1. Bernaerts S, Boets B, Steyaert J, Wenderoth N, Alaerts K. {{Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up}}. {Translational psychiatry}. 2020; 10(1): 383.
Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.
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2. Bradshaw J, Gillespie S, McCracken C, King BH, McCracken JT, Johnson CR, Lecavalier L, Smith T, Swiezy N, Bearss K, Sikich L, Donnelly C, Hollander E, McDougle CJ, Scahill L. {{Predictors of Caregiver Strain for Parents of Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2020.
Parents of children with autism spectrum disorder (ASD) face higher levels of caregiver strain compared to parents of children with other disabilities. This study examined child clinical features that predict high levels of caregiver strain for 374 parents of children with ASD. Caregiver strain was measured using the Caregiver Strain Questionnaire (CGSQ) objective, subjective internalized, and subjective externalized subscales. Confirmatory factor analysis indicated an acceptable fit for the original CGSQ three-factor solution. The strongest child predictors across CGSQ subscales were: disruptive behavior for objective strain, autism severity and disruptive behavior for subjective internalized strain, and oppositional behavior and hyperactivity for subjective externalized strain. Individualized interventions that attend to specific elements of parental strain may reduce strain and improve family wellbeing.
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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. Crutel V, Lambert E, Penelaud PF, Albarrán Severo C, Fuentes J, Rosier A, Hervás A, Marret S, Oliveira G, Parellada M, Kyaga S, Gouttefangeas S, Bertrand M, Ravel D, Falissard B. {{Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents with Autism Spectrum Disorder: Design of Two Phase III Studies (SIGN Trials)}}. {J Autism Dev Disord}. 2020.
There are currently no approved pharmacological treatments to improve social reciprocity and limit repetitive and rigid behaviors in autism spectrum disorder (ASD). We describe the design of two Phase III studies evaluating the efficacy/safety of bumetanide oral liquid formulation in ASD. These are international, multicenter, randomized, double-blind, placebo-controlled studies in children and adolescents with ASD aged 7 to 17 years (n = 200; study 1), or younger children with ASD aged 2 to 6 years (n = 200; study 2). The primary endpoint of each is change in Childhood Autism Rating Scale 2 total raw score after 6 months. These studies could contribute to the first pharmacological treatment to improve social reciprocity and limit repetitive and rigid behaviors in children and adolescents with ASD.
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5. 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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6. Eapen V, Hiscock H, Williams K. {{Adaptive innovations to provide services to children with developmental disabilities during the COVID-19 pandemic}}. {Journal of paediatrics and child health}. 2020.
Children with developmental disabilities are experiencing significant challenges to service access due to suspension of in-person assessments during the current COVID-19 pandemic. Telehealth is rapidly becoming the new service delivery model, which presents a unique opportunity for innovation in care that could be beneficial in the post-pandemic period. For example, using a combination of in-home video and telehealth options could form the first step in developmental assessment, allowing children to receive the necessary supports without delay. Recent telehealth funding is welcome but additional Medicare items for joint consultations including general practitioners (GPs), and paediatric, mental health and allied health professionals is critical.
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7. Fletcher S, Pawliuk C, Ip A, Oberlander T, Siden H. {{Symptoms, adverse events, and outcomes in the use of medicinal cannabis in children and adolescents with autism spectrum disorder: a scoping review protocol}}. {JBI evidence synthesis}. 2020.
OBJECTIVE: The objective of this scoping review is to map and identify the symptoms, adverse events, and outcomes in the use of medicinal cannabis in children and adolescents with autism spectrum disorder. INTRODUCTION: Autism spectrum disorder is a neurodevelopmental disorder that impacts social communication and social interaction, and is associated with restrictive and repetitive behaviors and interests. Medicinal cannabis has become a potential area of interest for parents for the treatment of ASD symptoms in their children. There is some evidence that cannabinoids may be involved in autism spectrum disorder, laying a potential foundation for medicinal cannabis utility; however, previous reviews did not identify any clinical research on this topic. INCLUSION CRITERIA: This scoping review will consider all published and unpublished studies that investigate the use of medicinal cannabis in autism spectrum disorder, where at least 50% of the participants have a diagnosis of autism spectrum disorder and at least 50% of the study population is 0-18 years of age, or where pediatric data are reported separately. Studies undertaken in any context (hospital or community) and in any geographic location will be included. METHODS: We will search MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar, and the gray literature sources for studies. Two independent team members will screen titles and abstract, review full texts for potential inclusion, and extract data for all studies. The results will be presented as a narrative synthesis and in tabular form.
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8. Gulisano M, Barone R, Mosa MR, Milana MC, Saia F, Scerbo M, Rizzo R. {{Incidence of Autism Spectrum Disorder in Youths Affected by Gilles de la Tourette Syndrome Based on Data from a Large Single Italian Clinical Cohort}}. {Brain Sci}. 2020; 10(11).
Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are etiologically related neurodevelopmental disorders with an onset age before 18 years and a reported comorbidity of 2.9-20%. The aim of the present study was to identify the incidence of ASD in a large clinical sample of individuals affected by GTS and to compare our results with previously reported incidences. We retrospectively analyzed clinical data (n = 1200) from January 2010 to March 2019 obtained from the outpatient Catania Tourette Clinic, part of the Child and Adolescent Neurology and Psychiatry of the Medical and Experimental Department of Catania University. We used internationally validated evaluation tools. The neuropsychological evaluation was carried out by an expert and a certificated team of child and adolescent neurologists, supervised by two expert child neurologists (R.R. and M.G.). We investigated 975 GTS-affected individuals of various socioeconomic levels aged 5-18 years, and 8.9% (n = 87) were affected by ASD. The incidence of GTS with ASD was significantly lower (p < 0.001) in children than in adolescents. No statistically significant differences were found in the sex distribution and age of onset of tics between individuals with GTS alone and those with GTS and ASD. The incidence of GTS and ASD comorbidity in this study was high, and this has several implications in terms of treatment and prognosis. Lien vers le texte intégral (Open Access ou abonnement)
9. 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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10. Kleiman JD, Veerapaneni K, Escovar J, Orsini J. {{COVID-19 Infection in a Patient With Fragile-X Syndrome}}. {Cureus}. 2020; 12(10): e11266.
Over the past several months we have learned about how pre-existent comorbidities may influence the outcome of patients infected with the coronavirus disease 2019 (COVID-19), with diabetes mellitus and obesity being commonly reported in association with increased mortality among these patients. In this report, the authors explore the case of a patient with Fragile-X Syndrome (FXS) who developed pneumonia due to COVID-19. FXS is an inherited cause of intellectual disability with potential neurologic and physiologic sequelae. In this narrative, we aim to describe how FXS may potentially play a role in the clinical course of patients with COVID-19.
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11. 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)
12. Niranjana Murthy AS, Suresh RV, Ramachandra NB. {{Comprehensive in silico mutational-sensitivity analysis of PTEN establishes signature regions implicated in pathogenesis of Autism Spectrum Disorders}}. {Genomics}. 2020.
An extensively studied cancer and Autism Spectrum Disorders (ASD) gene PTEN provided an exclusive opportunity to map its mutational-landscape, compare and establish plausible genotypic predictors of ASD-associated phenotypic outcomes. Our exhaustive in silico analysis on 4252 SNPs using >30 tools identified increased mutational-density in exon7. Phosphatase domain, although evolutionarily conserved, had the most nsSNPs localised within signature regions. The evolutionarily variable C-terminal contained the highest truncating-SNPs outside signature regions of C2 domain and highest PTMs within C-tail that displayed maximum intolerance to polymorphisms, permitting benign but destabilising nsSNPs that enhanced its intrinsically-disordered nature. ASD-associated SNPs localised within ATP-binding motifs and Nuclear-Localising-Sequences were the most potent triggers of ASD manifestation. These, along with variations within P, WPD and TI loops, M1 within phosphatase domain, M2 and MoRFs of C2 domain, caused severe long-range conformational fluctuations altering PTEN’s dynamic stability- not observed in variations outside signature regions. 3’UTR-SNPs affected 44 strong miRNA brain-specific targets; several 5′ UTR-SNPs targeted transcription-factor POLR2A and 10 pathogenic Splice-Affecting-Variants were identified.
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13. Olesova D, Galba J, Piestansky J, Celusakova H, Repiska G, Babinska K, Ostatnikova D, Katina S, Kovac A. {{A Novel UHPLC-MS Method Targeting Urinary Metabolomic Markers for Autism Spectrum Disorder}}. {Metabolites}. 2020; 10(11).
Autism spectrum disorder is a heterogeneous neurodevelopmental disease. Currently, no biomarker of this disease is known. Diagnosis is performed through observation, standardized behavioral scales, and interviews with parents. In practice, diagnosis is often delayed to the average age of four years or even more which adversely affects a child’s perspective. A laboratory method allowing to detect the disorder at earlier stages is of a great need, as this could help the patients to start with treatment at a younger age, even prior to the clinical diagnosis. Recent evidence indicates that metabolomic markers should be considered as diagnostic markers, also serving for further differentiation and characterization of different subgroups of the autism spectrum. In this study, we developed an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the simultaneous determination of six metabolites in human urine. These metabolites, namely methylguanidine, N-acetyl arginine, inosine, indole-3-acetic acid, indoxyl sulfate and xanthurenic acid were selected as potential biomarkers according to prior metabolomic studies. The analysis was carried out by means of reversed-phase liquid chromatography with gradient elution. Separation of the metabolites was performed on a Phenomenex Luna(®) Omega Polar C18 (100 × 1.0 mm, 1.6 µm) column at a flow rate of 0.15 mL/min with acetonitrile/water 0.1% formic acid aqueous as the mobile phase. The analysis was performed on a group of children with autism spectrum disorder and age-matched controls. In school children, we have detected disturbances in the levels of oxidative stress markers connected to arginine and purine metabolism, namely methylguanidine and N-acetylargine. Also, products of gut bacteria metabolism, namely indoxyl sulfate and indole-3-acetic acid, were found to be elevated in the patients’ group. We can conclude that this newly developed method is fast, sensitive, reliable, and well suited for the quantification of proposed markers.
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14. Robinson SM, Esplen N, Wells D, Bazalova-Carter M. {{Monte Carlo simulations of EBT3 film dose deposition for percentage depth dose (PDD) curve evaluation}}. {Journal of applied clinical medical physics}. 2020.
PURPOSE: To use Monte Carlo (MC) calculations to evaluate the effects of Gafchromic EBT3 film orientation on percentage depth dose (PDD) curves. METHODS: Dose deposition in films placed in a water phantom, and oriented either parallel or perpendicular with respect to beam axis, were simulated with MC and compared to PDDs scored in a homogenous water phantom. The effects of introducing 0.01-1.00 mm air gaps on each side of the film as well as a small 1°-3° tilt for film placed in parallel orientation were studied. PDDs scored based on two published EBT3 film compositions were compared. Three photon beam energies of 120 kVp, 220 kVp, and 6 MV and three field sizes between 1 × 1 and 5 × 5 cm(2) were considered. Experimental PDDs for a 6-MV 3 × 3 cm(2) beam were acquired. RESULTS: PDD curves for films in perpendicular orientation more closely agreed to water PDDs than films placed in parallel orientation. The maximum difference between film and water PDD for films in parallel orientation was -12.9% for the 220 kVp beam. For the perpendicular film orientation, the maximum difference decreased to 5.7% for the 120 kVp beam. The inclusion of an air gap had the largest effect on the 6-MV 1 × 1 cm(2) beam, for which the dose in the buildup region was underestimated by 21.2% compared to the simulation with no air gap. A 2° film tilt decreased the difference between the parallel film and homogeneous water phantom PDDs from -5.0% to -0.5% for the 6 MV 3 × 3 cm(2) beam. The « newer » EBT3 film composition resulted in larger PDD discrepancies than the previous composition. Experimental film data qualitatively agreed with MC simulations. CONCLUSIONS: PDD measurements with films should either be performed with film in perpendicular orientation to the beam axis or in parallel orientation with a ~ 2º tilt and no air gaps.
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15. Sharifzadeh N, Ghasemi A, Tavakol Afshari J, Moharari F, Soltanifar A, Talaei A, Pouryousof HR, Nahidi M, Fayyazi Bordbar MR, Ziaee M. {{Intrathecal autologous bone marrow stem cell therapy in children with autism: A randomized controlled trial}}. {Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists}. 2020: e12445.
INTRODUCTION: This study aimed to determine the safety and efficacy of treatment with autologous bone marrow mesenchymal stem cell (BMMSCs) compared with the routine treatment in children with autism spectrum disorder (ASD). METHODS: In this ethically approved randomized controlled trial, 32 ASD children aged 5-15 years were randomly assigned to receive either autologous BMMSC plus rehabilitation therapy and risperidone (intervention group) or rehabilitation therapy and risperidone (control group). Autologous BMMSCs were intrathecally injected in the intervention group twice in 4 weeks. Patients were assessed using childhood autism rating scale (CARS), Gilliam autism rating scale-second edition (GARS-II), and clinical global impression (CGI) at the baseline, as well as 6 and 12 months after intervention. RESULTS: Overall, 32 patients in two groups of intervention (n = 14) and control (n = 18) completed the study, of which 27 (84.4%) were male. Mean age was 9.50 ± 2.14 years. The improvements in CARS total score, GARS-II autism index, and CGI global improvement showed no significant differences between the groups over 12 months. However, the main effect for time*group interaction was significant regarding the CGI-severity of illness, showing a significantly more pronounced improvement in the intervention group (F = 6.719; P = .002). DISCUSSION: Intrathecal injection of autologous BMMSCs seems to be safe and feasible, but has limited clinical efficacy in treatment of children with ASD.
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16. Shattnawi KK, Bani Saeed WM, Al-Natour A, Al-Hammouri MM, Al-Azzam M, Joseph RA. {{Parenting a Child With Autism Spectrum Disorder: Perspective of Jordanian Mothers}}. {Journal of transcultural nursing : official journal of the Transcultural Nursing Society}. 2020: 1043659620970634.
INTRODUCTION: Parenting a child diagnosed with autism spectrum disorder (ASD) is challenging for mothers because of concerns related to behavior, difficulties in accessing specialized care, and lack of community acceptance, yet their stories in Jordanian context are still unknown. Common challenges in Jordan include financial burdens, lack of public awareness, and lack of specialized knowledge even among health care providers, which may lead to delays in obtaining the diagnosis and interventions for ASD. METHOD: A phenomenological descriptive approach was used to explore and understand the mothers’ everyday lived experiences of raising a child with ASD. Semistructured interviews were conducted with 14 mothers to identify their challenges so that nurses can identify gaps in services, empower families, and facilitate optimum care to these Jordanian families. FINDINGS: The main themes that emerged were (1) mothers’ journeys with the diagnosis, in which mothers recognized the abnormalities of their children, reported delays in getting the diagnosis and initiation of treatment, and described a wide range of reactions to the diagnosis from grief and guilt to a blessing from God; (2) the burden of care, by which mothers reported physical and emotional exhaustion, financial burdens, and concerns about the quality of available services; and (3) the consequences and the hurdle of having a child with ASD, which affected the family relationships and social life. DISCUSSION: Jordanian mothers caring for children with ASD face several challenges, including physical, psychological, financial, and social challenges, in addition to limited specialized services. Identifying their unique challenges and needs are essential to support them, provide appropriate services and resources, and develop policies and guidelines for culturally competent quality services.
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17. Shuai B, Jin H, Lin Y, Duan R, Zhao N, Li Z, Mao J, Luo Y, Shi M. {{Safety and efficacy of complementary and alternative medicine in the treatment of autism spectrum disorder: A protocol for systematic review and meta-analysis}}. {Medicine}. 2020; 99(45): e23128.
INTRODUCTION: The purpose of this study is to evaluate the efficacy and safety of complementary and alternative medicine in the treatment of autism spectrum disorder. METHODS AND ANALYSIS: We will electronically search Pubmed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to complementary and alternative medicine treating autism spectrum disorder will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using a fixed-effect model or random-effect model depend on the heterogeneity test. The Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) scores will be the primary outcomes. The scores of the Autism Treatment Evaluation Checklist and the Ritvo-Freeman Real Life Rating Scale will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), whereas dichotomous data will be expressed in the form of relative risk with 95% CIs. ETHICS AND DISSEMINATION: The protocol of this systematic review does not require ethical approval because it does not involve humans. We will publish this article in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION: OSF Registries, DOI: 10.17605/OSF.IO/ HA97R (https://osf.io/ha97r).
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18. Suzuki T, Wada K, Muzembo BA, Ngatu NR, Yoshii S, Ikeda S. {{Autistic and Attention Deficit/Hyperactivity Disorder Traits Are Associated with Suboptimal Performance among Japanese University Students}}. {JMA journal}. 2020; 3(3): 216-31.
INTRODUCTION: Recent estimates suggest that there is a substantial number of Japanese students with developmental disabilities. This study aimed to examine potential associations between autistic, autistic subcomponents, and attention deficit/hyperactivity disorder (ADHD) traits with student performance (as measured by presenteeism) and class attendance among Japanese university students. METHODS: Participants comprised 721 students from different regions of Japan who completed a self-administered internet survey. Autistic and ADHD traits were measured using an abridged version of the autism spectrum quotient (AQ-Short) and adult ADHD self-report scale (ASRS). Presenteeism, which is an indicator of student performance, was assessed using the modified World Health Organization Health and Work Performance Questionnaire. Class attendance during the past year was self-reported by participants. RESULTS: Students with high levels of autistic traits and high levels of ADHD traits were significantly more likely to report poor student performance (odds ratio [OR] = 3.07, 95% confidence interval [95% CI]: 1.90-4.96; and OR = 2.13, 95% CI: 1.32-3.42, respectively). Regarding autistic trait subcomponents, students with high levels of preference for routine (OR = 2.39, 95% CI: 1.38-4.13) and high levels of difficulties with social skills (OR = 1.81, 95% CI: 1.03-3.18) were also significantly more likely to report poor student performance. There were borderline significant associations between traits of attention-switching difficulties and poor student performance (OR = 1.78, 95% CI: 1.00-3.15). Regarding ADHD trait subcomponents, students with high levels of inattention (OR = 2.88, 95% CI: 1.32-6.26) were also significantly more likely to report poor student performance. Students with both high levels of autistic traits and high levels of ADHD traits were more likely to report poor student performance than those with high levels of only one trait type. There were, however, no statistically significant associations between these traits and low class attendance risk. CONCLUSIONS: Sickness presenteeism was significantly associated with high levels of both autistic traits and ADHD traits among Japanese university students.
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19. Thacker S, Sefyi M, Eng C. {{Alternative splicing landscape of the neural transcriptome in a cytoplasmic-predominant Pten expression murine model of autism-like Behavior}}. {Translational psychiatry}. 2020; 10(1): 380.
Alternative splicing (AS) is a posttranscriptional mechanism regulating gene expression that complex organisms utilize to expand proteome diversity from a comparatively limited set of genes. Recent research has increasingly associated AS with increased functional complexity in the central nervous systems in higher order mammals. This work has heavily implicated aberrant AS in several neurocognitive and neurodevelopmental disorders, including autism. Due to the strong genetic association between germline PTEN mutations and autism spectrum disorder (ASD), we hypothesized that germline PTEN mutations would alter AS patterns, contributing to the pathophysiology of ASD. In a murine model of constitutional mislocalization of Pten, recapitulating an autism-like phenotype, we found significant changes in AS patterns across the neural transcriptome by analyzing RNA-sequencing data with the program rMATS. A few hundred significant alternative splicing events (ASEs) that differentiate each m3m4 genotype were identified. These ASEs occur in genes enriched in PTEN signaling, inositol metabolism, and several other pathways relevant to the pathophysiology of ASD. In addition, we identified expression changes in several splicing factors known to be enriched in the nervous system. For instance, the master regulator of microexons, Srrm4, has decreased expression, and consequently, we found decreased inclusion of microexons in the Pten(m3m4/m3m4) cortex (~10% decrease). We also demonstrated that the m3m4 mutation disrupts the interaction between Pten and U2af2, a member of the spliceosome. In sum, our observations point to germline Pten disruption changing the landscape of alternative splicing in the brain, and these changes may be relevant to the pathogenesis and/or maintenance of PTEN-ASD phenotypes.
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20. Tziraki M, Garg S, Harrison E, Wright NB, Hawkes R, Akhtar K, Green J, Stivaros S. {{A Neuroimaging Preparation Protocol Tailored for Autism}}. {Autism Res}. 2020.
This paper describes the key basic elements required for a successful multi-parametric MRI data acquisition in awake children with autism. The procedure was designed by taking into account methodological challenges arising from the acquisition of Resting State fMRI (RS fMRI) data, and factors such as cost, time, and staff availability. The ultimate aim was to prepare an imaging preparation protocol with high transferability to the whole autism spectrum, adaptable for use in a multi-site research with multiple time points. As part of a randomized pharmaco-intervention study, 31 children aged 4-10 years with Neurofibromatosis 1 and autism underwent MR imaging at baseline and end of intervention. The protocol consisted of tailored habituation instructions including gradual exposure to scanner noise, a social stories booklet, positive incentive strategies, and Play Therapy support. Success rate for initial acquisition was 71% for GABA+ MR spectroscopy at either location, 87% for perfusion, and 67% for diffusion assessment, and 71% for RS fMRI. Qualitative data indicated that 84% parents found the habituation protocol helpful. LAY SUMMARY: Here we describe a protocol for brain Magnetic Resonance Imaging (MRI) tailored for children with ASD to help reduce stress and avoid sedation during scanning. This procedure can make advanced medical imaging more accessible and promote a better MRI experience for families of children with ASD.
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21. Zabihi M, Floris DL, Kia SM, Wolfers T, Tillmann J, Arenas AL, Moessnang C, Banaschewski T, Holt R, Baron-Cohen S, Loth E, Charman T, Bourgeron T, Murphy D, Ecker C, Buitelaar JK, Beckmann CF, Marquand A. {{Fractionating autism based on neuroanatomical normative modeling}}. {Translational psychiatry}. 2020; 10(1): 384.
Autism is a complex neurodevelopmental condition with substantial phenotypic, biological, and etiologic heterogeneity. It remains a challenge to identify biomarkers to stratify autism into replicable cognitive or biological subtypes. Here, we aim to introduce a novel methodological framework for parsing neuroanatomical subtypes within a large cohort of individuals with autism. We used cortical thickness (CT) in a large and well-characterized sample of 316 participants with autism (88 female, age mean: 17.2 ± 5.7) and 206 with neurotypical development (79 female, age mean: 17.5 ± 6.1) aged 6-31 years across six sites from the EU-AIMS multi-center Longitudinal European Autism Project. Five biologically based putative subtypes were derived using normative modeling of CT and spectral clustering. Three of these clusters showed relatively widespread decreased CT and two showed relatively increased CT. These subtypes showed morphometric differences from one another, providing a potential explanation for inconsistent case-control findings in autism, and loaded differentially and more strongly onto symptoms and polygenic risk, indicating a dilution of clinical effects across heterogeneous cohorts. Our results provide an important step towards parsing the heterogeneous neurobiology of autism.
