Publications by authors named "Lonnie Zwaigenbaum"

249 Publications

Early trajectories of motor skills in infant siblings of children with autism spectrum disorder.

Autism Res 2021 Nov 26. Epub 2021 Nov 26.

Autism Research Centre, IWK Health Centre, Halifax, Canada.

Delays in motor development are not considered a core feature of autism spectrum disorder (ASD). Yet, recent studies of infant siblings of children with ASD suggest that early delays in motor skills may be associated with later delays in developmental areas considered to be core features of an ASD diagnosis. While these studies demonstrate the longitudinal association between core features and motor delays observed at single time points, there is considerable interest in studying the trajectories of motor development over the first 3 years of life. To accomplish this, we investigated early trajectories of motor development in a cohort of 499 infant siblings of children with ASD and 176 children with no family history of ASD. Data for the current study were drawn from the prospective, multi-site, Canadian Infant Sibling Study. We evaluated trajectories of fine and gross motor development over the first 3 years using group-based trajectory modeling. Our results show that membership for both fine and gross motor trajectory groups was related to expressive language skills, receptive language skills, ASD symptom severity scores, and diagnostic classification at age 3. These results provide evidence that the trajectory of a child's early motor development may have important prognostic implications in ASD.
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http://dx.doi.org/10.1002/aur.2641DOI Listing
November 2021

Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years.

Child Dev 2021 Oct 28. Epub 2021 Oct 28.

Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.
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http://dx.doi.org/10.1111/cdev.13697DOI Listing
October 2021

Pre-symptomatic intervention for autism spectrum disorder (ASD): defining a research agenda.

J Neurodev Disord 2021 10 15;13(1):49. Epub 2021 Oct 15.

Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA.

Autism spectrum disorder (ASD) impacts an individual's ability to socialize, communicate, and interact with, and adapt to, the environment. Over the last two decades, research has focused on early identification of ASD with significant progress being made in understanding the early behavioral and biological markers that precede a diagnosis, providing a catalyst for pre-symptomatic identification and intervention. Evidence from preclinical trials suggest that intervention prior to the onset of ASD symptoms may yield more improved developmental outcomes, and clinical studies suggest that the earlier intervention is administered, the better the outcomes. This article brings together a multidisciplinary group of experts to develop a conceptual framework for behavioral intervention, during the pre-symptomatic period prior to the consolidation of symptoms into diagnosis, in infants at very-high-likelihood for developing ASD (VHL-ASD). The overarching goals of this paper are to promote the development of new intervention approaches, empirical research, and policy efforts aimed at VHL-ASD infants during the pre-symptomatic period (i.e., prior to the consolidation of the defining features of ASD).
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http://dx.doi.org/10.1186/s11689-021-09393-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520312PMC
October 2021

Affect and gaze responses during an Emotion-Evoking Task in infants at an increased likelihood for autism spectrum disorder.

Mol Autism 2021 Oct 6;12(1):63. Epub 2021 Oct 6.

McMaster University, Hamilton, ON, Canada.

Background: The majority of research examining emotional difficulties in autism spectrum disorder (ASD) prior to age 2 relies on parent report.

Methods: We examined behavioral responses (affect and gaze) during emotionally salient tasks designed to elicit mildly positive and negative emotional states in infants. At 12 and 18 months, infants at an increased likelihood for an ASD diagnosis (IL; have an older sibling with ASD; n = 60) and low likelihood (LL; no family history of ASD; n = 21) completed the Emotion-Evoking (EE) Task and parents completed the Infant Behavior Questionnaire-Revised (IBQ-R). All children received an Autism Diagnostic Observation Scale-second Edition assessment for ASD symptomatology at 24 months.

Results: The main findings were (1) the IL group displayed higher rates of negative affect and spent less time looking at the task objects compared to the LL group, and (2) affect and gaze scores at 12 and 18 months, but not scores on the IBQ-R, predicted ASD symptoms at 24 months.

Limitations: The data were drawn from an IL sample and may not be generalizable to the general ASD population, and the children were not followed to determine a diagnosis of ASD.

Conclusion: These results suggest that behavioral responses can provide important information that complements parent reports of emotional regulation in IL infants as early as 12 months of age.
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http://dx.doi.org/10.1186/s13229-021-00468-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493694PMC
October 2021

Facilitator Reflections on Shared Expertise and Adaptive Leadership in ECHO Autism: Center Engagement.

J Contin Educ Health Prof 2021 Oct 1. Epub 2021 Oct 1.

Vinson: Assistant Professor, Department of Learning Health Sciences, University of Michigan, Ann Arbor, MI. Iannuzzi: Psychiatric Social Worker, Brigham and Women's Hospital, Department of Psychiatry; Instructor, Harvard Medical School Department of Psychiatry, Boston MA. Bennett: Clinical Chair, Division of Developmental and Behavioral Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA. Butter: Chief & Associate Professor, Pediatrics, Psychiatry, & Psychology; Director, Child Development Center, Nationwide Children's Hospital, Ohio State University, Columbus, OH. Curran: Director of Strategic Initiatives, ECHO Autism; CDC's Act Early Ambassador in Missouri, Columbia, MO. Hess: Behavioral Health Outreach, Nationwide Children's Hospital, Columbus, OH. Hyman: Professor of Pediatrics, Division Chief, Developmental and Behavioral Pediatrics, University of Rochester, Rochester, NY. Kelly: National Director of Family Engagement, Devereux Advanced Behavioral Health, Philadelphia, PA. Murray: Vice President, Head of Clinical Programs, Autism Speaks, Adjunct Professor of Pediatrics, Department of Developmental & Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, OH. Nowinski: Clinical Director of Non- Physician Services, Lurie Center for Autism, Massachusetts General Hospital, MA, and Instructor, Harvard Medical School, Boston, MA. Zwaigenbaum: Professor, Division of Developmental Pediatrics, Department of Pediatrics, University of Alberta, Edmonton, AB. Sohl: Professor, Department of Child Health, University of Missouri, Columbia, MO; Executive Director ECHO Autism.

Introduction: Project Extension for Community Healthcare Outcomes (ECHO) is used to increase provider capacity in a wide range of health care specialties. ECHO Autism: Center Engagement is a program that promotes improvement in autism care by improving the management of autism care centers. The program's focus brought experienced clinicians together as both facilitators and participants in an ECHO series. ECHO Autism: Center Engagement facilitators devised a reflective writing exercise to prospectively study their experience leading this new curriculum.

Methods: Drawing on a qualitative thematic analysis of longitudinal reflective writing exercises from seven "Hub Team" facilitators, we describe how ECHO leaders cultivate a learning environment that emphasizes shared learning and acknowledges the expertise of ECHO participants.

Results: The analysis generated three main themes: (1) Hub Team facilitators valued reciprocal exchange with Spoke sites, a theme we name "shared learning," (2) Hub Team facilitators demonstrated high levels of awareness about their facilitation styles, and (3) Hub Team facilitators cultivated an interactional style they described as "all teach, all learn."

Discussion: Examining the experiences of ECHO facilitators produces qualitative accounts of continuing professional development that may not be captured in other program evaluation approaches. In the case of ECHO Autism: Center Engagement, facilitators cultivated an environment of shared learning, which acknowledged the expertise of both facilitators and participants. These findings are pertinent for scholars of continuing education in health professions who lead educational programs where participants and facilitators have high levels of overlap in their areas of expertise and years of experience.
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http://dx.doi.org/10.1097/CEH.0000000000000395DOI Listing
October 2021

Association of Epidural Analgesia During Labor and Delivery With Autism Spectrum Disorder in Offspring.

JAMA 2021 09;326(12):1178-1185

British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.

Importance: Evidence from studies investigating the association of epidural analgesia use during labor and delivery with risk of autism spectrum disorder (ASD) in offspring is conflicting.

Objective: To assess the association of maternal use of epidural analgesia during labor and delivery with ASD in offspring using a large population-based data set with clinical data on ASD case status.

Design, Setting, And Participants: This population-based retrospective cohort study included term singleton children born in British Columbia, Canada, between April 1, 2000, and December 31, 2014. Stillbirths and cesarean deliveries were excluded. Clinical ASD diagnostic data were obtained from the British Columbia Autism Assessment Network and the British Columbia Ministry of Education. All children were followed up until clinical diagnosis of ASD, death, or the study end date of December 31, 2016.

Exposures: Use of epidural analgesia during labor and delivery.

Main Outcomes And Measures: A clinical diagnosis of ASD made by pediatricians, psychiatrists, and psychologists with specialty training to assess ASD. Cox proportional hazards models were used to estimate the hazard ratio of epidural analgesia use and ASD. Models were adjusted for maternal sociodemographics; maternal conditions during pregnancy; labor, delivery, and antenatal care characteristics; infant sex; gestational age; and status of small or large for gestational age. A conditional logistic regression model matching women with 2 births or more and discordance in ASD status of the offspring also was performed.

Results: Of the 388 254 children included in the cohort (49.8% female; mean gestational age, 39.2 [SD, 1.2] weeks; mean follow-up, 9.05 [SD, 4.3] years), 5192 were diagnosed with ASD (1.34%) and 111 480 (28.7%) were exposed to epidural analgesia. A diagnosis of ASD was made for 1710 children (1.53%) among the 111 480 deliveries exposed to epidural analgesia (94 157 women) vs a diagnosis of ASD in 3482 children (1.26%) among the 276 774 deliveries not exposed to epidural analgesia (192 510 women) (absolute risk difference, 0.28% [95% CI, 0.19%-0.36%]). The unadjusted hazard ratio was 1.32 (95% CI, 1.24-1.40) and the fully adjusted hazard ratio was 1.09 (95% CI, 1.00-1.15). There was no statistically significant association of epidural analgesia use during labor and delivery with ASD in the within-woman matched conditional logistic regression (839/1659 [50.6%] in the exposed group vs 1905/4587 [41.5%] in the unexposed group; fully adjusted hazard ratio, 1.07 [95% CI, 0.87-1.30]).

Conclusions And Relevance: In this population-based study, maternal epidural analgesia use during labor and delivery was associated with a small increase in the risk of autism spectrum disorder in offspring that met the threshold for statistical significance. However, given the likelihood of residual confounding that may account for the results, these findings do not provide strong supporting evidence for this association.
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http://dx.doi.org/10.1001/jama.2021.14986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479579PMC
September 2021

Rethinking autism spectrum disorder assessment for children during COVID-19 and beyond.

Autism Res 2021 11 22;14(11):2251-2259. Epub 2021 Sep 22.

Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA.

The COVID-19 pandemic has posed unique challenges for families and caregivers, as well as for autism-focused clinicians, who are faced with providing a thorough and accurate evaluation of children's specific needs and diagnoses in the absence of in-person assessment tools. The shift to telehealth assessments has challenged clinicians to reconsider approaches and assumptions that underlie the diagnostic assessment process, and to adopt new ways of individualizing standard assessments according to family and child needs. Mandates for physical distancing have uncovered deficiencies in diagnostic practices for suspected autism and have illuminated biases that have posed obstacles preventing children and families from receiving the services that they truly need. This Commentary outlines several considerations for improving diagnostic practices as we move forward from the current pandemic and continue to strive to build an adaptable, sustainable, equitable, and family-centered system of care. LAY SUMMARY: Physical distancing and the abrupt end to in-person services for many children on the autism spectrum has forced clinicians to examine the existing challenges with autism spectrum disorder (ASD) diagnostic assessment and consider things they want to keep and things that should be changed in the years ahead. New approaches such as telehealth both alleviated and exacerbated existing disparities, and brought into stark focus the importance of equitable and timely access to family-centered care. This commentary suggests ways of improving clinical practices related to ASD assessment to continue along this path.
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http://dx.doi.org/10.1002/aur.2615DOI Listing
November 2021

: A novel method to access first-person perspective of autistic youth.

Autism 2021 Sep 4:13623613211042128. Epub 2021 Sep 4.

McGill University, Canada.

Lay Abstract: The perspective of autistic individuals is often left uncaptured, and as a result they are often excluded from making decisions that impact them. Conventional communication can be challenging for many autistic individuals, especially those who are minimally verbal or who have an associated intellectual disability. Currently, a lack of appropriate methods to capture voices across the spectrum is a barrier. In the present study, we developed the protocol using universal design principles to capture the perspectives and experiences of autistic youth with a range of language or intellectual abilities. This protocol was then used with 33 autistic youth aged 11 to 18 years. A scoring rubric was developed to capture the unconventional communication used by the participants and the mitigation strategies used by interviewers to facilitate the interview. Many components of the protocol were found to effectively facilitate communication between the participant and interviewer, including the use of picture cards to support verbal questions/prompts, the fact that participants could respond with their preferred communication methods (writing, texting, pointing), and the fact that interviews were applied flexibly to adapt to each participant. Unconventional communication and mitigation strategies were mostly observed in interviews with minimally verbal individuals, but a fine-grained analysis showed participants were still communicating something through this unconventional communication. Our protocol could help promote the inclusion of more autistic individuals in research and showed that unconventional modes of communication like echolalia provide an understanding that participants' are invested in conversations and certain topics are more meaningful than others.
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http://dx.doi.org/10.1177/13623613211042128DOI Listing
September 2021

Middle-childhood executive functioning mediates associations between early-childhood autism symptoms and adolescent mental health, academic and functional outcomes in autistic children.

J Child Psychol Psychiatry 2021 Aug 12. Epub 2021 Aug 12.

Cundill Centre for Child and Youth Depression, Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.

Background: Executive functioning (EF) varies in children with autism spectrum disorder (ASD) and is associated with clinical symptoms, academic, and adaptive functioning. Here, we examined whether middle-childhood EF mediates associations between early-childhood autism symptoms and adolescent outcomes in children with ASD.

Methods: The Pathways in ASD Cohort comprising children recruited at the time of ASD diagnosis (at 2-4 years-of-age) and followed prospectively across eight subsequent timepoints over ˜10 years was used. A subset of Pathways participants (n = 250) with Behavior Rating Inventory of Executive Function (BRIEF)-Parent Form data from at least one timepoint when participants were school-aged was analyzed. A mediation framework was used to examine whether BRIEF-measured EF across age 7-10 years (middle-childhood) mediated associations between early-childhood autism symptoms (measured using the parent-report Social Responsiveness Scale across age 2-6 years) and clinical, academic, and functional outcomes, indexed at age >10-11.8 years (early-adolescence) using the Child Behavior Checklist (CBCL)-Internalizing and Externalizing Scales, Academic Performance from the Teacher's Report Form, and Vineland Adaptive Behavior Scales. Models were rerun substituting clinician-rated and teacher-rated measures, where possible.

Results: Mediation models indicated a significant indirect effect of middle-childhood EF on associations between early-childhood autism symptoms and externalizing behavior, academic performance, or adaptive functioning in early adolescence; kappa squared (κ ) effect sizes ranged from large to small. Model findings were stable across raters. Middle-childhood EF did not mediate associations between early-childhood autism symptoms and adolescent internalizing behavior.

Conclusions: Among children with an ASD diagnosis, middle-childhood EF may be one pathway through which early-childhood autism symptoms influence a variety of outcomes in early-adolescence. An experimental study targeting middle-childhood EF to improve adolescent academic, emotional/behavioral, and adaptive functioning is needed to evaluate the clinical meaningfulness of these findings.
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http://dx.doi.org/10.1111/jcpp.13493DOI Listing
August 2021

Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review.

Autism Res 2021 09 26;14(9):1820-1836. Epub 2021 Jun 26.

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial-based therapies in ASD. With a robust double-blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results. LAY SUMMARY: There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.
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http://dx.doi.org/10.1002/aur.2560DOI Listing
September 2021

Social and non-social sensory responsivity in toddlers at high-risk for autism spectrum disorder.

Autism Res 2021 10 19;14(10):2143-2155. Epub 2021 Jun 19.

University of Minnesota, Minneapolis, Minnesota, USA.

Empirical evidence concerning sensory responsivity in young children who later develop autism spectrum disorder (ASD) remains relatively limited. It is unclear whether specific patterns or aspects of sensory responsivity underlay the emergence of the disorder. The goals of this study were to (a) examine whether social versus non-social context impacted the expression of sensory responsivity in infants at high risk for ASD, and (b) examine if sensory responsivity in social or non-social contexts was associated with severity of ASD symptoms. The Sensory Experiences Questionnaire 2.1 was collected for 338 infants (131 females, 207 males) at high-risk for ASD at 12 and/or 24 months of age. High-risk toddlers meeting diagnostic criteria for ASD (n = 75) showed elevated sensory responsivity in both social and non-social contexts at 12 months of age and differences widened over the second year of life. Individuals with ASD demonstrate higher responsivity in both contexts suggestive of generalized atypical sensory responsivity in ASD. LAY SUMMARY: Behaviors such as avoiding or noticing sensory input (e.g., sounds, touches) are often different in individuals with autism spectrum disorder (ASD) than those without. The reason for this is widely unknown. The findings from this study show that in toddlers, sensory responsivity increased in both social and non-social situations. Therefore, the setting of sensory input does not explain these differences.
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http://dx.doi.org/10.1002/aur.2556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487998PMC
October 2021

Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD.

Autism Res 2021 08 22;14(8):1710-1723. Epub 2021 May 22.

Institute of Child Development, University of Minnesota, Minneapolis, Minnesota, USA.

Intense interests are common in children with and without autism spectrum disorder (ASD), and little research has characterized aspects of interests that are unique to or shared among children with and without ASD. We aimed to characterize interests in a sample of infants at high-familial-risk (HR) and low-familial-risk (LR) for ASD using a novel interview. Participants included HR siblings who were diagnosed with ASD at 24 months (HR-ASD, n = 56), HR siblings who did not receive an ASD diagnosis at 24 months (HR-Neg, n = 187), and a LR comparison group (n = 109). We developed and collected data with the Intense Interests Inventory at 18- and 24-months of age, a semi-structured interview that measures intensity and peculiarity of interests in toddlers and preschool-aged children. Intensity of interests differed by familial risk at 24 months, with HR-ASD and HR-Neg groups demonstrating equivalent intensity of interests that were higher than the LR group. By contrast, peculiarity of interest differed by ASD diagnosis, with the HR-ASD group showing more peculiar interests than the HR-Neg and LR groups at 24 months. At 18 months the HR-ASD group had more peculiar interests than the LR group, though no differences emerged in intensity of interests. This measure may be useful in identifying clinically-relevant features of interests in young children with ASD. We also replicated previous findings of males showing more intense interests at 18 months in our non-ASD sample. These results reveal new information about the nature of interests and preoccupations in the early autism phenotype. LAY SUMMARY: Intense interests are common in young children with autism and their family members. Intense interests are also prevalent among typically-developing children, and especially boys. Here we catalog interests and features of these interests in a large sample of toddlers enriched for autism risk. Children who had family members with autism had more intense interests, and those who developed autism themselves had more unusual interests at 24 months. These results highlight the importance of different aspects of interest in autism.
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http://dx.doi.org/10.1002/aur.2543DOI Listing
August 2021

Investigating longitudinal associations between parent reported sleep in early childhood and teacher reported executive functioning in school-aged children with autism.

Sleep 2021 09;44(9)

Montreal Neurological Institute, Azrieli Centre for Autism Research, McGill University, Montreal, Canada.

Up to 80% of children with autism spectrum disorder (ASD) experience sleep disturbance. Poor sleep impairs executive functioning (EF), a lifelong difficulty in ASD. Evidence suggests EF difficulties in ASD are exacerbated by poor sleep. We examine whether early childhood sleep disturbances are associated with worsening EF trajectories in school-aged children with ASD. A subsample (n = 217) from the Pathways in ASD longitudinal study was analyzed. The Children's Sleep Habits Questionnaire captured sleep duration, onset, and night awakenings before age 5 (mean = 3.5 years). Metacognition (MI) and Behavioral Regulation (BRI) indices, on the Teacher Behavior Rating Inventory of Executive Functioning, were used to measure cognitive and affective components of EF respectively at four time-points (7.8-11.8 years). We applied latent growth curve models to examine associations between sleep and EF, accounting for relevant covariates, including school-age sleep (mean = 6.7 years). Sleep traits had different age-related impacts on behavioral regulation, but not metacognition. Longer sleep onset at 3.5 years was associated with a worsening BRI difficulties slope (b = 2.07, p < 0.04), but conversely associated with lower BRI difficulties at 7.7 years (b = -4.14, p = 0.04). A longer sleep onset at 6.7 years was related to higher BRI difficulties at 7.7 years (b = 7.78, p < 0.01). Longer sleep duration at 6.7 years was associated with higher BRI difficulties at age 7.7 (b = 3.15, p = 0.01), but subscale analyses revealed shorter sleep duration at age 6.7 was linked to a worsening inhibition slope (b = -0.60, p = 0.01). Sleep onset is a robust early correlate of behavior regulation in children with ASD, whereas sleep duration is a later childhood correlate.
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http://dx.doi.org/10.1093/sleep/zsab122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522468PMC
September 2021

Variability in Responding to Joint Attention Cues in the First Year is Associated With Autism Outcome.

J Am Acad Child Adolesc Psychiatry 2021 Jun 2. Epub 2021 Jun 2.

University of Minnesota, Minneapolis. Electronic address:

Objective: With development, infants become increasingly responsive to the many attention-sharing cues of adults; however, little work has examined how this ability emerges in typical development or in the context of early autism spectrum disorder (ASD). This study characterized variation in the type of cue needed to elicit a response to joint attention (RJA) using the Dimensional Joint Attention Assessment (DJAA) during naturalistic play.

Method: We measured the average redundancy of cue type required for infants to follow RJA bids from an experimenter, as well as their response consistency, in 268 infants at high (HR, n = 68) and low (LR, N = 200) familial risk for ASD. Infants were assessed between 8 and 18 months of age and followed up with developmental and clinical assessments at 24 or 36 months. Our sample consisted of LR infants, as well as HR infants who did (HR-ASD) and did not (HR-neg) develop ASD at 24 months.

Results: We found that HR and LR infants developed abilities to respond to less redundant (more sophisticated) RJA cues at different rates, and that HR-ASD infants displayed delayed abilities, identifiable as early as 9 months, compared to both HR-neg and LR infants. Interestingly, results suggest that HR-neg infants may exhibit a propensity to respond to less redundant (more sophisticated) RJA cues relative to both HR-ASD and LR infants.

Conclusions: Using an approach to characterize variable performance of RJA cue-reading abilities, findings from this study enhance our understanding of both typical and ASD-related proficiencies and deficits in RJA development.
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http://dx.doi.org/10.1016/j.jaac.2021.03.023DOI Listing
June 2021

Relations of Restricted and Repetitive Behaviors to Social Skills in Toddlers with Autism.

J Autism Dev Disord 2021 May 6. Epub 2021 May 6.

University of Minnesota, 56 East River Road, Minneapolis, MN, 55455, USA.

We examined the relations of restricted and repetitive behaviors (RRB; insistence on sameness, repetitive sensory-motor, self-injurious behavior) to social skills overall and aspects that comprise social skills as measured by the VABS-II (coping skills, play/leisure time, interpersonal relationships) in 24- (n = 63) and 36-month old (n = 35), high-familial-risk toddlers with ASD. Hierarchical linear regression results indicated that repetitive sensory-motor was the best predictor of social skills overall. Secondary results indicated that all three RRB subtypes were associated with each subdomain of social skills; however, repetitive sensory-motor was the strongest and most consistent among these effects. While our results suggests a general negative relation of subtypes of RRB to aspects of adaptive social function, repetitive sensory-motor behaviors may be of particular relevance to the development of social skills during toddlerhood.
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http://dx.doi.org/10.1007/s10803-021-05014-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571122PMC
May 2021

Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach.

J Child Psychol Psychiatry 2021 10 7;62(10):1236-1245. Epub 2021 Apr 7.

Center for Autism Research, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis.

Methods: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary.

Results: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change.

Conclusions: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses.
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http://dx.doi.org/10.1111/jcpp.13406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601115PMC
October 2021

Symptom trajectories in the first 18 months and autism risk in a prospective high-risk cohort.

J Child Psychol Psychiatry 2021 Dec 29;62(12):1435-1443. Epub 2021 Mar 29.

McMaster Children's Hospital Autism Program, Hamilton Health Sciences, Hamilton, ON, Canada.

Background: Although early autism spectrum disorder (ASD) detection strategies tend to focus on differences at a point in time, behavioral symptom trajectories may also be informative.

Methods: Developmental trajectories of early signs of ASD were examined in younger siblings of children diagnosed with ASD (n = 499) and infants with no family history of ASD (n = 177). Participants were assessed using the Autism Observation Scale for Infants (AOSI) from 6 to 18 months. Diagnostic outcomes were determined at age 3 years blind to previous assessments.

Results: Semiparametric group-based modeling using AOSI scores identified three distinct trajectories: Group 1 ('Low', n = 435, 64.3%) was characterized by a low level and stable evolution of ASD signs, group 2 ('Intermediate', n = 180, 26.6%) had intermediate and stable levels, and group 3 ('Inclining', n = 61, 9.3%) had higher and progressively elevated levels of ASD signs. Among younger siblings, ASD rates at age 3 varied by trajectory of early signs and were highest in the Inclining group, membership in which was highly specific (94.5%) but poorly sensitive (28.5%) to ASD. Children with ASD assigned to the inclining trajectory had more severe symptoms at age 3, but developmental and adaptive functioning did not differ by trajectory membership.

Conclusions: These prospective data emphasize variable early-onset patterns and the importance of a multipronged approach to early surveillance and screening for ASD.
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http://dx.doi.org/10.1111/jcpp.13417DOI Listing
December 2021

Association of Child and Family Attributes With Outcomes in Children With Autism.

JAMA Netw Open 2021 03 1;4(3):e212530. Epub 2021 Mar 1.

University of Alberta, Edmonton, Alberta, Canada.

Importance: The prevalence and attributes of positive outcomes (or doing well) among children with autism spectrum disorder (ASD) in midchildhood are not well known.

Objective: To estimate the prevalence of doing well according to metrics of proficiency and growth and to investigate the extent to which significant associations exist between child- and family-level variables and doing well.

Design, Setting, And Participants: This longitudinal cohort study included children with ASD from regional clinics across Canada. Participants were sampled 3 times between ages 2 and 4.9 years (T1) and twice in follow-up into middle childhood (T2). Data were analyzed March 2018 through January 2020.

Exposures: Language and IQ assessments at first sample; household income, parent coping, and family functioning.

Main Outcomes And Measures: Key outcome domains of developmental health included measures of socialization, communication, independent living skills, and measures of internalizing and externalizing behaviors. Thresholds for doing well in these domains by either proficiency or growth were established. The extent to which language, IQ, household income, parent coping, and family functioning were associated with assessed outcomes was determined by logistic regression. The association between outcomes and concurrent Autism Diagnostic Observation Schedule (ADOS) classification scores was also estimated.

Results: In a total cohort of 272 children (234 [86.0%] boys; mean [SD] age, 10.76 [0.26] years), approximately 78.8% (95% CI, 73.2%-84.4%) of the sample were estimated to be doing well by either metric on at least 1 domain, and 23.6% (95% CI, 17.7%-29.4%) were doing well in 4 or 5 domains. It was possible to be doing well by either proficiency or growth and still meet ADOS criteria for ASD. For the growth metric, between 61.5% (95% CI, 40.7%-79.1%) and 79.6% (95% CI, 66.0%-88.9%) of participants had ADOS scores of 4 or greater; for the proficiency metric, between 63.8% (95% CI, 48.4%-76.9%) and 75.8% (95% CI, 63.0%-85.4%) had scores of 4 or greater. Doing well by either metric for all domains was associated with T1 scores on that outcome domain (eg, T1 daily living skills associated with doing well at T2 daily living by the proficiency metric as measured by the Vineland Adaptive Behavior Scales-Second Edition daily living skills scale [202 participants]: β = 0.07; OR, 1.07; 95% CI, 1.03-1.11; P < .001). Doing well in socialization by the growth metric was also associated with better T1 language skills scores (202 participants) (β = 0.04; OR, 1.04; 95% CI, 1.00-1.07, P = .04). Doing well in externalizing by the growth metric was also associated with higher household income at T1 (178 participants) (β = 0.10; OR, 1.10; 95% CI, 1.06-1.15; P < .001). Better family functioning at T1 was associated with doing well on both socialization and externalizing by proficiency metric and on internalizing by growth metric (socialization by proficiency [202 participants]: β = -1.01; OR, 0.36; 95% CI, 0.14-0.93; P = .04; externalizing by proficiency [178 participants]: β = 1.00; OR, 0.37; 95% CI, 0.16-0.82; P = .02; internalizing by growth [178 participants]: β = -1.03; OR, 0.36; 95% CI, 0.16-0.79; P = .01).

Conclusions And Relevance: This cohort study found that a substantial proportion of children with ASD were doing well by middle childhood in at least 1 key domain of developmental health, and that doing well was possible even in the context of continuing to meet criteria for ASD. These results support a strengths-based approach to treatment planning that should include robust support for families to increase the potential likelihood of doing well later in life.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.2530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008283PMC
March 2021

The influence of disclosure of an autism diagnosis on peer engagement and interactions for a child with autism in summer camps: a case study.

Disabil Rehabil 2021 Mar 26:1-12. Epub 2021 Mar 26.

Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada.

Purpose: Little research has evaluated how disclosure of an autism diagnosis influences peer engagement and understanding of children with autism in community recreation programs. This study describes outcomes of disclosing an autism diagnosis for a child with autism participating in mainstream, community summer camps.

Methods: This case study includes a 9-year-old boy diagnosed with autism who participated in two camps, one in which he disclosed and one in which he did not disclose. Quantitative data on peer engagement states and reciprocal interactions were coded through structured behavioral observation of video recorded on the first, second, and last day of each program. Qualitative interviews about perceived outcomes of disclosure were completed with the child with autism, camp leaders, and peers in the disclosure camp.

Results: Peer engagement and reciprocal interactions improved following the disclosure protocol and continued to improve on the final day of the camp, which was not observed in the non-disclosure camp. A key qualitative theme revealed that changed behavioral attribution was the main contributor to improved inclusion following disclosure.

Conclusions: This study provides preliminary data to support that disclosure may be a simple intervention to improve peer engagement and understanding of children with autism in community programs.IMPLICATIONS FOR REHABILITATIONChildren with Autism Spectrum Disorder are at high risk of experiencing social exclusion, especially in community programs.A disclosure protocol (disclosure + explanation for behaviors) could be a simple intervention to facilitate peer acceptance and inclusion of children with autism, however this intervention has not been evaluated in a real life context.This study provides preliminary evidence to support the use of a simple disclosure protocol for families who want to disclose, within short-term community programs.
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http://dx.doi.org/10.1080/09638288.2021.1904012DOI Listing
March 2021

Trajectories of Symptom Severity in Children with Autism: Variability and Turning Points through the Transition to School.

J Autism Dev Disord 2021 Mar 11. Epub 2021 Mar 11.

Centre for Addition and Mental Health, Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, The Hospital for Sick Children, Toronto, Canada.

This study examined the trajectories of autistic symptom severity in an inception cohort of 187 children with ASD assessed across four time points from diagnosis to age 10. Trajectory groups were derived using multivariate cluster analysis. A two trajectory/cluster solution was selected. Change in trajectory slopes revealed a turning point marked by plateauing in symptom reduction during the period of transition to school (age 6) for one of the two trajectories. Trajectories were labelled: Continuously Improving (27%) and Improving then Plateauing (73% of sample). Children in the two trajectories differed in levels of symptom severity, language, cognitive, and adaptive functioning skills. Study findings can inform the development of more personalized services for children with ASD transitioning into the school system.
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http://dx.doi.org/10.1007/s10803-021-04949-2DOI Listing
March 2021

"Best Things": Parents Describe Their Children with Autism Spectrum Disorder Over Time.

J Autism Dev Disord 2021 Dec 2;51(12):4560-4574. Epub 2021 Feb 2.

University of Ottawa, Ottawa, ON, Canada.

This study examined parental perceptions of the character traits of children with autism from early childhood to age 11. Parents (n = 153) provided descriptions of the "best things" about their children on the Child Behavior Checklist (CBCL) at ages 3-4, 7-8, and 10-11 years. Descriptions were coded using the framework of the Values in Action Classification of Strengths, with additional traits added as needed. Parent-endorsed traits included love, kindness, happiness, and humor in children across all ages and traits such as perseverance as children entered school. Higher CBCL scores were associated with a lower likelihood of endorsement for Humanity traits. Results are congruent with a contemporary neurodiversity perspective that emphasizes strengths and resilience.
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http://dx.doi.org/10.1007/s10803-021-04890-4DOI Listing
December 2021

Assessment of Autism Symptoms From 6 to 18 Months of Age Using the Autism Observation Scale for Infants in a Prospective High-Risk Cohort.

Child Dev 2021 05 25;92(3):1187-1198. Epub 2020 Dec 25.

Hamilton Health Sciences.

The objectives were to characterize behavioral signs of autism spectrum disorder (ASD) in younger siblings of diagnosed children (high-risk; HR) and examine classification features of the Autism Observation Scale for Infants (AOSI). Participants (501 HR and 180 low-risk [LR]) were assessed between 6 and 18 months using the AOSI and at age 3 for ASD diagnoses. Total AOSI scores differentiated HR infants later diagnosed with ASD starting at 12 months. ROC analyses identified 12- and 18-month cutoff scores associated with 0.52 sensitivity and 0.74 specificity and 0.73 sensitivity and 0.65 specificity, respectively. Although classification accuracy does not support use as a standalone screen, the AOSI identifies features associated with ASD starting at 6 months and differentiates HR infants with ASD by 12 months.
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http://dx.doi.org/10.1111/cdev.13485DOI Listing
May 2021

Physiological measurement of emotion from infancy to preschool: A systematic review and meta-analysis.

Brain Behav 2021 02 17;11(2):e01989. Epub 2020 Dec 17.

University of Alberta/Autism Research Centre, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada.

Introduction: Emotion regulation, the ability to regulate emotional responses to environmental stimuli, develops in the first years of life and plays an important role in the development of personality, social competence, and behavior. Substantial literature suggests a relationship between emotion regulation and cardiac physiology; specifically, heart rate changes in response to positive or negative emotion-eliciting stimuli.

Method: This systematic review and meta-analysis provide an in-depth examination of research that has measured physiological responding during emotional-evoking tasks in children from birth to 4 years of age.

Results: The review had three main findings. First, meta-regressions resulted in an age-related decrease in baseline and task-related heart rate (HR) and increases in baseline and task-related respiratory sinus arrhythmia (RSA). Second, meta-analyses suggest task-related increases in HR and decreases in RSA and heart rate variability (HRV), regardless of emotional valence of the task. Third, associations between physiological responding and observed behavioral regulation are not consistently present in children aged 4 and younger. The review also provides a summary of the various methodology used to measure physiological reactions to emotional-evoking tasks, including number of sensors used and placement, various baseline and emotional-evoking tasks used, methods for extracting RSA, as well as percentage of loss and reasons for loss for each study.

Conclusion: Characterizing the physiological reactivity of typically developing children is important to understanding the role emotional regulation plays in typical and atypical development.
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http://dx.doi.org/10.1002/brb3.1989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882167PMC
February 2021

Autism Screening: An Important Step Forward but "Miles to Go Before We Sleep".

Pediatrics 2021 01 10;147(1). Epub 2020 Dec 10.

Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta and Women and Children's Health Research Institute, Edmonton, Alberta, Canada

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http://dx.doi.org/10.1542/peds.2020-033803DOI Listing
January 2021

Towards a Data-Driven Approach to Screen for Autism Risk at 12 Months of Age.

J Am Acad Child Adolesc Psychiatry 2021 08 5;60(8):968-977. Epub 2020 Nov 5.

Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill.

Objective: This study aimed to develop a classifier for infants at 12 months of age based on a parent-report measure (the First Year Inventory 2.0 [FYI]), for the following reasons: (1) to classify infants at elevated risk, above and beyond that attributable to familial risk status for ASD; and (2) to serve as a starting point to refine an approach for risk estimation in population samples.

Method: A total of 54 high-familial risk (HR) infants later diagnosed with ASD (HR-ASD), 183 HR infants not diagnosed with ASD at 24 months of age (HR-Neg), and 72 low-risk controls participated in the study. All infants contributed FYI data at 12 months of age and had a diagnostic assessment for ASD at age 24 months. A data-driven, cross-validated analytic approach was used to develop a classifier to determine screening accuracy (eg, sensitivity) of the FYI to classify HR-ASD and HR-Neg.

Results: The newly developed FYI classifier had an estimated sensitivity of 0.71 (95% CI: 0.50, 0.91) and specificity of 0.72 (95% CI: 0.49, 0.91).

Conclusion: This classifier demonstrates the potential to improve current screening for ASD risk at 12 months of age in infants already at elevated familial risk for ASD, increasing opportunities for detection of autism risk in infancy. Findings from this study highlight the utility of combining parent-report measures with machine learning approaches.
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http://dx.doi.org/10.1016/j.jaac.2020.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127075PMC
August 2021

Perceived Impacts of the COVID-19 Pandemic on Pediatric Care in Canada: A Roundtable Discussion.

Glob Pediatr Health 2020 30;7:2333794X20957652. Epub 2020 Sep 30.

University of Alberta, Edmonton, AB, Canada.

Like other recipients of health care services, pediatric patients and their families/caregivers have been profoundly impacted by health care shifts and broader societal restrictions associated with the COVID-19 pandemic. An online roundtable discussion was facilitated with 7 pediatric clinicians and investigators of a current study examining the impacts of COVID-19 on pediatric care at multiple Canadian sites. Discussants represented a range of pediatric specialities: developmental disability, mental health, cardiac transplantation, respiratory medicine, hematology, and palliative care. We offer the transcript of the roundtable in which discussants reflected on clinical and programmatic experiences of the pandemic, including perceived impacts on children receiving care and their families, potential opportunities for improved health care delivery, impacts on health care providers, and recommendations as we move toward easing restrictions and pandemic recovery. Discussants convey a range of considerations that may have varying relevance for pediatric specialities in terms of practice and program planning.
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http://dx.doi.org/10.1177/2333794X20957652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545748PMC
September 2020

Construct validity of the First-Year Inventory (FYI Version 2.0) in 12-month-olds at high-risk for Autism Spectrum Disorder.

Autism 2021 01 27;25(1):33-43. Epub 2020 Aug 27.

University of Southern California, USA.

Lay Abstract: The First-Year Inventory 2.0 is a parent-report screening instrument designed to identify 12-month-old infants at risk for an eventual diagnosis of Autism Spectrum Disorder. This instrument focuses on Social-Communication and Sensory-Regulatory areas of infant behavior. Although the First-Year Inventory 2.0 screening performance has been previously studied, its validity has not been examined. Establishing validity of an instrument is important because it supports the effectiveness and the reliability of the instrument. In this study, we examined relationship between the First-Year Inventory 2.0 (Social-Communication and Sensory-Regulatory areas) and other instruments that measure similar areas of infant behavior in a sample of high-risk infant siblings of children with Autism Spectrum Disorder. These other instruments share some common aims and theoretical areas with the First-Year Inventory 2.0: the Autism Observation Scale for Infants, the Mullen Scales of Early Learning, the Vineland Adaptive Behavior Scales-II, and the Infant Behavior Questionnaire. Findings generally supported the validity of the First-Year Inventory 2.0 with other instruments. In particular, the Social-Communication area of the First-Year Inventory 2.0 showed greater commonality with other instruments than in the Sensory-Regulatory area. The Sensory-Regulatory area seemed to be a unique feature of the First-Year Inventory 2.0 instrument. Considering different aims and strengths of assessments, researchers and clinicians are encouraged to utilize a variety of instruments in a comprehensive evaluation of a child.
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http://dx.doi.org/10.1177/1362361320947325DOI Listing
January 2021

The association between social emotional development and symptom presentation in autism spectrum disorder.

Dev Psychopathol 2020 10;32(4):1206-1216

Ron Joyce Children's Health Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Understanding differences in social-emotional behavior can help identify atypical development. This study examined the differences in social-emotional development in children at increased risk of an autism spectrum disorder (ASD) diagnosis (infant siblings of children diagnosed with the disorder). Parents completed the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) to determine its ability to flag children with later-diagnosed ASD in a high-risk (HR) sibling population. Parents of HR (n = 311) and low-risk (LR; no family history of ASD; n = 127) children completed the BITSEA when their children were 18 months old and all children underwent a diagnostic assessment for ASD at age 3 years. All six subscales of the BITSEA (Problems, Competence, ASD Problems, ASD Competence, Total ASD Score, and Red Flags) distinguished between those in the HR group who were diagnosed with ASD (n = 84) compared to non-ASD-diagnosed children (both HR-N and LR). One subscale (BITSEA Competence) differentiated between the HR children not diagnosed with ASD and the LR group. The results suggest that tracking early social-emotional development may have implications for all HR children, as they are at increased risk of ASD but also other developmental or mental health conditions.
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http://dx.doi.org/10.1017/S0954579420000711DOI Listing
October 2020

Genome-wide detection of tandem DNA repeats that are expanded in autism.

Nature 2020 10 27;586(7827):80-86. Epub 2020 Jul 27.

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Tandem DNA repeats vary in the size and sequence of each unit (motif). When expanded, these tandem DNA repeats have been associated with more than 40 monogenic disorders. Their involvement in disorders with complex genetics is largely unknown, as is the extent of their heterogeneity. Here we investigated the genome-wide characteristics of tandem repeats that had motifs with a length of 2-20 base pairs in 17,231 genomes of families containing individuals with autism spectrum disorder (ASD) and population control individuals. We found extensive polymorphism in the size and sequence of motifs. Many of the tandem repeat loci that we detected correlated with cytogenetic fragile sites. At 2,588 loci, gene-associated expansions of tandem repeats that were rare among population control individuals were significantly more prevalent among individuals with ASD than their siblings without ASD, particularly in exons and near splice junctions, and in genes related to the development of the nervous system and cardiovascular system or muscle. Rare tandem repeat expansions had a prevalence of 23.3% in children with ASD compared with 20.7% in children without ASD, which suggests that tandem repeat expansions make a collective contribution to the risk of ASD of 2.6%. These rare tandem repeat expansions included previously undescribed ASD-linked expansions in DMPK and FXN, which are associated with neuromuscular conditions, and in previously unknown loci such as FGF14 and CACNB1. Rare tandem repeat expansions were associated with lower IQ and adaptive ability. Our results show that tandem DNA repeat expansions contribute strongly to the genetic aetiology and phenotypic complexity of ASD.
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http://dx.doi.org/10.1038/s41586-020-2579-zDOI Listing
October 2020
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