1. Boulton KA, Guastella AJ. The Importance of Experimental Investigation of the CNS Oxytocin System. Methods in molecular biology (Clifton, NJ). 2022; 2384: 53-65.

This chapter provides an overview of the oxytocinergic system and its role in social behavior. We first consider the relationship between oxytocin and social behavior in neurotypical individuals, focusing on studies that have looked at effects of intranasal oxytocin treatment, as well as research investigating the genetic and epigenetic mechanisms associated with individual differences in social behavior. We then outline the proposed role of the oxytocinergic system in autism spectrum disorder and Williams syndrome, two neurodevelopmental disorders where a dysfunctional oxytocinergic system is thought to lead to difficulties in social behavior. Given the contrasting social phenotypes of these disorders, they provide an intriguing comparison through which we can better understand the role of the oxytocinergic system in social behavior. Finally, we consider how future research can best harness the potential of oxytocin, both by addressing measurement and administration issues inherent in many studies, and by developing our understanding of the oxytocinergic system so we are better able to identify the people who are likely to benefit from oxytocin treatment, and intervene at the right time.

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2. Gharehgazlou A, Vandewouw M, Ziolkowski J, Wong J, Crosbie J, Schachar R, Nicolson R, Georgiades S, Kelley E, Ayub M, Hammill C, Ameis SH, Taylor MJ, Lerch JP, Anagnostou E. Cortical Gyrification Morphology in ASD and ADHD: Implication for Further Similarities or Disorder-Specific Features?. Cerebral cortex (New York, NY : 1991). 2021.

Shared etiological pathways are suggested in ASD and ADHD given high rates of comorbidity, phenotypic overlap and shared genetic susceptibility. Given the peak of cortical gyrification expansion and emergence of ASD and ADHD symptomology in early development, we investigated gyrification morphology in 539 children and adolescents (6-17 years of age) with ASD (n=197) and ADHD (n=96) compared to typically developing controls (n=246) using the local Gyrification Index (lGI) to provide insight into contributing etiopathological factors in these two disorders. We also examined IQ effects and functional implications of gyrification by exploring the relation between lGI and ASD and ADHD symptomatology beyond diagnosis. General Linear Models yielded no group differences in lGI, and across groups, we identified an age-related decrease of lGI and greater lGI in females compared to males. No diagnosis-by-age interactions were found. Accounting for IQ variability in the model (n=484) yielded similar results. No significant associations were found between lGI and social communication deficits, repetitive and restricted behaviours, inattention or adaptive functioning. By examining both disorders and controls using shared methodology, we found no evidence of atypicality in gyrification as measured by the lGI in these conditions.

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3. Jiang Y, Urresti J, Pagel KA, Pramod AB, Iakoucheva LM, Radivojac P. Prioritizing de novo autism risk variants with calibrated gene- and variant-scoring models. Human genetics. 2021.

Whole-exome and whole-genome sequencing studies in autism spectrum disorder (ASD) have identified hundreds of thousands of exonic variants. Only a handful of them, primarily loss-of-function variants, have been shown to increase the risk for ASD, while the contributory roles of other variants, including most missense variants, remain unknown. New approaches that combine tissue-specific molecular profiles with patients’ genetic data can thus play an important role in elucidating the functional impact of exonic variation and improve understanding of ASD pathogenesis. Here, we integrate spatio-temporal gene co-expression networks from the developing human brain and protein-protein interaction networks to first reach accurate prioritization of ASD risk genes based on their connectivity patterns with previously known high-confidence ASD risk genes. We subsequently integrate these gene scores with variant pathogenicity predictions to further prioritize individual exonic variants based on the positive-unlabeled learning framework with gene- and variant-score calibration. We demonstrate that this approach discriminates among variants between cases and controls at the high end of the prediction range. Finally, we experimentally validate our top-scoring de novo mutation NP_001243143.1:p.Phe309Ser in the sodium/potassium-transporting ATPase ATP1A3 to disrupt protein binding with different partners.

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4. Kuenzel E, Seguin D, Nicolson R, Duerden EG. Early adversity and positive parenting: Association with cognitive outcomes in children with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2021; 14(12): 2654-62.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and repetitive behaviors. Children with ASD are statistically more likely to experience early adversity; however, little is known about the types of early adversity that place these children at risk, the role of parenting as a protective factor, and how this early life stress impacts cognitive outcomes. We assessed early adversity in 302 children (ASD = 98) aged 6-16 years old, using parent-based report. To identify protective factors, we assessed parenting styles using parent surveys. Executive functions were assessed in the children using the WISC-V. Children with ASD had an increased incidence of familial stressors compared to the typically developing (TD) group. Positive parenting was associated with a significant decrease in the incidence of familial adverse events for both children with ASD and TD children. Examining the relationship between adversity and cognitive outcomes, in young children (6-11 years) with ASD, environmental stressors were associated with cognitive impairments. Findings suggest children with ASD may be at higher risk for familial adversity than their TD peers. However, all children benefit from positive parenting styles, which may mitigate the adverse effects of family-based early life stress. LAY SUMMARY: Some key features of Autism Spectrum Disorder (ASD) include difficulties with communication and social impairments. This means that children with ASD may be more likely to experience early adversity (stressful social interactions which take place during childhood) than children without ASD. Research in typically developing (TD) children has shown that experiencing more stressful events in childhood can cause changes in the brain, which can potentially impact the child’s memory, reasoning, and decision-making skills later in life. However, there is evidence to suggest that having a nurturing relationship with a parent can offset some of the negative impacts of childhood adversity. In our study, we found that children with ASD are more likely to experience family-related stress compared to TD children. Having a positive relationship with a parent, however, was linked to experiencing this type of stress less often for all children, regardless of whether they were diagnosed with ASD. We also found that stressors related to environmental factors like financial instability were associated with lower cognitive abilities in children with ASD under 12 years of age. Understanding how these factors interact and differ in children with ASD can help to build stronger families and help children with ASD to thrive throughout their development.

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5. Laverty C, Surtees A, O’Sullivan R, Sutherland D, Jones C, Richards C. The prevalence and profile of autism in individuals born preterm: a systematic review and meta-analysis. Journal of neurodevelopmental disorders. 2021; 13(1): 41.

INTRODUCTION: Preterm birth (<37 weeks) adversely affects development in behavioural, cognitive and mental health domains. Heightened rates of autism are identified in preterm populations, indicating that prematurity may confer an increased likelihood of adverse neurodevelopmental outcomes. The present meta-analysis aims to synthesise existing literature and calculate pooled prevalence estimates for rates of autism characteristics in preterm populations. METHODS: Search terms were generated from inspection of relevant high-impact papers and a recent meta-analysis. Five databases were searched from database creation until December 2020 with PRISMA guidelines followed throughout. RESULTS: 10,900 papers were retrieved, with 52 papers included in the final analyses, further classified by assessment method (screening tools N=30, diagnostic assessment N=29). Pooled prevalence estimates for autism in preterm samples was 20% when using screening tools and 6% when using diagnostic assessments. The odds of an autism diagnosis were 3.3 times higher in individuals born preterm than in the general population. CONCLUSIONS: The pooled prevalence estimate of autism characteristics in individuals born preterm is considerably higher than in the general population. Findings highlight the clinical need to provide further monitoring and support for individuals born preterm.

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6. Mupaku WM, van Breda AD, Kelly B. Transitioning to adulthood from residential childcare during COVID-19: Experiences of young people with intellectual disabilities and/or autism spectrum disorder in South Africa. British journal of learning disabilities. 2021; 49(3): 341-51.

For young people with intellectual disabilities and/or autism, the transition from children’s residential care into adulthood during COVID-19 has been difficult.Opportunities for greater independence were blocked because of the lockdown.Some of these young people experienced an increase in depression or other mental health difficulties.But more time at home due to public health restrictions also helped to deepen the relationship with caregivers.Service continuity is crucial, both in person and online, to support care leavers with intellectual disability and/or autism, as well as training and support to caregivers to continue with independent and interdependent living programmes at home. BACKGROUND: This study focuses on young people with intellectual disabilities and/or autism who, due to child welfare concerns, have grown up in children’s residential care and are now transitioning out of care at the age of 18 years towards young adulthood. This transition is termed « care leaving » and the young people in transition « care leavers ». The care leaving transition can be particularly difficult for young people with intellectual disabilities and/or autism. These challenges can be magnified in a time of a global crisis like COVID-19, which has resulted in countries being on lockdown and care leavers’ transitions being curtailed. Many mental health problems have emerged due to the COVID-19 outbreak and resultant lockdown that may negatively impact on the care leaving transition of young people with intellectual disabilities. METHODS: Semi-structured interviews were conducted with six care leavers with intellectual disabilities and their three caregivers in June 2020 in the Cape Peninsula region of South Africa to explore the impact of COVID-19 on their transitional journeys. FINDINGS: Three core themes emerged from the analysis: young people evidenced regression of independence, rather than the expected growth in young adult independence, due to disruptions to routines and opportunities to move out into the world; some young people experienced an exacerbation or emergence of mental health problems, which impacted on their transition to young adulthood; and young people and their caregivers experienced a deepening of caregiver relationships, which enhanced the transition of the care leaver. CONCLUSIONS: Services must continue to facilitate progress towards independence and promote personal and caregiver well-being. Support service for care leavers with intellectual disabilities should be essential services, offered in person or online while adhering to COVID-19 regulations. Caregivers should be trained in continuing independent and interdependent living programmes for care leavers in their care, supported through in person or online training, mentoring and supervision. Service continuity is recommended to avoid the contraction of young people’s social world at a time when it should be opening up.

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7. Piguet O, Ahmed RM, Kumfor F. The Role of Oxytocin in Social Circuits and Social Behavior in Dementia. Methods in molecular biology (Clifton, NJ). 2022; 2384: 67-80.

Administration of intranasal oxytocin has been found to improve social cognition in a number of brain conditions, including autism spectrum disorder and schizophrenia. Whether this approach is relevant in dementias is currently unknown, particularly in frontotemporal dementia, a younger-onset dementia characterized clinically by marked changes in social cognition and behavior and focal atrophy of the frontal and temporal lobes. This chapter provides an overview of the deficits in social cognition in frontotemporal dementia and reviews the emerging evidence of intranasal oxytocin administration as a potential treatment option for these deficits. Future research directions will also be discussed.

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8. Schalock RL, Luckasson R, Tassé MJ. Ongoing Transformation in the Field of Intellectual and Developmental Disabilities: Taking Action for Future Progress. Intellectual and developmental disabilities. 2021; 59(5): 380-91.

There has been a significant transformation in the field of intellectual and developmental disabilities (IDD) over the last 5 decades. Although this transformation has profoundly influenced multiple stakeholders, the field is currently at a critical juncture and facing a number of social and political challenges. Given the relevance of the question, « where is the field of IDD and where do we go, » the present article describes the field’s transformation, and suggests future action steps to facilitate and sustain the transformation. The seven action steps discussed in the article relate to using precise terminology, incorporating a functional and holistic approach to IDD, embracing the supports model and evidence-based practices, implementing outcome evaluation, empowering individuals and families, understanding better the multidimensional properties of context, and incorporating an explicit notion of professional responsibility.

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9. Schulze M, Aslan B, Stöcker T, Stirnberg R, Lux S, Philipsen A. Disentangling early versus late audiovisual integration in adult ADHD: a combined behavioural and resting-state connectivity study. Journal of psychiatry & neuroscience : JPN. 2021; 46(5): E528-e37.

BACKGROUND: Studies investigating sensory processing in attention-deficit/hyperactivity disorder (ADHD) have shown altered visual and auditory processing. However, evidence is lacking for audiovisual interplay – namely, multisensory integration. As well, neuronal dysregulation at rest (e.g., aberrant within- or between-network functional connectivity) may account for difficulties with integration across the senses in ADHD. We investigated whether sensory processing was altered at the multimodal level in adult ADHD and included resting-state functional connectivity to illustrate a possible overlap between deficient network connectivity and the ability to integrate stimuli. METHODS: We tested 25 patients with ADHD and 24 healthy controls using 2 illusionary paradigms: the sound-induced flash illusion and the McGurk illusion. We applied the Mann-Whitney U test to assess statistical differences between groups. We acquired resting-state functional MRIs on a 3.0 T Siemens magnetic resonance scanner, using a highly accelerated 3-dimensional echo planar imaging sequence. RESULTS: For the sound-induced flash illusion, susceptibility and reaction time were not different between the 2 groups. For the McGurk illusion, susceptibility was significantly lower for patients with ADHD, and reaction times were significantly longer. At a neuronal level, resting-state functional connectivity in the ADHD group was more highly regulated in polymodal regions that play a role in binding unimodal sensory inputs from different modalities and enabling sensory-to-cognition integration. LIMITATIONS: We did not explicitly screen for autism spectrum disorder, which has high rates of comorbidity with ADHD and also involves impairments in multisensory integration. Although the patients were carefully screened by our outpatient department, we could not rule out the possibility of autism spectrum disorder in some participants. CONCLUSION: Unimodal hypersensitivity seems to have no influence on the integration of basal stimuli, but it might have negative consequences for the multisensory integration of complex stimuli. This finding was supported by observations of higher resting-state functional connectivity between unimodal sensory areas and polymodal multisensory integration convergence zones for complex stimuli.

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10. Shah ED. Gastro-Intestinal Symptoms and Autism Spectrum Disorder: A Potential Link [Response to Letter]. Clinical and experimental gastroenterology. 2021; 14: 375-6.

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11. Talbott MR, Dufek S, Young G, Rogers SJ. Leveraging telehealth to evaluate infants with prodromal autism spectrum disorder characteristics using the telehealth evaluation of development for infants. Autism : the international journal of research and practice. 2021: 13623613211045596.

Many families seeking early evaluations for autism spectrum disorder face long waitlists, must often travel to centers with appropriate expertise, and are frequently told by providers to « wait and see. » This results in significant stress for families and delayed supports to infants and their caregivers who could benefit. This study evaluated whether telehealth could be used to identify and evaluate infants with early autism spectrum disorder characteristics in the first year of life. In this study, we evaluated 41 infants via telehealth using a standard set of probes and scored behavior related to social communication, play, imitation, and other developmental domains. We found the majority of infants demonstrated elevated likelihood of autism spectrum disorder on both parent-reported questionnaires and examiner-rated behavior. Caregiver ratings of the overall utility of the protocol used in this study were high. Overall, this study demonstrates the feasibility for telehealth-based approaches to evaluate infants’ with elevated likelihood of autism spectrum disorder in the first year of life, which could help to improve families’ access to care and to expand our capacity to conduct studies evaluating possible intervention supports.

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12. Urresti J, Zhang P, Moran-Losada P, Yu NK, Negraes PD, Trujillo CA, Antaki D, Amar M, Chau K, Pramod AB, Diedrich J, Tejwani L, Romero S, Sebat J, Yates Iii JR, Muotri AR, Iakoucheva LM. Correction: Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism. Molecular psychiatry. 2021; 26(12): 7581.

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13. Weinstein O, Krieger I, Cohen AD, Tzur Bitan D. COVID-19 vaccination among individuals with autism spectrum disorder: A population-based study. Research in autism spectrum disorders. 2021; 89: 101865.

BACKGROUND: Individuals with autistic spectrum disorder (ASD) are more susceptible to COVID-19 morbidity and should therefore be prioritized for vaccination. Although individuals with neurodevelopmental disabilities are given some priority in Israel, it is unclear to what extent individuals with ASD are being vaccinated relative to that of the general population. This study was aimed to assess vaccination prevalence among individuals with ASD. METHOD: Individuals with ASD, and age- and sex-matched controls (total n = 11,080), were assessed for prevalence of COVID-19 vaccination by February 2021, approximately a month and a half after the national vaccination distribution plan was launched in Israel. Data were obtained from the database of Clalit Health Services (CHS), the largest healthcare organization in Israel. RESULTS: Individuals with ASD were more likely to be vaccinated for COVID-19 (OR = 2.55, 95 %CI 2.35-2.75, p < .001) across both sexes, but only in the 16-20 (OR = 2.04, 95 %CI 1.79-2.32, p < .001) and 21-40 (OR = 3.95, 95 %CI 3.52-4.43, p < .001) age groups. After adjusting for chronic illnesses, ASD remained significant in predicting the uptake of COVID-19 vaccination. CONCLUSIONS: Efforts to prioritize ASD patients may improve vaccination prevalence among individuals with ASD, especially among younger individuals. Healthcare providers worldwide should therefore consider prioritization policies so as to increase vaccination rates among this vulnerable population.

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