1. Billeiter KB, Froiland JM, Allen JP, Hajovsky DB. Neurodiversity and Intelligence: Evaluating the Flynn Effect in Children with Autism Spectrum Disorder. Child psychiatry and human development. 2021.

The Flynn Effect (FE) among child and adolescent populations indicates that intelligence scores improve by about three points per decade. Using nine years of data from the National Database for Autism Research, this study examined whether general intelligence changed significantly for nine cohorts with autism spectrum disorder (ASD; N = 671). Analyses demonstrated a downward trend such that Cohen’s d from 1998 to 2006 was – 0.27. The mean IQ is 92.74 for years 1-3, 91.54 for years 4-6, and 87.34 for years 7-9, indicating a reverse FE of 5.4 points per decade. A linear regression revealed a significant negative FE comparable to the positive effect of age on IQ among those with ASD. Implications for research, practice, and law are discussed.

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2. Bolbocean C, Andújar FN, McCormack M, Suter B, Holder JL, Jr. Health-Related Quality of Life in Pediatric Patients with Syndromic Autism and their Caregivers. Journal of autism and developmental disorders. 2022; 52(3): 1334-45.

Children with autism have a significantly lower quality of life compared with their neurotypical peers. While multiple studies have quantified the impact of autism on health-related quality of life (HRQoL) through standardized surveys such as the PedsQL, none have specifically investigated the impact of syndromic autism. Here we evaluate HRQoL in children diagnosed with three genetic disorders that strongly predispose to syndromic autism: Phelan-McDermid syndrome (PMD), Rett syndrome (RTT), and SYNGAP1-related intellectual disability (SYNGAP1-ID). We find the most severely impacted dimension is physical functioning. Strikingly, syndromic autism results in worse quality of life than other chronic disorders including idiopathic autism. This study demonstrates the utility of caregiver surveys in prioritizing phenotypes, which may be targeted as clinical endpoints for genetically defined ASDs.

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3. Brown KA, Sarkar IN, Chen ES. Mental Health Comorbidity Analysis in Pediatric Patients with Autism Spectrum Disorder Using Rhode Island Medical Claims Data. AMIA Annual Symposium proceedings AMIA Symposium. 2020; 2020: 263-72.

Identification of comorbidity subgroups linked with Autism Spectrum Disorder (ASD) could provide promising insight into learning more about this disorder. This study sought to use the Rhode Island All-Payer Claims Database to examine mental health conditions linked to ASD. Medical claims data for ASD patients and one or more mental health conditions were analyzed using descriptive statistics, association rule mining (ARM), and sequential pattern mining (SPM). The results indicated that patients with ASD have a higher proportion of mental health diagnoses than the general pediatric population. ARM and SPM methods identified patterns of comorbidities commonly seen among ASD patients. Based on the observed patterns and temporal sequences, suicidal ideation, mood disorders, anxiety, and conduct disorders may need focused attention prospectively. Understanding more about groupings of ASD patients and their comorbidity burden can help bridge gaps in knowledge and make strides toward improved outcomes for patients with ASD.

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4. Cook S, Hole R. Trauma, intellectual and/or developmental disability, and multiple, complex needs: A scoping review of the literature. Research in developmental disabilities. 2021; 115: 103939.

BACKGROUND: Trauma is a significant underlying factor in the multimorbidity of people with Intellectual and/or Development Disabilities (IDD). This relationship is further complicated by a growing recognition of a subset of multiply stigmatized individuals with an IDD and complex, intersecting health and social needs. AIM: The aim of this review was to examine what is known about trauma and people with an IDD and complex needs, as defined by Community Living British Columbia’s (CLBC) Multiple, Complex Needs (MCN) framework, through a broad review of relevant literature. METHOD AND PROCEDURES: We conducted a scoping review of the peer-reviewed (9 disability journals; 7 academic databases) and grey (2 grey literature databases) on IDD and trauma through an inclusive approach that used search criteria drawn from the defining features of CLBC’s MCN Framework. OUTCOMES AND RESULTS: Apart from there being a limited amount of research on trauma and IDD, two key findings emerged. Through differing approaches that get at issues of trauma in different ways (i.e., through adverse life events or experiences of abuse), the first finding is that the research related to trauma and IDD is not cleanly linked together. The second is the focus on treatment services or interventions and not on what’s happening at the organizational or system level. CONCLUSION AND IMPLICATIONS: There is limited research on trauma and IDD making it even more important to unify the evidence that exists. However, the literature is not integrated across different theoretical and disciplinary perspectives. In addition, the focus of trauma-related research that is occurring is interventions at the individual versus system level. Also needed are studies that explore trauma-informed practice from an organizational or top-down perspective.

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5. DiCarlo GE, Mabry SJ, Cao X, McMillan C, Woynaroski TG, Harrison FE, Reddy IA, Matthies HJG, Flynn CR, Wallace MT, Wu H, Galli A. Autism-Associated Variant in the SLC6A3 Gene Alters the Oral Microbiome and Metabolism in a Murine Model. Frontiers in psychiatry. 2021; 12: 655451.

Background: Altered dopamine (DA) signaling has been associated with autism spectrum disorder (ASD), a neurodevelopmental condition estimated to impact 1 in 54 children in the United States. There is growing evidence for alterations in both gastrointestinal function and oral microbiome composition in ASD. Recent work suggests that rare variants of the SLC6A3 gene encoding the DA transporter (DAT) identified in individuals with ASD result in structural and functional changes to the DAT. One such recently identified de novo mutation is a threonine to methionine substitution at position 356 of the DAT (DAT T356M). The DAT T356M variant is associated with ASD-like phenotypes in mice homozygous for the mutation (DAT T356M(+/+)), including social deficits, hyperactivity, and impaired DA signaling. Here, we determine the impact of this altered DA signaling as it relates to altered oral microbiota, and metabolic and gastrointestinal dysfunction. Methods: In the DAT T356M(+/+) mouse, we determine the oral microbiota composition, metabolic function, and gastrointestinal (GI) function. We examined oral microbiota by 16S RNA sequencing. We measured metabolic function by examining glucose tolerance and we probed gastrointestinal parameters by measuring fecal dimensions and weight. Results: In the DAT T356M(+/+) mouse, we evaluate how altered DA signaling relates to metabolic dysfunction and altered oral microbiota. We demonstrate that male DAT T356M(+/+) mice weigh less (Wild type (WT) = 26.48 ± 0.6405 g, DAT T356M(+/+) = 24.14 ± 0.4083 g) and have decreased body fat (WT = 14.89 ± 0.6206%, DAT T356M(+/+) = 12.72 ± 0.4160%). These mice display improved glucose handling (WT = 32.60 ± 0.3298 kcal/g, DAT T356M(+/+) = 36.97 ± 0.4910 kcal/g), and an altered oral microbiota. We found a significant decrease in Fusobacterium abundance. The abundance of Fusobacterium was associated with improved glucose handling and decreased body fat. Conclusions: Our findings provide new insights into how DAT dysfunction may alter gastrointestinal function, composition of the oral microbiota, and metabolism. Our data suggest that impaired DA signaling in ASD is associated with a number of metabolic and gastrointestinal changes which are common in individuals with ASD.

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6. Fasano RM, Perry LK, Zhang Y, Vitale L, Wang J, Song C, Messinger DS. A granular perspective on inclusion: Objectively measured interactions of preschoolers with and without autism. Autism research : official journal of the International Society for Autism Research. 2021; 14(8): 1658-69.

Children’s preschool experiences have consequences for development. However, it is not clear how children’s real-time interactions with peers affect their language development; nor is it clear whether these processes differ between children with autism spectrum disorder (ASD) and two other groups of children, those with general developmental delays (DD) and typically developing (TD) children. We used objective measures of movement and vocalizations to quantify children’s real-time dyadic vocal interactions and quantify classroom social networks. Participants included 56 preschoolers (22 female; M = 50.14 months) in five inclusive classrooms for children with ASD or DD and their TD peers. Each class was observed monthly on two to five occasions. Overall, children vocalized more to peers who had vocalized more to them in the previous observation. These dyadic vocalization patterns were associated with group differences in social network analyses. Modularity, the cohesiveness of group ties, was lower among children with ASD than it was among TD children or children with DD. Individually, children with ASD exhibited lower total levels of vocalizations with peers (lower degree centrality) than TD children and children with DD. In an exploratory analysis with a subset of the participants, children’s degree centrality was strongly associated with their end-of-year assessed language abilities, even when accounting for mean differences between groups. Findings highlight the impact peers and social networks play in real-time language use and in the developing language abilities of children with ASD in inclusion classrooms. LAY SUMMARY: This study objectively measured associations between children’s peer vocal interactions and assessed language abilities in inclusion classrooms for children with autism spectrum disorder (ASD) and their peers. All children benefited from peers talking to them, but children with ASD were less central to classroom speech networks than were typically developing children. Children’s centrality to social speech networks, regardless of ASD status, was associated with assessed language abilities.

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7. Floríndez LI, Como DH, Floríndez DC, Vigen C, Floríndez FM, Cermak SA. Identifying Gaps in Oral Care Knowledge, Attitudes, and Practices of Latinx Parents/Caregivers of Children With and Without Autism Spectrum Disorders. Health equity. 2021; 5(1): 185-93.

Purpose: This pilot study used data from a survey to examine the knowledge, attitudes, and practices about oral care of Latinx parents/caregivers of children with or without autism spectrum disorder (ASD) to identify gaps to focus future intervention. Methods: Sixty English-speaking Latinx parents/caregivers who had a child between 4 and 14 years with or without ASD (n=31 ASD, n=29 typically developing [TD]) completed a questionnaire on oral health knowledge, practices, access to care, and demographics. Caregiver responses were compared, and gaps in knowledge and practices were identified. Results: There were no significant differences in parent age, child age, income, insured status, or overall knowledge scores, only a significant difference in education (p=0.02), with the ASD group reporting less. Scores for knowledge, attitudes, access and practice were all nonsignificantly positively correlated, as was attitudes with access and practice. However, knowledge and attitudes were significantly negatively correlated. Additional significant findings were parents who had lower income and education, had lower oral knowledge scores, decreased frequency of dental visits, increased feelings of being discriminated against, children with increased fear of the dentist, and decreased ease of finding a dentist. Conclusion: Factors such as income, education, ethnicity, and having a child with ASD can influence what Latinx parents and caregivers know about oral health and how their children experience receiving dental care. Latinx parents/caregivers of children with and without ASD report barriers to dental care, including difficulty attending visits or feeling stigmatized by their dental provider due to their ethnicity. Fear of the dentist is significantly correlated with ASD diagnosis and lower social demographics of the parent, and may contribute to a reduction in preventative oral care visits as well. Health care providers should consider these perspectives when providing care to this population to mitigate further oral health inequities.

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8. Gevarter C, Najar AM, Flake J, Tapia-Alvidrez F, Lucero A. Naturalistic Communication Training for Early Intervention Providers and Latinx Parents of Children with Signs of Autism. Journal of developmental and physical disabilities. 2021: 1-23.

In this study, researchers implemented a brief training plus coaching program in naturalistic developmental behavioral intervention with three participant triads. Each triad consisted of an early intervention provider, an English-speaking Latinx parent, and that parent’s young child with autism spectrum disorder (ASD) or early signs of ASD who had limited vocal speech. The effects a single training session, plus two researcher coaching sessions were evaluated using a nonconcurrent multiple probes across participants design. Primary dependent variables included (a) the number of completed targeted communication turns between the parent and child and (b) the number of child independent target communication responses (gestures and manual signs) during family-selected routines. Additional measures examined whether parents used strategies taught to them during training, and whether early intervention providers addressed strategies taught via coaching. A social validity measure was used to determine parent and provider views of the training. Due to COVID-19 restrictions, training and post-training sessions were delivered via telehealth for two triads. While data trends and variability differed across triads, following training, all three families increased the number of completed target communication turns and all three children showed higher rates of independent communication responses. Parents and providers implemented strategies taught and reported positive effects of the program. Implications regarding the use of naturalistic intervention methods for Latinx families, the utility of brief training models to meet the needs of under-resourced early intervention programs, and potential uses of telehealth are discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10882-021-09794-w.

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9. Healy S, Brewer B, Palmiere K, Daly J, McGuire J, Patterson F. 24-h movement behaviors among autistic adults: Differences by sex, age, and level of independence. Disability and health journal. 2021; 14(4): 101108.

BACKGROUND: Autistic adults have low levels of physical activity [PA], high levels of sedentary behavior [SB], and insufficient sleep. Not known is the extent to which engagement in these movement behaviors vary by sex, age, and level of independence in activities of daily living (ADLs). OBJECTIVE: To characterize movement behaviors in a national sample of autistic adults by sex, age, and level of independence in ADLs. METHODS: A national sample of autistic adults and caregivers of autistic adults self-reported PA, SB and sleep behaviors as well as demographic variables using an electronic survey. Levels of engagement in movement behaviors were described, and compared by sex, age (young-adult versus middle-age), and level of independence in ADLs. RESULTS: Data were collected on 361 autistic adults (60.3% male, n = 217, m(age) = 30.82 years, SD = 10.24). Overall, 44% did not meet the PA guideline; PA guideline adherence was lowest among males and those who were dependent on others in ADLs. Overall, the SB guideline was not met by 43% of the sample at weekdays and 48% at weekends. SB guideline adherence was lowest among adults who were middle-aged, and those who were fully independent in ADLs. Overall, 35.2% did not meet the total sleep time (TST) guideline. Middle-aged autistic adults had the lowest adherence to the TST guideline. CONCLUSIONS: These finding should prompt researchers to consider these demographic differences, and tailor research and programmatic efforts to account for the unique movement behavior profiles of different segments of this heterogenous population.

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10. James DM, Davidson EA, Yanes J, Moshiree B, Dallman JE. The Gut-Brain-Microbiome Axis and Its Link to Autism: Emerging Insights and the Potential of Zebrafish Models. Frontiers in cell and developmental biology. 2021; 9: 662916.

Research involving autism spectrum disorder (ASD) most frequently focuses on its key diagnostic criteria: restricted interests and repetitive behaviors, altered sensory perception, and communication impairments. These core criteria, however, are often accompanied by numerous comorbidities, many of which result in severe negative impacts on quality of life, including seizures, epilepsy, sleep disturbance, hypotonia, and GI distress. While ASD is a clinically heterogeneous disorder, gastrointestinal (GI) distress is among the most prevalent co-occurring symptom complex, manifesting in upward of 70% of all individuals with ASD. Consistent with this high prevalence, over a dozen family foundations that represent genetically distinct, molecularly defined forms of ASD have identified GI symptoms as an understudied area with significant negative impacts on quality of life for both individuals and their caregivers. Moreover, GI symptoms are also correlated with more pronounced irritability, social withdrawal, stereotypy, hyperactivity, and sleep disturbances, suggesting that they may exacerbate the defining behavioral symptoms of ASD. Despite these facts (and to the detriment of the community), GI distress remains largely unaddressed by ASD research and is frequently regarded as a symptomatic outcome rather than a potential contributory factor to the behavioral symptoms. Allowing for examination of both ASD’s impact on the central nervous system (CNS) as well as its impact on the GI tract and the associated microbiome, the zebrafish has recently emerged as a powerful tool to study ASD. This is in no small part due to the advantages zebrafish present as a model system: their precocious development, their small transparent larval form, and their parallels with humans in genetics and physiology. While ASD research centered on the CNS has leveraged these advantages, there has been a critical lack of GI-centric ASD research in zebrafish models, making a holistic view of the gut-brain-microbiome axis incomplete. Similarly, high-throughput ASD drug screens have recently been developed but primarily focus on CNS and behavioral impacts while potential GI impacts have not been investigated. In this review, we aim to explore the great promise of the zebrafish model for elucidating the roles of the gut-brain-microbiome axis in ASD.

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11. Jangjoo M, Goodman SJ, Choufani S, Trost B, Scherer SW, Kelley E, Ayub M, Nicolson R, Georgiades S, Crosbie J, Schachar R, Anagnostou E, Grunebaum E, Weksberg R. An Epigenetically Distinct Subset of Children With Autism Spectrum Disorder Resulting From Differences in Blood Cell Composition. Frontiers in neurology. 2021; 12: 612817.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that often involves impaired cognition, communication difficulties and restrictive, repetitive behaviors. ASD is extremely heterogeneous both clinically and etiologically, which represents one of the greatest challenges in studying the molecular underpinnings of ASD. While hundreds of ASD-associated genes have been identified that confer varying degrees of risk, no single gene variant accounts for >1% of ASD cases. Notably, a large number of ASD-risk genes function as epigenetic regulators, indicating potential epigenetic dysregulation in ASD. As such, we compared genome-wide DNA methylation (DNAm) in the blood of children with ASD (n = 265) to samples from age- and sex-matched, neurotypical controls (n = 122) using the Illumina Infinium HumanMethylation450 arrays. Results: While DNAm patterns did not distinctly separate ASD cases from controls, our analysis identified an epigenetically unique subset of ASD cases (n = 32); these individuals exhibited significant differential methylation from both controls than the remaining ASD cases. The CpG sites at which this subset was differentially methylated mapped to known ASD risk genes that encode proteins of the nervous and immune systems. Moreover, the observed DNAm differences were attributable to altered blood cell composition, i.e., lower granulocyte proportion and granulocyte-to-lymphocyte ratio in the ASD subset, as compared to the remaining ASD cases and controls. This ASD subset did not differ from the rest of the ASD cases in the frequency or type of high-risk genomic variants. Conclusion: Within our ASD cohort, we identified a subset of individuals that exhibit differential methylation from both controls and the remaining ASD group tightly associated with shifts in immune cell type proportions. This is an important feature that should be assessed in all epigenetic studies of blood cells in ASD. This finding also builds on past reports of changes in the immune systems of children with ASD, supporting the potential role of altered immunological mechanisms in the complex pathophysiology of ASD. The discovery of significant molecular and immunological features in subgroups of individuals with ASD may allow clinicians to better stratify patients, facilitating personalized interventions and improved outcomes.

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12. Jodra M, García-Villamisar D. Transdiagnostic Predictors of Impaired Recognition of Facial Emotion Expression in Adults with Autism Spectrum Disorder and Intellectual Disability. Developmental neuropsychology. 2021; 46(3): 265-76.

This study aims to evaluate the predictive capacity of executive dysfunction and social adaptation in performance in facial emotion recognition. The sample consisted of 31 adults with Intellectual Disabilities (ID) and Autism Spectrum Disorder (ASD). The variables that maintain significant correlations with emotional perception were taken as independent variables. Multiple regression analysis was used to identify the predictors of the facial stimuli perception in population with ASD. The results demonstrated a relationship between social maturity and emotional perception. Better scores in communication, socialization and daily life skills predict better performance in the perception of facial stimuli, both emotional and non-emotional.

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13. Leader G, Hogan A, Chen JL, Maher L, Naughton K, O’Rourke N, Casburn M, Mannion A. Age of Autism Spectrum Disorder Diagnosis and Comorbidity in Children and Adolescents with Autism Spectrum Disorder. Developmental neurorehabilitation. 2022; 25(1): 29-37.

AIM: Research is required to study the relationship between age of autism spectrum disorder (ASD) diagnosis and the presence of comorbidities. METHOD: The Gastrointestinal Symptom Inventory, Autism Spectrum Disorder-Comorbid for Children, Behavior Problem Inventory-Short Form and Social Communication Questionnaire were completed by parents of 129 children and adolescents with a diagnosis of ASD. RESULTS: Results revealed significant relationships between the age of ASD diagnosis, the presence of comorbidities and intellectual disability. Significant correlations were found between the age of ASD diagnosis and self-injurious and stereotyped behavior. Comorbid psychopathology significantly predicted the presence of GI symptoms. In addition, the relationship between comorbid psychopathology and challenging behavior in this study was reported as bi-directional as both comorbidities predicted one another in the sample. CONCLUSION: Future research needs to consider the role of comorbidities in relation to ASD diagnosis.

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14. Markowitz G, Buzby M. Weighing in on Children with Autism: Rethinkingee e Strategies for Weight Management. Journal of pediatric nursing. 2021; 59: 209-10.

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15. McClure LA, Lee NL, Sand K, Vivanti G, Fein D, Stahmer A, Robins DL. Connecting the Dots: a cluster-randomized clinical trial integrating standardized autism spectrum disorders screening, high-quality treatment, and long-term outcomes. Trials. 2021; 22(1): 319.

BACKGROUND: Autism spectrum disorder (ASD) affects one in 54 children in the United States of America, and supporting people with ASD across the lifespan presents challenges that impact individuals, families, and communities and can be quite costly. The American Academy of Pediatrics has issued recommendations for routine ASD screening at 18 and 24 months, but some research suggests that few pediatricians perform high-fidelity, standardized screening universally. Furthermore, the United States Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against universal ASD screening. The objective of this study is to test the hypothesis that children with ASD who have high fidelity; standardized screening will achieve superior outcomes at 5 years of age compared to children receiving usual care ASD detection strategies. METHODS: This is a cluster-randomized, controlled clinical trial in 3 sites in the USA. Pediatric practices will be randomized to implement universal, standardized, high-fidelity toddler screening or usual care, with randomization stratified by the practice size. The study will enroll 3450 children, approximately half in each group. From this sample, we anticipate 100 children to be diagnosed with ASD. Children in both groups receiving an ASD diagnosis will be administered the Early Start Denver Model, an evidence-based early intervention addressing social, communication, and cognitive functioning. Treatment will last for 1 year, with up to 20 h per week of therapy for children with ASD. RESULTS: Primary outcomes measured at baseline, following treatment, and at 4 and 5 years of age include ASD symptom severity (Brief Observation of Social Communication Change (BOSCC)) and cognitive functioning (Mullen Scales of Early Learning (MSEL) and Differential Abilities Scale-II (DAS-II)). Secondary outcomes in children include measures of adaptive functioning, ASD symptoms, and kindergarten readiness; secondary analyses will also examine stress and empowerment among parents. Several novel exploratory measures will be included as well. The study will utilize a modified intention-to-treat analysis. CONCLUSIONS: This trial will evaluate the impact of universal, standardized, high-fidelity screening for ASD among children at 18 months of age, with a goal of providing evidence to support this strategy to detect ASD in toddlers in order to start treatment as young as possible and maximize outcomes. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at Drexel University (IRB protocol: 1607004653). All findings will be provided by the principal investigator via email; data will be available through the NIMH Data Archive ( https://nda.nih.gov/ ). TRIAL REGISTRATION: ClinicalTrials.gov NCT03333629 . Registered on November 7, 2017.

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16. McPartland JC. Refining biomarker evaluation in ASD. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2021; 48: 34-6.

This commentary reflects on reasonable biomarker expectations in ASD by addressing three key questions: What is a biomarker? What is required for a biomarker in ASD? How can biomarkers be useful in ASD? In addressing these queries, a path forward emerges based on clear definition of the objective for any given ASD biomarker and evaluation of each biomarker relative to current best practices.

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17. Mendonca LO, Prado AI, Costa IMC, Bandeira M, Dyer R, Barros SF, Khöler KF, Fonseca LAM, Kalil J, Castro FM, Toledo-Barros MAM. Case Report: Expanding Clinical, Immunological and Genetic Findings in Sideroblastic Anemia With Immunodeficiency, Fevers and Development Delay (SIFD) Syndrome. Frontiers in immunology. 2021; 12: 586320.

Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.

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18. Morgart K, Harrison JN, Hoon AH, Jr., Wilms Floet AM. Adverse childhood experiences and developmental disabilities: risks, resiliency, and policy. Developmental medicine and child neurology. 2021; 63(10): 1149-54.

Thanks to the seminal work of Robert Anda and Vincent Felitti, it is now widely accepted that adverse childhood experiences (ACEs) can have lifelong effects on physical, behavioral, and mental health and that many adult diseases can be considered developmental disorders that began early in life. Genomics has advanced the neurobiological understanding that underpins ACEs, wellness, and disease, which are modulated through stress pathways and epigenetic modifications. While data are currently limited, children with developmental disabilities have an increased ACE risk compared to typically developing peers. This recognition has important ramifications for health and policy interventions that address the root causes of ACEs, especially in this vulnerable population. With increased societal recognition, advances in policy will lead to medical, financial, and public benefits in years to come, hopefully changing healthcare models from ‘sick care’ to ‘well care’. What this paper adds Adverse childhood experience (ACE) research has refocused medicine from the question ‘What is wrong with you?’ to ‘What happened to you?’. Adopting ACE research into public policy can redirect healthcare models from providing ‘sick care’ to promoting ‘well care’. Not exploring the role of ACEs in children with developmental disabilities leads to further vulnerability and morbidity. ACEs can be mitigated by early identification and implementation of evidence-based interventions.

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19. Naguy A, Pridmore S, Alamiri B. Benzodiazepines in autism spectrum disorder-wise or otherwise?. CNS spectrums. 2021: 1.

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20. Poole D, Miles E, Gowen E, Poliakoff E. Shifting attention between modalities: Revisiting the modality-shift effect in autism. Attention, perception & psychophysics. 2021; 83(6): 2498-509.

Selective attention to a sensory modality has been observed experimentally in studies of the modality-shift effect – a relative performance benefit for targets preceded by a target in the same modality, compared to a different modality. Differences in selective attention are commonly observed in autism and we investigated whether exogenous (automatic) shift costs between modalities are increased. Autistic adults and neurotypical controls made speeded discrimination responses to simple visual, tactile and auditory targets. Shift costs were observed for each target modality in participant response times and were largest for auditory targets, reflective of fast responses on auditory repeat trials. Critically, shift costs were similar between the groups. However, integrating speed and accuracy data using drift-diffusion modelling revealed that shift costs in drift rates (reflecting the quality of information extracted from the stimulus) were reduced for autistic participants compared with neurotypicals. It may be that, unlike neurotypicals, there is little difference between attention within and between sensory modalities for autistic people. This finding also highlights the benefit of combining reaction time and accuracy data using decision models to better characterise selective attention in autism.

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21. Rampazzo ACM, Dos Santos RRP, Maluf FA, Simm RF, Marson FAL, Ortega MM, de Aguiar PHP. Dravet syndrome and Dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants. Neurogenetics. 2021; 22(2): 105-15.

Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. The present review aims to clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. A systematic review was conducted in PubMed and Virtual Health Library (VHL) databases, using « Dravet Syndrome » and « Severe Myoclonic Epilepsy in Infancy (SMEI) » search words, selecting cohort of studies published in journal with impact factor of two or greater. The systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Nineteen studies were included in the present review, and a significant proportion of patients with DS-carrying SCN1A was greater than patients with DS-like phenotype-harboring PCDH19 variants (76.6% versus 23.4%). When clinical and genetic data were correlated, autism was predominantly observed in patients with DS-like-carrying PCDH19 variants compared to SCN1A variant carriers (62.5% versus 37.5%, respectively, P-value = 0.044, P-value corrected = 0.198). In addition, it was noticed a significant predisposition to hyperthermia during epilepsy crisis in individuals carrying PCDH19 variants (P-value = 0.003; P-value corrected = 0.027). The present review is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.

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22. Smith IM, Waddell C, Ungar WJ, den Otter J, Murray P, Vezina F, D’Entremont B, Flanagan HE, Garon N. Preschool autism services: A tale of two Canadian provinces and the implications for policy. Paediatrics & child health. 2021; 26(3): 145-8.

For children with autism spectrum disorder (ASD), a lifelong neurodevelopmental condition, assessment and treatment services vary widely across Canada-potentially creating inequities. To highlight this, the Preschool Autism Treatment Impact study compared children’s services and outcomes in New Brunswick (NB) and Nova Scotia (NS). Diagnostic practices, service delivery models, wait times, and treatment approaches differed, as did children’s 1-year outcomes and costs for families and the public sector. Considering NB and NS strengths, we suggest that an optimal system would include: rapid access to high-quality diagnostic and intervention services; adherence to research-informed practice guidelines; interventions to enhance parents’ skills and self-efficacy; and measures to minimize financial burdens for families. Our results also suggest that provinces/territories must do more to ensure equitable access to effective services, including sharing and reporting on national comparative data. Canadian children with ASD deserve access to effective and consistent services, no matter where they live.

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23. Srancikova A, Bacova Z, Bakos J. The epigenetic regulation of synaptic genes contributes to the etiology of autism. Reviews in the neurosciences. 2021; 32(7): 791-802.

Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.

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24. Yui K, Imataka G, Sasaki H, Shiroki R, Koshiba M. Lipid Peroxidation With Implication of Organic Pollution in Autistic Behaviors. Cureus. 2021; 13(3): e14188.

Background Lipid metabolism has been associated with the development of autism. The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) readily undergo lipid peroxidation and conversion to malondialdehyde (MDA). MDA-modified low-density lipoprotein (MDA-LDL) is a marker of lipid peroxidation. However, the association between PUFAs and MDA-LDL in the pathophysiology of autism spectrum disorder (ASD) is unclear. Materials and methods We studied the association between PUFAs and MDA-LDL in 16 individuals with ASD (mean age: 11.5 ± 5.7 years) and seven age- and sex-matched healthy controls (mean age: 10.0 ± 4.1 years). The Aberrant Behavior Checklist (ABC) was used to assess behavioral symptoms. We overcame the small sample size by using the adaptive LASSO for enhancing the accuracy of prediction and interpretability. We also estimated the coefficient of variation for an appropriate variable selection and compared additional prior studies to support the findings. Thus, we conducted a careful selection of appropriate candidates to account for confounding variables. Results The ASD group had significantly higher plasma MDA levels, eicosapentaenoic acid levels, and a higher ratio of plasma docosahexaenoic acid (DHA)/arachidonic acid (ARA) levels than the control group. Plasma levels of the omega-6 PUFA fraction, dihomo-γ-linolenic acid, and superoxide dismutase levels were significantly lower in the ASD group than in the control group. Total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression and adaptive LASSO indicated that plasma DHA levels and plasma DHA/ARA ratios were significantly associated with total ABC scores and plasma levels of MDA-LDL. Conclusion Increased plasma levels of DHA and DHA/ARA ratio might be related to organic pollution. These neurobiological bases may induce neuronal deficiency associated with autistic behavioral symptoms in individuals with ASD.

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