Pubmed du 18/06/20

jeudi 18 juin 2020

1. Almehmadi W, Tenbrink T, Sanoudaki E. Pragmatic and Conversational Features of Arabic-Speaking Adolescents With Autism Spectrum Disorder : Examining Performance and Caregivers’ Perceptions. J Speech Lang Hear Res ;2020 (Jun 16):1-14.

Purpose This study investigates the features of pragmatic and conversational skills in the language of Arabic-speaking adolescents with autism spectrum disorder (ASD) by comparing them with typically developing (TD) Arabic-speaking adolescents in Saudi Arabia. It aims to identify the differences in the pragmatic skills of the two groups and the perception of those skills by caregivers, with respect to four main pragmatic areas : discourse management, communicative function, conversational repair, and presupposition abilities. Method Data for this study were collected from 15 Saudi adolescents with ASD and a control group of 15 TD adolescents, matched for gender and language abilities. All the participants were in the normal IQ range. The caregivers of the adolescents with ASD and TD adolescents also participated in this study. Data were collected on the adolescents’ performances using the Yale in vivo Pragmatic Protocol. In addition, the Pragmatics Profile of Everyday Communication Skills (PPECS) was used to collect data on the caregivers’ perceptions of the adolescents’ abilities. The combination of tools in this study allows for a unique comparison between actual performance and caregivers’ perceptions. Results As expected, both the adolescents’ performances and the caregivers’ perceptions reflected an overall deficit in the pragmatic and conversational skills of adolescents with ASD. However, we also identified an inconsistency between the caregivers’ estimation of the participant’s pragmatic abilities and the actual abilities demonstrated by the adolescents. In particular, TD adolescents performed significantly better than adolescents with ASD in the pragmatic areas of turn-taking, topic maintenance, and topic initiation, but the caregivers did not detect differences between the two groups in these discourse management abilities. Conclusions This study has important implications for both ASD interventions and assessment. It provides a comprehensive assessment approach for measuring pragmatic skills, including both direct (participants’ performances) and indirect (caregivers’ perceptions) measures. Future research may benefit from adopting the combined approach used in this study to explore pragmatics in ASD. Differences between caregivers’ perceptions and the performances of individuals with ASD should be considered, as well as the influence of various factors on their communication.

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2. Ames JL, Massolo ML, Davignon MN, Qian Y, Cerros HJ, Croen LA. Transitioning youth with autism spectrum disorders and other special health care needs into adult primary care : A provider survey. Autism ;2020 (Jun 18):1362361320926318.

The transition from pediatric to adult care is a critical inflection point for the long-term health of youth with autism spectrum disorders and other special health care needs. However, for many patients, their caregivers, and providers, the transition lacks coordination. This survey study demonstrates that pediatric and adult providers struggle to implement many components of transition best practices for youth with autism and other chronic conditions, highlighting the urgent need for enhanced medical coordination and additional transition training and resources.

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3. Cascio MA, Weiss JA, Racine E. Person-oriented ethics for autism research : Creating best practices through engagement with autism and autistic communities. Autism ;2020 (Jun 18):1362361320918763.

Research ethics means issues that concern the welfare and wellbeing of people who take part in research. It is important in all scientific studies. Ethics helps people who do research treat people who take part in research fairly and with respect. This article is about day-to-day ethics when autistic people take part in research. We present tips for researchers who want to do this type of study. We used two methods to create these tips. First, we wanted to know what other people said about this topic. We used a literature review to find out. Second, we wanted to know what autistic people, parents, and professionals thought, and had a working group meet to discuss it. The working group provided advice that researchers could consider around day-to-day ethics in research. This article talks about these methods and advice. The advice fits into five big groups : Tailor the research process for the unique needs of each person. Think about the world in which people who take part in research live. Make it easier for people to make their own choices. Value what people who take part in research have to share and consider their needs and strengths. Think about how researchers and people who take part in research work together. This project shows why it is useful for researchers and communities to talk about research ethics together.

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4. Cola ML, Plate S, Yankowitz L, Petrulla V, Bateman L, Zampella CJ, de Marchena A, Pandey J, Schultz RT, Parish-Morris J. Sex differences in the first impressions made by girls and boys with autism. Mol Autism ;2020 (Jun 16) ;11(1):49.

BACKGROUND : Individuals with autism spectrum disorder (ASD) are characterized by social communication challenges and repetitive behaviors that may be quickly detected by experts (Autism Res 10:653-62, 2017 ; American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013). Recent research suggests that even naïve non-experts judge a variety of human dimensions using narrow windows of experience called "first impressions." Growing recognition of sex differences in a variety of observable behaviors in ASD, combined with research showing that some autistic girls and women may "camouflage" outward symptoms, suggests it may be more difficult for naïve conversation partners to detect ASD symptoms in girls. Here, we explore the first impressions made by boys and girls with ASD and typically developing (TD) peers. METHODS : Ninety-three school-aged children with ASD or TD were matched on IQ ; autistic girls and boys were additionally matched on autism symptom severity using the ADOS-2. Participants completed a 5-minute "get-to-know-you" conversation with a new young adult acquaintance. Immediately after the conversation, confederates rated participants on a variety of dimensions. Our primary analysis compared conversation ratings between groups (ASD boys, ASD girls, TD boys, TD girls). RESULTS : Autistic girls were rated more positively than autistic boys by novel conversation partners (better perceived social communication ability), despite comparable autism symptom severity as rated by expert clinicians (equivalent true social communication ability). Boys with ASD were rated more negatively than typical boys and typical girls by novel conversation partners as well as expert clinicians. There was no significant difference in the first impressions made by autistic girls compared to typical girls during conversations with a novel conversation partner, but autistic girls were rated lower than typical girls by expert clinicians. LIMITATIONS : This study cannot speak to the ways in which first impressions may differ for younger children, adults, or individuals who are not verbally fluent ; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. CONCLUSIONS : First impressions made during naturalistic conversations with non-expert conversation partners could-in combination with clinical ratings and parent report-shed light on the nature and effects of behavioral differences between girls and boys on the autism spectrum.

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5. Dunn S, Jones M. Binocular rivalry dynamics associated with high levels of self-reported autistic traits suggest an imbalance of cortical excitation and inhibition. Behav Brain Res ;2020 (Jun 18) ;388:112603.

An imbalance in cortical excitation and inhibition (E/I) may underlie both social and non-social symptoms of autism spectrum conditions (ASC). Recent work suggests that an E/I imbalance may underlie some of the sensory differences that are characteristic of ASCs such as anomalous perception. Binocular rivalry dynamics are thought to reflect the balance of E/I in the brain and could serve as a behavioural biomarker for ASC. Previous studies of clinical ASC populations have found a slower rate of binocular rivalry transitions ; increased duration of the mixed percept and reduced perceptual suppression. There are some mixed reports of altered rivalry dynamics in the neurotypical population with high self-reported levels of autistic traits. Therefore, we used simple grating stimuli to measure binocular rivalry dynamics in a sample of seventy-nine adults aged 18-55 years. We additionally measured the level of autistic traits with the AQ-10 and used CAPS as a measure of anomalous perception. Bayesian correlations showed that those with higher AQ scores had a slower rate of perceptual switching and a longer mixed percept duration. Significant regression models with CAPS and AQ score revealed that AQ score was a significant predictor of switch rate and mixed percept duration, whereas CAPS was not. We also report that CAPS significantly predicted perceptual suppression, whereas AQ score did not. Overall, our findings suggest that in a non-clinical population, autistic traits are a predictor of binocular rivalry dynamics and the cortical E/I imbalance thought to underlie symptoms of ASC may extend to the broader phenotype.

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6. Fuller EA, Oliver K, Vejnoska SF, Rogers SJ. The Effects of the Early Start Denver Model for Children with Autism Spectrum Disorder : A Meta-Analysis. Brain Sci ;2020 (Jun 12) ;10(6)

This meta-analysis examined the effects of the Early Start Denver Model (ESDM) for young children with autism on developmental outcome measures. The 12 included studies reported results from 640 children with autism across 44 unique effect sizes. The aggregated effect size, calculated using a robust variance estimation meta-analysis, was 0.357 (p = 0.024), which is a moderate effect size with a statistically significant overall weighted averaged that favored participants who received the ESDM compared to children in control groups, with moderate heterogeneity across studies. This result was largely driven by improvements in cognition (g = 0.412) and language (g = 0.408). There were no significant effects observed for measures of autism symptomology, adaptive behavior, social communication, or restrictive and repetitive behaviors.

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7. Kutuk MO, Tufan E, Gokcen C, Kilicaslan F, Karadag M, Mutluer T, Yektas C, Coban N, Kandemir H, Buber A, Coskun S, Acikbas U, Guler G, Topal Z, Celik F, Altintas E, Giray A, Aka Y, Kutuk O. Cytokine expression profiles in Autism spectrum disorder : A multi-center study from Turkey. Cytokine ;2020 (Jun 18) ;133:155152.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1β, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-β in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p < 0.001) and significantly lower levels of IL-17 (p < 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1α correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms.

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8. McAuliffe T, Cordier R, Chen YW, Vaz S, Thomas Y, Falkmer T. In-the-moment experiences of mothers of children with autism spectrum disorder : a comparison by household status and region of residence. Disabil Rehabil ;2020 (Jun 18):1-15.

Purpose : This study compared the in-the-moment experiences among mothers of children with Autism Spectrum Disorders (ASD) by their household status (i.e., single versus coupled) and region of residence (i.e., regional versus major city area).Methods : An experience sampling method was employed to collect data, and a total of 40 mothers used an iOS device to record activity types and in-the-moment experiences for one week during school term. Mann-Whitney U test and multilevel analysis were conducted to compare the experiences of these mothers.Results : The analyses found the following results : 1) mothers spent most time in childcare and least time in self-care activities ; 2) coupled mothers were more likely to feel supported ; 3) coupled mothers were less likely to feel supported in domestic tasks ; 4) mothers from major city were more likely to feel challenged in self-care activities ; and 5) mothers from major city were more likely to feel supported in productivity tasks.Conclusion : Limited but significant differences between single and coupled mothers, as well as mothers from regional and major city areas, were found. Future research direction and service provisions were suggested.Implications for rehabilitationThis study shows that all mothers spent the most time on childcare and the least amount of time on self-care activities.In-the-moment experiences between single and coupled mothers, as well as mothers from major cities and mothers from regional areas, differ somewhat ; however, this study builds evidence to support that these mothers’ experiences are similar.The result of the study indicates that single mothers require extra support as they carry similar levels of responsibilities as coupled mothers, but without the support of a partner.Promoting a sense of control may assist all mothers to fully engage in parenting activities.

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9. McLeod JD, Hawbaker A, Meanwell E. The health of college students on the autism spectrum as compared to their neurotypical peers. Autism ;2020 (Jun 18):1362361320926070.

Studies have shown that children and older adults on the autism spectrum experience more physical and mental health problems than their neurotypical peers. Less is known about the physical and mental health of college students on the spectrum. Studying college students is important because young adults on the spectrum are enrolling in college at increasing rates and because health problems can be a barrier to succeeding in college. We collected data from 2820 students at 14 colleges and universities using an online survey, some of whom had registered for accommodations based on autism and others of whom had not. We used the data to compare the physical and mental health of students on the spectrum to their neurotypical peers. Because students with autism often report other disabilities that also affect health, we accounted for whether they experienced a learning disability, attention deficit hyperactivity disorder, sensory impairment, mobility impairment, mental health disorder, or any other disabilities. We assessed health using self-reports of how healthy they were physically and mentally, and reports of depressive symptoms, symptoms of anxiety, sleep deprivation, and binge drinking. We found that students with autism reported poorer physical and mental health, more depressive symptoms, and more symptoms of anxiety even after taking into account other disabilities they may have experienced. They were also less likely to report sleep deprivation and binge drinking. Our results argue for developing specialized services to address the physical and mental health challenges of college students on the spectrum.

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10. Nagai Y, Nomura K, Uemura O. Primitive reflexes in very low birth weight infants later diagnosed with autism spectrum disorder. Minerva Pediatr ;2020 (Jun 16)

BACKGROUND : As early screening and diagnosis is very important in treatment and intervention of Autism Spectrum Disorder, we investigated the relationship between primitive reflexes and Autism Spectrum Disorder (ASD). METHODS : Of 88 very low birth weight infants (<1500g) born from April 2010 to March 2012, subjects comprised 38 examined for 18 primitive reflexes between age 38 and 45 wks corrected age and followed-up over 6 yrs. ASD was diagnosed using Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) and Autism Diagnostic Observation Schedule Second Edition (ADOS-2). We compared the number of abnormal primitive reflexes between two groups (11 children with and 19 without ASD) after excluding eight children with cerebral palsy in this case-control study. RESULTS : Twenty cases showed one to four hypoactive reflex(es) and two showed one hyperactive reflex together with hypoactive reflex(es). Ten out of 11 cases with ASD had one to four abnormal reflex(es). The number of abnormal hypoactive primitive reflexes was significantly higher in the ASD group (p=0.002). CONCLUSIONS : The result suggests primitive reflexes can be one of the key elements in very early infancy to identify ASD in low birth weight infants. Abnormal hypoactive primitive reflex of low birth weight infants with ASD may inform future research of the pathogenesis of ASD.

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11. Narzisi A. Phase 2 and Later of COVID-19 Lockdown : Is it Possible to Perform Remote Diagnosis and Intervention for Autism Spectrum Disorder ? An Online-Mediated Approach. J Clin Med ;2020 (Jun 13) ;9(6)

COVID-19 is still in phase 2. The lockdown has been significantly reduced compared to phase 1. The centers and institutions that deal with the diagnosis and intervention of children with autism spectrum disorder (ASD) require rapid functional adaptation to respond to patients’ needs. The possibility of using technology to activate and manage diagnostic (preliminary diagnosis) and intervention processes should be explored. Two developed telemedicine working models for diagnosis and intervention, including synchronous and asynchronous transmissions, are presented. They are proposals not yet supported by the data. The diagnosis step is composed by two different and consecutives phases : (A) pre-specialistic consultation (PSC) and (B) specialistic assessment. The intervention step implemented well-recognized evidence-based models for preschoolers, school-aged, and older children in an online format. Parents’ support is also included. The described working models have the purpose of carrying out preliminary specialistic answers to the families without aiming to replace preferable in-person assessment. Based on previous research findings, the telemedicine approach is accepted by parents, increases their sense of competence, increases the parent intervention adhesion, and improves the social communication competencies for children with ASD. In conclusion, the presented working models must be considered partial responses to the current emergency status and at the same time as possible integrations into traditional approaches.

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12. Saby JN, Peters SU, Roberts TPL, Nelson CA, Marsh ED. Evoked Potentials and EEG Analysis in Rett Syndrome and Related Developmental Encephalopathies : Towards a Biomarker for Translational Research. Front Integr Neurosci ;2020 ;14:30.

Rett syndrome is a debilitating neurodevelopmental disorder for which no disease-modifying treatment is available. Fortunately, advances in our understanding of the genetics and pathophysiology of Rett syndrome has led to the development of promising new therapeutics for the condition. Several of these therapeutics are currently being tested in clinical trials with others likely to progress to clinical trials in the coming years. The failure of recent clinical trials for Rett syndrome and other neurodevelopmental disorders has highlighted the need for electrophysiological or other objective biological markers of treatment response to support the success of clinical trials moving forward. The purpose of this review is to describe the existing studies of electroencephalography (EEG) and evoked potentials (EPs) in Rett syndrome and discuss the open questions that must be addressed before the field can adopt these measures as surrogate endpoints in clinical trials. In addition to summarizing the human work on Rett syndrome, we also describe relevant studies with animal models and the limited research that has been carried out on Rett-related disorders, particularly methyl-CpG binding protein 2 (MECP2) duplication syndrome, CDKL5 deficiency disorder, and FOXG1 disorder.

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13. Smith AM, Natowicz MR, Braas D, Ludwig MA, Ney DM, Donley ELR, Burrier RE, Amaral DG. A Metabolomics Approach to Screening for Autism Risk in the Children’s Autism Metabolome Project. Autism Res ;2020 (Jun 18)

Autism spectrum disorder (ASD) is biologically and behaviorally heterogeneous. Delayed diagnosis of ASD is common and problematic. The complexity of ASD and the low sensitivity of available screening tools are key factors in delayed diagnosis. Identification of biomarkers that reduce complexity through stratification into reliable subpopulations can assist in earlier diagnosis, provide insight into the biology of ASD, and potentially suggest targeted interventions. Quantitative metabolomic analysis was performed on plasma samples from 708 fasting children, aged 18 to 48 months, enrolled in the Children’s Autism Metabolome Project (CAMP). The primary goal was to identify alterations in metabolism helpful in stratifying ASD subjects into subpopulations with shared metabolic phenotypes (i.e., metabotypes). Metabotypes associated with ASD were identified in a discovery set of 357 subjects. The reproducibility of the metabotypes was validated in an independent replication set of 351 CAMP subjects. Thirty-four candidate metabotypes that differentiated subsets of ASD from typically developing participants were identified with sensitivity of at least 5% and specificity greater than 95%. The 34 metabotypes formed six metabolic clusters based on ratios of either lactate or pyruvate, succinate, glycine, ornithine, 4-hydroxyproline, or α-ketoglutarate with other metabolites. Optimization of a subset of new and previously defined metabotypes into a screening battery resulted in 53% sensitivity (95% confidence interval [CI], 48%-57%) and 91% specificity (95% CI, 86%-94%). Thus, our metabolomic screening tool detects more than 50% of the autistic participants in the CAMP study. Further development of this metabolomic screening approach may facilitate earlier referral and diagnosis of ASD and, ultimately, more targeted treatments. LAY SUMMARY : Analysis of a selected set of metabolites in blood samples from children with autism and typically developing children identified reproducible differences in the metabolism of about half of the children with autism. Testing for these differences in blood samples can be used to help screen children as young as 18 months for risk of autism that, in turn, can facilitate earlier diagnoses. In addition, differences may lead to biological insights that produce more precise treatment options. We are exploring other blood-based molecules to determine if still a higher percentage of children with autism can be detected using this strategy.

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14. Sperati V, Özcan B, Romano L, Moretta T, Scaffaro S, Faedda N, Turturo G, Fioriello F, Pelosi S, Giovannone F, Sogos C, Guidetti V, Baldassarre G. Acceptability of the Transitional Wearable Companion "+me" in Children With Autism Spectrum Disorder : A Comparative Pilot Study. Front Psychol ;2020 ;11:951.

+me is an experimental interactive soft toy, looking like a panda, developed for young children. When touched on the paws or head (inputs), the toy can emit attractive responses such as colored lights and amusing sounds (outputs). +me is wirelessly connected to a control tablet through which an adult caregiver can modify its input-output contingencies so as to produce different, rewarding response patterns using the same device. Given these features, we propose +me as a potential novel tool to support the therapy of Autism Spectrum Disorder (ASD). The allure of the device could be exploited to capture the attention and encourage the social interaction of toddlers during play activities with therapists. In this pilot study, +me was tested on two small groups of children aged 30-48 months, one group diagnosed with ASD and the second with Communication Disorder, a condition that often presents-especially at an early age-overlapping symptoms with ASD. The proposed play activities aimed to foster simple imitative behaviors and stimulate the engagement of the children. The results were compared with those of a previous test run on Typically Developed children. Preliminary observations, based on the analysis of video recordings, suggest that, on average, +me is able to encourage a positive engagement and that different groups tend to manifest some different behaviors.

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15. Torrico B, Antón-Galindo E, Fernàndez-Castillo N, Rojo-Francàs E, Ghorbani S, Pineda-Cirera L, Hervás A, Rueda I, Moreno E, Fullerton JM, Casadó V, Buitelaar JK, Rommelse N, Franke B, Reif A, Chiocchetti AG, Freitag C, Kleppe R, Haavik J, Toma C, Cormand B. Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia : Genetics, Transcriptomics and Functional Analyses. J Clin Med ;2020 (Jun 13) ;9(6)

The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the : (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization ; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders ; (iii) burden of rare variants in ASD and schizophrenia ; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10(-7)), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia.

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16. Visser L, Linkersdörfer J, Rothe J, Görgen R, Hasselhorn M, Schulte-Körne G. Corrigendum to ’The role of ADHD symptoms in the relationship between academic achievement and psychopathological symptoms’ Research in Developmental Disabilities 97 (2020) 103552. Res Dev Disabil ;2020 (Jun 18):103691.

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17. Wieckowski AT, Flynn LT, Richey JA, Gracanin D, White SW. Measuring change in facial emotion recognition in individuals with autism spectrum disorder : A systematic review. Autism ;2020 (Jun 18):1362361320925334.

Children and adults with autism spectrum disorder show difficulty recognizing facial emotions in others, which makes social interaction challenging. While there are many treatments developed to improve facial emotion recognition, there is no agreement on the best way to measure such abilities in individuals with autism spectrum disorder. The purpose of this review is to examine studies that were published between January 1998 and November 2019 and have measured change in facial emotion recognition to evaluate the effectiveness of different treatments. Our search yielded 65 studies, and within these studies, 36 different measures were used to evaluate facial emotion recognition in individuals with autism spectrum disorder. Only six of these measures, however, were used in different studies and by different investigators. In this review, we summarize the different measures and outcomes of the studies, in order to identify promising assessment tools and inform future research.

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18. Yankowitz LD, Herrington JD, Yerys BE, Pereira JA, Pandey J, Schultz RT. Evidence against the "normalization" prediction of the early brain overgrowth hypothesis of autism. Mol Autism ;2020 (Jun 18) ;11(1):51.

BACKGROUND : The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growth leading to normalized brain volume in late childhood and beyond. While there is consistent evidence for early brain overgrowth, there is mixed evidence for normalization of brain volume by middle childhood. The outcome of this debate is important to understanding the etiology and neurodevelopmental trajectories of ASD. METHODS : Brain volume was examined in two very large single-site samples of children, adolescents, and adults. The primary sample comprised 456 6-25-year-olds (ASD n = 240, typically developing controls (TDC) n = 216), including a large number of females (n = 102) and spanning a wide IQ range (47-158). The replication sample included 175 males. High-resolution T1-weighted anatomical MRI images were examined for group differences in total brain, cerebellar, ventricular, gray, and white matter volumes. RESULTS : The ASD group had significantly larger total brain, cerebellar, gray matter, white matter, and lateral ventricular volumes in both samples, indicating that brain volume remains enlarged through young adulthood, rather than normalizing. There were no significant age or sex interactions with diagnosis in these measures. However, a significant diagnosis-by-IQ interaction was detected in the larger sample, such that increased brain volume was related to higher IQ in the TDCs, but not in the ASD group. Regions-of-significance analysis indicated that total brain volume was larger in ASD than TDC for individuals with IQ less than 115, providing a potential explanation for prior inconsistent brain size results. No relationships were found between brain volume and measures of autism symptom severity within the ASD group. LIMITATIONS : Our cross-sectional sample may not reflect individual changes over time in brain volume and cannot quantify potential changes in volume prior to age 6. CONCLUSIONS : These findings challenge the "normalization" prediction of the brain overgrowth hypothesis by demonstrating that brain enlargement persists across childhood into early adulthood. The findings raise questions about the clinical implications of brain enlargement, since we find that it neither confers cognitive benefits nor predicts increased symptom severity in ASD.

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