Pubmed du 08/09/20

mardi 8 septembre 2020

1. Beversdorf DQ. The Role of the Noradrenergic System in Autism Spectrum Disorders, Implications for Treatment. Semin Pediatr Neurol ;2020 (Oct) ;35:100834.

Autism spectrum disorder (ASD) is frequently associated with anxiety and hyperarousal. While the pathological changes in the noradrenergic system in ASD are not entirely clear, a number of functional indices of the sympathetic/parasympathetic balance are altered in individuals with ASD, often with a high degree of inter-individual variability. The neuropsychopharmacological effects of α(2) agonists and β-adrenergic antagonists make agents targeting these receptors of particular interest. α(2) agonists have shown beneficial effects for attention deficit hyperactivity disorder (ADHD) and in other domains in individuals with ASD, but effects on core ASD symptoms are less clear. Case series and single dose psychopharmacological challenges suggest that treatment with β-adrenergic antagonists has beneficial effects on language and social domains. Additionally, psychophysiological markers and premorbid anxiety may predict response to these medications. As a result, β-adrenergic antagonists are currently being utilized in a clinical trial for improving core symptoms as well as anxiety in individuals with ASD.

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2. Bostwick A, Snyder NW, Windham GC, Whitman C, Pearl M, Robinson L, Newschaffer CJ, Lyall K. Polyunsaturated Fatty Acids in Newborn Bloodspots : Associations With Autism Spectrum Disorder and Correlation With Maternal Serum Levels. Autism Res ;2020 (Sep 8)

We conducted a population-based case-control study to examine newborn polyunsaturated fatty acid (PUFA) levels in association with autism spectrum disorder (ASD) and assess PUFA correlation across two time points. ASD cases (n = 200) were identified through the Department of Developmental Services and matched to live-birth population controls (n = 200) on birth month, year (2010-2011), and sex. Nonesterified PUFAs were measured by isotope dilution liquid chromatography-high resolution mass spectrometry from archived newborn dried blood spots and maternal mid-pregnancy serum samples. Crude and adjusted conditional logistic regression models were used to examine the association between neonatal PUFA levels, categorized in quartiles and according to distributional extremes, and ASD. Cubic splines were utilized to examine nonlinear relationships between continuous neonatal PUFAs and ASD. The correlation between neonatal and maternal levels was examined using Pearson correlation coefficients. In adjusted analyses of neonatal PUFA levels, no clear trends emerged, though there was an elevated odds ratio of ASD for the third quartile of linoleic acid, relative to the first (adjusted odds ratio = 2.49, 95% confidence interval : 1.31, 4.70). Cubic spline analysis suggested a nonlinear association between linoleic acid and ASD, though this was not robust to sensitivity analyses. While individual PUFAs were significantly correlated with one another within a given time point, aside from docohexaseanoic acid, PUFAs were not correlated across maternal and neonatal samples. Overall, our findings do not support an association between neonatal PUFA levels and ASD. Future work should confirm and expand these findings by examining associations with phenotypic subgroups and considering PUFAs in other time points. LAY SUMMARY : In this study, we examined whether levels of fats known as polyunsaturated fatty acids, measured in newborns, were related to later child diagnosis of autism spectrum disorder (ASD). Overall, we did not find strong evidence for hypothesized reduction in risk of ASD based on newborn levels of these fats. Future studies in larger samples and considering other time points may be useful to explain whether these fats are important in brain development related to ASD.

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3. Breggin PR. Moving past the vaccine/autism controversy - to examine potential vaccine neurological harms. Int J Risk Saf Med ;2020 (Aug 28)

BACKGROUND : The vaccine/autism controversy has caused vast scientific and public confusion, and it has set back research and education into genuine vaccine-induced neurological disorders. The great strawman of autism has been so emphasized by the vaccine industry that it, and it alone, often appears in authoritative discussions of adverse effects of the MMR and other vaccines. By dismissing the chimerical vaccine/autism controversy, vaccine defenders often dismiss all genuinely neurological aftereffects of the MMR (measles, mumps, and rubella) and other vaccines, including well-documented events, such as relatively rare cases of encephalopathy and encephalitis. OBJECTIVE : This report explains that autism is not a physical or neurological disorder. It is not caused by injury or disease of the brain. It is a developmental disorder that has no physical origins and no physical symptoms. It is extremely unlikely that vaccines are causing autism ; but it is extremely likely that they are causing more neurological damage than currently appreciated, some of it resulting in psychosocial disabilities that can be confused with autism and other psychosocial disorders. This confusion between a developmental, psychosocial disorder and a physical neurological disease has played into the hands of interest groups who want to deny that vaccines have any neurological and associated neuropsychiatric effects. METHODS : A review of the scientific literature, textbooks, and related media commentary is integrated with basic clinical knowledge. RESULTS : This report shows how scientific sources have used the vaccine/autism controversy to avoid dealing with genuine neurological risks associated with vaccines and summarizes evidence that vaccines, including the MMR, can cause serious neurological disorders. Manufacturers have been allowed by the US Food and Drug Administration (FDA) to gain vaccine approval without placebo-controlled clinical trials. CONCLUSIONS : The misleading vaccine autism controversy must be set aside in favor of examining actual neurological harms associated with vaccines, including building on existing research that has been ignored. Manufacturers of vaccines must be required to conduct placebo-controlled clinical studies for existing vaccines and for government approval of new vaccines. Many probable or confirmed neurological adverse events occur within a few days or weeks after immunization and could be detected if the trials were sufficiently large. Contrary to current opinion, large, long-term placebo-controlled trials of existing and new vaccines would be relatively easy and safe to conduct.

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4. Burrell TL, Sharp WG, Criado KK, Berry R, Luevano C, Khan R, Scahill L. Feasibility of a Structured, Multidisciplinary Intervention for Weight Management in Children With Autism Spectrum Disorder. Semin Pediatr Neurol ;2020 (Oct) ;35:100830.

Children with autism spectrum disorder (ASD) are at an increased risk for obesity. Although treatments for obesity exist, they do not address unique ASD related characteristics. The current study evaluates a structured multidisciplinary treatment program, the Changing Health in Autism through Nutrition, Getting fit and Expanding (food) variety (CHANGE) program. Ten children (ages 5-12) with ASD who were overweight or obese participated in either CHANGE or parent education program for 16 weeks. CHANGE provided nutrition and behavior management strategies, while the parent education program provided ASD education. BMI-for-age percentile at screening was 92.8% ± 5.2. Ten eligible participants enrolled in the study and 2 (20%) dropped out prior to study completion. Attendance of sessions was moderate (57%) ; however, parental adherence (eg, homework completion, session participation) was high. All participants indicated that they would recommend the interventions to others. Preliminary evidence supports the feasibility of the CHANGE program in children with ASD.

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5. Casanova MF, Sokhadze EM, Casanova EL, Li X. Transcranial Magnetic Stimulation in Autism Spectrum Disorders : Neuropathological Underpinnings and Clinical Correlations. Semin Pediatr Neurol ;2020 (Oct) ;35:100832.

Despite growing knowledge about autism spectrum disorder (ASD), research findings have not been translated into curative treatment. At present, most therapeutic interventions provide for symptomatic treatment. Outcomes of interventions are judged by subjective endpoints (eg, behavioral assessments) which alongside the highly heterogeneous nature of ASD account for wide variability in the effectiveness of treatments. Transcranial magnetic stimulation (TMS) is one of the first treatments that targets a putative core pathologic feature of autism, specifically the cortical inhibitory imbalance that alters gamma frequency synchronization. Studies show that low frequency TMS over the dorsolateral prefrontal cortex of individuals with ASD decreases the power of gamma activity and increases the difference between gamma responses to target and nontarget stimuli. TMS improves executive function skills related to self-monitoring behaviors and the ability to apply corrective actions. These improvements manifest themselves as a reduction of stimulus bound behaviors and diminished sympathetic arousal. Results become more significant with increasing number of sessions and bear synergism when used along with neurofeedback. When applied at low frequencies in individuals with ASD, TMS appears to be safe and to improve multiple patient-oriented outcomes. Future studies should be conducted in large populations to establish predictors of outcomes (eg, genetic profiling), length of persistence of benefits, and utility of booster sessions.

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6. Chen LW, Wang ST, Wang LW, Kao YC, Chu CL, Wu CC, Chiang CH, Huang CC. Early Neurodevelopmental Trajectories for Autism Spectrum Disorder in Children Born Very Preterm. Pediatrics ;2020 (Sep 8)

BACKGROUND : Children born preterm are at high risk for autism spectrum disorder (ASD). However, there is still a lack of appropriate developmental markers. In this study, we aim to examine whether early mental performance trajectory is related to ASD outcome in the preterm population. METHODS : The population-based cohort included 414 very preterm survivors born between 2008 and 2014. After excluding children with severe neurosensory impairment, 319 children with available records of developmental quotients before age 2 years were enrolled. The trajectory of mental performance evaluated by using the Bayley Scales of Infant Development across 6, 12, and 24 months of age was analyzed with group-based trajectory modeling. At 5 years of age, the ASD diagnosis was established by using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. RESULTS : There were 29 children with ASD and 290 children without ASD. The mental performances from age 6 to 24 months could be classified into 3 trajectory patterns : low declining, high declining, and high stable, which corresponded to ASD prevalence at age 5 years of 35%, 9%, and 3%, respectively. ASD odds was 15 times higher in the low-declining group than in the high-stable group (odds ratio 15 ; 95% confidence interval 3.8-59 ; P < .001). Through the analysis of multinomial logistic regression, we found that male infants with longer exposure to oxygen therapy whose mothers had lower maternal education levels tended to follow the low-declining trajectory. CONCLUSIONS : The early-life mental trajectory patterns, by using the Bayley Scales of Infant Development, may lead to identification of vulnerable children born preterm for early ASD diagnosis and targeted intervention.

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7. Dada S, Flores C, Bastable K, Schlosser RW. The effects of augmentative and alternative communication interventions on the receptive language skills of children with developmental disabilities : A scoping review. Int J Speech Lang Pathol ;2020 (Sep 7):1-11.

PURPOSE : To map and synthesise research evidence of the effects that aided and unaided AAC interventions have on the receptive language of children with developmental disabilities. METHOD : This scoping review used a four-pronged search strategy (electronic databases, dissertations and theses, hand search, ancestry searches) to identify germane studies. A total of 16 studies met the inclusion criteria. These studies were described in terms of the number of participants, participant characteristics, research design, AAC interventions, intervention outcomes, intervention effects, and quality appraisal. RESULT : The review revealed positive associations between aided and unaided AAC, vocabulary acquisition and symbol comprehension. CONCLUSION : AAC interventions may have merit for the development of receptive language skills in children with developmental disabilities. Specific gaps in relation to unaided AAC, aided augmented input strategies, morphological and syntax development, and discourse comprehension are highlighted.

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8. De Luca F. Endocrinological Abnormalities in Autism. Semin Pediatr Neurol ;2020 (Oct) ;35:100582.

A number of chemical messengers, such as various hormones and hormone-like substances, along with neurotransmitters, such as serotonin, dopamine, and norepinephrine, are directly or indirectly linked with the encoding of social behavior via their action at the amygdala, hippocampus, and other related brain structures known to be involved in different aspects of social development. It is thought that any imbalance in the secretion and action of these chemicals may lead to defective or abnormal social behaviors that are the hallmarks of Autism Spectrum Disorders (ASDs). Many of the studies have described an association between ASDs and endocrine dysfunction, but have failed to establish a cause-effect connection between these 2 conditions. All together, the literature regarding the role of endocrine-related factors and ASDs is sparse and remains somewhat preliminary, controversial, and inconclusive. Thus, more research is needed in the future to shed more light on this topic.

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9. Frye RE. Mitochondrial Dysfunction in Autism Spectrum Disorder : Unique Abnormalities and Targeted Treatments. Semin Pediatr Neurol ;2020 (Oct) ;35:100829.

Several lines of evidence implicate mitochondria in the pathophysiology of autism spectrum disorder (ASD). In this review, we outline some of the evidence supporting this notion, as well as discuss novel abnormalities in mitochondrial function that appear to be related to ASD, and treatments that both target mitochondria and have evidence of usefulness in the treatment of ASD in clinical trials. A suspicion of the mitochondrion’s involvement in ASD can be traced back to 1985 when lactic acidosis was noted in a subset of children with ASD. A large population-based study in 2007 confirmed this notion and found that a subset of children with ASD (∼4%) could be diagnosed with a definite mitochondrial disease. Further studies suggested that children with ASD and mitochondrial disease may have certain characteristics such as fatigability, gastrointestinal disorders, unusual types of neurodevelopmental regression, seizures/epilepsy, and motor delay. Further research examining biomarkers of mitochondrial dysfunction and electron transport chain activity suggest that abnormalities of mitochondrial function could affect a much higher number of children with ASD, perhaps up to 80%. Recent research has identified a type of dysfunction of mitochondria in which the activity of the electron transport chain is significantly increased. This novel type of mitochondrial dysfunction may be associated with environmental exposures and neurodevelopmental regression. Several treatments that target mitochondria appear to have evidence for use in children with ASD, including cofactors such as L-Carnitine and the ketogenic diet. Although the understanding of the involvement of mitochondria in ASD is evolving, the mitochondrion is clearly a novel molecular target which can be helpful in understanding the etiology of ASD and treatments that may improve function of children with ASD.

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10. Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV. Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder. Semin Pediatr Neurol ;2020 (Oct) ;35:100835.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that currently has no approved medical therapy to address core symptoms or underling pathophysiological processes. Several compounds are under development that address both underlying pathophysiological abnormalities and core ASD symptoms. This article reviews one of these treatments, d,l-leucovorin calcium (also known as folinic acid) for treatment of folate pathway abnormalities in children with ASD. Folate is a water-soluble B vitamin that is essential for normal neurodevelopment and abnormalities in the folate and related pathways have been identified in children with ASD. One of these abnormalities involves a partial blockage in the ability of folate to be transported into the brain utilizing the primary transport mechanism, the folate receptor alpha. Autoantibodies which interfere with the function of the folate receptor alpha called folate receptor alpha autoantibodies have been identified in 58%-76% of children with ASD and independent studies have demonstrated that blood titers of these autoantibodies correlate with folate levels in the cerebrospinal fluid. Most significantly, case-series, open-label, and single and double-blind placebo-controlled studies suggest that d,l-leucovorin, a reduced folate that can bypass the blockage at the folate receptor alpha by using the reduced folate carrier, an alternate pathway, can substantially improve particular symptoms in children with ASD, especially those positive for folate receptor alpha autoantibodies. This article reviews the current evidence for treating core and associated symptoms and underlying pathophysiological mechanisms in children with ASD with d,l-leucovorin.

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11. Holroyd TA, Sauer MA, Limaye RJ. Vaccine decision-making among parents of children on Medicaid with and without autism spectrum disorder. Vaccine ;2020 (Sep 8)

BACKGROUND : The belief that there is a link between the MMR vaccine and autism has led to a decline in childhood-immunization uptake and a resurgence of preventable infectious diseases. This study aimed to understand how the vaccine decision-making process differed between parents with a child diagnosed with autism and parents with a child that did not have autism. METHODS : Interviews were conducted in September-December 2018 with 24 racially and demographically diverse parents of children on Medicaid at two Baltimore clinics serving Medicaid patients, one of which only serves families of children with autism. We conducted a semi-structured, qualitative, in-person in-depth interview study to explore parental perceptions of vaccine-decision making. Interviews with participants were transcribed from audio recordings. We then extracted and analyzed the types of barriers each participant experienced. RESULTS : Parent descriptions of their vaccine decision-making process focused on three primary factors : concerns about vaccines, the relationship between the child’s provider and the parent, and risk perception. These findings are in line with existing literature that has articulated key factors in the vaccine decision-making process generally. Parents of a child with autism were more likely to consider the idea that vaccines were linked to autism in their decision-making process, and were less likely to be influenced by personalized recommendations from the child’s health care provider. CONCLUSION : Parental concerns about vaccines, the parent-provider relationship, and vaccine risk perception all contribute to vaccine decision-making among parents of children with and without ASD. However, providers may find it especially difficult to manage parental misconceptions about vaccines and developmental disabilities. Future studies can identify alternative communication techniques and determine what mechanisms may be more effective in encouraging vaccine acceptance among parents of children with ASD.

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12. Hyman SL, Iadarola S. Simpler Than Possible : Insurance Mandates for Autism Spectrum Disorders. Pediatrics ;2020 (Sep 8)

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13. James SN, Smith CJ. Early Autism Diagnosis in the Primary Care Setting. Semin Pediatr Neurol ;2020 (Oct) ;35:100827.

As the prevalence of autism spectrum disorder (ASD) has increased in recent years, so too has the body of research describing the importance of early diagnosis and early intervention. Unfortunately, a large proportion of children with the disorder do not receive a diagnosis until after their fourth birthday. Various reasons exist for late diagnosis, including limited understanding of nuanced early warning signs and limited knowledge of effective early detection mechanisms among healthcare providers. Since early diagnosis enables access to treatment, and early intensive intervention improves long-term developmental outcomes, early detection by pediatric healthcare providers is critical. This article will review ASD prevalence rates, describe correlates and factors that might influence prevalence estimates, and highlight recent advances in early detection methods and intervention services.

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14. Kopec J, Hagmann C, Shea N, Prawl A, Batkin D, Russo N. Examining the Temporal Limits of Enhanced Visual Feature Detection in Children With Autism. Autism Res ;2020 (Sep 8)

The enhanced perceptual processing of visual features in children with autism spectrum disorder (ASD) is supported by an abundance of evidence in the spatial domain, with less robust evidence regarding whether this extends to information presented across time. The current study aimed to replicate and extend previous work finding that children with an ASD demonstrated enhanced perceptual accuracy in detecting feature-based (but not categorically defined) targets in time, when these were presented quickly, at a stimulus onset asynchrony (SOA) of 50 ms per item. Specifically, we extend the range of SOAs to examine the temporal boundaries of this enhanced accuracy and examine whether there is a relationship between ASD-related traits and detection accuracy on temporal visual search tasks. Individuals with autism perceived feature-based targets with statistically higher accuracy than their typically developing peers between SOAs of 39 and 65 ms and were numerically faster at all SOAs. No group differences were noted for category-based task accuracy. Our results also demonstrated that ASD-related traits measured by the autism spectrum quotient were positively correlated with accuracy on the feature-based task. Overall, results suggest that accurate visual perception of features (particularly color) is enhanced in children with ASD across time. LAY SUMMARY : Our results suggest that children with autism are able to process visual features, such as color, more accurately than typically developing children, even when these are presented very rapidly. Accuracy was higher in children with higher levels of autism-related traits and symptoms. Our findings suggest that more accurate visual perception exists not only across space in children with autism, as much of the existing literature demonstrates, but also over time.

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15. Lee TM, Lee KM, Lee CY, Lee HC, Tam KW, Loh EW. Effectiveness of N-acetylcysteine in autism spectrum disorders : A meta-analysis of randomized controlled trials. Aust N Z J Psychiatry ;2020 (Sep 8):4867420952540.

OBJECTIVE : Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder. N-acetylcysteine, which can be converted to glutathione and subsequently release glutamate into the extracellular space, and thus reduce glutamatergic neurotransmission at synapses, is considered a potential drug for autism spectrum disorder treatment. Here, we analyzed the treatment effects of N-acetylcysteine on autism spectrum disorder in randomized controlled trials. STUDY DESIGN : Updated systematic review and meta-analysis. DATA SOURCES : By systematically searching the PubMed, Embase and Cochrane Library, we obtained five randomized controlled trials. STUDY SELECTION : Meta-analyses were performed to examine the improvement in autistic behaviors as measured by the Aberrant Behavior Checklist, Social Responsiveness Scale and Repetitive Behavior Scale-Revised, using mean difference with a 95% confidence interval and a random-effects model. DATA SYNTHESIS : After 8-12 weeks of N-acetylcysteine supplementation, the pooled result of four trials revealed an improvement in Aberrant Behavior Checklist total score (mean difference = 1.31, 95% confidence interval = [0.42, 2.20]). When one trial was excluded, the sensitivity test result was stronger (mean difference = 1.88, 95% confidence interval = [0.92, 2.83]). The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and irritability (mean difference = 4.07, 95% confidence interval = [1.13, 7.04]). Regarding Social Responsiveness Scale, the pooled result of two trials showed significant improvement in social awareness after 8-12 weeks of N-acetylcysteine supplementation (mean difference = 1.34, 95% confidence interval = [0.09, 2.59]). No differences were observed in the pooled results of two trials using Repetitive Behavior Scale, either in the total or the subscales. CONCLUSION : We concluded that N-acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum disorder. However, further evidence should be sought before a general recommendation.

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16. Li B, Xu Y, Zhang X, Zhang L, Wu Y, Wang X, Zhu C. The effect of vitamin D supplementation in treatment of children with autism spectrum disorder : a systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci ;2020 (Sep 7):1-11.

Objective : The effect of vitamin D supplementation on the risk of Autism Spectrum Disorder (ASD) is conflicting. The aim of this study was to estimate the efficacy of vitamin D supplementation on ASD in children. Methods : We conducted a meta-analysis of randomized controlled trials (RCTs) in which vitamin D supplementation was used as a therapy in children with ASD. The PubMed, PsychINFO, Cochrane CENTRAL library, Web of Science, and Cinahl databases were searched from inception to March 20, 2019, for all publications on vitamin D and ASD with no restrictions. Studies involving individuals aged <18 years diagnosed with ASD and with all functional outcomes assessed by measurement scales for ASD were included. Mean differences were pooled, and a meta-analysis was performed using a random-effects model due to differences between the individual RCTs. Results : There were five RCTs with 349 children with ASD in the review, of which three RCTs were included in the meta-analysis. Vitamin D supplementation indicated a small but significant improvement in hyperactivity scores (pooled MD : -3.20 ; 95% CI : [-6.06, -0.34]) with low heterogeneity (I(2) = 10%, p = 0.33), but there were no other statistically significant differences in ASD symptoms between groups as measured by validated scales. Conclusion : Vitamin D supplementation appears to be beneficial for hyperactivity but not for core symptoms or other co-existing behaviors and conditions of ASD. Future RCTs with large sample sizes examining the effect of vitamin D supplementation on ASD among individuals with low serum vitamin D levels at baseline are needed.

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17. McBain RK, Cantor JH, Kofner A, Stein BD, Yu H. State Insurance Mandates and the Workforce for Children With Autism. Pediatrics ;2020 (Sep 8)

BACKGROUND : State mandates have required insurance companies to provide coverage for autism-related child health care services ; however, it has not been determined if insurance mandates have improved the supply of child health care providers. We investigate the effect of state insurance mandates on the supply of child psychiatrists, pediatricians, and board-certified behavioral analysts (BCBAs). METHODS : We used data from the National Conference of State Legislatures and Health Resources and Services Administration’s Area Health Resource Files to examine child psychiatrists, pediatricians, and BCBAs in all 50 states from 2003 to 2017. Fixed-effects regression models compared change in workforce density before versus one year after mandate implementation and the effect of mandate generosity across 44 US states implementing mandates between 2003 and 2017. RESULTS : From 2003 to 2017, child psychiatrists increased from 7.40 to 10.03 per 100 000 children, pediatricians from 62.35 to 68.86, and BCBAs from 1.34 to 29.88. Mandate introduction was associated with an additional increase of 0.77 BCBAs per 100 000 children (95% confidence interval [CI] : 0.18 to 1.42) one year after mandate enactment. Mandate introduction was also associated with a more modest increase among child psychiatrists (95% CI : 0.10 to 0.91) and was not associated with the prevalence of pediatricians (95% CI : -0.76 to 1.13). We also found evidence that more generous mandate benefits were associated with larger effects on workforce supply. CONCLUSIONS : State insurance mandates were associated with an ∼16% increase in BCBAs from 2003 to 2017, but the association with child psychiatrists was smaller and nonsignificant among pediatricians. In these findings, it is suggested that policies are needed that specifically address workforce constraints in the provision of services for children with autism spectrum disorder.

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18. McCarty P, Frye RE. Early Detection and Diagnosis of Autism Spectrum Disorder : Why Is It So Difficult ?. Semin Pediatr Neurol ;2020 (Oct) ;35:100831.

Autism spectrum disorder (ASD) affects approximately 2% of children in the United States (US). Therapeutic interventions are most effective if applied early, yet diagnosis often remains delayed, partly because the diagnosis is based on identifying abnormal behaviors that may not emerge until the disorder is well established. Universal screening has been recommended by the America Academy of Pediatrics at 18 and 24 months yet studies show low compliance by pediatricians and the US Preventive Services Task Force does not support universal screening. To better understand the limitations of universal screening this article looks at the performance of screening tests given the prevalence of ASD. Specifically, although the sensitivity and specificity of the Modified Checklist for Autism in Toddlers, Revised with Follow-up, the de facto screening tool, exceeds 90%, the relatively low prevalence of ASD in the general population (∼2%) results in a positive predictive value of about 33%, resulting in only 1 of 3 children identified by the Modified Checklist for Autism in Toddlers, Revised with Follow-up actually having ASD. To mitigate this issue, the America Academy of Pediatrics has recently recommended the use of a Level 2 screener after failing a Level 1 screener, before referring children on for a full comprehensive evaluation for ASD. In this way, a series of screening tools are used to enrich the population of children referred for further evaluation so fewer without an ASD diagnosis are evaluated. We have developed a program to train pediatricians to utilize these instruments as well as learn to diagnose ASD so children can effectively be referred for appropriate services at the front lines. Given the current burden on the medical system with the diagnosis and evaluation of children with ASD, it is important to create efficient systems for screening children which can best identify those most likely to have ASD. Developing methods to identify those children most at risk for developing ASD, either through consideration of medical or family history or through the use of biomarkers, may be helpful in identifying the children that require increased surveillance and those that do not need screening.

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19. Mostafavi M, Gaitanis J. Autism Spectrum Disorder and Medical Cannabis : Review and Clinical Experience. Semin Pediatr Neurol ;2020 (Oct) ;35:100833.

Autism spectrum disorder (ASD) is a multifactorial, pervasive neurodevelopmental disorder defined by the core symptoms of significant impairment in social interaction and communication as well as restricted, repetitive patterns of behavior. In addition to these core behaviors, persons with ASD frequently have associated noncore behavioral disturbance (ie, self-injury, aggression), as well as several medical comorbidities. Currently, no effective treatment exists for the core symptoms of ASD. This review reports the available preclinical and clinical data regarding the use of cannabis and cannabidiol in the treatment of core symptoms, noncore symptoms and comorbidities associated with ASD. Additionally, we describe our clinical experience working with children and young adults with ASD who have used cannabis or cannabidiol. At present, preclinical and clinical data suggest a potential for therapeutic benefit among some persons with ASD and that it is overall well tolerated. Further research is required to better identify patients who may benefit from treatment without adverse effects.

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20. O’Brolchain F, Gordijn B. Responsibility-Enhancing Assistive Technologies and People with Autism. Camb Q Healthc Ethics ;2020 (Oct) ;29(4):607-616.

This paper aims to explore the role assistive technologies (ATs) might play in helping people with autism spectrum disorder (ASD) and a concomitant responsibility deficit become more morally responsible. Toward this goal, the authors discuss the philosophical concept of responsibility, with a reliance on Nicole Vincent’s taxonomy of responsibility concepts. They then outline the ways in which ASD complicates ascriptions of responsibility, particularly responsibility understood as a capacity. Further, they explore the ways in which ATs might improve a person’s capacity so that responsibility can be properly ascribed to them. After demonstrating that although assistive technologies are likely to be able to enhance a person’s capacity in such a way so that responsibility can be ascribed to them, the authors assert that these technologies will have a number of additional effects on the other aspects of the concept of responsibility.

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21. Peña-Salazar C, López Cuiña M, Chavarría V, Robles Olmo B. Convulsive status epilepticus as a possible symptom of COVID-19 in a patient with intellectual disability and autistic spectrum disorder. Neurologia ;2020 (Jul 31)

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22. Rollins PR, De Froy A, Campbell M, Hoffman RT. Mutual Gaze : An Active Ingredient for Social Development in Toddlers with ASD : A Randomized Control Trial. J Autism Dev Disord ;2020 (Sep 7)

We examined the efficacy of an early autism intervention for use in early childhood intervention (ECI) and mutual gaze as a contributor to social development. Seventy-eight families were randomly assigned to one of three 12-week interventions : Pathways (with a mutual gaze component), communication, or services-as-usual (SAU). The Pathways/SAU comparison concerned the efficacy of Pathways for ECI, and the Pathways/communication comparison, mutual gaze. The Pathways group made significantly more change on social measures, communicative synchrony, and adaptive functioning compared with the SAU group and on social measures compared with the communication group. There were no group differences for communicative acts. The results support Pathways as a potential ECI program and mutual gaze as an active ingredient for social and communication development.

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23. Soul JS, Spence SJ. Predicting Autism Spectrum Disorder in Very Preterm Infants. Pediatrics ;2020 (Sep 8)

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24. Swanson MR. The role of caregiver speech in supporting language development in infants and toddlers with autism spectrum disorder. Dev Psychopathol ;2020 (Sep 7):1-10.

Parents play an essential role in supporting child development by providing a safe home, proper nutrition, and rich educational opportunities. In this article we focus on the role of caregiver speech in supporting development of young children with autism spectrum disorder (ASD). We review studies from typically developing children and children with autism showing that rich and responsive caregiver speech supports language development. Autism intervention studies that target caregiver speech are reviewed as are recent scientific advances from studies of typical development. The strengths and weakness of different techniques for collecting language data from caregivers and children are reviewed, and natural language samples are recommended as best practice for language research in autism. We conclude that caregivers play a powerful role in shaping their children’s development and encourage researchers to adapt parent-mediated intervention studies to acknowledge individual differences in parents by using a personalized medicine approach.

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25. Thom RP, Hazen MM, McDougle CJ, Hazen EP. Providing Inpatient Medical Care to Children With Autism Spectrum Disorder. Hosp Pediatr ;2020 (Sep 8)

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, affecting an estimated 1 in 40 children. Children with ASD have high rates of medical comorbidity and often experience high levels of distress during medical admissions, increasing the risk of agitation. Pediatric hospitalists receive minimal formal training on the inpatient care of children with ASD. In this article, we review strategies that pediatric hospitalists can use to optimize the care of children with ASD during inpatient admissions. These include gathering an ASD-related history early in the admission to understand the child’s baseline core ASD symptoms, including social and communication ability, sensory needs, and restricted or repetitive behaviors. This information can be used to tailor the hospitalist’s approach in each of these 3 domains. We conclude by reviewing procedure-related considerations, an approach to managing agitation, and quality improvement interventions.

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26. Thom RP, McDougle CJ. Immune Modulatory Treatments for Autism Spectrum Disorder. Semin Pediatr Neurol ;2020 (Oct) ;35:100836.

Several lines of evidence from family history studies, immunogenetics, maternal immune activation, neuroinflammation, and systemic inflammation support an immune subtype of autism spectrum disorder (ASD). Current Food and Drug Administration-approved medications for ASD do not address the underlying pathophysiology of ASD, have not consistently been shown to address the core symptoms of ASD, and are currently only approved for treating irritability in children and adolescents. In this article, we review the immune modulatory effects of the 2 currently Food and Drug Administration-approved treatments for ASD. We then provide an overview of current data on emerging treatments for ASD from multiple fields of medicine with immune modulatory effects. Although further research is needed to more clearly establish the efficacy and safety of immune modulatory treatments, early data on repurposing medications used to treat systemic inflammation for ASD demonstrate potential benefit and further research is warranted.

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27. Vernetti A, Shic F, Boccanfuso L, Macari S, Kane-Grade F, Milgramm A, Hilton E, Heymann P, Goodwin MS, Chawarska K. Atypical Emotional Electrodermal Activity in Toddlers with Autism Spectrum Disorder. Autism Res ;2020 (Sep 8)

Past studies in autism spectrum disorder (ASD) indicate atypical peripheral physiological arousal. However, the conditions under which these atypicalities arise and their link with behavioral emotional expressions and core ASD symptoms remain uncertain. Given the importance of physiological arousal in affective, learning, and cognitive processes, the current study examined changes in skin conductance level (ΔSCL) in 41 toddlers with ASD (mean age : 22.7 months, SD : 2.9) and 32 age-matched toddlers with typical development (TD) (mean age : 21.6 months, SD : 3.6) in response to probes designed to induce anger, joy, and fear emotions. The magnitude of ΔSCL was comparable during anger (P = 0.206, d = 0.30) and joy (P = 0.996, d = 0.01) conditions, but significantly lower during the fear condition (P = 0.001, d = 0.83) in toddlers with ASD compared to TD peers. In the combined samples, ΔSCL positively correlated with intensity of behavioral emotional expressivity during the anger (r[71] = 0.36, P = 0.002) and fear (r[68] = 0.32, P = 0.007) conditions, but not in the joy (r[69] = -0.15, P = 0.226) condition. Finally, ΔSCL did not associate with autism symptom severity in any emotion-eliciting condition in the ASD group. Toddlers with ASD displayed attenuated ΔSCL to situations aimed at eliciting fear, which may forecast the emergence of highly prevalent internalizing and externalizing problems in this population. The study putatively identifies ΔSCL as a dimension not associated with severity of autism but with behavioral responses in negatively emotionally challenging events and provides support for the feasibility, validity, and incipient utility of examining ΔSCL in response to emotional challenges in very young children. LAY SUMMARY : Physiological arousal was measured in toddlers with autism exposed to frustrating, pleasant, and threatening tasks. Compared to typically developing peers, toddlers with autism showed comparable arousal responses to frustrating and pleasant events, but lower responses to threatening events. Importantly, physiological arousal and behavioral expressions were aligned during frustrating and threatening events, inviting exploration of physiological arousal to measure responses to emotional challenges. Furthermore, this study advances the understanding of precursors to emotional and behavioral problems common in older children with autism.

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28. Yang D, Robertson HL, Condliffe EG, Carter MT, Dewan T, Gnanakumar V. Rehabilitation therapies in Rett syndrome across the lifespan : A scoping review of human and animal studies. J Pediatr Rehabil Med ;2020 (Aug 28)

PURPOSE : To perform a scoping review of the evidence for therapeutic interventions to manage functional impairments associated with Rett syndrome (RTT) throughout the lifespan. METHODS : MEDLINE, EMBASE, PsycINFO, CENTRAL, CINAHL, Scopus and Index to Chiropractic Literature were searched systematically up to December 2019. Two investigators independently reviewed all search results and extracted those that met the inclusion criteria. Human and animal model studies pertaining to therapies that increase functional ability or treat RTT-associated symptoms in all age groups were included. Relevant studies were grouped into intervention categories and rated using the Oxford Centre of Evidence Based Medicine Levels of Evidence. Demographics of participants, interventions, and outcomes were summarized. RESULTS : Ninety-one articles representing 88 studies met the inclusion criteria, of which 80 were human clinical studies and eight were studies using animal models. Study designs were primarily case series and only six studies involved participants above the age of 40. CONCLUSION : A small number of rigorously studied rehabilitation interventions have been published. Published studies aim to address a wide variety of functional impairments. Research regarding implementation of therapies for older patients with RTT is lacking and requires further exploration.

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29. Yarger HA, Redcay E. A conceptual model of risk and protective factors associated with internalizing symptoms in autism spectrum disorder : A scoping review, synthesis, and call for more research. Dev Psychopathol ;2020 (Sep 7):1-19.

This paper reviews and synthesizes key areas of research related to the etiology, development, and maintenance of internalizing symptoms in children, adolescents, and adults with autism spectrum disorder (ASD). In developing an integrated conceptual model, we draw from current conceptual models of internalizing symptoms in ASD and extend the model to include factors related to internalizing within other populations (e.g., children that have experienced early life stress, children with other neurodevelopmental conditions, typically developing children) that have not been systematically examined in ASD. Our review highlights the need for more research to understand the developmental course of internalizing symptoms, potential moderators, and the interplay between early risk and protective factors. Longitudinal studies incorporating multiple methods and both environmental and biological factors will be important in order to elucidate these mechanisms.

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30. Yusuf A, Peltekova I, Savion-Lemieux T, Frei J, Joober R, Howe J, Scherer SW, Elsabbagh M. Adaptation and validation of the Genetic Counseling Outcome Scale for autism spectrum disorders and related conditions. J Genet Couns ;2020 (Sep 6)

The genetics care pathway experienced by families affected by autism spectrum disorder (ASD) around the time of diagnosis is currently uncharacterized and potentially variable across contexts. The lack of consensus on outcome measures to capture the impact of genetic services for these families shows a gap in understanding and optimizing this genetics care pathway. The Genetic Counseling Outcome Scale (GCOS-24) is a validated outcome measure of clinical genetics services. The current study aims to adapt and validate the GCOS-24 as an outcome measure in the context routine genetic testing in ASD and related conditions. Families seen for their child’s developmental evaluation for ASD and related conditions were invited to participate in a genomics cohort between 2016 and 2018. Families (n = 111) completed the mGCOS-24 (modified GCOS-24), adapted from the original GCOS-24 by clinicians working in the target population’s routine care pathway. The mGCOS-24 has acceptable internal consistency (Cronbach’s α = 0.84) and high test-retest reliability (ICC = 0.88). It also inversely correlates with stress as measured by Perceived Stress Scale (PSS-10) and distress, as measured by the Distress Thermometer, rs ≥ 0.39, ps < 0.001. The mGCOS-24 had adequate readability, as supported by cognitive interviews completed by a sub-sample of five mothers of a child with ASD. Together, our findings show that the mGCOS-24 has good validity for the target population. Preliminary characterization of the genetics care pathway in this population revealed remarkable variability in pre-test counseling and limited post-test counseling. The use of the mGCOS-24 as an outcome measure is useful in filling some of these gaps by offering a way to assess, and in the future, optimize the genetics care pathway for families affected by autism and related neurodevelopmental conditions.

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