1. Abdulhaq A, Halboub E, Homeida HE, Kumar Basode V, Ghzwani AH, Zain KA, Baraniya D, Chen T, Al-Hebshi NN. Tongue microbiome in children with autism spectrum disorder. Journal of oral microbiology. 2021; 13(1): 1936434.

Background: A few recent studies have characterized the salivary microbiome in association with Autism Spectrum Disorder (ASD). Here, we sought to assess if there is an association between the tongue microbiome and ASD. Methods: Tongue scrapping samples were obtained from 25 children with ASD and 38 neurotypical controls. The samples were sequenced for the 16S rRNA gene (V1-V3) and the resultant high-quality reads were assigned to the species-level using our previously described BLASTn-based algorithm. Downstream analyses of microbial profiles were conducted using QIIME, LEfSe, and R. Results: Independent of grouping, Prevotella, Streptococcus, Leptotrichia, Veillonella, Haemophilus and Rothia accounted for > 60% of the average microbiome. Haemophilus parainfluenzae, Rothia mucilaginosa, Prevotella melaninogenica and Neisseria flavescens/subflava were the most abundant species. Species richness and diversity did not significantly differ between the study groups. Thirteen species and three genera were differentially abundant between the two groups, e.g. enrichment of Actinomyces odontolyticus and Actinomyces lingnae and depletion of Campylobacter concisus and Streptococcus vestibularis in the ASD group. However, none of them withstood adjustment for multiple comparisons. Conclusion: The tongue microbiome of children with ASD was not significantly different from that of healthy control children, which is largely consistent with results from the literature.

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2. Bakare AB, Daniel J, Stabach J, Rojas A, Bell A, Henry B, Iyer S. Quantifying Mitochondrial Dynamics in Patient Fibroblasts with Multiple Developmental Defects and Mitochondrial Disorders. International journal of molecular sciences. 2021; 22(12).

Mitochondria are dynamic organelles that undergo rounds of fission and fusion and exhibit a wide range of morphologies that contribute to the regulation of different signaling pathways and various cellular functions. It is important to understand the differences between mitochondrial structure in health and disease so that therapies can be developed to maintain the homeostatic balance of mitochondrial dynamics. Mitochondrial disorders are multisystemic and characterized by complex and variable clinical pathologies. The dynamics of mitochondria in mitochondrial disorders is thus worthy of investigation. Therefore, in this study, we performed a comprehensive analysis of mitochondrial dynamics in ten patient-derived fibroblasts containing different mutations and deletions associated with various mitochondrial disorders. Our results suggest that the most predominant morphological signature for mitochondria in the diseased state is fragmentation, with eight out of the ten cell lines exhibiting characteristics consistent with fragmented mitochondria. To our knowledge, this is the first comprehensive study that quantifies mitochondrial dynamics in cell lines with a wide array of developmental and mitochondrial disorders. A more thorough analysis of the correlations between mitochondrial dynamics, mitochondrial genome perturbations, and bioenergetic dysfunction will aid in identifying unique morphological signatures of various mitochondrial disorders in the future.

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3. Barone R, Bastin J, Djouadi F, Singh I, Karim MA, Ammanamanchi A, McCarty PJ, Delhey L, Shannon R, Casabona A, Rizzo R, Frye RE. Mitochondrial Fatty Acid β-Oxidation and Resveratrol Effect in Fibroblasts from Patients with Autism Spectrum Disorder. Journal of personalized medicine. 2021; 11(6).

Patients with autism spectrum disorder (ASD) may have an increase in blood acyl-carnitine (AC) concentrations indicating a mitochondrial fatty acid β-oxidation (mtFAO) impairment. However, there are no data on systematic mtFAO analyses in ASD. We analyzed tritiated palmitate oxidation rates in fibroblasts from patients with ASD before and after resveratrol (RSV) treatment, according to methods used for the diagnosis of congenital defects in mtFAO. ASD participants (N = 10, 60%; male; mean age (SD) 7.4 (3.2) years) were divided in two age-equivalent groups based on the presence (N = 5) or absence (N = 5) of elevated blood AC levels. In addition, electron transport chain (ETC) activity in fibroblasts and muscle biopsies and clinical characteristics were compared between the ASD groups. Baseline fibroblast mtFAO was not significantly different in patients in comparison with control values. However, ASD patients with elevated AC exhibited significantly decreased mtFAO rates, muscle ETC complex II activity, and fibroblast ETC Complex II/III activity (p < 0.05), compared with patients without an AC signature. RSV significantly increased the mtFAO activity in all study groups (p = 0.001). The highest mtFAO changes in response to RSV were observed in fibroblasts from patients with more severe symptoms on the Social Responsiveness Scale total (p = 0.001) and Awareness, Cognition, Communication and Motivation subscales (all p < 0.01). These findings suggested recognition of an ASD patient subset characterized by an impaired mtFAO flux associated with abnormal blood AC. The study elucidated that RSV significantly increased fibroblast mtFAO irrespective of plasma AC status, and the highest changes to RSV effects on mtFAO were observed in the more severely affected patients.

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4. Barton H, McIntyre LL. Caregiver-reported executive functioning and associated adaptive and challenging behaviour in children with histories of developmental delay. Journal of intellectual disability research : JIDR. 2022; 66(1-2): 121-32.

BACKGROUND: Deficits in executive functioning (EF) have been measured in individuals with developmental disabilities, such as autism spectrum disorder and attention-deficit/hyperactivity disorder, through the use of behaviour rating scales and performance-based assessment. Associations between EF and variables such as challenging and adaptive behaviour have been observed; however, limited research exists on EF profiles in children with heterogeneous developmental delay or with intellectual disability (ID) or the impact of EF on adaptive and challenging behaviour with this population. METHODS: The present study sought to examine the EF profile of 93 children (75 male and 18 female) previously identified with developmental delay in early childhood. EF was assessed using the Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF-2). Children were categorised into an ID group (n = 14) or no ID group (n = 79) based on scores from cognitive and adaptive behaviour assessments. EF profiles were investigated and compared by group. In addition, the impact of EF on both adaptive behaviour and challenging behaviour was measured using hierarchical linear regressions. RESULTS: Statistically significant differences in caregiver-reported EF were not observed between groups; however, both the ID and the no ID group scores were elevated as reported by their caregivers. For the overall sample, caregiver-EF accounted for significant variance in both adaptive (22%) and challenging (68%) behaviour after accounting for child age and sex. CONCLUSIONS: Results indicated deficits in EF for children with and without ID. The significance of EF was accounted for in both adaptive and challenging behaviour for all children in the sample. Future research could elucidate the role of adaptive and challenging behaviour in understanding EF variability among children with histories of developmental delay.

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5. Boulton KA, Guastella AJ. Social anxiety symptoms in autism spectrum disorder and social anxiety disorder: Considering the reliability of self-report instruments in adult cohorts. Autism research : official journal of the International Society for Autism Research. 2021; 14(11): 2383-92.

Adults with autism spectrum disorder (ASD) are at elevated risk for social anxiety disorder (SAD). Limited information exists on the reliability of social anxiety instruments with these adults and their performance when compared to individuals with SAD without ASD. This study examines psychometric properties of self-report social anxiety instruments in autistic adults without intellectual disability, compared to adults with SAD. Additionally, we compared instrument scores between a subgroup of autistic adults with a dual diagnosis of SAD (ASD + SAD) and adults with SAD only. Adults diagnosed with SAD (N = 316) or ASD (N = 102) were recruited from the Brain and Mind Centre in New South Wales, Australia. Sixty autistic participants also received a diagnosis of SAD (ASD + SAD). Participants completed the Liebowitz Social Anxiety Scale-self-report, the Social Interaction Anxiety Scale, the Social Phobia Scale, and the Brief Fear of Negative Evaluation Scale. All instruments showed excellent internal consistency in autistic adults. The instruments showed evidence of convergent validity, and the strength of relationships between measures were equivalent between ASD and SAD groups. For all instruments, performance of these instruments in autistic adults with a SAD diagnosis was very similar to performance in adults diagnosed with SAD but without ASD. Findings support the use of these instruments for identifying social anxiety symptoms in autistic adults without intellectual disability and have utility for mental health clinical services. LAY SUMMARY: Autistic adults often experience social anxiety. We examined the use of four social anxiety questionnaires in autistic adults, compared to adults with SAD. We found similar results between autistic adults and adults with SAD, suggesting that these questionnaires can be useful for measuring social anxiety symptoms in autistic adults. These findings have implications for clinical services, as they show that these instruments are reliable when used with autistic adults.

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6. Braden BB, Wallace GL, Floris DL, Pelphrey KA. Editorial: Sex Differences in the Autistic Brain. Frontiers in integrative neuroscience. 2021; 15: 708368.

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7. Brondino N, Bertoglio F, Forneris F, Faravelli S, Borghesi A, Damiani S, Provenzani U, Nola M, Olivola M, Caviglia M, Politi P, Fusar-Poli L, Fusar-Poli P. A Pilot Study on Covid and Autism: Prevalence, Clinical Presentation and Vaccine Side Effects. Brain sciences. 2021; 11(7).

Background: Several neurobiological mechanisms have been proposed to support the hypothesis of a higher COVID-19 risk in individuals with autism spectrum disorder (ASD). However, no real-world data are available on this population. Methods: We compared the period prevalence (March-May 2020) and symptom presentation of COVID-19 infections between a sample of individuals with severe ASD (n = 36) and the staff personnel (n = 35) of two specialized centers. Anti-SARS-Cov-2 antibody positivity was used as a proxy of infection. Additionally, we evaluated vaccine side effects in the same groups. Results: No significant difference was found between the prevalence of COVID-19 positivity between autistic participants and staff personnel. Levels of antibodies against the spike protein and the receptor binding domain were not significantly different between autistic and staff participants. The level of antibodies against the N-terminal domain were higher in autistic individuals. There was a significant difference between the prevalence of symptomatic COVID-19 in autistic participants (9.1%) compared to staff personnel (92.3%). The most frequent side effect among autistic participants was light fever. Conclusions: The present study provides preliminary data on COVID-19 transmission and presentation in ASD. Our data do not support the hypothesis of a higher susceptibility and severity of COVID-19 in people with ASD.

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8. Chen Q, Wang Z, Wan B, Chen Q, Zhai K, Jin Y. The Effect of Comorbid Attention-Deficit/Hyperactivity Disorder Symptoms on Face Memory in Children with Autism Spectrum Disorder: Insights from Transdiagnostic Profiles. Brain sciences. 2021; 11(7).

Face memory impairments are common but heterogeneous in autism spectrum disorder (ASD), which may be influenced by co-occurrence with attention-deficit/hyperactivity disorder (ADHD). Here, we aimed to investigate the phenotype change of face memory in children with ASD comorbid ADHD symptoms, and discuss the potential role of executive function (EF). Ninety-eight children were analyzed in the present study, including ASD- (ASD-only, n = 24), ADHD (n = 23), ASD+ (with ADHD symptoms, n = 23) and neurotypical controls (NTC, n = 28). All participants completed two tests: face encoding and retrieving task and Wisconsin Card Sorting Test (WCST) for measuring face memory and EF, respectively. Results revealed that: compared with the NTC group, children with ASD- exhibited lower accuracy in both face encoding and retrieving, and participants with ASD+ showed lower accuracy only in the retrieving, whereas no differences were found among participants with ADHD. Moreover, in the ASD+ group, face encoding performance was correlated with response perseverative errors (RPE) and failure to maintain sets (FMS) of WCST; significantly, there were no group differences between ASD+ and NTC in these two indices. The transdiagnostic profiles indicated that comorbid ADHD symptoms could modulate the face encoding deficiency of ASD, which may be partially compensated by EF. Shared and distinct intervention strategies to improve social cognition are recommended for children undergoing treatment for each condition.

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9. Chen WJ, Zhang Z, Wang H, Tseng TS, Ma P, Chen LS. Perceptions of Autism Spectrum Disorder (ASD) Etiology among Parents of Children with ASD. International journal of environmental research and public health. 2021; 18(13).

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted or repetitive behaviors. Parental perceptions of the etiology of their child’s ASD can affect provider-client relationships, bonding between parents and their children, and the prognosis, treatment, and management of children with ASD. Thus, this study sought to examine the perceptions of ASD etiology of parents of children with ASD. METHODS: Forty-two parents of children diagnosed with ASD were recruited across Texas. Semi-structured interviews were conducted individually. All interviews were recorded and later transcribed verbatim for content analysis utilizing NVivo 12.0 (QSR International, Doncaster, Australia). RESULTS: The content analysis identified the following themes regarding parental perceptions of ASD etiology: Genetic factors (40.5%), environmental factors (31.0%), problems that occurred during pregnancy or delivery (23.8%), vaccinations (16.7%), other health problems (7.1%), parental age at the time of pregnancy (4.8%), and spiritual or religious factors (2.4%). CONCLUSIONS: The parental perceptions of ASD etiology were diverse, but several views, such as vaccinations and spiritual or religious factors, were not based on scientific evidence. Health professionals and researchers can use these findings to develop and provide targeted education to parents who have children with ASD. Our findings also support policymakers in developing campaigns designed to increase parental ASD awareness and knowledge.

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10. Chen Y, Xu J, Chen Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients. 2021; 13(6).

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.

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11. Concerto C, Rodolico A, Avanzato C, Fusar-Poli L, Signorelli MS, Battaglia F, Aguglia E. Autistic Traits and Attention-Deficit Hyperactivity Disorder Symptoms Predict the Severity of Internet Gaming Disorder in an Italian Adult Population. Brain sciences. 2021; 11(6).

Over the last decade, internet gaming has been a fast-growing recreational activity. Gamers risk their leisure activity becoming an addiction. In the present study, we aimed to measure the prevalence of Internet Gaming Disorder (IGD) in an adult population of video game players and to investigate the association between demographic variables, Autism Spectrum Disorder (ASD) traits, Attention-Deficit Hyperactivity Disorder (ADHD) severity, and IGD in adults. Through an online survey, we recruited 4260 individuals aged between 18 and 55 years old, who were members of online communities of video gamers. We collected demographic data and administered three questionnaires: the Internet Gaming Disorder Scale-Short Form (IGD9-SF), the Autism Spectrum Quotient (AQ), and the Adult ADHD Self-Report Scale (ASRS). Of the overall sample, 29.67% scored above the cut-off of 21 points for the IGD9-SF. Multiple linear regression models showed that daily spare time, autistic traits, and ADHD symptoms were positively associated with the severity of IGD in adults, after controlling for demographic variables. Future studies are required in order to explore factors linked to IGD in adults.

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12. DaWalt LS, Taylor JL, Movaghar A, Hong J, Kim B, Brilliant M, Mailick MR. Health profiles of adults with autism spectrum disorder: Differences between women and men. Autism research : official journal of the International Society for Autism Research. 2021; 14(9): 1896-904.

The purpose of the present study was to investigate the hypothesis that women with autism have poorer health compared with men with autism, and compared with women without autism. Utilizing electronic health records drawn from a single health care system serving over 2 million individuals, 2119 adults with diagnosed autism spectrum disorders were compared with age- and sex-matched controls. When considering health care utilization, we found evidence of multiplicative risk for conditions within some domains (i.e., nutrition conditions, neurologic disease, psychiatric conditions, and sleep disorders) such that women with autism spectrum disorder (ASD) experienced double jeopardy-meaning they had greater rates of health care utilization within a domain than what would separately be expected by virtue of being a woman and having ASD. For other domains (i.e., endocrine disorders, gastrointestinal disorders), the risk was additive such that being a female and having ASD were both associated with higher health care utilization, but there were no significant interaction effects. It was only with respect to one domain (cardiovascular) that rates of health care utilization were reflective of neither ASD diagnosis nor sex. Overall, our findings suggest that women with ASD are a vulnerable subgroup with high levels of health care utilization. LAY SUMMARY: This study asked whether women with autism have poorer health compared with men with autism, and compared with women without autism. To answer this question, we used data from electronic health records. We found that women with autism spectrum disorder (ASD) were at the greatest risk for health problems such as nutrition conditions, neurologic disease, psychiatric conditions, and sleep disorders. More research on health of women with ASD is needed.

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13. Downs J, Wong K, Drummond C, Leonard H. Longitudinal Evaluation of the Stability of Hand Function in Rett Syndrome. The Journal of pediatrics. 2021; 237: 244-9.e3.

OBJECTIVE: To investigate the longitudinal stability of hand function in Rett syndrome and to analyze further the relationships between stability of hand function and genotype, age, and walking ability. STUDY DESIGN: Longitudinal video data of functional abilities of individuals with genetically confirmed Rett syndrome were collected by families of individuals registered with the Australian Rett Syndrome Database. A total of 120 individuals provided 290 recordings from which 170 observation pairs were available for comparison. The Rett Syndrome Hand Function Scale was used to classify a level of hand function observed in each video on a range from unable to grasp, pick up, and hold objects to skillful manipulation of large and small objects. RESULTS: Approximately one-third of the population lost some hand function over time. Younger children (<6 years) rather than adults were at greater risk of deterioration in hand function. Clinical severity, as indicated by walking ability or genotype, played a lesser role. There was no identified pattern between genotype and the stability of hand function skills. Rather, mutations associated with milder (p.Arg133Cys, p.Arg294∗) and greater (p.Arg106Trp, p.Thr158Met) clinical severity were both associated with greater risks of decline. CONCLUSIONS: Genotype was a lesser predictor of loss of hand function beyond the early regression period, and younger children were particularly vulnerable to further loss of hand function compared with adults.

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14. Ferreira ML, Loyacono N. Rationale of an Advanced Integrative Approach Applied to Autism Spectrum Disorder: Review, Discussion and Proposal. Journal of personalized medicine. 2021; 11(6).

The rationale of an Advanced Integrative Model and an Advanced Integrative Approach is presented. In the context of Allopathic Medicine, this model introduces the evaluation, clinical exploration, diagnosis, and treatment of concomitant medical problems to the diagnosis of Autism Spectrum Disorder. These may be outside or inside the brain. The concepts of static or chronic, dynamic encephalopathy and condition for Autism Spectrum Disorder are defined in this model, which looks at the response to the treatments of concomitant medical problemsto the diagnosis of Autism Spectrum Disorder. (1) Background: Antecedents and rationale of an Advanced Integrative Model and of an Advanced Integrative Approach are presented; (2) Methods: Concomitant medical problems to the diagnosis of Autism Spectrum Disorder and a discussion of the known responses of their treatments are presented; (3) Results: Groups in Autism are defined and explained, related to the responses of the treatments of the concomitant medical problems to ASD and (4) Conclusions: The analysis in the framework of an Advanced Integrative Model of three groups including the concepts of static encephalopathy; chronic, dynamic encephalopathy and condition for Autism Spectrum Disorder explains findings in the field, previously not understood.

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15. Gardner RM, Samuelsson I, Severance EG, Sjöqvist H, Yolken RH, Dalman C, Karlsson H. Maternal antibodies to gliadin and autism spectrum disorders in offspring-A population-based case-control study in Sweden. Autism research : official journal of the International Society for Autism Research. 2021; 14(9): 2002-16.

While individuals diagnosed with autism spectrum disorders (ASD) have higher levels of antibodies directed towards gliadin, a component of wheat gluten, no study has examined anti-gliadin antibodies (AGA) in etiologically relevant periods before diagnosis. The objective of this study was to investigate if maternal levels of AGA, during pregnancy and at the time of birth, are associated with ASD in offspring. We analyzed AGA in archived neonatal dried blood spots (NDBS) for 921 ASD cases and 1090 controls, and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls. We examined associations with ASD diagnoses as a group and considering common comorbidities (intellectual disability [ID] and attention-deficit/hyperactivity disorder). We compared 206 cases to their unaffected siblings to examine the potential for confounding by shared familial factors. Odds of ASD tended to be lower among those with the highest levels (≥90th percentile) of AGA compared to those with low levels (<80th percentile; OR 0.78, 95% CI 0.56-1.09, measured in NDBS). This pattern was more apparent for ASD with comorbid ID when measured in NDBS (0.51, 0.30-0.87), with a similar trend in maternal sera (0.55, 0.24-1.29). High levels of AGA were similarly associated with lower odds of ASD in the sibling comparison. In summary, we found little association between maternal antibodies raised against components of gluten and risk of ASD in general. Exposure to high levels of AGA in the pre- and perinatal periods may be protective in terms of risk for ASD with ID. LAY SUMMARY: There is a debate among both scientists and community members as to whether an immune reaction to gluten exposure could be considered a cause of autism. We examined antibodies that are directed against gliadin, a part of gluten, in samples collected from pregnant mothers and their newborn babies. We did not see any major differences in the antibody level among those children diagnosed with ASD or their mothers compared to children who were not diagnosed with ASD. High levels of the antibodies were in fact associated with a somewhat lower risk of ASD with co-occurring intellectual disabilities, though we cannot tell from this study why that might be the case.

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16. Hastert M, Goetz JR, Sullivan DK, Hull HR, Donnelly JE, Ptomey LT. Calcium, fiber, iron, and sodium intake in adolescents with intellectual and developmental disabilities and overweight and obesity. Disability and health journal. 2021; 14(4): 101155.

BACKGROUND: Adolescents with intellectual and developmental disabilities (IDD) and overweight or obesity (OW/OB) are a nutritionally vulnerable group with increased risk of nutritional deficiencies. However, there are limited data examining micronutrient intake in adolescents with IDD and OW/OB. OBJECTIVE: The purpose of this study was to assess the adequacy of calcium, iron, fiber, and sodium intake referenced against the United States Dietary Reference Intakes in adolescents with IDD and OW/OB. METHODS: Three-day image-assisted food records were used to assess dietary intake of 64 adolescents with IDD and OW/OB. A mean ± standard deviation was calculated for mean intake of calcium (mg), fiber (g/1000 kcals energy), iron (mg), and sodium (mg). RESULTS: A total of 157 nutrient intake observations were completed by 64 participants (56% female, 16.3 ± 2.3 years). Calcium intake for participants ages 14-18 years (n = 57) was 1027.4 ± 607.5 mg, which is below the EAR of 1050 mg. Calcium intake for participants ages ≥19 years (n = 7) was 921.1 ± 596.4 mg, which is greater than the EAR of 840 mg. Fiber intake was 8.4 ± 3.6 g/1000 kcals, which is below the AI of 14 g/1000 kcals. Iron intake for all participants exceeded their respective EARs. Sodium intake was 3180.9 ± 975.9 mg, which above the AI of 2300 mg. CONCLUSION: Calcium intake was adequate for participants ≥19 years of age, but inadequate for participants 14-18 years. For all participants, iron and sodium intake exceeded the DRI while fiber intake was below the DRI.

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17. Holloway JM, Long TM, Biasini FJ. The intersection of gross motor abilities and participation in children with autism spectrum disorder. Infants and young children. 2021; 34(3): 178-89.

Many children with autism spectrum disorder (ASD) demonstrate movement difficulties in addition to problems with social communication and interactions, and repetitive or restrictive behaviors. The goal of early intervention for children with disabilities is to promote participation in routines and activities, but little is known about the role gross motor abilities contribute to participation for young children with ASD. The purpose of this study was to examine relationships between gross motor abilities and participation in preschool-aged children with ASD. Twenty-two children with ASD participated in the study. Gross motor skills were measured using the Peabody Developmental Motor Scales, Second Edition. Participation was measured using the Preschool Activity Card Sort. Children who had greater gross motor skills also demonstrated greater participation in self-care, high demand leisure, and social interaction activities. Results also identified activities that may be difficult for preschoolers with ASD. Findings suggest that early childhood intervention providers consider the impact of gross motor deficits within the context of participation in daily routines and activities.

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18. Keller R, Costa T, Imperiale D, Bianco A, Rondini E, Hassiotis A, Bertelli MO. Stereotypies in the Autism Spectrum Disorder: Can We Rely on an Ethological Model?. Brain sciences. 2021; 11(6).

BACKGROUND: Stereotypic behaviour can be defined as a clear behavioural pattern where a specific function or target cannot be identified, although it delays on time. Nonetheless, repetitive and stereotypical behaviours play a key role in both animal and human behaviour. Similar behaviours are observed across species, in typical human developmental phases, and in some neuropsychiatric conditions, such as Autism Spectrum Disorder (ASD) and Intellectual Disability. This evidence led to the spread of animal models of repetitive behaviours to better understand the neurobiological mechanisms underlying these dysfunctional behaviours and to gain better insight into their role and origin within ASD and other disorders. This, in turn, could lead to new treatments of those disorders in humans. METHOD: This paper maps the literature on repetitive behaviours in animal models of ASD, in order to improve understanding of stereotypies in persons with ASD in terms of characterization, pathophysiology, genomic and anatomical factors. RESULTS: Literature mapping confirmed that phylogenic approach and animal models may help to improve understanding and differentiation of stereotypies in ASD. Some repetitive behaviours appear to be interconnected and mediated by common genomic and anatomical factors across species, mainly by alterations of basal ganglia circuitry. A new distinction between stereotypies and autotypies should be considered. CONCLUSIONS: Phylogenic approach and studies on animal models may support clinical issues related to stereotypies in persons with ASD and provide new insights in classification, pathogenesis, and management.

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19. Levante A, Petrocchi S, Bianco F, Castelli I, Colombi C, Keller R, Narzisi A, Masi G, Lecciso F. Psychological Impact of COVID-19 Outbreak on Families of Children with Autism Spectrum Disorder and Typically Developing Peers: An Online Survey. Brain sciences. 2021; 11(6).

BACKGROUND: When COVID-19 was declared as a pandemic, many countries imposed severe lockdowns that changed families’ routines and negatively impacted on parents’ and children’s mental health. Several studies on families with children with autism spectrum disorder (ASD) revealed that lockdown increased the difficulties faced by individuals with ASD, as well as parental distress. No studies have analyzed the interplay between parental distress, children’s emotional responses, and adaptive behaviors in children with ASD considering the period of the mandatory lockdown. Furthermore, we compared families with children on the spectrum and families with typically developing (TD) children in terms of their distress, children’s emotional responses, and behavioral adaptation. METHODS: In this study, 120 parents of children aged 5-10 years (53 with ASD) participated. RESULTS: In the four tested models, children’s positive and negative emotional responses mediated the impact of parental distress on children’s playing activities. In the ASD group, parents reported that their children expressed more positive emotions, but fewer playing activities, than TD children. Families with children on the spectrum reported greater behavioral problems during the lockdown and more parental distress. CONCLUSIONS: Our findings inform the interventions designed for parents to reduce distress and to develop coping strategies to better manage the caregiver-child relationship.

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20. Long M, Register-Brown K. Autism Spectrum Disorder. Pediatrics in review. 2021; 42(7): 360-74.

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21. Maini I, Caraffi SG, Peluso F, Valeri L, Nicoli D, Laurie S, Baldo C, Zuffardi O, Garavelli L. Clinical Manifestations in a Girl with NAA10-Related Syndrome and Genotype-Phenotype Correlation in Females. Genes. 2021; 12(6).

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 [NM_003491:c.247C > T, p.(Arg83Cys)] variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype-phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could have relevant consequences for the clinical management of known and newly identified individuals.

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22. Makris G, Chouliaras G, Apostolakou F, Papageorgiou C, Chrousos GP, Papassotiriou I, Pervanidou P. Increased Serum Concentrations of High Mobility Group Box 1 (HMGB1) Protein in Children with Autism Spectrum Disorder. Children (Basel, Switzerland). 2021; 8(6).

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, p = 0.039). The Spearman’s rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, p = 0.045) and with the SQ total score (rs = 0.42, p = 0.04) in the ASD group. These results show that HMGB1 serum concentrations are altered in ASD children, and suggest that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features observed in ASD.

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23. Marano D, Fioriniello S, D’Esposito M, Della Ragione F. Transcriptomic and Epigenomic Landscape in Rett Syndrome. Biomolecules. 2021; 11(7).

Rett syndrome (RTT) is an extremely invalidating, cureless, developmental disorder, and it is considered one of the leading causes of intellectual disability in female individuals. The vast majority of RTT cases are caused by de novo mutations in the X-linked Methyl-CpG binding protein 2 (MECP2) gene, which encodes a multifunctional reader of methylated DNA. MeCP2 is a master epigenetic modulator of gene expression, with a role in the organization of global chromatin architecture. Based on its interaction with multiple molecular partners and the diverse epigenetic scenario, MeCP2 triggers several downstream mechanisms, also influencing the epigenetic context, and thus leading to transcriptional activation or repression. In this frame, it is conceivable that defects in such a multifaceted factor as MeCP2 lead to large-scale alterations of the epigenome, ranging from an unbalanced deposition of epigenetic modifications to a transcriptional alteration of both protein-coding and non-coding genes, with critical consequences on multiple downstream biological processes. In this review, we provide an overview of the current knowledge concerning the transcriptomic and epigenomic alterations found in RTT patients and animal models.

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24. Marcé-Grau A, Elorza-Vidal X, Pérez-Rius C, Ruiz-Nel Lo A, Sala-Coromina J, Gabau E, Estévez R, Macaya A. Muscarinic acetylcholine receptor M1 mutations causing neurodevelopmental disorder and epilepsy. Human mutation. 2021; 42(10): 1215-20.

De novo rare damaging variants in genes involved in critical developmental pathways, notably regulation of synaptic transmission, have emerged as a frequent cause of neurodevelopmental disorders (NDD). NDD show great locus heterogeneity and for many of the associated genes, there is substantial phenotypic diversity, including epilepsy, intellectual disability, autism spectrum disorder, movement disorders, and combinations thereof. We report two unrelated patients, a young girl with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and a second girl with mild dysmorphism, global developmental delay, and moderate intellectual disability in whom trio-based whole-exome sequencing analysis uncovered de novo missense variants in CHRM1. Biochemical analyses of one of the NDD-associated variants proved that it caused a reduction in protein levels and impaired cellular trafficking. In addition, the mutated receptor showed defective activation of intracellular signaling pathways. Our data strengthen the concept that brain-reduced muscarinic signaling lowers the seizure threshold and severely impairs neurodevelopment.

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25. Marino F, Failla C, Chilà P, Minutoli R, Puglisi A, Arnao AA, Pignolo L, Presti G, Pergolizzi F, Moderato P, Tartarisco G, Ruta L, Vagni D, Cerasa A, Pioggia G. The Effect of Acceptance and Commitment Therapy for Improving Psychological Well-Being in Parents of Individuals with Autism Spectrum Disorders: A Randomized Controlled Trial. Brain sciences. 2021; 11(7).

BACKGROUND: Acceptance and Commitment Therapy (ACT) has been demonstrated as effective in improving psychological well-being in several clinical domains, but there is no evidence regarding the parents of children with Autism Spectrum Disorder (ASD). METHODS: In this randomized controlled trial, we evaluated the efficacy of the ACT matrix behavioral protocol in comparison to the Parent Training (PT) program, measuring several primary and secondary outcomes prior to and following treatments. Twelve parents were randomly and equally assigned to two demographically matched groups wherein individuals underwent 24 weekly meetings of ACT protocol (experimental group) or conventional PT (control group). RESULTS: Parents enrolled in the ACT protocol demonstrated significant improvement in psychological flexibility, awareness states, personal values in everyday life, and parental stress, whereas reduced scores were elicited in parents’ perceptions of their child’s disruptive behaviors. CONCLUSIONS: The results of this randomized controlled trial, if repeated with a large number of subjects, could open the way to include ACT protocols in daily practice to support the development of new parenting skills.

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26. Mayes SD, Puzino K, DiGiovanni C, Calhoun SL. Cross-Sectional Age Analysis of Sleep Problems in 2 to 17 Year Olds with ADHD Combined, ADHD Inattentive, or Autism. Journal of clinical psychology in medical settings. 2021.

Sleep problems are common in autism and ADHD. No study has compared sleep problems by age in 2 to 17 year olds with autism versus ADHD-Combined versus ADHD-Inattentive type. Mothers rated 1415 youth with autism and 1041 with ADHD on 10 Pediatric Behavior Scale sleep items. Nighttime sleep problems were most severe in autism, followed by ADHD-Combined, and then ADHD-Inattentive. Difficulty falling asleep, restless during sleep, and waking during the night were the most common problems. Adolescents slept more at night than other age groups, and youth who slept more at night were sleepier during the day. Sleep problems declined with age, but correlations were small. In adolescence, 63% with autism, 53% with ADHD-Combined, and 57% with ADHD-Inattentive had difficulty falling asleep. Given that the majority of children in all age groups had one or more sleep problem, developmentally appropriate interventions are needed to address sleep difficulties and limit their adverse effects.

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27. Mensi MM, Rogantini C, Marchesi M, Borgatti R, Chiappedi M. Lactobacillus plantarum PS128 and Other Probiotics in Children and Adolescents with Autism Spectrum Disorder: A Real-World Experience. Nutrients. 2021; 13(6).

Autism Spectrum Disorder is a neurodevelopmental disorder. Recent data suggest that probiotics can reduce some symptoms of this disorder and Lactobacillus plantarum PS128 has been reported to be especially useful. We recruited a sample of 131 autistic children and adolescents (M:F = 122:19; age: 86.1 ± 41.1 months) and evaluated their changes after use of probiotics by mean of CGI. We found some significant improvements with very few side effects; these positive effects were more evident in younger children. Patients taking Lactobacillus plantarum PS128 had greater improvements and fewer side effects than those taking other probiotics. Our real-life data are consistent with existing literature showing a specific effect of Lactobacillus plantarum PS128 in Autism Spectrum Disorder.

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28. Mostafa GA, Meguid NA, Shehab AAS, Elsaeid A, Maher M. Plasma levels of nerve growth factor in Egyptian autistic children: Relation to hyperserotonemia and autoimmunity. Journal of neuroimmunology. 2021; 358: 577638.

Hyperserotonemia and brain-specific autoantibodies are detected in some autistic children. Nerve growth factor (NGF) stimulates the proliferation of B lymphocytes with production of antibodies and also increases mast cell serotonin release. This work was the first to investigate the relationship between plasma NGF and both hyperserotonemia and the frequency of serum anti-myelin basic protein (anti-MBP) auto-antibodies in 22 autistic children aged between 4 and 12 years and 22 healthy-matched controls. Levels of NGF, serotonin and anti-MBP were significantly higher in autistic children than healthy control children (P < 0.001). There was a significant positive correlation between NGF and serotonin levels in autistic patients (P < 0.01). In contrast, there was a non-significant correlation between NGF and anti-MBP levels (P > 0.05). In conclusions, serum NGF levels were elevated and significantly correlated to hyperserotonemia found in many autistic children.

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29. Narzisi A, Masi G, Grossi E. Nutrition and Autism Spectrum Disorder: Between False Myths and Real Research-Based Opportunities. Nutrients. 2021; 13(6).

Autism Spectrum Disorder (ASD) is a multicomplex disorder characterized by an umbrella of specific issues in the areas of social communication, restricted interests, and repetitive behaviors […].

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30. Nguyen TD, Guinot M, Bricout VA. Effect of Daily Physical Activity on Sleep Characteristics in Children with Autism Spectrum Disorder. Sports (Basel, Switzerland). 2021; 9(7).

Background. Sleep problems have been reported in children with autism spectrum disorder (ASD). One of the methods proposed to improve sleep characteristics is based on physical activity (PA). Objective. To assess characteristics of sleep and the effect of PA level on sleep quality in children with ASD compared to controls. Methods. Fifty boys with ASD (ASD; 10.8 ± 2.6 years) and 18 controls (CONT, 10.1 ± 2.2 years) wore an accelerometer device for five consecutive days to obtain measures of activity and sleep characteristics. Results. Some significant differences were reported between ASD and CONT groups. Wake-up time resistance was significantly higher (p < 0.05) in ASD. Total time for PA, and daily steps number were significantly lower in the ASD group (p < 0.05). Time for sedentary behavior was significantly higher (p < 0.01) in the ASD group. Using a principal component analysis and an agglomerative hierarchical analysis, we observed three clusters. Two showed the same poor-quality indices of sleep but two opposing profiles of PA, either an insufficient PA volume (cluster 1, Total time PA = 75.1 min; Daily steps: 7704) or an important PA volume (cluster 3, Total time PA = 222.1 min; Daily steps: 17,164). Cluster 2 was characterized by moderate participation in PA and children with the best sleep indices (Total time PA = 166.8 min; Daily steps: 12,718). Conclusion. The dose-response effect of exercise on sleep may indicate large individual differences but the present findings are important to prevent sedentary behaviors or to correct over-activity that could be detrimental to the sleep quality in children with ASD.

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31. Park S, Ryu W, Yang H. A Study on the Life Experiences of Adolescents Who Grew up with Younger Siblings with Developmental Disabilities: Focusing on Phenomenological Analysis Methods. Brain sciences. 2021; 11(6).

This study aims to explore specific life experiences and what it means to « live as a sibling of a disabled person », by focusing on the brothers and sisters of persons with disabilities; this is a cohort that has been relatively marginalized in the field of welfare for the disabled. To this end, the author conducted 1:1 in-depth interviews with four adolescents who grew up with younger siblings who have developmental disabilities, and analyzed the meaning underlying their life experiences through phenomenological research methods. As a result, a total of five core themes of those life experiences were identified: (1) the birth of a disabled younger sibling, wherein their trials began; (2) surviving differentiation within the family; (3) ambivalence toward parents; (4) adolescence, with resurfaced psychological conflicts and relieving emotions; and (5) a future to be planned around a life of coexisting with disabled siblings. This study aims to provide basic data for social welfare intervention through an illuminating and deeper understanding of the lives of siblings of the developmentally disabled who require a high level of care.

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32. Pecorelli A, Cordone V, Schiavone ML, Caffarelli C, Cervellati C, Cerbone G, Gonnelli S, Hayek J, Valacchi G. Altered Bone Status in Rett Syndrome. Life (Basel, Switzerland). 2021; 11(6).

Rett syndrome (RTT) is a monogenic neurodevelopmental disorder primarily caused by mutations in X-linked MECP2 gene, encoding for methyl-CpG binding protein 2 (MeCP2), a multifaceted modulator of gene expression and chromatin organization. Based on the type of mutation, RTT patients exhibit a broad spectrum of clinical phenotypes with various degrees of severity. In addition, as a complex multisystem disease, RTT shows several clinical manifestations ranging from neurological to non-neurological symptoms. The most common non-neurological comorbidities include, among others, orthopedic complications, mainly scoliosis but also early osteopenia/osteoporosis and a high frequency of fractures. A characteristic low bone mineral density dependent on a slow rate of bone formation due to dysfunctional osteoblast activity rather than an increase in bone resorption is at the root of these complications. Evidence from human and animal studies supports the idea that MECP2 mutation could be associated with altered epigenetic regulation of bone-related factors and signaling pathways, including SFRP4/WNT/β-catenin axis and RANKL/RANK/OPG system. More research is needed to better understand the role of MeCP2 in bone homeostasis. Indeed, uncovering the molecular mechanisms underlying RTT bone problems could reveal new potential pharmacological targets for the treatment of these complications that adversely affect the quality of life of RTT patients for whom the only therapeutic approaches currently available include bisphosphonates, dietary supplements, and physical activity.

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33. Pretzsch CM, Floris DL, Voinescu B, Elsahib M, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Pretzsch E, Williams S, Murphy DGM, Daly E, McAlonan GM. Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin. Molecular autism. 2021; 12(1): 49.

BACKGROUND: Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal ‘excitatory-inhibitory’ metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. METHODS: To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. RESULTS: Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. LIMITATIONS: Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. CONCLUSION: In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1 .

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34. Priolo M, Radio FC, Pizzi S, Pintomalli L, Pantaleoni F, Mancini C, Cordeddu V, Africa E, Mammì C, Dallapiccola B, Tartaglia M. Co-Occurring Heterozygous CNOT3 and SMAD6 Truncating Variants: Unusual Presentation and Refinement of the IDDSADF Phenotype. Genes. 2021; 12(7).

Objective, the application of genomic sequencing in clinical practice has allowed us to appreciate the contribution of co-occurring pathogenic variants to complex and unclassified clinical phenotypes. Besides the clinical relevance, these findings have provided evidence of previously unrecognized functional links between genes in the context of developmental processes and physiology. Patients and Methods, a 5-year-old patient showing an unclassified phenotype characterized by developmental delay, speech delay, peculiar behavioral features, facial dysmorphism and severe cardiopathy was analyzed by trio-based whole exome sequencing (WES) analysis to identify the genomic events underlying the condition. Results, two co-occurring heterozygous truncating variants in CNOT3 and SMAD6 were identified. Heterozygous loss-of-function variants in CNOT3, encoding a subunit of the CCR4-NOT protein complex, have recently been reported to cause a syndromic condition known as intellectual developmental disorder with speech delay, autism and dysmorphic facies (IDDSADF). Enrichment of rare/private variants in the SMAD6 gene, encoding a protein negatively controlling transforming growth factor β/bone morphogenetic protein (TGFB/BMP) signaling, has been described in association with a wide spectrum of congenital heart defects. We dissected the contribution of individual variants to the complex clinical manifestations and profiled a previously unappreciated set of facial features and signs characterizing IDDSADF. Conclusions, two concomitant truncating variants in CNOT3 and SMAD6 are the cause of the combination of features documented in the patient resulting in the unique multisystem neurodevelopmental condition. These findings provide evidence for a functional link between the CCR4-NOT complex and TGFB/BMP signaling in processes controlling cardiac development. Finally, the present revision provides evidence that IDDSADF is characterized by a distinctive facial gestalt.

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35. Roch M, Cain K, Jarrold C. Reading for Comprehension in Individuals with Down Syndrome, Autism Spectrum Disorder and Typical Development: Similar or Different Patterns of Ability?. Brain sciences. 2021; 11(7).

Reading for meaning is one of the most important activities in school and everyday life. The simple view of reading (SVR) has been used as a framework for studies of reading comprehension in individuals with Down syndrome (DS). These tend to show difficulties in reading comprehension despite better developed reading accuracy. Reading comprehension difficulties are influenced by poor oral language. These difficulties are common in individuals with DS and autism spectrum disorder (ASD), but they have never been compared directly. Moreover, the components of reading for comprehension have rarely been investigated in these populations: a better understanding of the nature of reading comprehension difficulties may inform both theory and practice. The aim of this study was to determine whether reading comprehension in the two populations is accounted for by the same component skills and to what extent the reading profile of the two atypical groups differs from that of typically developing children (TD). Fifteen individuals with DS (mean age = 22 years 4 months, SD = 5 years 2 months), 21 with ASD (mean age = 13 years 2 months, SD = 1 year 6 months), and 42 TD children (mean age = 8 years 1 month, SD = 7 months) participated and were assessed on measures of receptive vocabulary, text reading and listening comprehension, oral language comprehension, and reading accuracy. The results showed similar levels in word reading accuracy and in receptive vocabulary in all three groups. By contrast, individuals with DS and ASD showed poorer non-word reading and reading accuracy in context than TD children. Both atypical groups showed poorer listening and reading text comprehension compared to TD children. Reading for comprehension, investigated through a homograph reading accuracy task, showed a different pattern for individuals with DS with respect to the other two groups: they were less sensitive to meaning while reading. According to the SVR, the current results confirm that the two atypical groups have similar profiles that overlap with that of poor comprehenders in which poor oral language comprehension constrains reading for comprehension.

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36. Rotschafer SE. Auditory Discrimination in Autism Spectrum Disorder. Frontiers in neuroscience. 2021; 15: 651209.

Autism spectrum disorder (ASD) is increasingly common with 1 in 59 children in the United States currently meeting the diagnostic criteria. Altered sensory processing is typical in ASD, with auditory sensitivities being especially common; in particular, people with ASD frequently show heightened sensitivity to environmental sounds and a poor ability to tolerate loud sounds. These sensitivities may contribute to impairments in language comprehension and to a worsened ability to distinguish relevant sounds from background noise. Event-related potential tests have found that individuals with ASD show altered cortical activity to both simple and speech-like sounds, which likely contribute to the observed processing impairments. Our goal in this review is to provide a description of ASD-related changes to the auditory system and how those changes contribute to the impairments seen in sound discrimination, sound-in-noise performance, and language processing. In particular, we emphasize how differences in the degree of cortical activation and in temporal processing may contribute to errors in sound discrimination.

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37. Salloum-Asfar S, Elsayed AK, Elhag SF, Abdulla SA. Circulating Non-Coding RNAs as a Signature of Autism Spectrum Disorder Symptomatology. International journal of molecular sciences. 2021; 22(12).

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder that becomes apparent during early childhood development. The complexity of ASD makes clinically diagnosing the condition difficult. Consequently, by identifying the biomarkers associated with ASD severity and combining them with clinical diagnosis, one may better factionalize within the spectrum and devise more targeted therapeutic strategies. Currently, there are no reliable biomarkers that can be used for precise ASD diagnosis. Consequently, our pilot experimental cohort was subdivided into three groups: healthy controls, individuals those that express severe symptoms of ASD, and individuals that exhibit mild symptoms of ASD. Using next-generation sequencing, we were able to identify several circulating non-coding RNAs (cir-ncRNAs) in plasma. To the best of our knowledge, this study is the first to show that miRNAs, piRNAs, snoRNAs, Y-RNAs, tRNAs, and lncRNAs are stably expressed in plasma. Our data identify cir-ncRNAs that are specific to ASD. Furthermore, several of the identified cir-ncRNAs were explicitly associated with either the severe or mild groups. Hence, our findings suggest that cir-ncRNAs have the potential to be utilized as objective diagnostic biomarkers and clinical targets.

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38. Sha Z, Schijven D, Francks C. Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization. Molecular psychiatry. 2021; 26(12): 7652-60.

Autism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing vs. empathizing cognitive styles, with resemblances to male vs. female average sex differences. Left-right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness, and subcortical volume measures in 32,256 participants from the UK Biobank. Polygenic risks for the two disorders were positively correlated (r = 0.08, p = 7.13 × 10(-50)) and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each polygenic risk score was associated with multivariate brain asymmetry after adjusting for sex, ASD r = 0.03, p = 2.17 × 10(-9), and schizophrenia r = 0.04, p = 2.61 × 10(-11), but the multivariate patterns were mostly distinct for the two polygenic risks and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both polygenic risks were associated with asymmetries of regions important for language and executive functions, consistent with behavioral associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risks for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.

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39. Sheridan E, Gillespie S, Johnson CR, Lecavalier L, Smith T, Swiezy N, Turner K, Pritchett J, Mruzek DW, Evans AN, Bearss K, Scahill L. Using Parent Target Problem Narratives to Evaluate Outcomes in Children with Autism Spectrum Disorder. Research on child and adolescent psychopathology. 2021; 49(11): 1527-35.

This paper examines the reliability and validity of parent target problems (PTPs) in a multi-site randomized controlled trial of parent training (PT) versus psychoeducation (PEP) in children (150 boys, 19 girls; mean age 4.7 ± 1.2 years) with autism spectrum disorder (ASD) and disruptive behavior. At baseline, treatment blind, independent evaluators asked parents to nominate the child’s top two problems. Each problem was documented in a brief narrative. Narratives were reviewed and revised at follow-up visits during the six-month trial. When the trial was completed, five judges, blind to treatment condition, independently rated change from baseline on a 9-point scale (1 = normal; 2 = markedly improved; 3 = definitely improved; 4 = equivocally improved; 5 = no change; 6 = possibly worse; 7 = definitely worse; 8 = markedly worse; 9 = disastrously worse) at Weeks 8, 12, 16, and 24 (inter-rater intraclass correlation = 0.78). PTP scores for the two target problems were averaged across the five raters, yielding a mean score for each child at each time point. Mean PTP scores showed improvement in both treatment groups over the 24-week study. Compared to PEP, PTP ratings showed a steeper decline in PT based on significant interaction of group and time (t(df) = 2.14(155.9), p = 0.034; Week 24 effect size = 0.75). In categorical analysis, we compared cutoffs mean PTP scores of 3.0 (definitely improved), 3.25, and 3.5 with the positive response rate on the Clinical Global Impressions-Improvement scale from the original study. Sensitivities ranged from 52-78%. PTP narratives offer a systematic, reliable, and valid way to track child-specific outcomes in clinical trials and clinical practice.

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40. Silva V, Soares F, Leão CP, Esteves JS, Vercelli G. Skeleton Driven Action Recognition Using an Image-Based Spatial-Temporal Representation and Convolution Neural Network. Sensors (Basel, Switzerland). 2021; 21(13).

Individuals with Autism Spectrum Disorder (ASD) typically present difficulties in engaging and interacting with their peers. Thus, researchers have been developing different technological solutions as support tools for children with ASD. Social robots, one example of these technological solutions, are often unaware of their game partners, preventing the automatic adaptation of their behavior to the user. Information that can be used to enrich this interaction and, consequently, adapt the system behavior is the recognition of different actions of the user by using RGB cameras or/and depth sensors. The present work proposes a method to automatically detect in real-time typical and stereotypical actions of children with ASD by using the Intel RealSense and the Nuitrack SDK to detect and extract the user joint coordinates. The pipeline starts by mapping the temporal and spatial joints dynamics onto a color image-based representation. Usually, the position of the joints in the final image is clustered into groups. In order to verify if the sequence of the joints in the final image representation can influence the model’s performance, two main experiments were conducted where in the first, the order of the grouped joints in the sequence was changed, and in the second, the joints were randomly ordered. In each experiment, statistical methods were used in the analysis. Based on the experiments conducted, it was found statistically significant differences concerning the joints sequence in the image, indicating that the order of the joints might impact the model’s performance. The final model, a Convolutional Neural Network (CNN), trained on the different actions (typical and stereotypical), was used to classify the different patterns of behavior, achieving a mean accuracy of 92.4% ± 0.0% on the test data. The entire pipeline ran on average at 31 FPS.

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41. Sun W, Wu X, Zhang T, Lin F, Sun H, Li J. Narrowband Resting-State fNIRS Functional Connectivity in Autism Spectrum Disorder. Frontiers in human neuroscience. 2021; 15: 643410.

Hemispheric asymmetry in the power spectrum of low-frequency spontaneous hemodynamic fluctuations has been previously observed in autism spectrum disorder (ASD). This observation may imply a specific narrow-frequency band in which individuals with ASD could show more significant alteration in resting-state functional connectivity (RSFC). To test this assumption, we evaluated narrowband RSFC at several frequencies for functional near-infrared spectroscopy signals recorded from the bilateral temporal lobes on 25 children with ASD and 22 typically developing (TD) children. In several narrow-frequency bands, we observed altered interhemispheric RSFC in ASD. However, in the band of 0.01-0.02 Hz, more mirrored channel pairs (or cortical sites) showed significantly weaker RSFC in the ASD group. Receiver operating characteristic analysis further demonstrated that RSFC in the narrowband of 0.01-0.02 Hz might have better differentiation ability between the ASD and TD groups. This may indicate that the narrowband RSFC could serve as a characteristic for the prediction of ASD.

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42. Tamada K, Fukumoto K, Toya T, Nakai N, Awasthi JR, Tanaka S, Okabe S, Spitz F, Saitow F, Suzuki H, Takumi T. Genetic dissection identifies Necdin as a driver gene in a mouse model of paternal 15q duplications. Nature communications. 2021; 12(1): 4056.

Maternally inherited duplication of chromosome 15q11-q13 (Dup15q) is a pathogenic copy number variation (CNV) associated with autism spectrum disorder (ASD). Recently, paternally derived duplication has also been shown to contribute to the development of ASD. The molecular mechanism underlying paternal Dup15q remains unclear. Here, we conduct genetic and overexpression-based screening and identify Necdin (Ndn) as a driver gene for paternal Dup15q resulting in the development of ASD-like phenotypes in mice. An excess amount of Ndn results in enhanced spine formation and density as well as hyperexcitability of cortical pyramidal neurons. We generate 15q dupΔNdn mice with a normalized copy number of Ndn by excising its one copy from Dup15q mice using a CRISPR-Cas9 system. 15q dupΔNdn mice do not show ASD-like phenotypes and show dendritic spine dynamics and cortical excitatory-inhibitory balance similar to wild type animals. Our study provides an insight into the role of Ndn in paternal 15q duplication and a mouse model of paternal Dup15q syndrome.

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43. Tavassoli T, Layton C, Levy T, Rowe M, George-Jones J, Zweifach J, Lurie S, Buxbaum JD, Kolevzon A, Siper PM. Sensory Reactivity Phenotype in Phelan-McDermid Syndrome Is Distinct from Idiopathic ASD. Genes. 2021; 12(7).

Phelan-McDermid syndrome (PMS) is one of the most common genetic forms of autism spectrum disorder (ASD). While sensory reactivity symptoms are widely reported in idiopathic ASD (iASD), few studies have examined sensory symptoms in PMS. The current study delineates the sensory reactivity phenotype and examines genotype-phenotype interactions in a large sample of children with PMS. Sensory reactivity was measured in a group of 52 children with PMS, 132 children with iASD, and 54 typically developing (TD) children using the Sensory Assessment for Neurodevelopmental Disorders (SAND). The SAND is a clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on the DSM-5 criteria for ASD. Children with PMS demonstrated significantly greater hyporeactivity symptoms and fewer hyperreactivity and seeking symptoms compared to children with iASD and TD controls. There were no differences between those with Class I deletions or sequence variants and those with larger Class II deletions, suggesting that haploinsufficiency of SHANK3 is the main driver of the sensory phenotype seen in PMS. The syndrome-specific sensory phenotype identified in this study is distinct from other monogenic forms of ASD and offers insight into the potential role of SHANK3 deficiency in sensory reactivity. Understanding sensory reactivity abnormalities in PMS, in the context of known glutamatergic dysregulation, may inform future clinical trials in the syndrome.

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44. Taylor MJ, Larsson H, Lundström S, Lichtenstein P, Butwicka A. Etiological links between autism and difficulties in initiating and maintaining sleep: a familial co-aggregation and twin study. Journal of child psychology and psychiatry, and allied disciplines. 2022; 63(3): 315-23.

BACKGROUND: Difficulties initiating and maintaining sleep (DIMS) are frequent features of autism, yet little is known about why these conditions co-occur. One possibility is that they share etiological factors, yet this hypothesis remains to be tested using quantitative genetic designs. We thus investigated etiological links between autism and DIMS using familial co-aggregation and twin methods. METHODS: Twins, siblings, half-siblings, and cousins of 50,097 individuals with autism were identified from Swedish population registries. Their risk of DIMS, defined through diagnoses of insomnia and/or melatonin prescriptions, was then estimated. Twin analyses conducted on 15,279 child and adolescent twin pairs investigated etiological links between DIMS and ASD. RESULTS: 22.8% of autistic individuals had DIMS. Monozygotic co-twins of individuals with autism were most at risk of DIMS compared to the reference group (OR = 6.6 [2.5-17.4]), followed by dizygotic co-twins (OR = 2.6 [1.5-4.5]) and full siblings (OR = 2.5 [2.4-2.6]). Half-siblings and cousins of individuals with autism were least likely to have DIMS relative to the reference group (OR range = 1.3-1.5). Twin analyses estimated a correlation of 0.57 (0.53-0.61) between autism and DIMS, with a genetic correlation of 0.62 (0.60-0.68). These overlapping genetic factors explained 94% of the covariance between these conditions. Autistic traits also showed genetic overlap with DIMS. CONCLUSIONS: Our results suggest that shared genetic mechanisms underlie autism and DIMS, which may lead them to co-occur. Untangling the etiological overlap between these conditions has potential to assist in understanding the etiology of each condition, as well as their associated outcomes.

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45. Thornton AM, Humphrey RM, Kerr DM, Finn DP, Roche M. Increasing Endocannabinoid Tone Alters Anxiety-Like and Stress Coping Behaviour in Female Rats Prenatally Exposed to Valproic Acid. Molecules (Basel, Switzerland). 2021; 26(12).

Given the sex differences evident in the prevalence of autism, there is an increased awareness of the importance of including females in autism research to determine sexual dimorphism and sex-specific treatments. Cannabinoids and endocannabinoid modulators have been proposed as potential novel treatments for autism-related symptoms; however, few studies to date have examined if these pharmacological agents elicit sex-specific effects. The aim of the present study was to use the valproic acid (VPA) model of autism to compare the behavioural responses of male and female rats and examine the effects of increasing endocannabinoid tone on the behavioural responses of VPA-exposed female rats. These data revealed that VPA-exposed male, but not female, rats exhibit reduced social responding in the three-chamber and olfactory habituation/dishabituation (OHD) test during adolescence. In comparison, VPA-exposed female, but not male, adolescent rats exhibited anxiety-like behaviour in the elevated plus maze (EPM) and open field test (OFT). In VPA-exposed female rats, increasing 2-AG levels augmented anxiety-like behaviour in the EPM and OFT, while increasing AEA levels reduced stress coping behaviour in the swim stress test. These data highlight sexual dimorphic behaviours in the VPA model and indicate that enhancing endocannabinoid levels may exacerbate negative affective behaviour in VPA-exposed females. Thus, considerations should be paid to the possible sex-specific effects of cannabinoids for the treatment of symptoms associated with autism.

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46. Thorsteinsdottir S, Olsen A, Olafsdottir AS. Fussy Eating among Children and Their Parents: Associations in Parent-Child Dyads, in a Sample of Children with and without Neurodevelopmental Disorders. Nutrients. 2021; 13(7).

Parents are important agents in shaping children’s eating habits. However, the associations between children’s and parents’ eating behaviors are complex and may be convoluted for various reasons, such as parenting feeding styles, stressful mealtimes, and children’s neurodevelopmental disorders (ND), such as Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The purpose of this study was to analyze associations between parents and their children’s fussy eating, in a cross-sectional sample of children, with and without ND. Ninety-seven parents answered screening questionnaires prior to an intervention study. Associations were investigated using two-way ANOVAs and chi-square analyses. Overall, children with ND accepted fewer food items and consumed unhealthier foods more frequently than children without ND. Fussy eating parents had children who accepted fewer food items and consumed unhealthier foods more frequently than children whose parents were not fussy eaters. Interaction effects were not significant. A higher proportion of fussy eating parents, than non-fussy eating parents, had children who had difficulties with combined foods and hidden ingredients. The findings highlight the need for further investigation into the relationships between parents’ influence on their children’s eating behavior and food consumption, as well as possible reciprocal impacts.

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47. Trimarchi G, Caraffi SG, Radio FC, Barresi S, Contrò G, Pizzi S, Maini I, Pollazzon M, Fusco C, Sassi S, Nicoli D, Napoli M, Pascarella R, Gargano G, Zuffardi O, Tartaglia M, Garavelli L. Adducted Thumb and Peripheral Polyneuropathy: Diagnostic Supports in Suspecting White-Sutton Syndrome: Case Report and Review of the Literature. Genes. 2021; 12(7).

One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is White-Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the POGZ gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet. The phenotypic spectrum of the WHSUS is broad and includes moderate to severe ID, microcephaly, variable cerebral malformations, short stature, brachydactyly, visual abnormalities, sensorineural hearing loss, hypotonia, sleep difficulties, autistic features, self-injurious behaviour, feeding difficulties, gastroesophageal reflux, and other less frequent features. Here, we report the case of a girl with microcephaly, brain malformations, developmental delay (DD), peripheral polyneuropathy, and adducted thumb-a remarkable clinical feature in the first years of life-and heterozygous for a previously unreported, de novo splicing variant in POGZ. This report contributes to strengthen and expand the knowledge of the clinical spectrum of WHSUS, pointing out the importance of less frequent clinical signs as diagnostic handles in suspecting this condition.

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48. Tritto G, Ricca I, Turi M, Gemma A, Muratori F, Scarano G, Lonardo F. Clinical Characterization of a 6-Year-Old Patient with Autism and Two Adjacent Duplications on 10q11.22q11.23. A Case Report. Children (Basel, Switzerland). 2021; 8(6).

Autism is a neurodevelopmental disorder presenting in the first 3 years of life. Deficits occur in the core areas of social communication and interaction and restricted, repetitive patterns of behavior, interests or activities. The causes of autism are unknown, but clinical genetic studies show strong evidence in favor of the involvement of genetic factors in etiology. Molecular genetic studies report some associations with candidate genes, and candidate regions have emerged from several genome-wide linkage studies. Here, we report a clinical case of autism in a 6-year-old boy with double duplication on 10q11.22q11.23 with ASD (Autism Spectrum Disorder), intellectual disability, developmental delay, hypotonia, gross-motor skills deficit, overgrowth and mild dysmorphic features. In the literature, only five cases of ASD with 10q11.21q11.23 duplication are reported. This is the first extensive clinical description of an ASD subject with 10q11.22q11.23 duplication. Our findings suggest that 10q11.21q11.23 microduplication could represent a copy number variant that predisposes to autism.

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49. Urbinati C, Cosentino L, Germinario EAP, Valenti D, Vigli D, Ricceri L, Laviola G, Fiorentini C, Vacca RA, Fabbri A, De Filippis B. Treatment with the Bacterial Toxin CNF1 Selectively Rescues Cognitive and Brain Mitochondrial Deficits in a Female Mouse Model of Rett Syndrome Carrying a MeCP2-Null Mutation. International journal of molecular sciences. 2021; 22(13).

Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene and a major cause of intellectual disability in females. No cure exists for RTT. We previously reported that the behavioural phenotype and brain mitochondria dysfunction are widely rescued by a single intracerebroventricular injection of the bacterial toxin CNF1 in a RTT mouse model carrying a truncating mutation of the MeCP2 gene (MeCP2-308 mice). Given the heterogeneity of MECP2 mutations in RTT patients, we tested the CNF1 therapeutic efficacy in a mouse model carrying a null mutation (MeCP2-Bird mice). CNF1 selectively rescued cognitive defects, without improving other RTT-related behavioural alterations, and restored brain mitochondrial respiratory chain complex activity in MeCP2-Bird mice. To shed light on the molecular mechanisms underlying the differential CNF1 effects on the behavioural phenotype, we compared treatment effects on relevant signalling cascades in the brain of the two RTT models. CNF1 provided a significant boost of the mTOR activation in MeCP2-308 hippocampus, which was not observed in the MeCP2-Bird model, possibly explaining the differential effects of CNF1. These results demonstrate that CNF1 efficacy depends on the mutation beared by MeCP2-mutated mice, stressing the need of testing potential therapeutic approaches across RTT models.

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50. Van Gils J, Magdinier F, Fergelot P, Lacombe D. Rubinstein-Taybi Syndrome: A Model of Epigenetic Disorder. Genes. 2021; 12(7).

The Rubinstein-Taybi syndrome (RSTS) is a rare congenital developmental disorder characterized by a typical facial dysmorphism, distal limb abnormalities, intellectual disability, and many additional phenotypical features. It occurs at between 1/100,000 and 1/125,000 births. Two genes are currently known to cause RSTS, CREBBP and EP300, mutated in around 55% and 8% of clinically diagnosed cases, respectively. To date, 500 pathogenic variants have been reported for the CREBBP gene and 118 for EP300. These two genes encode paralogs acting as lysine acetyltransferase involved in transcriptional regulation and chromatin remodeling with a key role in neuronal plasticity and cognition. Because of the clinical heterogeneity of this syndrome ranging from the typical clinical diagnosis to features overlapping with other Mendelian disorders of the epigenetic machinery, phenotype/genotype correlations remain difficult to establish. In this context, the deciphering of the patho-physiological process underlying these diseases and the definition of a specific episignature will likely improve the diagnostic efficiency but also open novel therapeutic perspectives. This review summarizes the current clinical and molecular knowledge and highlights the epigenetic regulation of RSTS as a model of chromatinopathy.

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51. Varesio C, Grumi S, Zanaboni MP, Mensi MM, Chiappedi M, Pasca L, Ferraris C, Tagliabue A, Borgatti R, De Giorgis V. Ketogenic Dietary Therapies in Patients with Autism Spectrum Disorder: Facts or Fads? A Scoping Review and a Proposal for a Shared Protocol. Nutrients. 2021; 13(6).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing incidence. An expanding body of literature is examining connections between ASD and dietary interventions. Existing reports suggest a beneficial effect of ketogenic dietary therapies (KDTs) in improving behavioral symptoms in ASD. In this context, the purpose of this scoping review was to identify and map available evidence in the literature about the feasibility and potential efficacy of KDTs in pediatric patients with ASD and to inform clinical practice in the field. Moreover, based on the resulting data from the literature review, we aimed to provide a shared protocol to develop a personalized KDT intervention in patients with ASD. A comprehensive and structured web-based literature search was performed using PubMed and Scopus and it yielded 203 records. Seven papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study designs and dietary aspects emerged among selected studies. Results supported the effectiveness of KDTs in promoting behavioral improvements. Clinical recommendations on which patients may benefit most from KDTs implementation and difficulties in dietary adherence were discussed.

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52. Wallis KE. The Roadmap to Early and Equitable Autism Identification. Pediatrics. 2021; 148(Suppl 1): s21-s4.

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53. Wang L, Pfordresher PQ, Jiang C, Liu F. Individuals with autism spectrum disorder are impaired in absolute but not relative pitch and duration matching in speech and song imitation. Autism research : official journal of the International Society for Autism Research. 2021; 14(11): 2355-72.

Individuals with autism spectrum disorder (ASD) often exhibit atypical imitation. However, few studies have identified clear quantitative characteristics of vocal imitation in ASD. This study investigated imitation of speech and song in English-speaking individuals with and without ASD and its modulation by age. Participants consisted of 25 autistic children and 19 autistic adults, who were compared to 25 children and 19 adults with typical development matched on age, gender, musical training, and cognitive abilities. The task required participants to imitate speech and song stimuli with varying pitch and duration patterns. Acoustic analyses of the imitation performance suggested that individuals with ASD were worse than controls on absolute pitch and duration matching for both speech and song imitation, although they performed as well as controls on relative pitch and duration matching. Furthermore, the two groups produced similar numbers of pitch contour, pitch interval-, and time errors. Across both groups, sung pitch was imitated more accurately than spoken pitch, whereas spoken duration was imitated more accurately than sung duration. Children imitated spoken pitch more accurately than adults when it came to speech stimuli, whereas age showed no significant relationship to song imitation. These results reveal a vocal imitation deficit across speech and music domains in ASD that is specific to absolute pitch and duration matching. This finding provides evidence for shared mechanisms between speech and song imitation, which involves independent implementation of relative versus absolute features. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) often exhibit atypical imitation of actions and gestures. Characteristics of vocal imitation in ASD remain unclear. By comparing speech and song imitation, this study shows that individuals with ASD have a vocal imitative deficit that is specific to absolute pitch and duration matching, while performing as well as controls on relative pitch and duration matching, across speech and music domains.

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54. Way H, Williams G, Hausman-Cohen S, Reeder J. Genomics as a Clinical Decision Support Tool: Successful Proof of Concept for Improved ASD Outcomes. Journal of personalized medicine. 2021; 11(7).

Considerable evidence is emerging that Autism Spectrum Disorder (ASD) is most often triggered by a range of different genetic variants that interact with environmental factors such as exposures to toxicants and changes to the food supply. Up to 80% of genetic variations that contribute to ASD found to date are neither extremely rare nor classified as pathogenic. Rather, they are less common single nucleotide polymorphisms (SNPs), found in 1-15% or more of the population, that by themselves are not disease-causing. These genomic variants contribute to ASD by interacting with each other, along with nutritional and environmental factors. Examples of pathways affected or triggered include those related to brain inflammation, mitochondrial dysfunction, neuronal connectivity, synapse formation, impaired detoxification, methylation, and neurotransmitter-related effects. This article presents information on four case study patients that are part of a larger ongoing pilot study. A genomic clinical decision support (CDS) tool that specifically focuses on variants and pathways that have been associated with neurodevelopmental disorders was used in this pilot study to help develop a targeted, personalized prevention and intervention strategy for each child. In addition to an individual’s genetic makeup, each patient’s personal history, diet, and environmental factors were considered. The CDS tool also looked at genomic SNPs associated with secondary comorbid ASD conditions including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections/pediatric acute-onset neuropsychiatric syndrome (PANDAS/PANS). The interpreted genomics tool helped the treating clinician identify and develop personalized, genomically targeted treatment plans. Utilization of this treatment approach was associated with significant improvements in socialization and verbal skills, academic milestones and intelligence quotient (IQ), and overall increased ability to function in these children, as measured by autism treatment evaluation checklist (ATEC) scores and parent interviews.

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55. Wise E, Holingue C, Klein A, Caoili A, Charlot L, Barnhill J, Beasley JB. Psychiatric Presentations and Medication Use in Older Adults With Intellectual and Developmental Disabilities. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2022; 30(1): 65-77.

OBJECTIVE: Adults with intellectual and developmental disabilities (IDD) are living longer, yet research about the medical and psychiatric needs of older adults still lags behind that of younger individuals with IDD. The aim of this study was to assess age-related differences in the mental health presentations of adults with IDD. METHODS: Fully deidentified data for adults 30 years and older were extracted from the START (Systemic, Therapeutic, Assessment, Resources, and Treatment) Information Reporting System, a deidentified database housed at the Center for START Services. Caregivers and START team documents reported psychiatric diagnoses, service use, recent stressors, and challenging behaviors. t Tests, Mann Whitney U tests, χ(2) tests, and multinominal logistic regression models were used to compare the two age groups, 30-49 years (n = 1,188) versus 50 years and older (n = 464). RESULTS: Older adults had more medical conditions, fewer reported psychiatric conditions, and were more likely to be taking more psychiatric medications compared to younger adults, after adjusting for demographic variables, disability level, and number of recent stressors. CONCLUSION: Although older individuals reported fewer psychiatric diagnoses, they were more likely to take higher numbers of psychiatric medications and have more medical conditions. Clinicians and researchers ought to devote more attention to the healthcare needs of older adults with IDD, a vulnerable group exposed to polypharmacy and at risk of adverse events.

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56. Wong V, Pham M, Godfrey K, Milstein A. Distilling innovative US autism care programs that address widely perceived unmet patient and family needs. Autism : the international journal of research and practice. 2022; 26(1): 281-6.

Currently, the quality of care for autistic individuals is not good. Many care services for autistic individuals are not well coordinated, nor are they tailored. We wanted to find out a better model for autism care and believed that the autism community knows where these programs are. So, we had conversations with and surveyed 55 autistic adults, family members, clinicians, and researchers. They shared 90 innovative autism care programs that had been collaboratively designed with patients and families and that are likely to improve the quality of life of autistic individuals and their families. We then narrowed down the 90 nominated programs to 15 programs across the United States by applying researcher-selected criteria, such as providing services actively and having data on program effectiveness. We compiled a list of these innovative, quality autism care programs.

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