1. Asiminas A, Booker SA, Dando OR, Kozic Z, Arkell D, Inkpen FH, Sumera A, Akyel I, Kind PC, Wood ER. Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome. Molecular autism. 2022; 13(1): 49.

BACKGROUND: Fragile X syndrome (FXS) is a common single gene cause of intellectual disability and autism spectrum disorder. Cognitive inflexibility is one of the hallmarks of FXS with affected individuals showing extreme difficulty adapting to novel or complex situations. To explore the neural correlates of this cognitive inflexibility, we used a rat model of FXS (Fmr1(-/y)). METHODS: We recorded from the CA1 in Fmr1(-/y) and WT littermates over six 10-min exploration sessions in a novel environment-three sessions per day (ITI 10 min). Our recordings yielded 288 and 246 putative pyramidal cells from 7 WT and 7 Fmr1(-/y) rats, respectively. RESULTS: On the first day of exploration of a novel environment, the firing rate and spatial tuning of CA1 pyramidal neurons was similar between wild-type (WT) and Fmr1(-/y) rats. However, while CA1 pyramidal neurons from WT rats showed experience-dependent changes in firing and spatial tuning between the first and second day of exposure to the environment, these changes were decreased or absent in CA1 neurons of Fmr1(-/y) rats. These findings were consistent with increased excitability of Fmr1(-/y) CA1 neurons in ex vivo hippocampal slices, which correlated with reduced synaptic inputs from the medial entorhinal cortex. Lastly, activity patterns of CA1 pyramidal neurons were dis-coordinated with respect to hippocampal oscillatory activity in Fmr1(-/y) rats. LIMITATIONS: It is still unclear how the observed circuit function abnormalities give rise to behavioural deficits in Fmr1(-/y) rats. Future experiments will focus on this connection as well as the contribution of other neuronal cell types in the hippocampal circuit pathophysiology associated with the loss of FMRP. It would also be interesting to see if hippocampal circuit deficits converge with those seen in other rodent models of intellectual disability. CONCLUSIONS: In conclusion, we found that hippocampal place cells from Fmr1(-/y) rats show similar spatial firing properties as those from WT rats but do not show the same experience-dependent increase in spatial specificity or the experience-dependent changes in network coordination. Our findings offer support to a network-level origin of cognitive deficits in FXS.

Lien vers le texte intégral (Open Access ou abonnement)

2. Berard M, Peries M, Loubersac J, Picot MC, Bernard JY, Munir K, Baghdadli A. Screen time and associated risks in children and adolescents with autism spectrum disorders during a discrete COVID-19 lockdown period. Frontiers in psychiatry. 2022; 13: 1026191.

BACKGROUND: The COVID-19 pandemic may affect the screen time of children and adolescents with Autism Spectrum Disorders (ASD). This study aimed to examine the screen time of children and adolescents with ASD during a discrete lockdown period in France and identify risk factors for excessive screen time. METHODS: The study sample consisted of 249 ASD subjects, 3-17 years of age, enrolled in the ELENA cohort. Information about the screen time was collected using the COVID-19 questionnaire specially created for this study. The clinical, socio-demographic and familial characteristics were collected from the last ELENA follow-up visit. RESULTS: More than one third of subjects exceeded recommended levels of screen time and almost half of parents reported that their child spent more time using screen since COVID-19 pandemic beginning. Excessive screen time was significantly related to age with higher screen time in adolescents. Risk factors for excessive screen time were high withdrawn behaviors and low socioeconomic status for children, and older age and male gender for adolescents. CONCLUSION: These results imply to adapt the recommendations already formulated in general population concerning the good use of screens in youth with ASD. Specific recommendations and suitable guidance are needed to help children and adolescents with ASD and their parents implement the more optimal use of screen time activities for educational, therapeutic and social goals. TRIAL REGISTRATION NUMBER: NCT02625116.

Lien vers le texte intégral (Open Access ou abonnement)

3. Bhat A. Multidimensional motor performance in children with autism mostly remains stable with age and predicts social communication delay, language delay, functional delay, and repetitive behavior severity after accounting for intellectual disability or cognitive delay: A SPARK dataset analysis. Autism research : official journal of the International Society for Autism Research. 2022.

When motor difficulties continue into adolescence/adulthood, they could negatively impact an individual with autism spectrum disorder (ASD)’s daily living skills, physical fitness, as well as physical and mental health/well-being. Few studies have examined motor difficulties in children with ASD as a function of sex or age; however, greater cognitive challenges are associated with worse general motor performance. Based on the Developmental Coordination Disorder-Questionnaire (DCD-Q) data from the SPARK study sample, 87%-88% children with ASD were at-risk for a general motor impairment that persisted until 15 years and was related to their core and co-occurring difficulties. Bhat et al. confirmed motor difficulties in children with ASD on multiple motor dimensions that predicted core and co-occurring conditions after accounting for age and sex. However, presence of intellectual disability (ID) or cognitive delay was not controlled in the previous analysis. Additionally, the effects of age, sex, and cognitive ability on multidimensional motor difficulties of the SPARK sample have not been discussed before. Therefore, this analysis examines the effects of age, sex, and cognitive ability (presence of ID or level of cognitive delay) on the motor performance of children from the SPARK sample using the DCD-Q. Except fine motor skills, multiple motor domains did not change with age in children with ASD. Females without ID improved their fine motor scores with age, and performed better compared to males without ID. Children with ASD and ID had greater motor difficulties across multiple motor domains than those without ID. Even after controlling for age, sex, and presence of ID/cognitive delay; motor performance was predictive of social communication skills, repetitive behavior severity, as well as language and functional delays. Gross motor skills contributed more than fine motor and general motor competence skills in predicting social communication delay. However, fine motor and general motor competence skills contributed more than gross motor skills in predicting repetitive behavior severity and language delay. Both, fine and gross motor skills predicted functional delay. In light of consistent findings on motor difficulties in children with ASD, adding motor issues as a specifier within the ASD definition could provide a clear clinical route for movement clinicians to address motor difficulties of individuals with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

4. Boucher TQ, McIntyre CL, Iarocci G. Facilitators and Barriers to Physical Activity Involvement as Described by Autistic Youth with Mild Intellectual Disability. Advances in neurodevelopmental disorders. 2022: 1-13.

OBJECTIVES: Physical activity involvement among autistic youth and youth with an intellectual disability is significantly lower than the general population. Few studies have included youth with comorbid diagnoses of ASD and intellectual disability. Fewer studies collect information from the youth themselves. This study examined barriers and facilitators to physical activity in autistic youth with mild intellectual disability using semi-structured interviews with youth and through caregiver reports. METHODS: Fourteen caregivers and their children ages 8 to 16 years old participated. Caregivers completed a questionnaire about their thoughts on their child’s physical activity while their children completed the semi-structured interview. A descriptive phenomenological approach was followed. RESULTS: Four themes were inductively identified: intrapersonal barriers (factors that are within the person which impede physical activity involvement, such as exhibiting challenging behaviors that inhibit engagement), interpersonal barriers (factors external to the person, such as lack of community support), intrapersonal facilitators (factors within the person that enhance physical activity involvement, such as being intrinsically motivated to improve skills), and interpersonal facilitators (external factors such as supports from caregivers). CONCLUSIONS: Interviewing youth is important to capture a holistic picture of factors influencing physical activity. Future research may focus on implementing and assessing the efficacy of strategies to address the barriers facing youth diagnosed with ASD and intellectual disability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41252-022-00310-5.

Lien vers le texte intégral (Open Access ou abonnement)

5. Boydston P, Redner R, Wold K. Examination of a Telehealth-Based Parent Training Program in Rural or Underserved Areas for Families Impacted by Autism. Behavior analysis in practice. 2022: 1-17.

Families of children with disabilities in rural areas face challenges accessing services due to location and lack of health-care providers. Telehealth-based intervention can mitigate challenges in accessing services. The present study sought to replicate and extend the telehealth-based, behavioral parent-training program, the Online and Applied System for Intervention Skills (OASIS), utilizing a multiple-baseline approach. Four parent-child dyads participated, with all children diagnosed with autism spectrum disorder. All dyads resided in rural/underserved areas. All dyads demonstrated an improvement on skill and knowledge assessments. The mean gain from baseline-to-treatment completion on skills assessments was 80.9% (range: 67.6%-95.5% points). The mean gain on knowledge assessments was 35.3% (range: 19.0%-49.0% points). It should be noted that parent skill gains were maintained over time. The present results provided additional empirical evidence demonstrating the effectiveness of OASIS, a telehealth-based parent-training model.

Lien vers le texte intégral (Open Access ou abonnement)

6. Chen YL, Ho HY. Comprehensive Comparisons of Family Health Between Families With One Immigrant Parent and Native Families in Taiwan: Nationwide Population-Based Cohort Study. JMIR public health and surveillance. 2022; 8(12): e33624.

BACKGROUND: Mothers and children in families with one immigrant parent have been reported to be healthier than those in native families; however, the health of the fathers in these families has rarely been discussed in literature. OBJECTIVE: We aimed to comprehensively compare the health of all the family members between families with one immigrant parent (native fathers, immigrant mothers, and their children) and native families (native fathers, native mothers, and their children). METHODS: We conducted a cohort study by using the Taiwan Maternal and Child Health Database to recruit live-born children and their parents from 2004 to 2016. Overall, we identified 90,670 fathers, 91,270 mothers, and 132,457 children in families with one immigrant parent and 1,666,775 fathers, 1,734,104 mothers, and 2,637,191 children in native families and followed up with them from 2004 to 2017. The outcomes comprised common physical and mental disorders, catastrophic illnesses, mortality, and child adversities and accidents. The covariates comprised the child’s year of birth, parental age, low-income status, and physical or mental disorder status. Logistic regression was performed to compare the risks of the outcomes between families with one immigrant parent and native families. RESULTS: The parents in families with one immigrant parent were more likely to be of low-income status and were older than the parents in native families. After adjusting for the covariates, fathers in families with one immigrant parent were found to have higher risks of physical and mental disorders, catastrophic illness, and mortality than fathers in native families. Conversely, mothers in families with one immigrant parent had lower risks of physical and mental disorders, catastrophic illness, and mortality than mothers in native families. Finally, the children in families with one immigrant parent generally had better physical and mental health but higher risks for leukemia, liver diseases, autism spectrum disorder, and road traffic accidents than children in native families. CONCLUSIONS: The health status of the members of families with one immigrant parent was nonhomogeneous, and the poorer general health of fathers in such families suggests health inequalities in families with one immigrant parent.

Lien vers le texte intégral (Open Access ou abonnement)

7. Cheng S, Cheng S, Liu S, Li Y. Parents’ pandemic stress, parental involvement, and family quality of life for children with autism. Frontiers in public health. 2022; 10: 1061796.

BACKGROUND: Research has shown that parents of children with autism spectrum disorder (ASD) suffered high levels of stress during the COVID-19 pandemic and faced poor family quality of life (FQOL). However, little is known about the inherent dynamic interaction between pandemic stress and FQOL, especially in the Chinese cultural context. AIMS: This study provides preliminary evidence by examining the relationships among pandemic stress, parental involvement, and FQOL for children with autism in mainland China. METHOD: A total of 709 parents of children with autism completed measures of FQOL, parental involvement, and pandemic stress. Structural equation modeling was employed to examine the interrelations among these variables. RESULTS: Pandemic stress has direct effect and indirect effect mediated by parental involvement on FQOL. Two dimensions of pandemic stress had a direct effect on FQOL (β1 = 0.11; β2 = -0.55) and three dimensions had an indirect effect on FQOL through parental involvement (β1 = -0.097; β2 = 0.257; β3 = 0.114). CONCLUSION: Stress related to the COVID-19 pandemic affects family quality of life for children with autism in complex ways. Policies may be developed to enhance parental pragmatic hopefulness in the anti-epidemic victory and alleviate negative physical and mental reactions caused by the pandemic.

Lien vers le texte intégral (Open Access ou abonnement)

8. Das S, Zomorrodi R, Enticott PG, Kirkovski M, Blumberger DM, Rajji TK, Desarkar P. Resting state electroencephalography microstates in autism spectrum disorder: A mini-review. Frontiers in psychiatry. 2022; 13: 988939.

Atypical spatial organization and temporal characteristics, found via resting state electroencephalography (EEG) microstate analysis, have been associated with psychiatric disorders but these temporal and spatial parameters are less known in autism spectrum disorder (ASD). EEG microstates reflect a short time period of stable scalp potential topography. These canonical microstates (i.e., A, B, C, and D) and more are identified by their unique topographic map, mean duration, fraction of time covered, frequency of occurrence and global explained variance percentage; a measure of how well topographical maps represent EEG data. We reviewed the current literature for resting state microstate analysis in ASD and identified eight publications. This current review indicates there is significant alterations in microstate parameters in ASD populations as compared to typically developing (TD) populations. Microstate parameters were also found to change in relation to specific cognitive processes. However, as microstate parameters are found to be changed by cognitive states, the differently acquired data (e.g., eyes closed or open) resting state EEG are likely to produce disparate results. We also review the current understanding of EEG sources of microstates and the underlying brain networks.

Lien vers le texte intégral (Open Access ou abonnement)

9. Díaz Vargas D, Leonario Rodríguez M. Effectiveness of nutritional interventions on behavioral symptomatology of autism spectrum disorder: a systematic review. Nutricion hospitalaria. 2022; 39(6): 1378-88.

Introduction: the main treatment for people with autism spectrum disorder (ASD) corresponds to cognitive behavioral therapy in conjunction with pharmacotherapy. Together they seek to attenuate the behavioral symptoms of these patients, as well as to increase their social functionality. However, other strategies have become popular to achieve the same goal of classical treatment. Particularly, nutritional interventions are positioned above others, and it is necessary to investigate their effectiveness, considering that children with ASD present a marked food selectivity, as well as gastrointestinal alterations. Objective: to evaluate the effectiveness of nutritional interventions in the behavioral symptomatology of infants with ASD. Methods: a systematic search was carried out in the Scopus and PubMed databases, in Spanish and English. The filters of clinical studies and original articles were used, choosing only nutritional interventions in children under 19 years of age and who had had at least 4 weeks of intervention. Results: evidence was found on gluten- and casein-free diets, ketogenic diet, omega-3 supplementation, prebiotics/probiotics, and vitamins/minerals presenting positive results in most of the articles analyzed; however, the heterogeneity presented requires a greater body of evidence to promote its use. Conclusion: the five types of nutritional interventions evaluated show varied evidence that does not allow defining the degree of effectiveness between one or the other in terms of behavioral improvements in the population with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

10. Dooling SW, Sgritta M, Wang IC, Duque A, Costa-Mattioli M. The Effect of Limosilactobacillus reuteri on Social Behavior Is Independent of the Adaptive Immune System. mSystems. 2022; 7(6): e0035822.

Gut microbes can modulate almost all aspects of host physiology throughout life. As a result, specific microbial interventions are attracting considerable attention as potential therapeutic strategies for treating a variety of conditions. Nonetheless, little is known about the mechanisms through which many of these microbes work. Recently, we and others have found that the commensal bacterium Limosilactobacillus reuteri (formerly Lactobacillus reuteri) reverses social deficits in several mouse models (genetic, environmental, and idiopathic) for neurodevelopmental disorders in a vagus nerve-, oxytocin-, and biopterin-dependent manner. Given that gut microbes can signal to the brain through the immune system and L. reuteri promotes wound healing via the adaptive immune response, we sought to determine whether the prosocial effect mediated by L. reuteri also depends on adaptive immunity. Here, we found that the effects of L. reuteri on social behavior and related changes in synaptic function are independent of the mature adaptive immune system. Interestingly, these findings indicate that the same microbe (L. reuteri) can affect different host phenotypes through distinct mechanisms. IMPORTANCE Because preclinical animal studies support the idea that gut microbes could represent novel therapeutics for brain disorders, it is essential to fully understand the mechanisms by which gut microbes affect their host’s physiology. Previously, we discovered that treatment with Limosilactobacillus reuteri selectively improves social behavior in different mouse models for autism spectrum disorder through the vagus nerve, oxytocin reward signaling in the brain, and biopterin metabolites (BH4) in the gut. However, given that (i) the immune system remains a key pathway for host-microbe interactions and that (ii) L. reuteri has been shown to facilitate wound healing through the adaptive immune system, we examined here whether the prosocial effects of L. reuteri require immune signaling. Unexpectedly, we found that the mature adaptive immune system (i.e., conventional B and T cells) is not required for L. reuteri to reverse social deficits and related changes in synaptic function. Overall, these findings add new insight into the mechanism through which L. reuteri modulates brain function and behavior. More importantly, they highlight that a given bacterial species can modulate different phenotypes (e.g., wound healing versus social behavior) through separate mechanisms.

Lien vers le texte intégral (Open Access ou abonnement)

11. Eapen V, Islam R, Azim SI, Masi A, Klein L, Karlov L. Factors Impacting Parental Quality of Life in Preschool Children on the Autism Spectrum. Journal of autism and developmental disorders. 2022.

This study examined connections between parental quality of life (QoL) and features of children (autism severity, cognitive ability, behavioral profile, and sociodemographic factors). Parents of 97 children attending an autism-specific preschool completed the Quality of Life in Autism, Vineland Adaptive Behavior Scales and Child Behavior Checklist. The Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning were also administered. Reduced restrictive/repetitive behavior and higher socialization and play/leisure scores were associated with better parental QoL. Better behavioral regulation and attention also predicted better QoL, as did stronger communication and reduced internalising behaviours. Findings indicate that a child’s level of autism specific traits, adaptive functioning and behavioral profile has greater impact on parental QoL than cognitive level.

Lien vers le texte intégral (Open Access ou abonnement)

12. Hull L, Heuvelman H, Golding J, Mandy W, Rai D. Gendered play behaviours in autistic and non-autistic children: A population-based cohort study. Autism : the international journal of research and practice. 2022: 13623613221139373.

Non-autistic children tend to show gendered patterns of play behaviours – boys are more likely to play with ‘masculine’ toys, and girls are more likely to play with ‘feminine’ toys. However, little is known about whether autistic children follow these patterns as well. We looked at the masculinity and femininity of autistic and non-autistic children’s play behaviours at multiple time points. Parents reported their children’s play behaviours at ages 30, 42 and 57 months, and children reported their own play behaviours at 8 years old. We found no difference between autistic and non-autistic girls, who both showed more feminine play behaviours as they got older. Autistic boys’ play behaviours were reported as less masculine than non-autistic boys at 42 and 57 months, and at 8 years old. We also found that non-autistic boys’ play tended to become more masculine as they got older, but this was not the case for autistic boys. Our findings suggest that differences in autistic and non-autistic boys’ play behaviours may develop at around 42 months old.

Lien vers le texte intégral (Open Access ou abonnement)

13. Ji Y, Xu M, Liu X, Dai Y, Zhou L, Li F, Zhang L. Temporopolar volumes are associated with the severity of social impairment and language development in children with autism spectrum disorder with developmental delay. Frontiers in psychiatry. 2022; 13: 1072272.

BACKGROUND: Children with autism spectrum disorder (ASD) and developmental delay (DD; ASD + DD) have more severe clinical symptoms than those with ASD without DD (ASD-only). However, little is known about the underlying neuroimaging mechanisms. The aim of this study was to explore the volumetric difference between patients with ASD + DD and ASD-only and investigate the relationship between brain alterations and clinical manifestations. MATERIALS AND METHODS: A total of 184 children with ASD aged 2-6 years were included in this study, who were divided into two groups according to their cognitive development: ASD + DD and ASD-only. Clinical symptoms and language development were assessed using the Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), and the Putonghua Communicative Development Inventory. Of the 184 children, 60 age-matched males (30 ASD + DD and 30 ASD-only patients) with high-resolution structural neuroimaging scans were included for further voxel-based morphometry analysis to examine the relationship between clinical symptoms and gray matter volumes. RESULTS: The ASD + DD group had higher CARS and ADOS scores, lower gesture scores, and poorer performance in « responding to joint attention » (RJA) and « initiating joint attention » than the ASD-only group. Larger gray matter volumes in the temporal poles of the right and left middle temporal gyri were associated with the co-occurrence of DD in patients with ASD. Moreover, temporopolar volumes were correlated with CARS and ADOS scores, gesture scores, and RJA ability. Pre-language development significantly mediated the relationship between temporopolar volumes and both CARS and ADOS scores; RJA ability, but not gesture development, contributed to this mediating effect. CONCLUSION: In this study, we found that temporopolar volumes were enlarged in patients with ASD who had comorbid DD, and these patients showed an association between symptom severity and language ability during the pre-language stage. Offering early interventions focused on RJA and the temporal pole may help improve clinical symptoms.

Lien vers le texte intégral (Open Access ou abonnement)

14. Kassa AM, Håkanson CA, Lilja HE. The risk of autism spectrum disorder and intellectual disability but not attention deficit/hyperactivity disorder is increased in individuals with esophageal atresia. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2022.

Knowledge of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability (ID) in patients with esophageal atresia (EA) is scarce. The aims of this study were to investigate the prevalence and risk of ADHD, ASD and ID in individuals with EA. Data were obtained from four longitudinal population-based registries in Sweden and analyzed using Cox proportional hazards regression. Patients with EA born in Sweden in 1973-2018 were included together with five controls for each individual with the exposure matched on sex, gestational age at birth, birth year and birth county. Individuals with chromosomal aberrations and syndromes were excluded. In total, 735 individuals with EA and 3675 controls were included. Median age at time of the study was 20 years (3-48). ASD was found in 24 (3.9%), ADHD in 34 (5.5%) and ID in 28 (4.6%) individuals with EA. Patients with EA had a 1.66 times higher risk of ASD (95% confidence interval [CI], 1.05-2.64) and a 3.62 times higher risk of ID (95% CI, 2.23-5.89) compared with controls. The risk of ADHD was not significantly increased. ADHD medication had been prescribed to 88.2% of patients with EA and ADHD and to 84.5% of controls with ADHD. Individuals with EA have a higher risk of ASD and ID than individuals without the exposure. These results are important when establishing follow-up programs for children with EA to allow timely detection and consequentially an earlier treatment and support especially before school start.

Lien vers le texte intégral (Open Access ou abonnement)

15. Kraft C, Chamanadjian C, Aylward BS. Autism Spectrum Disorder: The New Asthma?. Clinical pediatrics. 2022: 99228221144146.

While autism spectrum disorder (ASD) has traditionally been diagnosed in specialty care, rising prevalence rates have strained specialist capacity and created significant diagnostic bottlenecks. With long wait times for specialist evaluations, pediatricians are increasingly being asked to play a greater role in identifying, diagnosing, and managing ASD within the medical home. In this commentary we draw parallels between the challenges pediatricians faced two decades ago learning how to manage pediatric asthma in the medical home, to those faced today in the field of primary care ASD management. Reflecting on the lessons learnt in primary care asthma management may help us construct a roadmap towards a higher and more consistent standard of ASD primary care for patients and their families.

Lien vers le texte intégral (Open Access ou abonnement)

16. Krieger B, Moser A, Morgenthaler T, Beurskens A, Piškur B. Parents’ Perceptions: Environments and the Contextual Strategies of Parents to Support the Participation of Children and Adolescents with Autism Spectrum Disorder-A Descriptive Population-Based Study from Switzerland. Journal of autism and developmental disorders. 2022: 1-23.

Environments have a modifying effect on the participation of children and adolescents with autism spectrum disorder (ASD) in all areas of life. This cross-sectional study investigated parental perspectives on supportive or hindering environments and the daily contextual strategies parents used to enhance their children’s participation. Qualitative and quantitative data gathered from 115 parents from German-speaking Switzerland using the participation and environment measure-child and youth (PEM-CY) were analyzed. Results revealed 45 environmental supports and barriers at home, at school, and in the community. Contextual strategies were identified in combination with people, activities, time, objects, and places. Parental perspectives on participation and their contextual strategies should be considered in environmental-based interventions to support the participation of children and adolescents with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

17. Lawson LP, Richdale AL, Denney K, Morris EMJ. ACT-i, an insomnia intervention for autistic adults: a pilot study. Behavioural and cognitive psychotherapy. 2022: 1-18.

BACKGROUND: Insomnia and disturbed sleep are more common in autistic adults compared with non-autistic adults, contributing to significant social, psychological and health burdens. However, sleep intervention research for autistic adults is lacking. AIMS: The aim of the study was to implement an acceptance and commitment therapy group insomnia intervention (ACT-i) tailored for autistic adults to examine its impact on insomnia and co-occurring mental health symptoms. METHOD: Eight individuals (6 male, 2 female) aged between 18 and 70 years, with a clinical diagnosis of autism spectrum disorder, and scores ranging from 9 to 26 on the Insomnia Severity Index (ISI) participated in the trial. Participants were assigned to one of two intervention groups (4 per group) within a multiple baseline over time design for group. Participants completed questionnaires pre-intervention, post-intervention, and at 2-month follow-up, actigraphy 1 week prior to intervention and 1 week post-intervention, and a daily sleep diary from baseline to 1 week post-intervention, and 1 week at follow-up. RESULTS: At a group level there were significant improvements in ISI (λ(2)=10.17, p=.006) and HADS-A (anxiety) (λ(2)=8.40, p=.015) scores across the three time points. Clinically reliable improvement occurred for ISI scores (n=5) and HADS-A scores (n=4) following intervention. Client satisfaction indicated that ACT-i was an acceptable intervention to the participants (median 4 out of 5). CONCLUSIONS: This pilot study with eight autistic adults indicates that ACT-i is both an efficacious and acceptable intervention for reducing self-reported insomnia and anxiety symptoms in autistic adults.

Lien vers le texte intégral (Open Access ou abonnement)

18. Li YJ, Li CY, Li CY, Hu DX, Xv ZB, Zhang SH, Li Q, Zhang P, Tian B, Lan XL, Chen XQ. KMT2E Haploinsufficiency Manifests Autism-Like Behaviors and Amygdala Neuronal Development Dysfunction in Mice. Molecular neurobiology. 2022.

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental disorders characterized by impaired social interaction skills. Whole exome sequencing has identified loss-of-function mutations in lysine methyltransferase 2E (KMT2E, also named MLL5) in ASD patients and it is listed as an ASD high-risk gene in humans. However, experimental evidence of KMT2E in association with ASD-like manifestations or neuronal function is still missing. Relying on KMT2E(+/-) mice, through animal behavior analyses, positron emission tomography (PET) imaging, and neuronal morphological analyses, we explored the role of KMT2E haploinsufficiency in ASD-like symptoms. Behavioral results revealed that KMT2E haploinsufficiency was sufficient to produce social deficit, accompanied by anxiety in mice. Whole-brain (18)F-FDG-PET analysis identified that relative amygdala glycometabolism was selectively decreased in KMT2E(+/-) mice compared to wild-type mice. The numbers and soma sizes of amygdala neurons in KMT2E(+/-) mice were prominently increased. Additionally, KMT2E mRNA levels in human amygdala were significantly decreased after birth during brain development. Our findings support a causative role of KMT2E in ASD development and suggest that amygdala neuronal development abnormality is likely a major underlying mechanism.

Lien vers le texte intégral (Open Access ou abonnement)

19. Liu C, Liu J, Gong H, Liu T, Li X, Fan X. Implication of Hippocampal Neurogenesis in Autism Spectrum Disorder: Pathogenesis and Therapeutic Implications. Current neuropharmacology. 2022.

Autism spectrum disorder (ASD) is a cluster of heterogeneous neurodevelopmental condi- tions with atypical social communication and repetitive sensory-motor behaviors. The formation of new neurons from neural precursors in the hippocampus has been unequivocally demonstrated in the dentate gyrus of rodents and non-human primates. Accumulating evidence sheds light on how the deficits in the hippocampal neurogenesis may underlie some of the abnormal behavioral phenotypes in ASD. In this review, we describe the current evidence concerning pre-clinical and clinical studies supporting the significant role of hippocampal neurogenesis in ASD pathogenesis, discuss the possibility of improving hippocampal neurogenesis as a new strategy for treating ASD, and highlight the prospect of emerging pro-neurogenic therapies for ASD.

Lien vers le texte intégral (Open Access ou abonnement)

20. Long F, Zheng J, Zhou J, Hu P, Xiong B. Knockout of tanc2 causes autism-like behavior and sleep disturbance in zebrafish. Autism research : official journal of the International Society for Autism Research. 2022.

Tanc2 is a large multi-domain postsynaptic scaffold protein mainly expressed in the brain. In humans, tanc2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders. However, the role of tanc2 in neurodevelopment and in controlling behaviors are not fully understood. Here, we generated and characterized a tanc2 knockout allele in zebrafish. Loss of tanc2 increases the larval brain size and body length by promoting proliferation and inhibiting apoptosis. We observed that the glutamatergic neuron population is significantly increased in tanc2 mutants while the GABAergic and the glycinergic neurons are not affected, suggesting that an excitatory/inhibitory (E/I) imbalance. Indeed, the tanc2 knockout larvae exhibited increase sleep. In adult zebrafish, the mutants display anxiolytic-behavior, reduced aggression, and impaired social preference. The alterations in these behaviors are phenotypically similar to the ASD patients carrying tanc2 mutations. Therefore, the tanc2 knockout allele could serve as a valuable model to further study the role of tanc2 in the nervous system.

Lien vers le texte intégral (Open Access ou abonnement)

21. Maejima Y, Yokota S, Ono T, Yu Z, Yamachi M, Hidema S, Nollet KE, Nishimori K, Tomita H, Yaginuma H, Shimomura K. Identification of oxytocin expression in human and murine microglia. Progress in neuro-psychopharmacology & biological psychiatry. 2022; 119: 110600.

BACKGROUND: Oxytocin is a neuropeptide synthesized in the hypothalamus. In addition to its role in parturition and lactation, oxytocin mediates social behavior and pair bonding. The possibility of using oxytocin to modify behavior in neurodevelopmental disorders, such as autism spectrum disorder, is of clinical interest. Microglia are tissue-resident macrophages with roles in neurogenesis, synapse pruning, and immunological mediation of brain homeostasis. Recently, oxytocin was found to attenuate microglial secretion of proinflammatory cytokines, but the source of this oxytocin was not established. This prompted us to investigate whether microglia themselves were the source. METHODS: We examined oxytocin expression in human and murine brain tissue in both sexes using immunohistochemistry. Oxytocin mRNA expression and secretion were examined in isolated murine microglia from wild type and oxytocin-knockout mice. Also, secretion of oxytocin and cytokines was measured in cultured microglia (MG6) stimulated with lipopolysaccharide (LPS). RESULTS: We identified oxytocin expression in microglia of human brain tissue, cultured microglia (MG6), and primary murine microglia. Furthermore, LPS stimulation increased oxytocin mRNA expression in primary murine microglia and MG6 cells, and oxytocin secretion as well. A positive correlation between oxytocin and IL-1β, IL-10 secretion emerged, respectively. CONCLUSION: This may be the first demonstration of oxytocin expression in microglia. Functionally, oxytocin might regulate inflammatory cytokine release from microglia in a paracrine/autocrine manner.

Lien vers le texte intégral (Open Access ou abonnement)

22. Mason D, Taylor H, Ingham B, Finch T, Wilson C, Scarlett C, Urbanowicz A, Nicolaidis C, Lennox N, Moss S, Buckley C, Cooper SA, Osborne M, Garland D, Raymaker D, Parr JR. Views about primary care health checks for autistic adults: UK survey findings. BJGP open. 2022; 6(4).

BACKGROUND: Compared with the general population, autistic adults experience higher rates of physical and mental health conditions, premature morbidity and mortality, and barriers to health care. A health check for autistic people may improve their health outcomes. AIM: To establish the views of autistic people towards a primary care health check for autistic people. DESIGN & SETTING: Cross-sectional questionnaire study in England and Wales. METHOD: A questionnaire was sent to autistic adults with physical health conditions in England and Wales. A total of 458 people (441 autistic adults and 17 proxy responders) completed the questionnaire. RESULTS: Most responders (73.4%, n = 336) thought a health check is needed for all autistic people. Around half of the participants thought a health check should be offered from childhood and the health check appointment should last between 15 and 30 minutes. Autistic people were positive about providing primary care staff with contextual information regarding their health and the reasonable adjustments they would like before their health check appointment. Training about autism and the health check was considered important, alongside adequate time for discussions in the health check appointment (all by over 70% of responders). The clinician’s autism knowledge, seeing a familiar clinician, environmental adaptations, appropriate information, and accessible appointments were considered particularly important in making a health check accessible. CONCLUSION: Autistic people and relatives were supportive of a primary care health check for autistic people. Information gathered was used to support the design of a primary care health check for autistic adults.

Lien vers le texte intégral (Open Access ou abonnement)

23. Mello C, Rivard M, Patel S, Morin D, Morin M. Assessing the quality of care and service trajectories in autism from families’ perspective: Early intervention and interim services. Research in developmental disabilities. 2022; 133: 104387.

BACKGROUND: Following the Evaluation of the Autism Trajectory for Parents – Diagnostic Services (ETAP-1), the ETAP-2 instrument was created to assess the quality of the post-diagnostic phase of the care and service trajectory of families of children with autism. The instrument, based on an integrated care perspective, was developed with the input of multiple stakeholders (parents, service providers, researchers). AIMS: This study sought to evaluate the factor structure, reliability, and convergent and discriminant validity of ETAP-2. METHODS AND PROCEDURES: Parents (N = 197) of children recently diagnosed with autism (M = 5.1 years) were recruited from an assessment center and organizations providing early behavioral intervention and other supports for autism in the province of Québec, Canada. They completed the ETAP-2 questionnaire along with measures of satisfaction and family quality of life. OUTCOMES AND RESULTS: The instrument presented a five-construct structure generally consistent with previously identified dimensions of quality, except for three items previously associated with the continuity of the service trajectory. ETAP-2 had excellent internal consistency and demonstrated convergent and discriminant validity with other measures. CONCLUSIONS AND IMPLICATIONS: ETAP-2 is a brief parent-report measure with good psychometric properties. It can assist in gathering information on families’ perception and experiences with early intervention and other post-diagnostic, interim services.

Lien vers le texte intégral (Open Access ou abonnement)

24. Milne N, Longeri L, Patel A, Pool J, Olson K, Basson A, Gross AR. Spinal manipulation and mobilisation in the treatment of infants, children, and adolescents: a systematic scoping review. BMC pediatrics. 2022; 22(1): 721.

PURPOSE: To i) identify and map the available evidence regarding effectiveness and harms of spinal manipulation and mobilisation for infants, children and adolescents with a broad range of conditions; ii) identify and synthesise policies, regulations, position statements and practice guidelines informing their clinical use. DESIGN: Systematic scoping review, utilising four electronic databases (PubMed, Embase, CINHAL and Cochrane) and grey literature from root to 4(th) February 2021. PARTICIPANTS: Infants, children and adolescents (birth to < 18 years) with any childhood disorder/condition. INTERVENTION: Spinal manipulation and mobilisation OUTCOME MEASURES: Outcomes relating to common childhood conditions were explored. METHOD: Two reviewers (A.P., L.L.) independently screened and selected studies, extracted key findings and assessed methodological quality of included papers using Joanna Briggs Institute Checklist for Systematic Reviews and Research Synthesis, Joanna Briggs Institute Critical Appraisal Checklist for Text and Opinion Papers, Mixed Methods Appraisal Tool and International Centre for Allied Health Evidence Guideline Quality Checklist. A descriptive synthesis of reported findings was undertaken using a levels of evidence approach. RESULTS: Eighty-seven articles were included. Methodological quality of articles varied. Spinal manipulation and mobilisation are being utilised clinically by a variety of health professionals to manage paediatric populations with adolescent idiopathic scoliosis (AIS), asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), back/neck pain, breastfeeding difficulties, cerebral palsy (CP), dysfunctional voiding, excessive crying, headaches, infantile colic, kinetic imbalances due to suboccipital strain (KISS), nocturnal enuresis, otitis media, torticollis and plagiocephaly. The descriptive synthesis revealed: no evidence to explicitly support the effectiveness of spinal manipulation or mobilisation for any condition in paediatric populations. Mild transient symptoms were commonly described in randomised controlled trials and on occasion, moderate-to-severe adverse events were reported in systematic reviews of randomised controlled trials and other lower quality studies. There was strong to very strong evidence for 'no significant effect' of spinal manipulation for managing asthma (pulmonary function), headache and nocturnal enuresis, and inconclusive or insufficient evidence for all other conditions explored. There is insufficient evidence to draw conclusions regarding spinal mobilisation to treat paediatric populations with any condition. CONCLUSION: Whilst some individual high-quality studies demonstrate positive results for some conditions, our descriptive synthesis of the collective findings does not provide support for spinal manipulation or mobilisation in paediatric populations for any condition. Increased reporting of adverse events is required to determine true risks. Randomised controlled trials examining effectiveness of spinal manipulation and mobilisation in paediatric populations are warranted.

Lien vers le texte intégral (Open Access ou abonnement)

25. Nair AS, Priya RS, Rajagopal P, Pradeepa C, Senthil R, Dhanalakshmi S, Lai KW, Wu X, Zuo X. A case study on the effect of light and colors in the built environment on autistic children’s behavior. Frontiers in psychiatry. 2022; 13: 1042641.

BACKGROUND: The importance of strategies and services by caregivers and family members substantially impact the psychological and emotional wellbeing of autistic children. The rapid research developments in clinical and non-clinical methods benefit the features of autistic children. Among various internal and external factors, the influence of the built environment also impacts the characteristics of autistic children. This study investigates primarily the psychological effect of light and colors on the mood and behavior of autistic children to identify the most favorable and preferred indoor lights and color shades. METHODS: A questionnaire survey was conducted at an autism center among autistic children and their parents. This study included autistic children aged between 6 and 16 (45 males, 42 females, mean age 8.7 years, standard deviation 2.3). Eighty-seven participants were involved in the survey to determine the sensory perceptions, intolerance, preferences, and sensitivities of children with an autism spectrum disorder toward colors and lighting. The margin of error at the statistical analysis’s 95% confidence level is ± 0.481. RESULTS: As per this case report, the children have various color preferences and respond differently to different shades. Different hues have varying effects on autistic children, with many neutral tones and mellow shades proven to be autistic-friendly with their calming and soothing effect, while bright, bold, and intense colors are refreshing and stimulating. The stimulus of bright-lighting causes behavioral changes in autistic children prone to light sensitivity. CONCLUSION: The insights gained from this interaction with parents and caretakers of autistic children could be helpful for designers to incorporate specific autistic-friendly design elements that make productive interior spaces. A complete understanding of the effect of factors like color and lighting on the learning ability and engagement of autistic children in an indoor environment is essential for designers and clinicians. The main findings of this study could be helpful for a designer and clinicians to address designing an autism-friendly built environment with a color palette and lighting scheme conducive to their wellbeing and to maximize their cognitive functioning.

Lien vers le texte intégral (Open Access ou abonnement)

26. Pollak T. « Constitutive-intervention »- structuring primal psycho-physical space. The International journal of psycho-analysis. 2022; 103(6): 948-64.

This paper describes a specific type of therapeutic intervention relevant to therapeutic communication with patients exhibiting non-symbolic autistic defenses or traumatic characteristics. The paper focuses on clinical manifestations of developmental deficiencies and communication problems that stem from a primal psychophysical space that is unmatured, traumatized, deformed and/or chaotic. The concept of the body-container is presented as a proto-scheme of primal psychophysical space, organizing the intersections of one’s anatomical structure and potentials for intersubjectivity.This conceptual context allows the therapist to conceive the patient’s non-representational and non-communicative physical actions in the therapeutic setting as presence-in-action. Such presence is discussed as a crucial invitation for the emergence of the therapist’s intuitive pre-symbolic creativity, which may eventually crystallize into a perceptually-presented ‘constitutive intervention’. This unique kind of intervention is designed to support the patient’s creative capacity for pre-symbolic realization of this multi-dimensional psychophysical proto-scheme. Various constitutive interventions, utilizing concrete gestures that involve the therapist’s body and the physical aspect of the therapeutic environment, are examined theoretically and illustrated through clinical vignettes.

Lien vers le texte intégral (Open Access ou abonnement)

27. Surgent O, Riaz A, Ausderau KK, Adluru N, Kirk GR, Guerrero-Gonzalez J, Skaletski EC, Kecskemeti SR, Dean Iii DC, Weismer SE, Alexander AL, Travers BG. Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children. Molecular autism. 2022; 13(1): 48.

BACKGROUND: Elevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism. METHODS: Diffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6-11 years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis. RESULTS: Results revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections. LIMITATIONS: All participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum. CONCLUSIONS: These findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations.

Lien vers le texte intégral (Open Access ou abonnement)

28. Verbinnen I, Procknow SS, Lenaerts L, Reynhout S, Mehregan A, Ulens C, Janssens V, King KA. Clinical and molecular characteristics of a novel rare de novo variant in PPP2CA in a patient with a developmental disorder, autism, and epilepsy. Frontiers in cell and developmental biology. 2022; 10: 1059938.

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are PPP2R5D, encoding the PP2A regulatory B56δ subunit; PPP2R1A, encoding the scaffolding Aα subunit; and PPP2CA, encoding the catalytic Cα subunit-in that order of frequency. Patients with a pathogenic de novo mutation in one of these genes, in part, present with overlapping features, such as generalized hypotonia, intellectual and developmental delay, facial dysmorphologies, seizures, and autistic features, and, in part, with opposite features, e.g., smaller versus larger head sizes or normal versus absent corpus callosum. Molecular variant characterization has been consistent so far with loss-of-function or dominant-negative disease mechanisms for all three affected genes. Here, we present a case report of another PPP2CA-affected individual with a novel de novo missense variant, resulting in a one-amino acid substitution in the Cα subunit: p.Cys196Arg. Biochemical characterization of the variant revealed its pathogenicity, as it appeared severely catalytically impaired, showed mildly affected A subunit binding, and moderately decreased binding to B/B55, B »/PR72, and all B56 subunits, except B56γ1. Carboxy-terminal methylation appeared unaffected, as was binding to B »‘/STRN3-all being consistent with a partial loss of function. Clinically, the girl presented with mild-to-moderate developmental delay, a full-scale IQ of 83, mild dysmorphic facial features, tonic-clonic seizures, and autistic behaviors. Brain MRI appeared normal. We conclude that this individual falls within the milder end of the clinical and molecular spectrum of previously reported PPP2CA cases.

Lien vers le texte intégral (Open Access ou abonnement)

29. Wang J, Xu C, Liu C, Zhou Q, Chao G, Jin Y. Effects of different doses of lithium on the central nervous system in the rat valproic acid model of autism. Chemico-biological interactions. 2022; 370: 110314.

Epidemiological studies have shown that low doses of lithium in the environment can have beneficial effects on mental health. Autism spectrum disorder, a neurodevelopmental disorder in which patients exhibit abnormal behaviors, pharmacological interventions usually relied on a range of psychotropic medications. However, such medications often produce severe side effects or are ineffective in symptoms. Finding alternative ways to improve abnormal behaviors in individuals with autism are warranted, in which case lithium may be a relatively safe and effective medication. Lithium salt therapy is used to treat a variety of neuropsychiatric disorders and has neuroprotective effects. In this study, we investigated the effects of different doses of lithium on neurobehavioural disorders using the rat model of autism established by valproic acid (VPA) injection. Lithium was observed to have an ameliorative effect on the social cognitive, social memory and anxiety levels in the rat model of autism. Immunofluorescence staining showed that subchronic LiCl administration (1.0 mmol/kg) significantly reduced the number of Iba-1 positive cells in the CA1 region of the hippocampus in VPA group and brought it close to the levels of control group. Significantly lower levels of the pro-inflammatory marker IL-6 were observed in the hippocampus and serum after lithium treatment. In addition, the lithium treatment increased the levels of H3K9 acetylation in the hippocampus of VPA-exposed rats. The results showed a defensive effect of environment-related lithium exposure doses on neurobehavioural deficits in the rat valproic acid model of autism, suggesting that it may be a potential drug for the treatment of autism.

Lien vers le texte intégral (Open Access ou abonnement)

30. Waterhouse L. Heterogeneity thwarts autism explanatory power: A proposal for endophenotypes. Frontiers in psychiatry. 2022; 13: 947653.

Many researchers now believe that autism heterogeneity is likely to include many disorders, but most research is based on samples defined by the DSM-5 Autism Spectrum Disorder (ASD) criteria. However, individuals diagnosed with autism have complex and varied biological causes for their symptoms. Therefore, autism is not a unitary biological entity. And although autism is significantly different from typical development, autism is not a unitary clinical disorder because diagnosed individuals vary in symptom patterns, comorbidities, biomarkers, and gene variants. The DSM-5 ASD criteria were designed to reduce heterogeneity, and there have been many other efforts to reduce autism heterogeneity including using more stringent clinical criteria, dividing autism into low and high functioning groups, creating subgroups, and by studying larger samples. However, to date these efforts have not been successful. Heterogeneity is extensive and remains unexplained, and no autism pathophysiology has been discovered. Most importantly, heterogeneity has hindered the explanatory power of the autism diagnosis to discover drug regimens and effective behavioral treatments. The paper proposes that possible transdiagnostic endophenotypes may reduce autism heterogeneity. Searching for transdiagnostic endophenotypes requires exploring autism symptoms outside of the framework of the DSM-5 autism diagnosis. This paper proposes that researchers relax diagnostic criteria to increase the range of phenotypes to support the search for transdiagnostic endophenotypes. The paper proposes possible candidates for transdiagnostic endophenotypes. These candidates are taken from DSM-5 ASD criteria, from concepts that have resulted from researched theories, and from symptoms that are the result of subtyping. The paper then sketches a possible basis for a future transdiagnostic endophenotypes screening tool that includes symptoms of autism and other neurodevelopmental disorders.

Lien vers le texte intégral (Open Access ou abonnement)

31. Xiong H, Liu X, Yang F, Yang T, Chen J, Chen J, Li T. Developmental Language Differences in Children with Autism Spectrum Disorders and Possible Sex Difference. Journal of autism and developmental disorders. 2022.

Developmental difference is a common characteristic of autism spectrum disorder (ASD) with unclear sex differences. The current study included 610 children with ASD, aged between 2 and 7 years, with completed language profiles. We used a nonparametric item response theory model called Mokken scale analysis to examine the order of acquisition of developmental language milestones in children with ASD. Our results demonstrated the developmental language differences in the expressive and receptive language dimensions in children with ASD compared with typical developmental sequences. Furthermore, The acquisition of gestures and pragmatics was more impaired in the female subgroup than in the male subgroup. The identified developmental language sequence could help provide a more comprehensive ASD developmental profile.

Lien vers le texte intégral (Open Access ou abonnement)