1. Asadi-Pooya AA. {{Yield of EEG monitoring in children with developmental disabilities is high}}. {Epilepsy Behav};2018 (May 11);84:105-106.
PURPOSE: The purpose of this study was to investigate the yield of a 2-hour electroencephalography (EEG) monitoring (awake and sleep) in children with developmental disabilities and without any clinically apparent seizures. METHODS: In this retrospective study, I investigated all children below 9years of age who had developmental disabilities and were referred to Shiraz Comprehensive Epilepsy center for electroencephalographic investigation from June 2017 until January 2018. Exclusion criteria included any past history of neonatal seizures, febrile or afebrile seizures, and parental suspicion for seizures. We systematically obtained a brief clinical history and performed a 2-hour, awake and asleep EEG monitoring for all patients. RESULTS: Thirty-two patients (23 males and 9 females) met all the inclusion and exclusion criteria; mean age (+/-standard deviation) was 4.1 (+/-2.1) years. Nineteen patients (59%) had an abnormal EEG: 15 patients (47%) had epileptiform discharges, and four children had abnormal background activity with no epileptiform discharges. CONCLUSION: Considering the high diagnostic yield of an awake and asleep EEG monitoring, as it was observed in the current study, this test on a screening basis can be reasonably justified in all children with developmental disabilities.
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2. Atherton G, Cross L. {{Seeing More Than Human: Autism and Anthropomorphic Theory of Mind}}. {Front Psychol};2018;9:528.
Theory of mind (ToM) is defined as the process of taking another’s perspective. Anthropomorphism can be seen as the extension of ToM to non-human entities. This review examines the literature concerning ToM and anthropomorphism in relation to individuals with Autism Spectrum Disorder (ASD), specifically addressing the questions of how and why those on the spectrum both show an increased interest for anthropomorphism and may even show improved ToM abilities when judging the mental states of anthropomorphic characters. This review highlights that while individuals with ASD traditionally show deficits on a wide range of ToM tests, such as recognizing facial emotions, such ToM deficits may be ameliorated if the stimuli presented is cartoon or animal-like rather than in human form. Individuals with ASD show a greater interest in anthropomorphic characters and process the features of these characters using methods typically reserved for human stimuli. Personal accounts of individuals with ASD also suggest they may identify more closely with animals than other humans. It is shown how the social motivations hypothesized to underlie the anthropomorphizing of non-human targets may lead those on the spectrum to seek social connections and therefore gain ToM experience and expertise amongst unlikely sources.
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3. Bacon EC, Osuna S, Courchesne E, Pierce K. {{Naturalistic language sampling to characterize the language abilities of 3-year-olds with autism spectrum disorder}}. {Autism};2018 (May 1):1362361318766241.
Characterization of language in naturalistic settings in autism spectrum disorder has been lacking, particularly at young ages, but such information is important for parents, teachers, and clinicians to better support language development in real-world settings. Factors contributing to this lack of clarity include conflicting definitions of language abilities, use of non-naturalistic standardized assessments, and restricted samples. The current study examined one of the largest datasets of naturalistic language samples in toddlers with autism spectrum disorder, and language delay and typically developing contrast groups at age 3. A range of indices including length of phrase, grammatical markings, and social use of language was assayed during a naturalistic observation of a parent-child play session. In contrast to historical estimates, results indicated only 3.7% of children with autism spectrum disorder used no words, and 34% were minimally verbal. Children with autism spectrum disorder and language delay exhibited similar usage of grammatical markings, although both were reduced compared to typically developing children. The greatest difference between autism spectrum disorder and language delay groups was the quantity of social language. Overall, findings highlight a range of language deficits in autism spectrum disorder, but also illustrate that the most severe level of impairments is not as common in naturalistic settings as previously estimated by standardized assessments.
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4. Bischof NL, Rapee RM, Hudry K, Bayer JK. {{Acceptability and caregiver-reported outcomes for young children with autism spectrum disorder whose parents attended a preventative population-based intervention for anxiety: A pilot study}}. {Autism Res};2018 (May 15)
This pilot study explored acceptability to parents and outcomes for children of a preventive intervention for anxiety problems in pre-schoolers with autism spectrum disorder (ASD) who were an identified sub-group within a population-based randomised trial of the Cool Little Kids parenting group programme. The population trial included 545 temperamentally inhibited pre-schoolers recruited across eight economically diverse areas of Melbourne, Australia. Within this sample, 26 parents reported that their child had received an ASD diagnosis. Trial measures included baseline inhibited temperament and developmental problems, post-intervention feedback on the programme, and caregiver-reported child mental health outcomes (anxiety diagnoses and internalising symptoms) at 1- and 2-year follow-up. Sample retention for the children with ASD over 2 years was strong (92%). At follow-up, fewer intervention than control children with ASD had anxiety disorders after 1 year (% (n): 25 (3) vs. 77 (10), P = .028) and separation anxiety symptoms after 2 years (M (SD): 4.22 (2.68) vs. 9.38 (5.91), P = .017). Similar effects favouring the intervention group were apparent across other child emotional outcome measures but without statistical significance in this small sample. Parents of the children with ASD reported that Cool Little Kids was « quite useful » in relation to their child’s anxiety but also gave feedback that they would appreciate some tailoring of programme content to the context of ASD. These pilot findings suggest Cool Little Kids may be helpful for reducing comorbid anxiety in pre-schoolers with ASD. Further research is warranted to develop an ASD-specific adaptation which can be trialled with a larger sample of children with confirmed ASD diagnosis. Trial registration ISRCTN30996662 http://www.isrctn.com/ISRCTN30996662. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Many children with autism spectrum disorder (ASD) also have anxiety. This pilot study explored acceptability to parents and outcomes for pre-schoolers with ASD of a parenting group programme to prevent anxiety problems. Among the sample of 26 pre-schoolers with ASD, we found reduced anxiety disorders and separation symptoms when their parents had received the intervention, as reported by caregivers in checklists and clinical interviews. Parents gave feedback that the programme was useful but suggested content be adapted to the context of ASD.
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5. Dong D, Zielke HR, Yeh D, Yang P. {{Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder}}. {Autism Res};2018 (May 15)
The molecular pathogenesis of autism spectrum disorder, a neurodevelopmental disorder, is still elusive. In this study, we investigated the possible roles of endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis as molecular mechanisms underlying autism. This study compared the activation of ER stress signals (protein kinase R-like endoplasmic reticulum kinase [PERK], activating transcription factor 6 [ATF6], inositol-requiring enzyme 1 alpha [IRE1alpha]) in different brain regions (prefrontal cortex, hippocampus, cerebellum) in subjects with autism and in age-matched controls. Our data showed that the activation of three signals of ER stress varies in different regions of the autistic brain. IRE1alpha was activated in cerebellum and prefrontal cortex but ATF6 was activated in hippocampus. PERK was not activated in the three regions. Furthermore, the activation of ER stress was confirmed because the expression of C/EBP-homologous protein (CHOP), which is the common downstream indicators of ER stress signals, and most of ER chaperones were upregulated in the three regions. Consistent with the induction of ER stress, apoptosis was found in the three regions by detecting the cleavage of caspase 8 and poly(ADP-ribose) polymerase as well as using the transferase dUTP nick end labeling assay. Moreover, our data showed that oxidative stress was responsible for ER stress and apoptosis because the levels of 4-Hydroxynonenal and nitrotyrosine-modified proteins were significantly increased in the three regions. In conclusion, these data indicate that cellular stress and apoptosis may play important roles in the pathogenesis of autism. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism results in significant morbidity and mortality in children. The functional and molecular changes in the autistic brains are unclear. The present study utilized autistic brain tissues from the National Institute of Child Health and Human Development’s Brain Tissue Bank for the analysis of cellular and molecular changes in autistic brains. Three key brain regions, the hippocampus, the cerebellum, and the frontal cortex, in six cases of autistic brains and six cases of non-autistic brains from 6 to 16 years old deceased children, were analyzed. The current study investigated the possible roles of endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis as molecular mechanisms underlying autism. The activation of three signals of ER stress (protein kinase R-like endoplasmic reticulum kinase, activating transcription factor 6, inositol-requiring enzyme 1 alpha) varies in different regions. The occurrence of ER stress leads to apoptosis in autistic brains. ER stress may result from oxidative stress because of elevated levels of the oxidative stress markers: 4-Hydroxynonenal and nitrotyrosine-modified proteins in autistic brains. These findings suggest that cellular stress and apoptosis may contribute to the autistic phenotype. Pharmaceuticals and/or dietary supplements, which can alleviate ER stress, oxidative stress and apoptosis, may be effective in ameliorating adverse phenotypes associated with autism.
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6. Feczko E, Balba NM, Miranda-Dominguez O, Cordova M, Karalunas SL, Irwin L, Demeter DV, Hill AP, Langhorst BH, Grieser Painter J, Van Santen J, Fombonne EJ, Nigg JT, Fair DA. {{Subtyping cognitive profiles in Autism Spectrum Disorder using a Functional Random Forest algorithm}}. {Neuroimage};2018 (May 15);172:674-688.
DSM-5 Autism Spectrum Disorder (ASD) comprises a set of neurodevelopmental disorders characterized by deficits in social communication and interaction and repetitive behaviors or restricted interests, and may both affect and be affected by multiple cognitive mechanisms. This study attempts to identify and characterize cognitive subtypes within the ASD population using our Functional Random Forest (FRF) machine learning classification model. This model trained a traditional random forest model on measures from seven tasks that reflect multiple levels of information processing. 47 ASD diagnosed and 58 typically developing (TD) children between the ages of 9 and 13 participated in this study. Our RF model was 72.7% accurate, with 80.7% specificity and 63.1% sensitivity. Using the random forest model, the FRF then measures the proximity of each subject to every other subject, generating a distance matrix between participants. This matrix is then used in a community detection algorithm to identify subgroups within the ASD and TD groups, and revealed 3 ASD and 4 TD putative subgroups with unique behavioral profiles. We then examined differences in functional brain systems between diagnostic groups and putative subgroups using resting-state functional connectivity magnetic resonance imaging (rsfcMRI). Chi-square tests revealed a significantly greater number of between group differences (p<.05) within the cingulo-opercular, visual, and default systems as well as differences in inter-system connections in the somato-motor, dorsal attention, and subcortical systems. Many of these differences were primarily driven by specific subgroups suggesting that our method could potentially parse the variation in brain mechanisms affected by ASD. Lien vers le texte intégral (Open Access ou abonnement)
7. Karvelis P, Seitz AR, Lawrie SM, Series P. {{Autistic traits, but not schizotypy, predict increased weighting of sensory information in Bayesian visual integration}}. {Elife};2018 (May 14);7
Recent theories propose that schizophrenia/schizotypy and autistic spectrum disorder are related to impairments in Bayesian inference that is, how the brain integrates sensory information (likelihoods) with prior knowledge. However existing accounts fail to clarify: (i) how proposed theories differ in accounts of ASD vs. schizophrenia and (ii) whether the impairments result from weaker priors or enhanced likelihoods. Here, we directly address these issues by characterizing how 91 healthy participants, scored for autistic and schizotypal traits, implicitly learned and combined priors with sensory information. This was accomplished through a visual statistical learning paradigm designed to quantitatively assess variations in individuals’ likelihoods and priors. The acquisition of the priors was found to be intact along both traits spectra. However, autistic traits were associated with more veridical perception and weaker influence of expectations. Bayesian modeling revealed that this was due, not to weaker prior expectations, but to more precise sensory representations.
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8. Kita Y, Katayama Y, Shiraishi T, Oka T, Sato T, Suyama M, Ohkawa Y, Miyata K, Oike Y, Shirane M, Nishiyama M, Nakayama KI. {{The Autism-Related Protein CHD8 Cooperates with C/EBPbeta to Regulate Adipogenesis}}. {Cell Rep};2018 (May 15);23(7):1988-2000.
The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8 give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown. Here, we show that CHD8 interacts with CCAAT/enhancer-binding protein beta (C/EBPbeta) and promotes its transactivation activity during adipocyte differentiation. Adipogenesis was impaired in Chd8-deleted preadipocytes, with the upregulation of C/EBPalpha and peroxisome-proliferator-activated receptor gamma (PPARgamma), two master regulators of this process, being attenuated in mutant cells. Furthermore, mice with CHD8 ablation in white preadipocytes had a markedly reduced white adipose tissue mass. Our findings reveal a mode of C/EBPbeta regulation by CHD8 during adipogenesis, with CHD8 deficiency resulting in a defect in the development of white adipose tissue.
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9. Kripke C. {{Adults with Developmental Disabilities: A Comprehensive Approach to Medical Care}}. {Am Fam Physician};2018 (May 15);97(10):649-656.
Developmental disabilities are attributable to a cognitive impairment, physical impairment, or both. They manifest during the developmental period from birth to early adulthood, and are likely to continue indefinitely. The life expectancy of most persons with developmental disabilities now approaches that of the general population. According to the neurodiversity model of care, developmental disability is accepted as a valued part of human neurologic diversity. The social model focuses on improving participation in society with accommodations such as adaptive equipment or improvements to the social and physical environment. The goal of health care for patients with developmental disabilities is to improve their well-being, function, and participation in family and community. Physicians should communicate directly with their patients, even those who have communication or cognitive differences. Communication may include speech, sign language, writing, letter boards, voice output devices, pictures, facial expressions, gestures, vocalizations, and behavior. Supported decision making is a paradigm, support practice, and emerging legal structure that focuses on assisting patients with communicating their wants and needs as an alternative to guardianship or power of attorney. When establishing care, it is critical to get a detailed history of baseline traits and characteristics in the areas of cognition and communication; neuromuscular function; sensory function such as vision, hearing, and sensory processing; seizure threshold; mental health; and behavior. In general, guidelines for age-appropriate health maintenance in the general population should be followed unless the risk outweighs the benefit for an individual patient. With accurate diagnosis, psychiatric conditions can be treated effectively with the same medical, behavioral, and therapeutic modalities used in the general population. Just like any patient, those with developmental disabilities should have access to a full range of life-sustaining, curative, and end-of-life services.
10. Levie D, Korevaar TIM, Bath SC, Dalmau-Bueno A, Murcia M, Espada M, Dineva M, Ibarluzea JM, Sunyer J, Tiemeier H, Rebagliato M, Rayman MP, Peeters RP, Guxens M. {{Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: a Meta-analysis of Individual-participant Data}}. {J Clin Endocrinol Metab};2018 (May 10)
Context: Low maternal free thyroxine (FT4) has been associated with poor child neurodevelopment in some single-centre studies. Evidence remains scarce for potential adverse effects of high FT4 and whether associations differ in countries with a different iodine status. Objective: To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status. Design, Setting and Participants: Meta-analysis of individual-participant data compromising 9,036 mother-child pairs from three prospective population-based birth cohorts: INMA (Spain), Generation R (The Netherlands) and ALSPAC (United Kingdom). Exclusion criteria were multiple pregnancies, fertility treatments, thyroid interfering medication usage, and known thyroid disease. Main outcomes: Child non-verbal IQ at 5-8 years of age, verbal IQ at 1.5-8 years of age, and autistic traits within the clinical range at 5-8 years of age. Results: FT4 <2.5th percentile was associated with a 3.9 [95% confidence interval -5.7 to -2.2)] point lower non-verbal IQ and a 2.1 (-4.0 to -0.1) point lower verbal IQ. A suggestive association of hypothyroxinemia with a higher risk of autistic traits was observed. FT4 >97.5th percentile was associated with a 1.9 (1.0 to 3.4) fold higher risk of autistic traits. No independent associations were found with thyrotropin. Conclusions: Low maternal FT4 was consistently associated with lower IQ across cohorts. Further studies should replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay.
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11. Morales-Hidalgo P, Ferrando PJ, Canals J. {{Assessing the heterogeneity of autism spectrum symptoms in a school population}}. {Autism Res};2018 (May 15)
The aim of the present study was to assess whether the nature of the main autistic features (i.e., social communication problems and repetitive and restrictive patterns) are better conceptualized as dimensional or categorical in a school population. The study was based on the teacher ratings of two different age groups: 2,585 children between the ages of 10 and 12 (Primary Education; PE) and 2,502 children between the ages of 3 and 5 (Nursery Education; NE) from 60 mainstream schools. The analyses were based on Factor Mixture Analysis, a novel approach that combines dimensional and categorical features and prevents spurious latent classes from appearing. The results provided evidence of the dimensionality of autism spectrum symptoms in a school age population. The distribution of the symptoms was strongly and positively skewed but continuous; and the prevalence of high-risk symptoms for autism spectrum disorders (ASD) and social-pragmatic communication disorder (SCD) was 7.55% of NE children and 8.74% in PE. A categorical separation between SCD and ASD was not supported by our sample. In view of the results, it is necessary to establish clear cut points for detecting and diagnosing autism and to develop specific and reliable tools capable of assessing symptom severity and functional consequences in children with ASD. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The results of the present study suggest that the distribution of autism spectrum symptoms are continuous and dimensional among school-aged children and thus support the need to establish clear cut-off points for detecting and diagnosing autism. In our sample, the prevalence of high-risk symptoms for autism spectrum disorders and social-pragmatic communication disorder was around 8%.
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12. Tachibana Y, Miyazaki C, Mikami M, Ota E, Mori R, Hwang Y, Terasaka A, Kobayashi E, Kamio Y. {{Meta-analyses of individual versus group interventions for pre-school children with autism spectrum disorder (ASD)}}. {PLoS One};2018;13(5):e0196272.
There is little evidence regarding the effects of individual and group intervention for children with autism spectrum disorder (ASD) on important outcomes. We performed meta-analyses using a random effects model to investigate the effectiveness of the individual and group intervention studies and to compare the effectiveness of these two types if possible. The main analysis which excluded studies at a high risk of bias (Analysis I) included 14 randomised controlled trials targeting children with ASDLien vers le texte intégral (Open Access ou abonnement)
13. van Esch L, Vanmarcke S, Ceulemans E, Van Leeuwen K, Noens I. {{Parenting adolescents with ASD: A multimethod study}}. {Autism Res};2018 (May 15)
A number of studies have concluded that parents of children with ASD experience high levels of parenting stress. However, little is known about their parenting behaviors. Especially few studies investigated parenting in adolescence, although this period is associated with additional challenges for both adolescents and their parents. In the present study, a multi-method approach was used, combining data from a self-report questionnaire and observation of mother-child interactions during different semi-structured (e.g., inventing and building a vehicle of the future with construction toys) and structured tasks (e.g., solving marble maze). Linear mixed models (LMM) were used to compare the means of parenting behaviors among mothers of adolescents with (n = 44) and without ASD (n = 38), aged 12 to 16 years old. During the observations, mothers of adolescents with ASD showed more sensitivity and creativity, compared to the general population control group. In addition, mothers in the ASD group reported on the self-report questionnaire to adapt the environment more, for example, by establishing routines. Furthermore, this study investigated the role of maternal characteristics, that is, ASD characteristics and parenting stress. Parenting stress was associated with less self-reported positive parenting. Higher levels of ASD characteristics of the mother were related to more negativity and less sensitivity during the observation, and more self-reported harsh punishment and adapting the environment. This study additionally examined whether the impact of these maternal characteristics was the same across the two groups. Whereas group by parenting stress interaction effects were not significant for any of the observed and self-reported parenting behaviors, significant group by ASD characteristics interaction effects were noticed for self-reported harsh punishment and adapting the environment. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A number of studies have concluded that parents of children with ASD experience high levels of parenting stress. However, little is known about their parenting behaviors. Especially parenting in adolescence remains under investigated, although this period is associated with additional challenges for both adolescents and their parents. In this study, 44 adolescents with ASD and a control group of 38 adolescents without ASD, aged 12-16 years old, participated together with their mother. We compared parenting behaviors between the two groups, based on observations of mother-child interactions and a questionnaire that was filled out by the mother. During the observation, mothers of adolescents with ASD showed more sensitivity and creativity, compared to the control group. In addition, the questionnaire responses indicated that mothers in the ASD group adapted the environment more by for example, establishing routines. Furthermore, this study investigated the role of parenting stress and ASD characteristics of the mother on parenting behavior. Parenting stress was associated with less self-reported positive parenting. Higher levels of ASD characteristics of the mother were related to more negativity and less sensitivity during the observation in both groups, and more self-reported harsh punishment and adapting the environment in the control group only.
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14. West KL. {{Infant Motor Development in Autism Spectrum Disorder: A Synthesis and Meta-analysis}}. {Child Dev};2018 (May 15)
Studies of infant motor development in autism spectrum disorder (ASD) have increased in recent years. This article synthesized this literature through meta-analysis to assess (a) whether infant motor ability differs in ASD relative to neurotypical controls; and (b) whether motor ability and communication are related in infants with ASD. Study 1 aggregated data from 1,953 infants with ASD (ages 3.0-42.0 months), and Study 2 included 890 infants with ASD (age 6.0-42.9 months). Study 1 revealed that infant motor ability differed significantly in ASD compared with neurotypical infants-this difference was robust to variation in measurement and design. Furthermore, this group difference amplified as age increased. Study 2 indicated that within ASD, infant motor ability and communication are related.
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15. Zhang F, Savadjiev P, Cai W, Song Y, Rathi Y, Tunc B, Parker D, Kapur T, Schultz RT, Makris N, Verma R, O’Donnell LJ. {{Whole brain white matter connectivity analysis using machine learning: An application to autism}}. {Neuroimage};2018 (May 15);172:826-837.
In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering.
