1. Baweja R, Brown SL, Edwards EM, Murray MJ. COVID-19 Pandemic and Impact on Patients with Autism Spectrum Disorder. J Autism Dev Disord. 2021 : 1-10.

The COVID-19 infectious disease pandemic has caused significant fear and uncertainty around the world and had significant adverse psychological impact. Children, adolescents and adults with autism spectrum disorder (ASD) are a particularly vulnerable population, impacted by stay-at-home orders, closures at nonessential services, and social distancing standards. This commentary describes various challenges faced by individuals with ASD in the United States including disruptions caused by educational and vocational changes, challenges to home and leisure routines, limited access to behavioral health services and changes in health services delivery due to the pandemic. We highlight the need for ongoing skills development for individuals and development within systems to better respond to needs of the ASD population in future emergencies.

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2. Brooks JD, Arneja J, Fu L, Saxena FE, Tu K, Pinzaru VB, Anagnostou E, Nylen K, Saunders NR, Lu H, McLaughlin J, Bronskill SE. Assessing the validity of administrative health data for the identification of children and youth with autism spectrum disorder in Ontario. Autism Res. 2021.

Population-level identification of children and youth with ASD is essential for surveillance and planning for required services. The objective of this study was to develop and validate an algorithm for the identification of children and youth with ASD using administrative health data. In this retrospective validation study, we linked an electronic medical record (EMR)-based reference standard, consisting 10,000 individuals aged 1-24 years, including 112 confirmed ASD cases to Ontario administrative health data, for the testing of multiple case-finding algorithms. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and corresponding 95% confidence intervals (CI) were calculated for each algorithm. The optimal algorithm was validated in three external cohorts representing family practice, education, and specialized clinical settings. The optimal algorithm included an ASD diagnostic code for a single hospital discharge or emergency department visit or outpatient surgery, or three ASD physician billing codes in 3 years. This algorithm’s sensitivity was 50.0% (95%CI 40.7-88.7%), specificity 99.6% (99.4-99.7), PPV 56.6% (46.8-66.3), and NPV 99.4% (99.3-99.6). The results of this study illustrate limitations and need for cautious interpretation when using administrative health data alone for the identification of children and youth with ASD. LAY SUMMARY : We tested algorithms (set of rules) to identify young people with ASD using routinely collected administrative health data. Even the best algorithm misses more than half of those in Ontario with ASD. To understand this better, we tested how well the algorithm worked in different settings (family practice, education, and specialized clinics). The identification of individuals with ASD at a population level is essential for planning for support services and the allocation of resources.

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3. Bürki L, Höfer J, Kamp-Becker I, Poustka L, Roessner V, Stroth S, Wolff N, Hoffmann F, Bachmann C. Special educational support in children and adolescents with Autism Spectrum Disorder in Germany : Results from a parent survey. Res Dev Disabil. 2021 ; 112 : 103931.

OBJECTIVE : Children and adolescents with Autism Spectrum Disorder (ASD) often receive special educational support (SES). This study aimed to evaluate SES prevalence in children and adolescents with ASD in Germany. METHODS : A mail survey was distributed to the caregivers of 637 children and adolescents recruited at three German ASD outpatient clinics. RESULTS : Among the 211 respondents (response : 33.1 %), 82.5 % were provided with a special educational needs statement, and 63.9 % received special education, most of them attending a public special school (57.9 %). The most frequently indicated additional support was a classroom assistant (69.0 %), followed by smaller learning groups (31.7 %). Special education was less frequently provided to individuals with Asperger syndrome than to those with childhood or atypical autism (36.0 %, 76.1 %, and 63.4 %, respectively). Using logistic regression analysis, receiving special education was significantly associated with lower IQ (<85) (Odds Ratio (OR) : 8.72 ; 95 % confidence interval (CI) : 3.41-22.32) and younger age (≤11 years, OR : 2.87 ; 95 % CI : 1.11-7.38), but not with ASD symptom severity. CONCLUSIONS : The majority of children and adolescents with ASD received SES, indicating a satisfactory supply of such services in Germany. The finding that lower IQ but not ASD symptom severity predicted access to SES raises questions about the specificity of the used selection criteria.

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4. Dellapiazza F, Audras-Torrent L, Michelon C, Baghdadli A. Clinical characteristics of children with ASD and comorbid ADHD : Association with social impairment and externalizing and internalizing behaviours. Res Dev Disabil. 2021 ; 113 : 103930.

BACKGROUND : Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are frequently occurring conditions that are often associated (ASD + ADHD). However, there are few comparative studies concerning the clinical presentation in patients formally diagnosed with both ASD and ADHD. Here, we aimed to 1) compare social impairment and externalizing/internalizing behavioural problems across four groups of children : ASD + ADHD, ASD alone, ADHD alone, and typical development and 2) examine their bidirectional relationship with ASD and/or ADHD symptoms. METHODS : This study included 186 participants from 6 to 12 years of age : single ASD (n = 98), ASD + ADHD (n = 29), single ADHD (n = 28), and TD (n = 31). RESULTS : The results showed that children in the ASD + ADHD and single ASD groups had a higher level of social impairment than those in the single ADHD group. In addition, children in the single ADHD group presented a greater attention deficit than those in the single ASD group. Externalizing /internalizing behaviours were more frequent in all groups with neuro-developmental disorders than in typical development. In addition, externalizing behavioural problems were related to ADHD severity in the ASD + ADHD and single ADHD groups, whereas internalizing behaviours were related to ASD severity. CONCLUSIONS : These findings highlight the specific needs of children who have both ASD and ADHD and underscore the necessity of individualizing their interventions.

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5. Du RY, Yang W, Lam PPY, Yiu CKY, McGrath CP. Developing a Toothbrushing Visual Pedagogy (TBVP) for Preschool Children with Autism Spectrum Disorder. J Autism Dev Disord. 2021.

Visual pedagogy and social stories have been widely used to assist children with Autism Spectrum Disorder (ASD) in learning various skills. A toothbrushing visual pedagogy (TBVP) was developed adapting existing toothbrushing social stories for children with ASD. This TBVP consists of 13 toothbrushing steps with scripts describing the toothbrushing technique. To evaluate its feasibility, a review panel was formed to provide feedback on the TBVP and three other published toothbrushing social stories. Effectiveness of the TBVP was further evaluated among 119 preschool children with ASD with significant improvements in toothbrushing skills observed at 3-month and 6-month follow-ups. It is concluded that TBVP is a feasible and an effective educational means that assists children with ASD in learning toothbrushing skills.

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6. Ghosn F, Navalón P, Pina-Camacho L, Almansa B, Sahuquillo-Leal R, Moreno-Giménez A, Diago V, Vento M, García-Blanco A. Early signs of autism in infants whose mothers suffered from a threatened preterm labour : a 30-month prospective follow-up study. Eur Child Adolesc Psychiatry. 2021.

Infants born after a threatened preterm labour (TPL infants) are at high risk of autism spectrum disorder (ASD). Studying this population may provide insight on the pathophysiological underpinnings of this condition. This study aimed to (i) ascertain the presence and autistic symptom load in TPL infants aged age 30 months relative to non-TPL infants, regardless of preterm birth ; (ii) explore the association between early (at 6 months) psychomotor development and temperament features with the autistic symptom load of TPL infants at age 30 months and (iii) examine the association among perinatal risk factors for ASD development with the autistic symptom load of TPL infants at age 30 months. A group of 111 mother-infant pairs recruited at TPL diagnosis and a group of 47 healthy mother-infant controls completed the follow-up. Irrespective of preterm birth, TPL infants showed higher autistic symptom load at age 30 months than non-TPL infants. TPL infants presented poorer communication and problem-solving skills, reduced smiling and laughter, and greater vocal reactivity at age 6 months, predicting higher autistic symptom load at age 30 months. Higher levels of anxiety symptoms in TPL mothers after a TPL diagnosis also predicted higher autistic symptom load for the infants at age 30 months. These results suggest that TPL infants may be an undescribed cluster, with features that differentiate them from other « at-risk » populations. These findings support the need for routine assessment of TPL infants and screening of anxiety symptoms in mothers.

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7. Hammill C, Lerch JP, Taylor MJ, Ameis SH, Chakravarty MM, Szatmari P, Anagnostou E, Lai MC. Quantitative and Qualitative Sex-Modulations in the Brain Anatomy of Autism. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021.

BACKGROUND : Sex-based neurobiological heterogeneity in autism is poorly understood. Research is disproportionately biased to males, leading to an unwarranted presumption that autism neurobiology is the same across sexes. Previous neuroimaging studies using amalgamated multi-center datasets to increase autistic female samples are characterized by large statistical noise. METHODS : We used a better-powered dataset of 1,183 scans of 839 individuals-299 (467 scans) autistic males, 74 (102 scans) autistic females, 240 (334 scans) control males and 226 (280 scans) control females-to test two whole-brain models of overall/global sex-modulations on autism neuroanatomy, by summary measures computed across the brain : local magnitude model, where the same brain regions/circuitries are involved across sexes but effect sizes are larger in females, indicating quantitative sex-modulation ; and spatial dissimilarity model, where the neuroanatomy differs spatially between sexes, indicating qualitative sex-modulation. The male and female autism groups were matched on age, IQ and autism symptoms. Autism brain features were defined by comparisons to same-sex controls. RESULTS : Across five metrics (cortical thickness, surface area, volume, mean absolute curvature, and subcortical volume), we found no evidence supporting the local magnitude model. We found indicators supporting the spatial dissimilarity model on cortical mean absolute curvature and subcortical volume, but not other metrics. CONCLUSIONS : The overall/global autism neuroanatomy in females and males does not simply differ quantitatively in the same brain regions/circuitries. They may differ qualitatively in spatial involvement in cortical curvature and subcortical volume. The neuroanatomy of autism may be partly sex-specific. Sex-stratification to inform autism preclinical/clinical research is needed to identify sex-informed neurodevelopmental targets.

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8. Joon P, Kumar A, Parle M. What is autism ?. Pharmacological reports : PR. 2021.

The term « Autism spectrum disorder » (ASD), in vogue at present, has evolved after continual substantial developments taking place over more than a century. ASD is a heterogeneous, multi-factorial, developmental disability in which an unusual pattern of development takes place during infant and toddler years. As per DSM-5, Autism spectrum disorder is a combined phrase for a family of complex developmental disabilities inclusive of « Autistic Disorder, Pervasive Developmental Disorder not Otherwise Specified (PDD-NOS), and Asperger’s Disorder ». « ASD is characterized not only by persistent impairments in reciprocal social communication and social interactions, but is also manifested by restricted, repetitive patterns of behavior, interests, or activities ». The classical clinical signs that exist in two major domains, viz. the ‘social domain’ and the ‘behavioral domain’ for the precise diagnosis of ASD have been tabulated and major differences between DSM-5 and DSM-4 are depicted with the help of a figure in this basic review article. A sharp rise in the incidence of ASD cases has been observed worldwide owing to various risk factors such as genetic predisposition coupled with adverse environmental conditions, gynecological interventions, etc. Two official manuals viz. the « Diagnostic and Statistical Manual of Mental Disorders » (DSM) (published by the American Psychiatric Association), and the « International Classification of Diseases » (ICD) (published by the World Health Organization) is being regularly updated to facilitate diagnosis of ASD. ICD-11 guidelines being prospectively implemented with effect from January 2022 have attracted global attention.

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9. Kalandadze T, Braeken J, Brynskov C, Næss KB. Metaphor Comprehension in Individuals with Autism Spectrum Disorder : Core Language Skills Matter. J Autism Dev Disord. 2021.

Poor metaphor comprehension was considered a hallmark of autism spectrum disorder (ASD), but recent research has questioned the extent and the sources of these difficulties. In this cross-sectional study, we compared metaphor comprehension in individuals with ASD (N = 29) and individuals with typical development (TD ; N = 31), and investigated the relationship between core language and metaphor comprehension. Individuals with ASD showed more difficulty but also a more variable performance in both metaphor and literal items of the task used than individuals with TD did. This indicates that core language ability accounts for metaphor comprehension and should be considered in future research and interventions aiming to improve metaphor comprehension in individuals with ASD.

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10. Liu KX, Sethi RV, Pulsifer MB, D’Gama AM, LaVally B, Ebb DH, Tarbell NJ, Yock TI, MacDonald SM. Clinical outcomes of pediatric patients with autism spectrum disorder and other neurodevelopmental disorders and intracranial germ cell tumors. Pediatric blood & cancer. 2021 : e28935.

INTRODUCTION : Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Given the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs) in patients with IGCTs and characterized outcomes for patients with NDD and IGCTs. METHODS : A retrospective review of medical records was conducted for 111 patients diagnosed with IGCTs between 1998 and 2018 and evaluated at the Massachusetts General Hospital. Kaplan-Meier method and log-rank test was used for survival analyses. Cox regression analyses were performed for parameters associated with progression-free survival (PFS). RESULTS : Median age at IGCT diagnosis was 12.8 years (range : 4.3-21.7) and median follow-up was 6.5 years (range : 0.2-20.5). Eighteen patients were diagnosed with NDDs prior to IGCT diagnosis, including five patients with autism spectrum disorder (ASD). Of the 67 patients with pure germinomas, four (6.0 %) had prior ASD diagnoses. Patients with NDD had significantly inferior PFS in the nongerminomatous germ cell tumor (NGGCT) cohort. On univariate and multivariable analyses, craniospinal irradiation (CSI) was significantly associated with improved PFS in the NGGCT cohort. CONCLUSIONS : Our study found an ASD prevalence in the pure germinoma cohort more than threefold greater than the national prevalence, suggesting an association between ASD and pure germinomas. Furthermore, patients with NDD and NGGCT had worse PFS, possibly due to fewer patients with NDD receiving CSI. Future prospective studies with larger cohorts are needed to examine associations between NDDs and IGCTs, and further characterize outcomes for patients with NDDs and IGCTs.

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11. Nezgovorova V, Ferretti CJ, Taylor BP, Shanahan E, Uzunova G, Hong K, Devinsky O, Hollander E. Potential of cannabinoids as treatments for autism spectrum disorders. Journal of psychiatric research. 2021 ; 137 : 194-201.

Current treatments for autism spectrum disorders (ASD) are limited in efficacy and are often associated with substantial side effects. These medications typically ameliorate problem behaviors associated with ASD, but do not target core symptom domains. As a result, there is a significant amount of research underway for development of novel experimental therapeutics. Endocannabinoids are arachidonic acid-derived lipid neuromodulators, which, in combination with their receptors and associated metabolic enzymes, constitute the endocannabinoid (EC) system. Cannabinoid signaling may be involved in the social impairment and repetitive behaviors observed in those with ASD. In this review, we discuss a possible role of the EC system in excitatory-inhibitory (E-I) imbalance and immune dysregulation in ASD. Novel treatments for the core symptom domains of ASD are needed and phytocannabinoids could be useful experimental therapeutics for core symptoms and associated domains.

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12. Schwartzman JM, Hardan AY, Gengoux GW. Parenting stress in autism spectrum disorder may account for discrepancies in parent and clinician ratings of child functioning. Autism. 2021 : 1362361321998560.

Elevated parenting stress among parents of children with autism spectrum disorder is well-documented ; however, there is limited information about differences in parenting stress and potential relationships with parent ratings of child functioning. The aim of this study was to explore profiles of parenting stress among 100 parents of young children with autism spectrum disorder enrolled in two clinical trials and to explore relationships between parenting stress level and parent ratings of child functioning before treatment. Secondary aims examined differential patterns of association between parenting stress profiles and parent versus clinician ratings of child functioning. We show that stress may influence parent ratings of certain child behaviors (e.g. problem behaviors) and not others (e.g. language), yet clinician ratings of these same children do not differ. This new understanding of parenting stress has implications for parent-rated measures, tracking treatment outcome, and the design of clinical trials.

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13. Siyambalapitiya S, Paynter J, Nair VKK, Reuterskiöld C, Tucker M, Trembath D. Longitudinal Social and Communication Outcomes in Children with Autism Raised in Bi/Multilingual Environments. J Autism Dev Disord. 2021.

Globally, there are more bilingual speakers than monolingual speakers ; however, scant research evidence exists regarding social communication development and outcomes for bilingual children with autism spectrum disorder (ASD). A stronger evidence base will facilitate health professionals and educators providing accurate recommendations regarding language use. This study employed a longitudinal cohort design to compare social and communication skills, at baseline and over 12 months, for 60 monolingual and 60 bilingual children with ASD receiving community based early intervention. We found few differences at intake, and no difference in the magnitude of change over 12 months for this cohort. Findings support the notion that there is no basis on which to discourage home language use with bilingual children with ASD.

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14. Temelturk RD, Yurumez E, Cıkılı Uytun M, Oztop DB. Parent-child interaction, parental attachment styles and parental alexithymia levels of children with ASD. Res Dev Disabil. 2021 ; 112 : 103922.

AIM : Given the recent findings regarding the increased evidence for the presence of the alexithymia in parents of children with autism spectrum disorder (ASD), the construct of alexithymia in parents of children with ASD and its effect on adult romantic attachment style of parents, family functioning and parent-child relationship were investigated. METHODS : The sample included children diagnosed as having ASD, developmental delay (DD), and 27 typically developing children aged 1-5 years and their parents. The Crowell procedure, an observational and structured assessment was performed, and the quality of the parent-child relationship was assessed using the Parent-Infant Relationship-Global Assessment Scale (PIR-GAS) based on DC : 0-5. The Toronto Alexithymia Scale-20, Experiences in Close Relationships Revised, and the Family Assessment Device were administered to the parents. RESULTS : PIR-GAS scores were lower in the ASD group compared with the scores of the other groups. Family functioning rated by fathers of children with DD was lower than in the other groups. However, there was no significant difference between the groups in terms of alexithymia levels, and parent’s own attachment styles in romantic relationships. CONCLUSIONS : ASD was found to be an independent predictor for disordered relationship between children and their parents. Appropriate family interventions focusing on enhancing social interaction and emotional development may be beneficial in the treatment of ASD.

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