1. Andrews SV, Ellis SE, Bakulski KM, Sheppard B, Croen LA, Hertz-Picciotto I, Newschaffer CJ, Feinberg AP, Arking DE, Ladd-Acosta C, Fallin MD. {{Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder}}. {Nat Commun}. 2017; 8(1): 1011.
Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly. Lien vers le texte intégral (Open Access ou abonnement)
2. Berridge MJ. {{Vitamin D deficiency: infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism and schizophrenia)}}. {Am J Physiol Cell Physiol}. 2017: ajpcell 00188 2017.
The process of development depends on a progressive sequence of events that are carefully orchestrated by a number of signalling systems. Alteration in these signalling events results in infertility and neurodevelopmental diseases such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and schizophrenia. A prominent role throughout development beginning at fertilization and continuing through early development, implantation and organ differentiation such as heart and brain development is regulated by Ca2+ signalling. There is increasing evidence that Vitamin D plays a major role in regulating these developmental processes. When Vitamin D is deficient, there is an increase in infertility and an onset of neurodevelopmental diseases. The aim of this review is to describe why Vitamin D deficiency has such a serious effect on development. The main conclusion is that one of the primary functions of Vitamin D is to maintain the phenotypic stability of both the Ca2+ and redox signalling pathways that play such a key role throughout development.
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3. Blacher J, Baker BL. {{Collateral Effects of Youth Disruptive Behavior Disorders on Mothers’ Psychological Distress: Adolescents with Autism Spectrum Disorder, Intellectual Disability, or Typical Development}}. {J Autism Dev Disord}. 2017.
Disruptive behavior disorders were assessed in 160 youth aged 13 years, with Autism Spectrum Disorder (ASD, n = 48), intellectual disability (ID, n = 28), or typical development (TD, n = 84). Mothers’ reported collateral effects on their psychological adjustment were related to both youth disability status and clinical level behavior disorders. More youth with ASD or ID had clinical level behavior disorders than their TD peers, and their mothers reported significantly higher personal stress and psychological symptoms, as well as lower positive impact of the youth on the family. The youth’s clinical level behavior disorders accounted for these differences more than the diagnostic status. Mothers high in dispositional optimism reported the lowest stress and psychological symptoms in relationship to youth behavior challenges.
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4. Cage E, Di Monaco J, Newell V. {{Experiences of Autism Acceptance and Mental Health in Autistic Adults}}. {J Autism Dev Disord}. 2017.
Mental health difficulties are highly prevalent in individuals on the autism spectrum. The current study examined how experiences and perceptions of autism acceptance could impact on the mental health of autistic adults. 111 adults on the autism spectrum completed an online survey examining their experiences of autism acceptance, along with symptoms of depression, anxiety and stress. Regression analyses showed that autism acceptance from external sources and personal acceptance significantly predicted depression. Acceptance from others also significantly predicted stress but acceptance did not predict anxiety. Further analyses suggested that experiences of « camouflaging » could relate to higher rates of depression. The current study highlights the importance of considering how autism acceptance could contribute to mental health in autism.
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5. Clements CC, Wenger TL, Zoltowski AR, Bertollo JR, Miller JS, de Marchena AB, Mitteer LM, Carey JC, Yerys BE, Zackai EH, Emanuel BS, McDonald-McGinn DM, Schultz RT. {{Critical region within 22q11.2 linked to higher rate of autism spectrum disorder}}. {Mol Autism}. 2017; 8: 58.
BACKGROUND: Previous studies have reported no clear critical region for medical comorbidities in children with deletions or duplications of 22q11.2. The purpose of this study was to evaluate whether individuals with small nested deletions or duplications of the LCR-A to B region of 22q11.2 show an elevated rate of autism spectrum disorder (ASD) compared to individuals with deletions or duplications that do not include this region. METHODS: We recruited 46 patients with nested deletions (n = 33) or duplications (n = 13) of 22q11.2, including LCR-A to B (ndel = 11), LCR-A to C (ndel = 4), LCR-B to D (ndel = 14; ndup = 8), LCR-C to D (ndel = 4; ndup = 2), and smaller nested regions (n = 3). Parent questionnaire, record review, and, for a subset, in-person evaluation were used for ASD diagnostic classification. Rates of ASD in individuals with involvement of LCR-B to LCR-D were compared with Fisher’s exact test to LCR-A to LCR-B for deletions, and to a previously published sample of LCR-A to LCR-D for duplications. The rates of medical comorbidities and psychiatric diagnoses were determined from questionnaires and chart review. We also report group mean differences on psychiatric questionnaires. RESULTS: Individuals with deletions involving LCR-A to B showed a 39-44% rate of ASD compared to 0% in individuals whose deletions did not involve LCR-A to B. We observed similar rates of medical comorbidities in individuals with involvement of LCR-A to B and LCR-B to D for both duplications and deletions, consistent with prior studies. CONCLUSIONS: Children with nested deletions of 22q11.2 may be at greater risk for autism spectrum disorder if the region includes LCR-A to LCR-B. Replication is needed.
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6. Cohen S, Fulcher BD, Rajaratnam SMW, Conduit R, Sullivan JP, Hilaire MAS, Phillips AJ, Loddenkemper T, Kothare SV, McConnell K, Ahearn W, Braga-Kenyon P, Shlesinger A, Potter J, Bird F, Cornish KM, Lockley SW. {{Behaviorally-determined sleep phenotypes are robustly associated with adaptive functioning in individuals with low functioning autism}}. {Sci Rep}. 2017; 7(1): 14228.
Despite sleep disturbance being a common complaint in individuals with autism, specific sleep phenotypes and their relationship to adaptive functioning have yet to be identified. This study used cluster analysis to find distinct sleep patterns and relate them to independent measures of adaptive functioning in individuals with autism. Approximately 50,000 nights of care-giver sleep/wake logs were collected on school-days for 106 individuals with low functioning autism (87 boys, 14.77 +/- 3.11 years) for 0.5-6 years (2.2 +/- 1.5 years) from two residential schools. Using hierarchical cluster analysis, performed on summary statistics of each individual across their recording duration, two clusters of individuals with clearly distinguishable sleep phenotypes were found. The groups were summarized as ‘unstable’ sleepers (cluster 1, n = 41) and ‘stable’ sleepers (cluster 2, n = 65), with the former exhibiting reduced sleep duration, earlier sleep offset, and less stability in sleep timing. The sleep clusters displayed significant differences in properties that were not used for clustering, such as intellectual functioning, communication, and socialization, demonstrating that sleep phenotypes are associated with symptom severity in individuals with autism. This study provides foundational evidence for profiling and targeting sleep as a standard part of therapeutic intervention in individuals with autism.
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7. Dahm MR, Georgiou A, Balandin S, Hill S, Hemsley B. {{Health Information Infrastructure for People with Intellectual and Developmental Disabilities (I/DD) Living in Supported Accommodation: Communication, Co-Ordination and Integration of Health Information}}. {Health Commun}. 2017: 1-9.
People with intellectual and/or developmental disability (I/DD) commonly have complex health care needs, but little is known about how their health information is managed in supported accommodation, and across health services providers. This study aimed to describe the current health information infrastructure (i.e., how data and information are collected, stored, communicated, and used) for people with I/DD living in supported accommodation in Australia. It involved a scoping review and synthesis of research, policies, and health documents relevant in this setting. Iterative database and hand searches were conducted across peer-reviewed articles internationally in English and grey literature in Australia (New South Wales) up to September 2015. Data were extracted from the selected relevant literature and analyzed for content themes. Expert stakeholders were consulted to verify the authors’ interpretations of the information and content categories. The included 286 sources (peer-reviewed n = 27; grey literature n = 259) reflect that the health information for people with I/DD in supported accommodation is poorly communicated, coordinated and integrated across isolated systems. ‘Work-as-imagined’ as outlined in policies, does not align with ‘work-as-done’ in reality. This gap threatens the quality of care and safety of people with I/DD in these settings. The effectiveness of the health information infrastructure and services for people with I/DD can be improved by integrating the information sources and placing people with I/DD and their supporters at the centre of the information exchange process.
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8. de Verdier K, Fernell E, Ek U. {{Challenges and Successful Pedagogical Strategies: Experiences from Six Swedish Students with Blindness and Autism in Different School Settings}}. {J Autism Dev Disord}. 2017.
The prevalence of autism in children with blindness is much higher than in the general population. There are many challenges regarding the school situation for children with this complex dual disability. This study explored challenges and successful strategies in school for a sample of six Swedish children with blindness and autism, with and without intellectual disability, through qualitative interviews with students, teachers and parents. All students displayed executive functioning deficits, and the teaching situation entailed several challenges. Our research points to the importance of adopting evidence-based practices for ASD, but adapted according to the students lack of vision. For this to be possible, close collaboration between teachers, parents and specialists in the field of visual impairment and autism is necessary.
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9. Duvekot J, van der Ende J, Verhulst FC, Greaves-Lord K. {{Examining bidirectional effects between the autism spectrum disorder (ASD) core symptom domains and anxiety in children with ASD}}. {J Child Psychol Psychiatry}. 2017.
BACKGROUND: Although a bidirectional relationship between autism spectrum disorder (ASD) and anxiety symptoms is assumed, few studies have investigated this. Moreover, little is known about potential differential relationships of the two core symptom domains of ASD – social communication impairment and restricted, repetitive behavior – with anxiety over time. METHOD: Participants were 130 children with an ASD (M age 6.7 years, 81.5% boys) of whom 79 participated in a follow-up assessment 2 years later. We used cross-lagged models to test whether social communication impairment and restricted, repetitive behavior at T0 predicted anxiety at T2 and vice versa. RESULTS: Crossed-lagged models showed that anxiety symptoms predicted social communication impairment over time (beta = .22, p = .008), but not vice versa (beta = -.07, p = .49). There were no significant paths from anxiety symptoms to later restricted, repetitive behavior (beta = .11, p = .34) or vice versa (beta = -.11, p = .27). CONCLUSIONS: Our results do not support a bidirectional relationship between the ASD core symptom domains and anxiety, but suggest that higher levels of anxiety symptoms increase the risk of more social communication impairment over time in children with ASD. This underlines the importance of treating anxiety symptoms to improve both social and emotional functioning.
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10. Epstein A, Whitehouse A, Williams K, Murphy N, Leonard H, Davis E, Reddihough D, Downs J. {{Parent-observed thematic data on quality of life in children with autism spectrum disorder}}. {Autism}. 2017: 1362361317722764.
Domains of quality of life in children with autism spectrum disorder have not previously been explored and there has been no quality of life measure developed for this population. Our study investigated parent observations to identify the domains important to children with autism spectrum disorder who also had an intellectual disability. In all, 21 parents (19 mothers, 2 fathers) of children with autism spectrum disorder (aged 6-17 years) participated in a qualitative study to discuss their child’s quality of life. Thematic analysis using a grounded theory framework was conducted and 10 domains emerged in relation to health and well-being, capacity to perform and develop skills in daily life, and connections with the community and environment. Unique aspects of quality of life included varying levels of social desire, consistency of routines, and time spent in nature and the outdoors, which are not comprehensively captured in existing measures. Parent observations provide an initial framework for understanding quality of life in autism spectrum disorder and support the development of a new measure for this population.
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11. Han J, Zeng K, Kang J, Tong Z, Cai E, Chen H, Ding M, Gu Y, Ouyang G, Li X. {{Development of Brain Network in Children with Autism from Early Childhood to Late Childhood}}. {Neuroscience}. 2017; 367: 134-46.
Extensive studies have indicated brain function connectivity abnormalities in autism spectrum disorder (ASD). However, there is a lack of longitudinal or cross-sectional research focused on tracking age-related developmental trends of autistic children at an early stage of brain development or based on a relatively large sample. The present study examined brain network changes in a total of 186 children both with and without ASD from 3 to 11years, an early and key development period when significant changes are expected. The study aimed to investigate possible abnormal connectivity patterns and topological properties of children with ASD from early childhood to late childhood by using resting-state electroencephalographic (EEG) data. The main findings of the study were as follows: (1) From the connectivity analysis, several inter-regional synchronizations with reduction were identified in the younger and older ASD groups, and several intra-regional synchronization increases were observed in the older ASD group. (2) From the graph analysis, a reduced clustering coefficient and enhanced mean shortest path length in specific frequencies was observed in children with ASD. (3) Results suggested an age-related decrease of the mean shortest path length in the delta and theta bands in TD children, whereas atypical age-related alteration was observed in the ASD group. In addition, graph measures were correlated with ASD symptom severity in the alpha band. These results demonstrate that abnormal neural communication is already present at the early stages of brain development in autistic children and this may be involved in the behavioral deficits associated with ASD.
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12. Hess S, Self T, DiLollo A. {{Assessing Personal Constructs of Adolescents with Autism Spectrum Disorder: A Person-Centered Measure of Social Cognition}}. {J Autism Dev Disord}. 2017.
Many protocols assessing social communication skills of adolescents with autism spectrum disorder (ASD) are based on behavioral observations. It has been suggested, however, that social cognition encompasses processes underlying observable behaviors. Such processes include personal constructs, which can be assessed using repertory grids. Personal constructs of five adolescents with ASD with average or above average intelligence and receptive and expressive language skills were explored using repertory grids in this study. With visual structure and verbal scaffolding, all participants successfully engaged in the repertory grid process. Data suggest participants had well organized, complex construct systems, a significant understanding of social roles, and were interested in social interactions. Repertory grids may provide additional person-centered information for assessing social communication skills in ASD.
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13. Jozefczuk J, Konopka E, Bierla JB, Trojanowska I, Sowinska A, Czarnecki R, Sobol L, Jozefczuk P, Surdy W, Cukrowska B. {{The Occurrence of Antibodies Against Gluten in Children with Autism Spectrum Disorders Does Not Correlate with Serological Markers of Impaired Intestinal Permeability}}. {J Med Food}. 2017.
There is evidence that children with autism spectrum disorders (ASDs) display an increased immune reactivity against gluten, which is supposed to be the effect of intestinal barrier abnormalities. The aim of study was to evaluate the relation of antibody induced by gluten to zonulin and intestinal fatty acid binding proteins (I-FABP), that is, serological markers of an impaired gut barrier. The study included 77 patients with ASDs. Zonulin, I-FABP, celiac-specific antibodies, anti-gliadin antibodies (AGA), and antibodies against neural transglutaminase 6 (TG6) of immunoglobulin (Ig) A and IgG classes were detected in sera. Celiac-specific antibodies were negative in all ASD children, four children (5.2%) had positive anti-TG6 antibodies, and increased AGA-IgG production was found in 21 patients (27.3%). Mean levels of zonulin and I-FABP in ASD patients were similar to those found in healthy controls and revealed a negative correlation with age, whereas regression analysis revealed a significant positive relationship between antibody production and the age. Serum concentrations of zonulin and I-FABP showed no statistically significant association with antibody positivity. An increased production of antibodies related to gliadin and neural TG6 in ASD children is not related to serological markers of an impaired intestinal barrier.
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14. Koemans TS, Kleefstra T, Chubak MC, Stone MH, Reijnders MRF, de Munnik S, Willemsen MH, Fenckova M, Stumpel C, Bok LA, Sifuentes Saenz M, Byerly KA, Baughn LB, Stegmann APA, Pfundt R, Zhou H, van Bokhoven H, Schenck A, Kramer JM. {{Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder}}. {PLoS Genet}. 2017; 13(10): e1006864.
Kleefstra syndrome, caused by haploinsufficiency of euchromatin histone methyltransferase 1 (EHMT1), is characterized by intellectual disability (ID), autism spectrum disorder (ASD), characteristic facial dysmorphisms, and other variable clinical features. In addition to EHMT1 mutations, de novo variants were reported in four additional genes (MBD5, SMARCB1, NR1I3, and KMT2C), in single individuals with clinical characteristics overlapping Kleefstra syndrome. Here, we present a novel cohort of five patients with de novo loss of function mutations affecting the histone methyltransferase KMT2C. Our clinical data delineates the KMT2C phenotypic spectrum and reinforces the phenotypic overlap with Kleefstra syndrome and other related ID disorders. To elucidate the common molecular basis of the neuropathology associated with mutations in KMT2C and EHMT1, we characterized the role of the Drosophila KMT2C ortholog, trithorax related (trr), in the nervous system. Similar to the Drosophila EHMT1 ortholog, G9a, trr is required in the mushroom body for short term memory. Trr ChIP-seq identified 3371 binding sites, mainly in the promoter of genes involved in neuronal processes. Transcriptional profiling of pan-neuronal trr knockdown and G9a null mutant fly heads identified 613 and 1123 misregulated genes, respectively. These gene sets show a significant overlap and are associated with nearly identical gene ontology enrichments. The majority of the observed biological convergence is derived from predicted indirect target genes. However, trr and G9a also have common direct targets, including the Drosophila ortholog of Arc (Arc1), a key regulator of synaptic plasticity. Our data highlight the clinical and molecular convergence between the KMT2 and EHMT protein families, which may contribute to a molecular network underlying a larger group of ID/ASD-related disorders.
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15. Kolakowska A, Landowska A, Anzulewicz A, Sobota K. {{Automatic recognition of therapy progress among children with autism}}. {Sci Rep}. 2017; 7(1): 13863.
The article presents a research study on recognizing therapy progress among children with autism spectrum disorder. The progress is recognized on the basis of behavioural data gathered via five specially designed tablet games. Over 180 distinct parameters are calculated on the basis of raw data delivered via the game flow and tablet sensors – i.e. touch screen, accelerometer and gyroscope. The results obtained confirm the possibility of recognizing progress in particular areas of development. The recognition accuracy exceeds 80%. Moreover, the study identifies a subset of parameters which appear to be better predictors of therapy progress than others. The proposed method – consisting of data recording, parameter calculation formulas and prediction models – might be implemented in a tool to support both therapists and parents of autistic children. Such a tool might be used to monitor the course of the therapy, modify it and report its results.
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16. Konopko MA, Densmore AL, Krueger BK. {{Sexually Dimorphic Epigenetic Regulation of Brain-Derived Neurotrophic Factor in Fetal Brain in the Valproic Acid Model of Autism Spectrum Disorder}}. {Dev Neurosci}. 2017.
Prenatal exposure to the antiepileptic, mood-stabilizing drug, valproic acid (VPA), increases the incidence of autism spectrum disorders (ASDs); in utero administration of VPA to pregnant rodents induces ASD-like behaviors such as repetitive, stereotyped activity, and decreased socialization. In both cases, males are more affected than females. We previously reported that VPA, administered to pregnant mice at gestational day 12.5, rapidly induces a transient, 6-fold increase in BDNF (brain-derived neurotrophic factor) protein and mRNA in the fetal brain. Here, we investigate sex differences in the induction of Bdnf expression by VPA as well as the underlying epigenetic mechanisms. We found no sex differences in the VPA stimulation of total brain Bdnf mRNA as indicated by probing for the BDNF protein coding sequence (exon 9); however, stimulation of individual transcripts containing two of the nine 5′-untranslated exons (5’UTEs) in Bdnf (exons 1 and 4) by VPA was greater in female fetal brains. These Bdnf transcripts have been associated with different cell types or subcellular compartments within neurons. Since VPA is a histone deacetylase inhibitor, covalent histone modifications at Bdnf 5’UTEs in the fetal brain were analyzed by chromatin immunoprecipitation. VPA increased the acetylation of multiple H3 and H4 lysine residues in the vicinity of exons 1, 2, 4, and 6; minimal differences between the sexes were observed. H3 lysine 4 trimethylation (H3K4me3) at those exons was also stimulated by VPA. Moreover, the VPA-induced increase in H3K4me3 at exons 1, 4, and 6 was significantly greater in females than in males, i.e., sexually dimorphic stimulation of H3K4me3 by VPA correlated with Bdnf transcripts containing exons 1 and 4, but not 6. Neither H3K27me3 nor cytosine methylation at any of the 117 CpGs in the vicinity of the transcription start sites of exons 1, 4, and 6 was affected by VPA. Thus, of the 6 epigenetic marks analyzed, only H3K4me3 can account for the sexually dimorphic expression of Bdnf transcripts induced by VPA in the fetal brain. Preferential expression of exon 1- and exon 4-Bdnf transcripts in females may contribute to sex differences in ASDs by protecting females from the adverse effects of genetic variants or environmental factors such as VPA on the developing brain.
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17. Korzeniewski SJ. {{Why Stratify Autism Spectrum Disorder by Co-Occurrence with Intellectual Disability?}}. {Paediatr Perinat Epidemiol}. 2017; 31(6): 595-7.
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18. Lalani SJ, Duffield TC, Trontel HG, Bigler ED, Abildskov TJ, Froehlich A, Prigge MBD, Travers BG, Anderson JS, Zielinski BA, Alexander A, Lange N, Lainhart JE. {{Auditory attention in autism spectrum disorder: An exploration of volumetric magnetic resonance imaging findings}}. {J Clin Exp Neuropsychol}. 2017: 1-16.
Studies have shown that individuals with autism spectrum disorder (ASD) tend to perform significantly below typically developing individuals on standardized measures of attention, even when controlling for IQ. The current study sought to examine within ASD whether anatomical correlates of attention performance differed between those with average to above-average IQ (AIQ group) and those with low-average to borderline ability (LIQ group) as well as in comparison to typically developing controls (TDC). Using automated volumetric analyses, we examined regional volume of classic attention areas including the superior frontal gyrus, anterior cingulate cortex, and precuneus in ASD AIQ (n = 38) and LIQ (n = 18) individuals along with 30 TDC. Auditory attention performance was assessed using subtests of the Test of Memory and Learning (TOMAL) compared among the groups and then correlated with regional brain volumes. Analyses revealed group differences in attention. The three groups did not differ significantly on any auditory attention-related brain volumes; however, trends toward significant size-attention function interactions were observed. Negative correlations were found between the volume of the precuneus and auditory attention performance for the AIQ ASD group, indicating larger volume related to poorer performance. Implications for general attention functioning and dysfunctional neural connectivity in ASD are discussed.
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19. Laptook AR, Shankaran S, Tyson JE, Munoz B, Bell EF, Goldberg RN, Parikh NA, Ambalavanan N, Pedroza C, Pappas A, Das A, Chaudhary AS, Ehrenkranz RA, Hensman AM, Van Meurs KP, Chalak LF, Hamrick SEG, Sokol GM, Walsh MC, Poindexter BB, Faix RG, Watterberg KL, Frantz ID, 3rd, Guillet R, Devaskar U, Truog WE, Chock VY, Wyckoff MH, McGowan EC, Carlton DP, Harmon HM, Brumbaugh JE, Cotten CM, Sanchez PJ, Hibbs AM, Higgins RD. {{Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial}}. {JAMA}. 2017; 318(16): 1550-60.
Importance: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions: Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5 degrees C (acceptable range, 33 degrees C-34 degrees C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0 degrees C (acceptable range, 36.5 degrees C-37.3 degrees C). Main Outcomes and Measures: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results: Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance: Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration: clinicaltrials.gov Identifier: NCT00614744.
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20. Liu J, Gong J, Nie G, He Y, Xiao B, Shen Y, Luo X. {{The mediating effects of childhood neglect on the association between schizotypal and autistic personality traits and depression in a non-clinical sample}}. {BMC Psychiatry}. 2017; 17(1): 352.
BACKGROUND: Autistic personality traits (APT) and schizotypal personality traits (SPT) are associated with depression. However, mediating factors within these relationships have not yet been explored. Thus, the focus of the current study was to examine the effects of childhood neglect on the relationship between APT/SPT and depression. METHODS: This cross-sectional study was conducted on first-year students (N = 2469) at Hunan University of Chinese Medicine and Hengyang Normal College (Changsha, China). Participants completed surveys on APT, SPT, childhood neglect, abuse and depression. RESULTS: Through correlational analyses, APT and SPT traits were positively correlated with childhood neglect and depression (p < 0.05). In a hierarchical regression analysis, among types of childhood maltreatment, emotional neglect (beta = 0.112, p < 0.001) and physical neglect (beta = 0.105, p < 0.001) were the strongest predictors of depression. Childhood neglect did not account for the relationships between APT/SPT and depression. Further analysis found that childhood neglect mediated the relationship between SPT and depression but not APT and depression. CONCLUSIONS: Among types of childhood maltreatment, neglect was the strongest predicting factor for depression. Neglect did not account for the relationship between APT/SPT and depression but was a strong mediating factor between SPT and depression. Lien vers le texte intégral (Open Access ou abonnement)
21. Maloret P, Scott T. {{Don’t ask me what’s the matter, ask me what matters: Acute mental health facility experiences of people living with autism spectrum conditions}}. {J Psychiatr Ment Health Nurs}. 2017.
WHAT IS KNOWN ON THE SUBJECT?: There is a growing body of evidence that many people with an autism spectrum condition suffer anxiety in their daily life and a realization among practitioners that admission to a mental health unit for this population is usually a negative anxiety-inducing experience. Anxiety is driven by the intolerance of uncertainty that is being unsure of what is going to happen, how long the uncertainty will exist and the insistence of sameness which, when compromised, can be anxiety provoking. Equally, confusion in understanding personal emotional responses and those of others is a source of anxiety. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This paper builds upon existing understanding of anxiety as a causative factor of mental ill-health for people with an autism spectrum condition. Specifically, this paper explores the potentially anxiety-inducing experience of mental health unit admission; how anxiety is felt, triggered, expressed and managed. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: As many different anxiety responses could be exhibited during hospitalization, including violent acts and self-harming, for mental health practitioners working in the inpatient units, it is essential that the thoughts, feelings and responses of the patient with an autistic spectrum condition (ASC) are better understood and that support offered during their stay in a mental health facility is from an informed position. ABSTRACT: Background This qualitative study explored how mental health inpatients with autistic spectrum conditions (ASCs) experience and cope with anxiety when admitted to an acute mental health inpatient facility in the United Kingdom. Anxiety is a common characteristic for people who live with ASCs and whilst a plethora of studies on anxiety in this population is published which correlate anxiety with mental health service experience, little is known about the actual triggers of anxiety and its manifestations. This study adds to a body of evidence which considers anxiety experienced by people with autism. The rationale for this study includes the need to heighten mental health practitioners’ understanding, of the responses, motivations to engage and support required to overcome fears and anxieties when admitted to a mental health inpatient unit. Method The study used a qualitative naturalistic research design, to explore the emotional and psychological experiences of being a mental health inpatient living with an ASC. During 2015-2017. audio-recorded semistructured interviews captured the experiences of 20 adults from the east of England who were former psychiatric inpatients with an established diagnosis of ASC. Interpretative phenomenological analysis enabled the identification of broad themes which explained in rich detail, participant reflections regarding the situations and events within the acute care mental health facility that triggered their anxiety, manifestations of anxiety and responses to their anxiety. Findings Broad response patterns were identified that could be associated with their anxiety that is isolating themselves from others, including patients and staff, ceasing to eat and sleep adequately and all too often self-harming or exhibiting aggressive and violent responses. Conclusions The anxiety caused by the physical environment appears to be overlooked by mental health practitioners so attention to anxiety-inducing encounters is needed when planning acute care mental health service improvement and research is required to clearly understand the experiences of this vulnerable group.
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22. Maras K, Gamble T, Brosnan M. {{Supporting metacognitive monitoring in mathematics learning for young people with autism spectrum disorder: A classroom-based study}}. {Autism}. 2017: 1362361317722028.
Previous research suggests impaired metacognitive monitoring and mathematics under-achievement in autism spectrum disorder. Within educational settings, metacognitive monitoring is supported through the provision of feedback (e.g. with goal reminders and by explicitly correcting errors). Given the strength of the relationship between metacognition, learning and educational attainment, this research tested new computer-based metacognitive support (the ‘Maths Challenge’) for mathematics learners with autism spectrum disorder within the context of their classroom. The Maths Challenge required learners to engage in metacognitive monitoring before and after answering each question (e.g. intentions and judgements of accuracy) and negotiate with the system the level of difficulty. Forty secondary school children with autism spectrum disorder and 95 typically developing learners completed the Maths Challenge in either a Feedback condition, with metacognitive monitoring support regarding the accuracy of their answers, goal reminders and strategy support, or with No Feedback. Contrary to previous findings, learners with autism showed an undiminished ability to detect errors. They did, however, demonstrate reduced cohesion between their pre- and post-test intentions. Crucially, support from the Feedback condition significantly improved task performance for both groups. Findings highlight important implications for educational interventions regarding the provision of metacognitive support for learners with autism to ameliorate under-performance in mathematics within the classroom.
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23. Nicholas DB, Mitchell W, Dudley C, Clarke M, Zulla R. {{An Ecosystem Approach to Employment and Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Relatively little is yet known about employment readiness and elements that promote access to, and the retention of, employment for adults with autism spectrum disorder (ASD). This paper posits elements within the ecosystem of employment and ASD. The ecosystem approach locates employment among persons with ASD as inextricably linked with broader community resources, family support, workplace capacity building (e.g., employer, co-workers) and policy. Application of the approach is offered through process evaluation data yielded from an ecosystem-informed job readiness program entitled, ‘EmploymentWorks Canada’. Findings illustrate job readiness in the context of the broader ecosystem that envelopes salient components in the aim of community engagement and quality of life. Recommendations are offered for community-based applications and for program and research development.
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24. Oshodi Y, Ojewunmi O, Oshodi TA, Ijarogbe GT, Ogun OC, Aina OF, Lesi F. {{Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria}}. {Niger J Clin Pract}. 2017; 20(9): 1161-7.
BACKGROUND: The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. MATERIALS AND METHODS: Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. RESULTS: Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. CONCLUSION: Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.
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25. Pijl MK, Buitelaar JK, de Korte MW, Rommelse NN, Oosterling IJ. {{Sustainability of an early detection program for autism spectrum disorder over the course of 8 years}}. {Autism}. 2017: 1362361317717977.
The importance of early detection of autism spectrum disorder followed by early intervention is increasingly recognized. This quasi-experimental study evaluated the long-term effects of a program for the early detection of autism spectrum disorder (consisting of training of professionals and use of a referral protocol and screening instrument), to determine whether the positive effects on the age at referral were sustained after the program ended while controlling for overall changes in the number of referrals. Before, during, and after the program, the proportion of children referred before 3 years (versus 3-6 years) of age was calculated for children subsequently diagnosed with autism spectrum disorder ( N = 513) or another, non-autism spectrum disorder, condition ( N = 722). The odds of being referred before 3 years of age was higher in children with autism spectrum disorder than in children with another condition during the program than before (3.1, 95% confidence interval: 1.2-7.6) or after (1.7, 95% confidence interval: 1.0-3.0) the program but was not different before versus after the program. Thus, although the program led to earlier referral of children with autism spectrum disorder, after correction for other referrals, the effect was not sustained after the program ended. This study highlights the importance of continued investment in the early detection of autism spectrum disorder.
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26. Prelock PA, Potvin MC, Savard L. {{Interprofessional Education and Practice: A Family-Centered Approach to Autism}}. {Semin Speech Lang}. 2017; 38(5): 360-7.
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27. Sha YW, Ding L, Ji ZY, Mei LB, Li P, Li Z. {{[Familial fragile X syndrome: A pedigree analysis]}}. {Zhonghua Nan Ke Xue}. 2016; 22(9): 797-804.
Objective: To investigate the clinical (including reproductive) manifestations and genetic characteristics of familial fragile X syndrome (FXS). METHODS: We collected the clinical data about a case of familial FXS by inquiry, testicular ultrasonography, semen analysis, determination of sex hormone levels, and examinations of the peripheral blood karyotype and Y chromosome microdeletions. Using Southern blot hybridization, we measured the size of the CGG triple repeat sequence of the fragile X mental retardation-1 (FMR1) gene and determined its mutation type of the pedigree members with a genetic map of the FXS pedigree. RESULTS: Among the 34 members of 4 generations in the pedigree, 3 males and 1 female (11.76%) carried full mutation and 9 females (26.47%) premutation of the FMR1 gene. Two of the males with full FMR1 mutation, including the proband showed a larger testis volume (>30 ml) and a higher sperm concentration (>250 x10(6)/ml), with a mean sperm motility of 50.5%, a mean morphologically normal sperm rate of 17.5%, an average sperm nuclear DNA fragmentation index (DFI) of 18.5%, a low level of testosterone, normal karyotype in the peripheral blood, and integrity of the azoospermia factor (AZF) region in the Y chromosome. One of the second-generation females carrying FMR1 premutation was diagnosed with premature ovarian failure and another 3 with uterine myoma. CONCLUSIONS: Some of the FXS males in the pedigree may present macroorchidism and polyzoospermia but with normal semen parameters. In the intergenerational transmission, premutation might extend to full mutation, with even higher risks of transmission and extension of mutation in males, especially in those with >80 CGG triple repeat sequences. Therefore, it is recommended that the couples wishing for childbearing receive genetic testing, clinical guidance, and genetic counseling before pregnancy and, if necessary, prenatal diagnosis and preimplantation genetic diagnosis.
28. Solomon M, Iosif AM, Reinhardt VP, Libero LE, Nordahl CW, Ozonoff S, Rogers SJ, Amaral DG. {{What will my child’s future hold? phenotypes of intellectual development in 2-8-year-olds with autism spectrum disorder}}. {Autism Res}. 2017.
We examined phenotypes of autism spectrum disorder (ASD) based on trajectories of intellectual development from early (ages 2-3 (1/2)) to middle (ages 5-8) childhood in a recent clinically ascertained cohort. Participants included 102 children (82 males) initially diagnosed with ASD from the Autism Phenome Project longitudinal sample. Latent class growth analysis was used to identify distinct IQ trajectories. Baseline and developmental course differences among groups were assessed using univariate techniques and repeated measures regression models, respectively. A four class model best represented the data. Using the highest posterior probability, participants were assigned to High Challenges (25.5%), Stable Low (17.6%), Changers (35.3%), and Lesser Challenges (21.6%) groups. The High Challenges and Stable Low groups exhibited persistently low IQ, although, the High Challenges group experienced declines while the Stable Low group’s scores remained more constant. Changers showed IQ improvement of > 2 standard deviations. The Lesser Challenges group had IQs in the average range at both times that were about 1 standard deviation higher at T2. In summation, 75% of the participants experienced some relative improvements in intellectual and/or other areas of functioning between ages 2 and 8 years. The Changers group demonstrated the most significant IQ change that was accompanied by adaptive communication improvement and declining externalizing symptoms. Only the Lesser Challenges group showed a significant reduction in ASD symptom severity, such that by age 8, 14% of them no longer met ADOS-2 criteria for ASD. All groups showed reductions in internalizing symptoms. Intervention history was not associated with group status. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We examined how the IQs of children with autism spectrum disorder change between ages 2 and 8, and identified four patterns. Two groups exhibited persistently lower IQs. One group showed IQ increases of greater than 30 points with improved communicate abilities and declining disruptive behaviors. The final group had IQs in the average or better range at both time points, and 14% of them lost their diagnoses. Over half of the children experienced improved intellectual functioning between ages 2 and 8, whereas about 25% showed declines. Findings were not associated with intervention history.
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29. Summers J, Shahrami A, Cali S, D’Mello C, Kako M, Palikucin-Reljin A, Savage M, Shaw O, Lunsky Y. {{Self-Injury in Autism Spectrum Disorder and Intellectual Disability: Exploring the Role of Reactivity to Pain and Sensory Input}}. {Brain Sci}. 2017; 7(11).
This paper provides information about the prevalence and topography of self-injurious behavior in children and adults with autism spectrum disorder and intellectual disability. Dominant models regarding the etiology of self-injury in this population are reviewed, with a focus on the role of reactivity to pain and sensory input. Neuroimaging studies are presented and suggestions are offered for future research.
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30. Thomas N, Blake S, Morris C, Moles DR. {{Autism and primary care dentistry: parents’ experiences of taking children with autism or working diagnosis of autism for dental examinations}}. {Int J Paediatr Dent}. 2017.
BACKGROUND: Accessing and receiving preventative dental treatment can be difficult for children with autism due to sensory processing disorders and/or challenging behaviours coupled with a reported reluctance by dentists to treat these children. AIM: To gather dental experiences of UK parents of children with autism or working diagnosis of autism and explore how they feel primary care dental services can be improved. DESIGN: A total of 17 parents of children with a diagnosis or working diagnosis of autism took part in semi-structured interviews. Data were analysed thematically. RESULTS: Key themes identified were flexibility of the dental team and environment, confidence of the parents to advocate for their children’s needs, continuity of services and clear referral pathways to specialist services. Cross-cutting all themes was the value of clear communication. The experiences provide greater understanding of issues such as hyper-empathy, the dental chair, challenges of the waiting room, perceived medical authority, and the importance of continuation of care. CONCLUSION: In line with previous research about the importance of family-centred care, a strong relationship between parents and the whole dental team is essential for children with autism to access dental examinations and have satisfactory experience of care.
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31. Tudor ME, Rankin J, Lerner MD. {{A Model of Family and Child Functioning in Siblings of Youth with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
The potential clinical needs of typically developing (TD) siblings of youth with autism spectrum disorder (ASD) remain disputed. A total of 239 mothers of youth aged 6-17, including one youth with ASD (M = 11.14 years; simplex families) and at least one other youth (M = 11.74 years) completed online standardized measures of various familial factors and TD youth outcomes. Overall, only 6-23% of siblings were identified within the clinical range of emotional, behavioral, or social functioning. Both maternal depression and sibling relationship were identified as key pathways in predicting siblings’ functioning within a good-fitting path analysis model. The current model is presented as a novel base for the development of future research and services for this unique population of children.
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32. Wessel K, Suleiman J, Khalaf TE, Kishore S, Rolfs A, El-Hattab AW. {{17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report}}. {BMC Med Genet}. 2017; 18(1): 119.
BACKGROUND: Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes, located in 17q23.2, have been proposed to be responsible for the phenotypes observed in individuals with 17q23.1q23.2 deletions and duplications. In this report, we present the clinical phenotype of a child with a previously unreported de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region. CASE PRESENTATION: We report a 7.5-year-old boy with speech and language disorder, learning difficulties, incoordination, fine motor skill impairment, infrequent seizures with abnormal EEG, and behavior disturbances (mild self-inflicted injuries, hyperactivity-inattention, and stereotyped hand movements). Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3. Both parents did not have the duplication indicating that this duplication is de novo in the child. CONCLUSIONS: The duplicated region encompasses 16 genes. It is possible that increased dosage of one or more genes in this region is responsible for the observed phenotype. The TANC2 gene is one of the genes in the duplicated region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family which includes TANC1 and TANC2. These proteins are highly expressed in brain and play major roles in synapsis regulation. Hence, it is suggestive that TANC2 is the likely candidate gene responsible for the observed phenotype as an increased TANC2 dosage can potentially alter synapsis, resulting in neuronal dysfunction and the neurobehavioral phenotype observed in this child with 17q23.2q23.3 duplication.
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33. Xu X, Li C, Gao X, Xia K, Guo H, Li Y, Hao Z, Zhang L, Gao D, Xu C, Xu H, Xiong ZQ, Qiu Z, Mei L, Xie X, Ruan K, Hu R. {{Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders}}. {Cell Res}. 2017.
The autism spectrum disorders (ASDs) are a collection of human neurological disorders with heterogeneous etiologies. Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner. Excessive UBE3A dosage was found to impair RA-mediated neuronal homeostatic synaptic plasticity. ASD-like symptoms were recapitulated in mice by overexpressing UBE3A in the prefrontal cortex or by administration of an ALDH1A antagonist, whereas RA supplements significantly alleviated excessive UBE3A dosage-induced ASD-like phenotypes. By identifying reduced RA signaling as an underlying mechanism in ASD phenotypes linked to UBE3A hyperactivities, our findings introduce a new vista of ASD etiology and facilitate a mode of therapeutic development against this increasingly prevalent disease.Cell Research advance online publication 27 October 2017; doi:10.1038/cr.2017.132.
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34. Zhang JS, Zhang XT, Zou LP, Zhang R, Han SP, Han JS. {{[A Preliminary Study on Effect of Transcutaneous Electrical Acupoint Stimulation for Children with Autism]}}. {Zhen Ci Yan Jiu}. 2017; 42(3): 249-53.
OBJECTIVE: To investigate the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) in treating children with autism spectrum disorders. METHODS: Forty-one autistic children receiving rehabilitation training were randomized into TEAS (n=21) and control (n=20) groups. The control group only received rehabilitation training. The TEAS group received both rehabilitation training and TEAS treatment[2 Hz/15 Hz alternating frequencies through two pairs of skin electrodes placed at Hegu (LI 4)-Neiguan (PC 6) on unilateral side, and Zusanli (ST 36)-Sanyinjiao (SP 6) on the contralateral side]. The treatment was given 30 min per day for 12 weeks. The outcome assessment was quantified with a series of rating scales including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Parent Symptom Questionnaire (PSQ). RESULTS: (1) The TEAS group showed more significant improvement than the control group in ABC (P<0.01). 38.1% effective rate (8/21) was observed in the TEAS group compared to 5.0% (1/20) in the control group (P<0.05). The CARS scores of both groups were reduced (P<0.0001) after treatment. The TEAS group showed significantly lower score compared to the control group (P<0.0001). (2)There was a distinctly reduced PSQ score in both TEAS and control groups (P<0.001) after treatment.(3)TEAS intervention showed better effect in children under 6 years old with moderate or severe autistic symptoms. CONCLUSIONS: TEAS intervention can significantly improve the autistic symptoms. Lien vers Pubmed
