1. Au AH, Shum KK, Cheng Y, Tse HM, Wong RM, Li J, Au TK. {{Autism spectrum disorder screening in preschools}}. {Autism}. 2020: 1362361320967529.
With professional training and regular opportunities to observe children interacting with their peers, preschool teachers are in a good position to notice children’s autism spectrum disorder symptomatology. Yet even when a preschool teacher suspects that a child may have autism spectrum disorder, fear of false alarm may hold the teacher back from alerting the parents, let alone suggesting them to consider clinical assessment for the child. A valid and convenient screening tool can help preschool teachers make more informed and hence more confident judgment. We set out to develop a screening tool that capitalizes on peer interaction as a naturalistic « stress test » to identify children more likely than their peers to have autism spectrum disorder. A total of 304 3- to 4-year-olds were observed at school with an 84-item preliminary checklist; data-driven item reduction yielded a 13-item Classroom Observation Scale. The Classroom Observation Scale scores correlated significantly with Autism Diagnostic Observation Schedule-2 scores. To validate the scale, another 322 2- to 4-year-olds were screened using the Classroom Observation Scale. The screen-positive children and randomly selected typically developing peers were assessed for autism spectrum disorder 1.5 years later. The Classroom Observation Scale as used by teachers and researchers near preschool onset predicted autism spectrum disorder diagnoses 1.5 years later. This user-friendly 13-item Classroom Observation Scale enables teachers and healthcare workers with little or no clinical training to identify, with reliable and valid results, preschoolers more likely than their peers to have autism spectrum disorder.
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2. Buxbaum JD, Cutler DJ, Daly MJ, Devlin B, Roeder K, Sanders SJ. {{Not All Autism Genes Are Created Equal: A Response to Myers et al}}. {Am J Hum Genet}. 2020; 107(5): 1000-3.
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3. Carter CK, Hartley C. {{Are Children With Autism More Likely to Retain Object Names When Learning From Colour Photographs or Black-and-White Cartoons?}}. {J Autism Dev Disord}. 2020.
For the first time, this study investigated whether children with autism spectrum disorder (ASD) and typically developing (TD) children matched on language comprehension (M age equivalent = ~ 44 months) are more likely to retain words when learning from colour photographs than black-and-white cartoons. Participants used mutual exclusivity to fast map novel word-picture relationships and retention was assessed following a 5-min delay. Children with ASD achieved significantly greater retention accuracy when learning from photographs rather than cartoons and, surprisingly, responded more accurately than TD children when learning from photographs. Our results demonstrate that children with ASD benefit from greater iconicity when learning words from pictures, providing a data-grounded rationale for using colour photographs when administering picture-based interventions.
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4. Cunniff MM, Markenscoff-Papadimitriou E, Ostrowski J, Rubenstein JL, Sohal VS. {{Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz}}. {eLife}. 2020; 9.
Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozygous for Pogz, a high confidence autism gene. Pogz(+/-) mice exhibit reduced anxiety-related avoidance in the elevated plus maze (EPM). Theta-frequency communication between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) is known to be necessary for normal avoidance in the EPM. We found deficient theta-frequency synchronization between the vHPC and mPFC in vivo. When we examined vHPC-mPFC communication at higher resolution, vHPC input onto prefrontal GABAergic interneurons was specifically disrupted, whereas input onto pyramidal neurons remained intact. These findings illustrate how the loss of a high confidence autism gene can impair long-range communication by causing inhibitory circuit dysfunction within pathways important for specific behaviors.
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5. Guo H, Zhang Q, Dai R, Yu B, Hoekzema K, Tan J, Tan S, Jia X, Chung WK, Hernan R, Alkuraya FS, Alsulaiman A, Al-Muhaizea MA, Lesca G, Pons L, Labalme A, Laux L, Bryant E, Brown NJ, Savva E, Ayres S, Eratne D, Peeters H, Bilan F, Letienne-Cejudo L, Gilbert-Dussardier B, Ruiz-Arana IL, Merlini JM, Boizot A, Bartoloni L, Santoni F, Karlowicz D, McDonald M, Wu H, Hu Z, Chen G, Ou J, Brasch-Andersen C, Fagerberg CR, Dreyer I, Chun-Hui Tsai A, Slegesky V, McGee RB, Daniels B, Sellars EA, Carpenter LA, Schaefer B, Sacoto MJG, Begtrup A, Schnur RE, Punj S, Wentzensen IM, Rhodes L, Pan Q, Bernier RA, Chen C, Eichler EE, Xia K. {{NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism}}. {Am J Hum Genet}. 2020; 107(5): 963-76.
NCKAP1/NAP1 regulates neuronal cytoskeletal dynamics and is essential for neuronal differentiation in the developing brain. Deleterious variants in NCKAP1 have been identified in individuals with autism spectrum disorder (ASD) and intellectual disability; however, its clinical significance remains unclear. To determine its significance, we assemble genotype and phenotype data for 21 affected individuals from 20 unrelated families with predicted deleterious variants in NCKAP1. This includes 16 individuals with de novo (n = 8), transmitted (n = 6), or inheritance unknown (n = 2) truncating variants, two individuals with structural variants, and three with potentially disruptive de novo missense variants. We report a de novo and ultra-rare deleterious variant burden of NCKAP1 in individuals with neurodevelopmental disorders which needs further replication. ASD or autistic features, language and motor delay, and variable expression of intellectual or learning disability are common clinical features. Among inherited cases, there is evidence of deleterious variants segregating with neuropsychiatric disorders. Based on available human brain transcriptomic data, we show that NCKAP1 is broadly and highly expressed in both prenatal and postnatal periods and demostrate enriched expression in excitatory neurons and radial glias but depleted expression in inhibitory neurons. Mouse in utero electroporation experiments reveal that Nckap1 loss of function promotes neuronal migration during early cortical development. Combined, these data support a role for disruptive NCKAP1 variants in neurodevelopmental delay/autism, possibly by interfering with neuronal migration early in cortical development.
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6. Huggins CF, Donnan G, Cameron IM, Williams JH. {{Emotional self-awareness in autism: A meta-analysis of group differences and developmental effects}}. {Autism}. 2020: 1362361320964306.
Autistic people are thought to have difficulties with identifying and understanding their own emotions. This is referred to as emotional self-awareness. It is important to study emotional self-awareness as people who are more able to understand their own emotions, whether they are autistic or not, are more able to respond to them appropriately, as well as to identify them in other people. It has not yet been confirmed whether autistic people have difficulties with emotional self-awareness, or if any reported difficulties are actually due to the way in which emotional self-awareness is measured in autistic people. If these difficulties do exist, it is also not known when these difficulties emerge. In this research, we reviewed 47 existing studies that measured emotional self-awareness in autistic and non-autistic adults and children. We also compared studies that measured emotional self-awareness in different ways. We found that autistic adults did seem to have poorer emotional self-awareness compared to their neurotypical peers. However, this was not the case with autistic children of age 12 years and below. Instead, differences in emotional self-awareness only seemed to emerge during adolescence. Moreover, these difficulties seemed to increase with age. These results suggest that difficulties with emotional self-awareness may not be inherent in autism. Instead, they may emerge alongside the greater social and mental health difficulties that are experienced by many autistic people during adolescence. We therefore suggest that it is important to find out more about, and subsequently support, the emotional self-awareness difficulties that autistic adolescents may encounter.
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7. Jayanath S, Ozonoff S. {{First Parental Concerns and Age at Diagnosis of Autism Spectrum Disorder: A Retrospective Review from Malaysia}}. {The Malaysian journal of medical sciences : MJMS}. 2020; 27(5): 78-89.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder. This is the first study to examine first parental concerns in ASD in Malaysia. We examined: i) age and type of first parental concerns (AOC); ii) association between AOC and severity; iii) time lag between AOC and diagnosis; and iv) factors associated with diagnostic delay. METHODS: Medical records of 366 patients (aged 1-18 years) with ASD, at the Developmental Paediatrics Clinic of University of Malaya Medical Centre (UMMC), Kuala Lumpur, were reviewed for this 16-month retrospective cohort study. A validated coding system was used for initial parent concerns. Severity was classified via the Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) criteria. Time lag between AOC and age at diagnosis (AOD) was calculated. Potential predictors of delayed diagnosis were extracted. RESULTS: Three-quarters (75.1%) of parents had concerns by 36 months. Speech/language/communication concerns were most frequent (60.1%). Number of first concerns was significantly correlated with severity (social communication/interaction, SCI [P = 0.019] and restricted, repetitive patterns of behaviours and/or interests/activities, RRB [P < 0.001]). AOC and AOD were significantly negatively correlated with SCI and RRB (P < 0.001). Medians; AOC: 24 months, AOD: 46 months and time lag: 17 months. Higher initial screen time was associated with diagnostic delay (P = 0.031). CONCLUSION: First parental concerns and AOD were comparable to studies across countries. Speech/communication delays may represent universal first parental recognition of ASD. Lien vers le texte intégral (Open Access ou abonnement)
8. Jiménez E, Haebig E, Hills TT. {{Identifying Areas of Overlap and Distinction in Early Lexical Profiles of Children with Autism Spectrum Disorder, Late Talkers, and Typical Talkers}}. {J Autism Dev Disord}. 2020.
This study compares the lexical composition of 118 children with autism spectrum disorder (ASD) aged 12 to 84 months with 4626 vocabulary-matched typically developing toddlers with and without language delay, aged 8 to 30 months. Children with ASD and late talkers showed a weaker noun bias. Additionally, differences were identified in the proportion of nouns and verbs, and in the semantic categories of animals, toys, household items and vehicles. Most differences appear to reflect the extent of the age differences between the groups. However, children with ASD produced fewer high-social verbs than typical talkers and late talkers, a difference that might be associated with ASD features. In sum, our findings identified areas of overlap and distinction across the developing lexical profiles.
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9. Komatsu H, Ono T, Maita Y, Ishida Y, Kikuchi T, Maki T, Hase S, Sakurai H, Oba A, Teshirogi O, Suzuki A, Mori Y, Shoji C, Fujita A, Takahashi S, Ebina T, Ozaki S, Honma R, Tomita H, Kakuto Y. {{Association Between Autistic Symptoms and Self-Stigma in Patients with Schizophrenia Spectrum Disorders}}. {Neuropsychiatr Dis Treat}. 2020; 16: 2553-61.
PURPOSE: Self-stigma negatively influences self-esteem, quality of life, self-efficacy, treatment adherence, and recovery in psychiatric patients. By revealing personality traits that influence self-stigma, we can gain useful knowledge for the management of self-stigma. A previous meta-analysis indicated that patients with schizophrenia have higher scores on the Autism-Spectrum Quotient (AQ) than healthy controls. However, the relationship between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders remains unclear. Therefore, the present study aimed to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. PATIENTS AND METHODS: We recruited 127 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, and delusional disorder). We assessed participants’ self-stigma and autistic symptoms using the Internalized Stigma for Mental Illness (ISMI) scale and the Autism-Spectrum Quotient (AQ), respectively. The differences in the scores of ISMI and AQ according to patient characteristics were investigated. Multiple regression analysis controlling for age and gender was performed to determine the relationship between the total scores on the AQ and IMSI scale. RESULTS: Female patients showed a higher level of self-stigma than males. Unmarried patients showed a significantly higher score on the AQ than married patients. Multiple regression analysis adjusted for age and gender indicated that the total score on AQ might be a predictor of the overall rating on ISMI in patients with schizophrenia spectrum disorders. CONCLUSION: This study is the first to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. Our results highlight the importance of considering autistic symptoms in the assessment and management of self-stigma in patients with schizophrenia spectrum disorders.
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10. Meert KL, Reeder RW, Maddux AB, Banks R, Berg RA, Newth CJ, Hall MW, Quasney M, Carcillo JA, McQuillen PS, Mourani PM, Chima RS, Holubkov R, Sorenson S, McGalliard J, Dean JM, Zimmerman JJ. {{Health-Related Quality of Life After Community-Acquired Septic Shock in Children With Preexisting Severe Developmental Disabilities}}. {Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies}. 2020.
OBJECTIVES: To serially evaluate health-related quality of life during the first year after community-acquired septic shock in children with preexisting severe developmental disabilities and explore factors associated with health-related quality of life changes in these children. DESIGN: Secondary analysis of the Life after Pediatric Sepsis Evaluation investigation. SETTING: Twelve academic PICU in the United States. PATIENTS: Children greater than or equal to 1 month and less than 18 years old identified by their family caregiver (e.g., parent/guardian) as having severe developmental disability prior to septic shock. INTERVENTIONS: Family caregivers completed the Stein-Jessop Functional Status II-R Short Form as a measure of their child’s health-related quality of life at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Stein-Jessop Functional Status II-R Short Form scores were linearly transformed to a 0-100 scale, with higher scores indicating better health-related quality of life. MEASUREMENTS AND MAIN RESULTS: Of 392 Life after Pediatric Sepsis Evaluation participants, 137 were identified by their caregiver as having a severe developmental disability. Sixteen children (11.6%) with severe disability died during the 12 months following septic shock. Among 121 survivors, Stein-Jessop Functional Status II-R Short Form scores declined from preadmission baseline to day 7 (70.7 ± 16.1 vs 55.6 ± 19.2; p < 0.001). Stein-Jessop Functional Status II-R Short Form scores remained below baseline through month 12 (59.1 ± 21.0, p < 0.001 vs baseline). After adjusting for baseline Stein-Jessop Functional Status II-R Short Form, the caregiver being a single parent/guardian was associated with lower month 3 Stein-Jessop Functional Status II-R Short Form scores (p = 0.041). No other baseline child or caregiver characteristic, or critical illness-related factors were significantly associated with month 3 Stein-Jessop Functional Status II-R Short Form scores. CONCLUSIONS: Health-related quality of life among children with severe developmental disability remains, on average, below baseline during the first year following community-acquired septic shock. Children with severe disability and septic shock that are in single parent families are at increased risk. Clinical awareness of the potential for decline in health-related quality of life among disabled children is essential to prevent this adverse outcome from being missed. Lien vers le texte intégral (Open Access ou abonnement)
11. Migliarese G, Torriero S, Gesi C, Venturi V, Reibman Y, Cerveri G, Viganò V, Decaroli G, Ricciardelli P, Mencacci C. {{Sleep quality among adults with attention deficit hyperactivity disorder or autism spectrum disorder: which is the role of gender and chronotype?}}. {Sleep medicine}. 2020; 76: 128-33.
Both Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) present increased prevalence rates of sleep difficulties, which persist into adulthood. However, it is still unclear whether in adults these disorders show specific sleep patterns and which role is played by comorbidities, circadian preferences and gender. This study aimed to describe and compare subjective measures of sleep in adults with ADHD and high-functioning ASD, in relation to the levels of anxiety and depression, chronotype and gender. In a sample of 136 adults (43 ADHD, 43 high-functioning ASD, 50 controls) subjective sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI), and clinical scales were used to assess chronotype and the levels of anxiety and depression. The three groups showed a significant difference in the distribution of chronotypes, with greater prevalence of an Evening chronotype among ASD compared to controls. The MANCOVA using PSQI subscale scores as dependent variables and MEQ-SA score and depression range as covariates showed that the three groups significantly differ in quality, latency, efficiency, and dysfunction scores with a significant differences between ASD and ADHD in efficiency and dysfunction. Compared to men, women showed higher scores on PSQI total and quality subscale across the three groups and higher duration scores only within ASD group. Our results indicate that both ADHD and ASD adults show unique sleep disturbances and suggest that ASD patients, especially women, may display more pronounced disordered sleep.
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12. Mithal DS, Chandel NS. {{Mitochondrial Dysfunction in Fragile-X Syndrome: Plugging the Leak May Save the Ship}}. {Molecular cell}. 2020; 80(3): 381-3.
Recent work by Licznerski et al. suggests that mutant FMRP linked to Fragile-X syndrome elevates the inner mitochondrial membrane proton leak, leading to increased metabolism and changes in protein synthesis that trigger impaired synaptic maturation and autistic behaviors.
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13. Qin X, Feng Y, Qu F, Luo Y, Chen B, Chen M, Zou Y, Zhang L. {{Posttraumatic growth among parents of children with autism spectrum disorder in China and its relationship to family function and mental resilience: A cross-sectional study}}. {Journal of pediatric nursing}. 2020.
OBJECTIVE: This study was conducted to examine the posttraumatic growth (PTG) of parents of children with autism spectrum disorder (ASD) and the association among family function, mental resilience and PTG. DESIGN AND METHODS: This descriptive cross-sectional study was conducted with 205 parents of children with ASD in the clinical department of a university-affiliated hospital in Guangzhou from January to October 2019. The Posttraumatic Growth Inventory, Family Assessment Device, and Connor-Davidson Resilience Scale were employed for data collection. RESULTS: The mean PTG score of parents was 59.56±18.46; and 24.63%, 43.84%, and 32.51% of parents exhibited a high level, moderate level and low level, respectively, of PTG. The problem-solving dimension of family function (p = 0.005) and the strength dimension of mental resilience (p ≤0.001) were positively related to PTG. CONCLUSIONS: Parents of children with ASD experienced moderate PTG overall. The problem-solving dimension of family function and the strength dimension of mental resilience were significant predictors of PTG. PRACTICAL IMPLICATIONS: Interventions to improve family function and the mental resilience of parents with ASD children could contribute to improving the PTG of parents.
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14. Van Dyke MV, Guevara MVC, Wood KS, McLeod BD, Wood JJ. {{The Pediatric Autism Spectrum Therapy Observation System: Development, Psychometric Properties, and Sensitivity to Treatment}}. {Child Psychiatry Hum Dev}. 2020.
An observational coding system was developed to track clinical change in children with autism spectrum disorder (ASD) during psychotherapy. The Pediatric Autism Spectrum Therapy Observation System (PASTOS) consists of 23 items divided into 5 subscales and is used to rate child behaviors in individual psychotherapy sessions. Manual-based cognitive behavioral therapy session transcripts of 22 children diagnosed with ASD (IQ > 70) and a concurrent anxiety disorder (M = 9.41 years, SD = 1.56 years) enrolled in a randomized, controlled trial were coded. Results suggested that the PASTOS exhibited promising interrater reliability, internal consistency, convergent validity at post-treatment, and treatment sensitivity. The PASTOS may be a useful tool for studying process and outcome in psychotherapy research on children with ASD.
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15. Wang J, Wang L. {{Prediction and prioritization of autism-associated long non-coding RNAs using gene expression and sequence features}}. {BMC Bioinformatics}. 2020; 21(1): 505.
BACKGROUND: Autism spectrum disorders (ASD) refer to a range of neurodevelopmental conditions, which are genetically complex and heterogeneous with most of the genetic risk factors also found in the unaffected general population. Although all the currently known ASD risk genes code for proteins, long non-coding RNAs (lncRNAs) as essential regulators of gene expression have been implicated in ASD. Some lncRNAs show altered expression levels in autistic brains, but their roles in ASD pathogenesis are still unclear. RESULTS: In this study, we have developed a new machine learning approach to predict candidate lncRNAs associated with ASD. Particularly, the knowledge learnt from protein-coding ASD risk genes was transferred to the prediction and prioritization of ASD-associated lncRNAs. Both developmental brain gene expression data and transcript sequence were found to contain relevant information for ASD risk gene prediction. During the pre-training phase of model construction, an autoencoder network was implemented for a representation learning of the gene expression data, and a random-forest-based feature selection was applied to the transcript-sequence-derived k-mers. Our models, including logistic regression, support vector machine and random forest, showed robust performance based on tenfold cross-validations as well as candidate prioritization with hypothetical loci. We then utilized the models to predict and prioritize a list of candidate lncRNAs, including some reported to be cis-regulators of known ASD risk genes, for further investigation. CONCLUSIONS: Our results suggest that ASD risk genes can be accurately predicted using developmental brain gene expression data and transcript sequence features, and the models may provide useful information for functional characterization of the candidate lncRNAs associated with ASD.
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16. Zhu Y, Mordaunt CE, Durbin-Johnson BP, Caudill MA, Malysheva OV, Miller JW, Green R, James SJ, Melnyk SB, Fallin MD, Hertz-Picciotto I, Schmidt RJ, LaSalle JM. {{Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment}}. {Autism Res}. 2020.
The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5′-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children’s later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients.
