Signs of Winning and Losing from Brief Video Clips?}}. {J Autism Dev Disord}. 2016.
Typically developing children are able to judge who is winning or losing from very short clips of video footage of behaviour between active match play across a number of sports. Inferences from « thin slices » (short video clips) allow participants to make complex judgments about the meaning of posture, gesture and body language. This study extends the use of the thin slice research paradigm to children with high-functioning autism spectrum disorder (ASD). We tested 38 children with ASD, in two age groups: 15 participants aged 5-8 years and 23 participants aged 9-13 years. We found that the children with ASD had a rate of accuracy similar to that of typically developing peers tested in a previous study.
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19. Scott RC, Tuchman R. {{Epilepsy and autism spectrum disorders: Relatively related}}. {Neurology}. 2016.
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20. Self TL, Parham DF. {{Students’ self-perceptions of interprofessional education following participation on a diagnostic team for autism spectrum disorder}}. {J Interprof Care}. 2016: 1-3.
Interprofessional education is essential for producing future allied-health and education professionals. Unfortunately, opportunities for students to get authentic interprofessional field-based experiences are lacking. This pilot study explored students’ self-perceptions towards interprofessional education (IPE) following participation on an interprofessional diagnostic team designed to rule in or out the diagnosis of autism spectrum disorder (ASD). Thirty-nine students from seven professions responded to a survey before and after completing this interprofessional education experience. The results indicated that the students’ self-perceptions remained consistent during the experience. They reflected positive self-perceptions in the areas of collaboration, professional identity, and the desire to work with others, all in the context of an ASD-focused team. The findings suggest that students entering the IPE experience with positive expectations remained positive during the experience. This pilot study provides support for the benefits of providing students with the opportunity to engage in authentic collaborative practice when working with children with ASD.
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21. Sundelin HE, Larsson H, Lichtenstein P, Almqvist C, Hultman CM, Tomson T, Ludvigsson JF. {{Autism and epilepsy: A population-based nationwide cohort study}}. {Neurology}. 2016.
OBJECTIVE: To investigate the risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives to determine shared etiology. METHODS: Through the Swedish Patient Register, we identified 85,201 individuals with epilepsy, as well as all their siblings (n = 80,511) and offspring (n = 98,534). Each individual with epilepsy was compared with 5 controls, matched for age, sex, calendar period, and county, while siblings and offspring were compared with siblings and offspring of controls. We excluded siblings and offspring with epilepsy. Using Cox regression, we calculated hazard ratios (HRs) for future diagnosis of ASD. Logistic regression was applied to calculate odds ratios (ORs) for prior diagnosis of ASD. RESULTS: During follow-up, 1,381 (1.6%) individuals with epilepsy and 700 (0.2%) controls were diagnosed with ASD. Individuals with epilepsy were therefore at increased risk of future ASD (HR 10.49, 95% confidence interval [CI] 9.55-11.53), with the highest risk seen in individuals diagnosed with epilepsy in childhood. Both siblings (HR 1.62, 95% CI 1.43-1.83) and offspring (HR 1.64, 95% CI 1.46-1.84) of epilepsy patients were at increased risk of ASD. The risk in the offspring was particularly high in mothers with epilepsy (HR 1.91; 95% CI 1.63-2.23). Epilepsy was also associated with a prior diagnosis of ASD (OR 4.56, 95% CI 4.02-5.18). CONCLUSIONS: Individuals with epilepsy are at increased risk of ASD, especially if epilepsy appears in childhood. Further, ASD is more common in the siblings and offspring of individuals with epilepsy, suggesting shared etiology.
