1. Cervantes PE, Matheis M, Estabillo J, Seag DEM, Nelson KL, Peth-Pierce R, Hoagwood KE, Horwitz SM. {{Trends Over a Decade in NIH Funding for Autism Spectrum Disorder Services Research}}. {J Autism Dev Disord}. 2020.
Investments in autism spectrum disorder (ASD) research, guided by the Interagency Autism Coordinating Committee (IACC), have focused disproportionately on etiology over a well-established stakeholder priority area: research to improve accessibility and quality of community-based services. This study analyzed National Institutes of Health ASD services research funding from 2008 to 2018 to examine funding patterns, evaluate the impact of IACC objectives, and identify future directions. Approximately 9% of total funds were allocated to services research. This investment remained relatively stable across time and lacked diversity across domains (e.g., area of focus, ages sampled, implementation strategies used). While advancements were observed, including increased prevalence of projects focused on adult samples and on dissemination/implementation and prevention areas, greater investment in service research is critically needed.
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2. Corbett BA, Vandekar S, Muscatello RA, Tanguturi Y. {{Pubertal Timing During Early Adolescence: Advanced Pubertal Onset in Females with Autism Spectrum Disorder}}. {Autism Res}. 2020.
Autism spectrum disorder (ASD) is characterized by impaired social communication and poor adaptation to change; thus, the onset of puberty may be a pivotal transition. This cross-sectional study measured pubertal timing to examine hypothesized differences for sex (female vs. male) and group (ASD vs. typical development [TD]). Participants included 239 children (137 ASD, 102 TD) between 10 and 13 years. The ASD group included 35 females and 102 males; the TDs included 44 females and 58 males. Pubertal onset measured by genital or pubic stage was investigated with linear regression using main effects of sex and age-by-sex interactions in TD and ASD groups and main effects of diagnosis and diagnosis-by-age interactions in males and females, controlling for body mass index, socioeconomic status, and race. In TD, examination of main effects for genital (penis/breast) stage showed no difference for male and female children (t = 1.33, P = 0.187, rdf = 92); however, there were significant differences in ASD (t = 2.70, P = 0.008, rdf = 121). For diagnosis modeled separately by sex, there was significantly earlier pubertal development in females with ASD (t = 1.97, P = 0.053, rdf = 70, but not males (t = 1.329, P = 0.186, rdf = 143). In addition, analysis of menses revealed females with ASD had significantly earlier onset than TD (t = -2.56, P = 0.018, rdf = 21). Examination of pubic stage revealed expected sex differences for TD (t = 2,674, P = 0.009, rdf = 91) and ASD (t = 3.482, P = 0.001, rdf = 121). Females with ASD evidence advanced pubertal onset relative to ASD males and TD females. Findings underscore the need for enhanced understanding of pubertal development in ASD, as differences may have significant psychological, social, physiological, and developmental consequences. LAY SUMMARY: Children with autism spectrum disorder (ASD) have difficulty with social communication and respond poorly to change, which may include the onset and course of puberty. The study measured the timing of puberty in 239 children (137 ASD and 102 typical development [TD]) between 10 and 13 years based on pubertal stage of genital (breast/penis) and pubic hair development. Females with ASD evidence advanced pubertal onset relative to ASD males and TD females. Findings underscore the need for an enhanced understanding of pubertal development in ASD.
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3. Hart LC. {{Improving Transition to Adult Care for Those With Developmental Disabilities: An Unclear Path}}. {Pediatrics}. 2020.
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4. Hirota T, McElroy E, So R. {{Network Analysis of Internet Addiction Symptoms Among a Clinical Sample of Japanese Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2020.
In the present study, we employed network analysis that conceptualizes internet addiction (IA) as a complex network of mutually influencing symptoms in 108 adolescents with autism spectrum disorder (ASD) to examine the network architecture of IA symptoms and identify central/influential symptoms. Our analysis revealed that defensive and secretive behaviors and concealment of internet use were identified as central symptoms in this population, suggesting that mitigating these symptoms potentially prevent the development and/or maintenance of IA in adolescents with ASD. Providing adolescents and their caregivers with psychoeducation on the role of central symptoms above in IA can be a salient intervention. Doing so may facilitate nonconflicting conversations between them about adolescents’ internet use and promote more healthy adolescents’ internet use behavior.
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5. Li D, Choque-Olsson N, Jiao H, Norgren N, Jonsson U, Bölte S, Tammimies K. {{The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder}}. {NPJ genomic medicine}. 2020; 5: 45.
Social skills group training (SSGT) is a frequently used behavioral intervention in autism spectrum disorder (ASD), but the effects are moderate and heterogeneous. Here, we analyzed the effect of polygenic risk score (PRS) and common variants in gene sets on the intervention outcome. Participants from the largest randomized clinical trial of SSGT in ASD to date were selected (N = 188, 99 from SSGT, 89 from standard care) to calculate association between the outcomes in the SSGT trial and PRSs for ASD, attention-deficit hyperactivity disorder (ADHD), and educational attainment. In addition, specific gene sets were selected to evaluate their role on intervention outcomes. Among all participants in the trial, higher PRS for ADHD was associated with significant improvement in the outcome measure, the parental-rated Social Responsiveness Scale. The significant association was due to better outcomes in the standard care group for individuals with higher PRS for ADHD (post-intervention: β = -4.747, P = 0.0129; follow-up: β = -5.309, P = 0.0083). However, when contrasting the SSGT and standard care group, an inferior outcome in the SSGT group was associated with higher ADHD PRS at follow-up (β = 6.67, P = 0.016). Five gene sets within the synaptic category showed a nominal association with reduced response to interventions. We provide preliminary evidence that genetic liability calculated from common variants could influence the intervention outcomes. In the future, larger cohorts should be used to investigate how genetic contribution affects individual response to ASD interventions.
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6. Qiu C, Lin JC, Shi JM, Chow T, Desai VN, Nguyen VT, Riewerts RJ, Feldman RK, Segal S, Xiang AH. {{Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring}}. {JAMA Pediatr}. 2020.
IMPORTANCE: Although the safety of labor epidural analgesia (LEA) for neonates has been well documented, the long-term health effects of LEA on offspring remain to be investigated. OBJECTIVE: To assess the association between maternal LEA exposure and risk of autism spectrum disorders (ASDs) in offspring. DESIGN, SETTING, AND PARTICIPANTS: Data for this retrospective longitudinal birth cohort study were derived from electronic medical records from a population-based clinical birth cohort. A total of 147 895 singleton children delivered vaginally between January 1, 2008, and December 31, 2015, in a single integrated health care system were included. Children were followed up from the age of 1 year until the first date of the following occurrences: clinical diagnosis of ASD, last date of health plan enrollment, death, or the study end date of December 31, 2018. EXPOSURES: Use and duration of LEA. MAIN OUTCOMES AND MEASURES: The main outcome was clinical diagnosis of ASD. Cox proportional hazards regression analysis was used to estimate the hazard ratio (HR) of ASD associated with LEA exposure. RESULTS: Among the cohort of 147 895 singleton children (74 425 boys [50.3%]; mean [SD] gestational age at delivery, 38.9 [1.5] weeks), 109 719 (74.2%) were exposed to maternal LEA. Fever during labor was observed in 13 055 mothers (11.9%) in the LEA group and 510 of 38 176 mothers (1.3%) in the non-LEA group. Autism spectrum disorders were diagnosed in 2039 children (1.9%) in the LEA group and 485 children (1.3%) in the non-LEA group. After adjusting for potential confounders, including birth year, medical center, maternal age at delivery, parity, race/ethnicity, educational level, household income, history of comorbidity, diabetes during pregnancy, smoking during pregnancy, preeclampsia or eclampsia, prepregnancy body mass index, gestational weight gain, gestational age at delivery, and birth weight, the HR associated with LEA vs non-LEA exposure was 1.37 (95% CI, 1.23-1.53). Relative to the unexposed group, the adjusted HR associated with LEA exposure of less than 4 hours was 1.33 (95% CI, 1.17-1.53), with LEA exposure of 4 to 8 hours was 1.35 (95% CI, 1.20-1.53), and with LEA exposure of more than 8 hours was 1.46 (95% CI, 1.27-1.69). Within the LEA group, there was a significant trend of ASD risk associated with increasing duration of LEA exposure after adjusting for covariates (HR for linear trend, 1.05 [95% CI, 1.01-1.09] per 4 hours). Adding fever to the model did not change the HR estimate associated with LEA exposure (adjusted HR for LEA vs non-LEA, 1.37 [95% CI, 1.22-1.53]). CONCLUSIONS AND RELEVANCE: This study suggests that maternal LEA may be associated with increased ASD risk in children. The risk appears to not be directly associated with epidural-related maternal fever.
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7. Rajagopal S, Nicholson K, Putri TR, Addington J, Felde A. {{Teaching children with autism to tact private events based on public accompaniments}}. {Journal of applied behavior analysis}. 2020.
We evaluated a method for teaching children with autism spectrum disorder to respond to tactile stimulation of multiple body parts. Various objects (e.g., hairbrush) produced the sensations (e.g., prickly). In a multiple baseline design across participants, participants learned 9 sensation body part tacts and the evaluation concluded with tests of generalization to 3 novel body parts, 6 novel objects, and 3 novel sensations. Participants demonstrated generalization to novel objects, and to a lesser extent, novel body parts, but did not generalize tacts to novel sensations. These findings are discussed in terms of implications for teaching children with autism to tact sensations.
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8. Sacai H, Sakoori K, Konno K, Nagahama K, Suzuki H, Watanabe T, Watanabe M, Uesaka N, Kano M. {{Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex}}. {Nat Commun}. 2020; 11(1): 5140.
Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interaction and induced mild vocalization abnormality. Although the causes of reduced excitatory transmission were different, pharmacological enhancement of AMPA receptor function effectively restored impaired social behavior in both CNTNAP2- and AHI1-knockdown mice. We conclude that reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons of the PFC leads to impaired social interaction and mild vocalization abnormality in mice.
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9. Sappok T, Heinrich M, Böhm J. {{The impact of emotional development in people with autism spectrum disorder and intellectual developmental disability}}. {J Intellect Disabil Res}. 2020.
BACKGROUND: Intellectual developmental disabilities (IDDs) and autism spectrum disorders (ASDs) are developmental conditions, which may also be associated with impairments in emotional development (ED). ED can be assessed using the Scale of Emotional Development – Short (SED-S), a five-stage model consisting of eight domains, which allows to study the relationship between ASD and ED in people with IDD. METHODS: In this retrospective study, the level of ED was compared in 327 adults with IDD with [n = 83; mean age 38.3 years; level of IDD: mild (6), moderate (21), severe (45) and profound (11)] and without [n = 244, mean age 36.9 years; level of IDD: mild (67), moderate (73), severe (68) and profound (36)] ASD. The discriminative ability of the SED-S was determined by a regression in a training and a validation sample. RESULTS: The level of ED correlated with the severity of IDD (r(s) = -.654) and the presence of ASD (r(s) = -.316). People with additional ASD showed lower levels of ED compared with those with IDD only (mean reference ages 7-18 vs 19-36 months). The developmental profiles were equally balanced in ASD and IDD-only. A regression analysis revealed three domains (‘Relating-to-Peers’, ‘Differentiating-Emotions’, and ‘Regulating-Affect’) to be useful for ASD assignment (AUC > 0.70, sensitivity 0.76-0.80, specificity 0.62-0.63). CONCLUSIONS: In people with IDD, additional ASD was associated with delays in ED, which may be considered in diagnostics, treatment and care.
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10. Simacek J, Elmquist M, Dimian AF, Reichle J. {{Current Trends in Telehealth Applications to Deliver Social Communication Interventions for Young Children with or at Risk for Autism Spectrum Disorder}}. {Current developmental disorders reports}. 2020: 1-9.
PURPOSE OF REVIEW: Early, intensive, and high-quality interventions can often improve social communication outcomes for children with autism spectrum disorder (ASD). Many children experience barriers to intervention, resulting in significant delays to intervention onset or missed opportunities for intervention altogether. With constant advances in technology, the field is experiencing a rapid increase in investigation of telehealth applications to intervention delivery. This article highlights the current trends in social communication intervention via telehealth used in early intervention practices for children with ASD over the past 5 years, including a brief review of studies (from 2014 to January 2020) and our team’s experiences in this area. RECENT FINDINGS: Based on our experience and the 22 studies we identified in this area, we describe the current trends in telehealth applications used and how interventions were delivered. We also provide recommendations, limitations, and future directions on this topic. SUMMARY: Telehealth offers innovative intervention delivery options by increasing intervention access, overcoming barriers such as geography and costs of service delivery for young children with ASD.
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11. Sulaiman R, Wang M, Ren X. {{Exposure to Aluminum, Cadmium, and Mercury and Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis}}. {Chemical research in toxicology}. 2020.
Autism spectrum disorder (ASD) is a complex neurobehavioral disorder that is believed to be multifactorial in origin. As the incidence of ASD is rising along with industrialization, and because certain metals have been linked to neurological problems, it is important to consider whether such metals may play a role in the development of ASD. Previously, we performed a meta-analysis of existing literature to examine the potential link between inorganic arsenic and lead exposure and ASD. This is a continuation of that study investigating the association of the exposure to aluminum (Al), cadmium (Cd), and mercury (Hg) and ASD. These metals were chosen because they are abundant in our environment, are known to cause neurological problems in humans, and have multiple published studies examining their potential links with ASD. Following the same approach as our previous paper, we conducted a systematic review of the existing literature and performed a meta-analysis to evaluate the current evidence regarding these metals and their potential relationship with autism. We reviewed 18 studies on Al, 18 on Cd, and 23 on Hg, and the individual studies showed inconsistent results. When the measurements were integrated into the meta-analysis, we found significant associations between all the metals and ASD, but the associations were not always in the same direction. Levels of Hg in hair, urine, and blood were all positively associated with ASD. Levels of Al in hair and urine were positively associated with ASD, while levels of Al in blood were negatively associated. In comparison, levels of Cd in hair and urine were negatively associated with ASD. These results imply that, while these metals are all neurotoxic, their impact on the development of ASD and their modes of action could be different. Further research is warranted to examine the longitudinal effects of these toxic metals on the risk of ASD, to assess the critical period when exposure may affect development, and to investigate potential factors that may enhance or ameliorate the effect of metals. Overall, these findings support policies that advocate limiting exposure to neurotoxic metals, particularly for pregnant women and young children, in order to help reduce the rising incidence of ASD.
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12. Tran XA, McDonald N, Dickinson A, Scheffler A, Frohlich J, Marin A, Kure Liu C, Nosco E, Senturk D, Dapretto M, Spurling Jeste S. {{Functional connectivity during language processing in 3-month-old infants at familial risk for autism spectrum disorder}}. {Eur J Neurosci}. 2020.
Auditory statistical learning (ASL) plays a role in language development and may lay a foundation for later social communication impairment. As part of a longitudinal study of infant siblings, we asked whether electroencephalography (EEG) measures of connectivity during ASL at 3 months of age differentiated infants who showed signs of autism spectrum disorder (ASD) at age 18 months. We measured spectral power and phase coherence in the theta (4-6 Hz) and alpha (6-12 Hz) frequency bands within putative language networks. Infants were divided into ASD-concern (n = 14) and No-ASD-concern (n = 49) outcome groups based on their ASD symptoms at 18 months, measured using the Autism Diagnostic Observation Scale Toddler Module. Using permutation testing, we identified a trend towards reduced left fronto-central phase coherence at the electrode pair F9-C3 in both theta and alpha frequency bands in infants who later showed ASD symptoms at 18 months. Across outcome groups, alpha coherence at 3 months correlated with greater word production at 18 months on the MacArthur-Bates Communicative Development Inventory. This study introduces signal processing and analytic tools that account for the challenges inherent in infant EEG studies, such as short duration of recordings, considerable movement artifact and variable volume conduction. Our results indicate that connectivity, as measured by phase coherence during 2.5 minutes of ASL, can be quantified as early as 3 months and suggest that early alternations in connectivity may serve as markers of resilience for neurodevelopmental impairments.
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13. Ward R, Sanoudaki E. {{Bilingualism in children with a dual diagnosis of Down syndrome and Autism Spectrum Disorder}}. {Clinical linguistics & phonetics}. 2020: 1-27.
Research shows that a substantial proportion of children with Down syndrome (DS) also meet the clinical criteria for Autism Spectrum Disorder (ASD). Children with this dual diagnosis display a linguistic profile that includes significant language delays and language impairments which often differ from the impairments observed in each developmental disability (DD) separately. Given the challenges observed with language acquisition for children with DS-ASD, concerns might be raised regarding the outcomes and suitability of a bilingual environment for children with this dual diagnosis specifically. The aim of this research was to explore the language profiles of four children with DS-ASD. A multiple case-study approach was employed. Four children with a confirmed DS-ASD diagnosis who had received exposure to two languages (English and Welsh) were assessed on a range of cognitive and linguistic measures. Performance was compared to three control groups; bilinguals with DS, English monolinguals with DS and mental age-matched typically developing bilinguals. Assessments comprised of expressive and receptive language, phonological awareness, working memory and non-verbal cognitive abilities. Considerable variability was found in the cognitive and linguistic profiles of the case-study participants. Children with DS-ASD displayed similar language profiles to that of the bilingual and monolingual children with DS in the areas tested, although performance was generally lower than that of the TD bilingual children. Although substantial variability was found, participants were developing bilingual abilities in a similar trajectory to children with DS in line with the degree of exposure to each language. This research highlights the need to assess bilingual children with complex dual diagnoses with an individualistic approach and carefully consider how to appropriately assess and treat bilingual children within speech and language therapy provisions.
