1. Alshahrani MS, Algashmari H. The moderating effect of financial stress and autism severity on development of depression among parents and caregivers of Autistic children in Taif, Saudi Arabia. Journal of family medicine and primary care. 2021; 10(3): 1227-33.

BACKGROUND: Autistic spectrum disorder (ASD) is a common problem in the Kingdom of Saudi Arabia. However, little research explored the extent of anxiety and depressive disorders in parents of children with ASD. METHOD: Descriptive questionnaire-based cross-sectional survey of a sample of parents of children with ASD who attended Prince Mohammed Bin Salman Autistic Centre, Ministry of defense, Taif city. RESULTS: The study included (n = 50) parents. The prevalence of mild depression was 30%, whereas the prevalence of moderately severe depression was 68%. Increased ASD severity level was associated with a significant impact on the PHQ-9 total score (level II was 1.293 times level I to have an increased PHQ-9 score, and level III was 1.530 times level I to have an increased PHQ-9 score). Economic status did not significantly alter depressive symptoms. DISCUSSION AND CONCLUSION: ASD diagnosis in Saudi children is associated with high parental depressive prevalence. However, this result could be bidirectional. Stigma, future-related worry, and stress could mediate parental depressive symptoms. Our findings in Saudi parents of children with ASD corroborate the established association between parental depressive symptoms and ASD severity. Our results corroborated previous findings that neither parental gender nor child gender exert any substantial effect on predictability of depressive symptoms among parents of children with ASD. Comprehensive therapeutic packages for children with ASD should include treatment of emotional problems arising out of carer burden among their parents. Screening for parental emotional problems should be routine in autism treatment facilities.

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2. Bishop J, Zhou C, Antolovic K, Grebe L, Hwang KH, Imaezue G, Kistanova E, Lee KE, Paulino K, Zhang S. Brief Report: Autistic Traits Predict Spectral Correlates of Vowel Intelligibility for Female Speakers. Journal of autism and developmental disorders. 2022; 52(5): 2344-9.

A growing body of research finds that neurotypical autistic traits are predictive of speech perception and language comprehension patterns, but considerably less is known about the influence of these traits on speech production. In this brief report, we present an analysis of vowel productions from 74 American English speakers who participated in a communicative speaking task. Results show higher autistic trait load to be broadly and inversely related to spectral correlates of vowel intelligibility. However, the statistical significance of this relationship is specific to autistic traits along the pragmatic communication dimension, and limited to female speakers.

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3. Brett JD, Maybery MT. Understanding Oneself to Understand Others: The Role of Alexithymia and Anxiety in the Relationships Between Autistic Trait Dimensions and Empathy. Journal of autism and developmental disorders. 2022; 52(5): 1971-83.

People on the autism spectrum may have difficulty inferring others’ emotions (cognitive empathy), but may share another’s emotions (affective empathy) and exhibit heightened personal distress. The present study examined independent autistic trait dimensions (social difficulties and restricted/repetitive behaviours) and the roles alexithymia and trait anxiety have in explaining this profile of empathy. Results from the general population (n = 301) revealed that pronounced social difficulties and not restricted/repetitive behaviours related to reduced cognitive and affective empathy, and heightened personal distress. However, both dimensions, through alexithymia and anxiety, indirectly influenced empathy. Surprisingly, while the dimensions indirectly improved affective empathy, pronounced social difficulties directly reduced affective empathy. This study motivates a nuanced model of empathy by including autistic trait dimensions, anxiety, and alexithymia.

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4. de Almeida JS, Fernandes RF, Andrade Á CB, Almeida BDC, Amorim A, Lustosa J, Mendes RF, Prado Júnior RR. Impact of dental treatment on the oral health-related quality of life of children and adolescents with Autism Spectrum Disorder. Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2021; 41(6): 658-69.

AIM: To evaluate the impact of dental treatment on the oral health-related quality of life (OHRQoL) of children and adolescents with Autism Spectrum Disorder (ASD), through the perception of caregivers. METHODS AND RESULTS: A prospective longitudinal study was conducted on 115 individuals with ASD, 6-14 years of age, recruited from the referral centers for special needs individuals at Teresina, Brazil. A clinical examination was carried out and the OHRQoL was measured using the Brazilian version of the Parental-Caregiver Perceptions Questionnaire (P-CPQ) before and 3 months after dental treatment. Data were analyzed using Kolmogorov-Smirnov, Levene, Mann-Whitney, Kruskall-Wallis, and Wilcoxon tests, and the Poison regression with backward method (P < .05). Treatment needs of children with ASD consisted of dental restorations (81.7%), oral prophylaxis (66.1%), endodontic treatment (10.4%), and tooth extractions (10.4%). The baseline P-CPQ total score varied from 1 to 33 (mean score = 13.2 [±6.4]), and at 3 months after treatment it ranged from 0 to 10 (mean score 3.4 [±2.2] (P < .001). The effect magnitude varied between 0.55 and 0.56. CONCLUSION: According to the perception of the caregivers, dental treatment had a positive impact on the OHRQoL of children and adolescents with ASD.

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5. Ernst ME, Baugh EH, Thomas A, Bier L, Lippa N, Stong N, Mulhern MS, Kushary S, Akman CI, Heinzen EL, Yeh R, Bi W, Hanchard NA, Burrage LC, Leduc MS, Chong JSC, Bend R, Lyons MJ, Lee JA, Suwannarat P, Brilstra E, Simon M, Koopmans M, van Binsbergen E, Groepper D, Fleischer J, Nava C, Keren B, Mignot C, Mathieu S, Mancini GMS, Madan-Khetarpal S, Infante EM, Bluvstein J, Seeley A, Bachman K, Klee EW, Schultz-Rogers LE, Hasadsri L, Barnett S, Ellingson MS, Ferber MJ, Narayanan V, Ramsey K, Rauch A, Joset P, Steindl K, Sheehan T, Poduri A, Vasquez A, Ruivenkamp C, White SM, Pais L, Monaghan KG, Goldstein DB, Sands TT, Aggarwal V. CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity. Epilepsia. 2021; 62(7): e103-e9.

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

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6. Karimzadeh MR, Omidi F, Sahebalzamani A, Saeidi K. A Novel VPS13B Mutation Identified by Whole-Exome Sequencing in Iranian Patients with Cohen Syndrome. Journal of molecular neuroscience : MN. 2021; 71(12): 2566-74.

Cohen syndrome is caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B, also referred to as COH1) gene on chromosome 8q22.2. The VPS13B protein is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Clinical manifestations of Cohen syndrome are mainly intellectual disability, developmental delay, facial abnormalities, and eye disorders. This study aimed to identify the causative variant in two unrelated families with Cohen syndrome. To this end, whole-exome sequencing (WES) was performed to identify the pathogenic variants. A homozygous nonsense variant (NM_017890:c.10369C > T; NP_060360.3: p.Q3457X) in the VPS13B gene was identified and co-segregated with all affected individuals in both families. In silico analysis highly suggested this variant as damaging for protein function. The present study increases the mutation spectrum of the VPS13B gene and could be useful in genetic diagnosis and genetic counseling in Cohen syndrome patients.

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7. Karpur A, Vasudevan V, Shih A, Frazier T. Brief Report: Impact of COVID-19 in Individuals with Autism Spectrum Disorders: Analysis of a National Private Claims Insurance Database. Journal of autism and developmental disorders. 2022; 52(5): 2350-6.

The COVID-19 pandemic continues to have a detrimental impact on individuals with disabilities. Data from FAIR Health’s FH® NPIC (National Private Insurance Claims) database, one of the nation’s largest databases of private insurance claim records, were analyzed to understand the experiences of individuals with ASD in the COVID-19 pandemic. Multivariate logistic regression models revealed that individuals with ASD + ID were nine times more likely to be hospitalized following COVID-19 infection (OR = 9.3; 95% CI: 6.9-12.5) and were nearly six times more likely to have an elevated length of hospital stay (OR = 5.9; 95% CI: 3.5-10.1) compared to those without ASD + ID. These findings point to the need for prioritizing access to vaccines to prevent COVID-19 infection and morbidities. This is the first study to illustrate a higher likelihood of hospitalization and elevated length of hospital stay from COVID-19 in individuals with ASD and other comorbidities.

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8. Landes SD, Turk MA, Ervin DA. COVID-19 case-fatality disparities among people with intellectual and developmental disabilities: Evidence from 12 US jurisdictions. Disability and health journal. 2021; 14(4): 101116.

BACKGROUND: There is evidence from two US states that people with intellectual and developmental disabilities (IDD) are at more severe risk during the COVID-19 pandemic. Research has not explored whether this increased risk is consistent across the US. OBJECTIVE: This study compared COVID-19 case-fatality rates among people with IDD in 11 states and the District of Columbia that are publicly reporting data. METHODS: Cumulative data reported through March 31 – April 13, 2021 were analyzed. Case-fatality rates and risk ratio with 95% confidence intervals for IDD settings were compared the overall case-fatality rate for the jurisdictions from Johns Hopkins’ Center for Systems Science and Engineering COVID-19 data. RESULTS: Settings were reported as receiving any services, community or institutional residential services, or living in own/family home. Comparison of case-fatality rates between people with IDD and their respective jurisdiction populations demonstrates that case-fatality rates were consistently higher for people with IDD living in congregate residential settings (fifteen instances) and receiving 24/7 nursing services (two instances). Results were mixed for people with IDD living in their own or a family home (eight instances). CONCLUSIONS: These findings highlight that people with IDD, especially those living in residential settings, are experiencing higher case-fatality rates from COVID-19 than the general population across multiple US jurisdictions. Short-term and long-term public health interventions addressing COVID-19 risks will not be able to properly address the needs of people with IDD until all states begin reporting COVID-19 outcomes for this population.

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9. Mason D, Ronald A, Ambler A, Caspi A, Houts R, Poulton R, Ramrakha S, Wertz J, Moffitt TE, Happé F. Autistic traits are associated with faster pace of aging: Evidence from the Dunedin study at age 45. Autism research : official journal of the International Society for Autism Research. 2021; 14(8): 1684-94.

Growing evidence indicates that the defining characteristics of autism spectrum disorder (ASD) are distributed throughout the general population; hence, understanding the correlates of aging in people with high autistic traits could shed light on ASD and aging. 915 members of the Dunedin longitudinal birth cohort completed a measure of autistic traits at age 45. A composite measure of the « pace of aging » was derived by tracking the decline in 19 biomarkers across ages 26, 32, 38, and 45 years. Facial age was also assessed. Reports of perceived health were collected from participants themselves, informants, and interviewers. Higher self-reported autistic traits significantly correlated with a faster pace of aging, older facial age, and poorer self-, informant-, and interviewer-rated health. After control for sex, SES and IQ, autistic traits were significantly associated with each variable: pace of aging (β = 0.09), facial age (β = 0.08), self- (β = -0.15), informant (β = -0.12), and interviewer-rated (β = -0.17) health. Autistic traits measured at age 45 are associated with faster aging. Participants with high autistic traits appear to be more vulnerable to poor health outcomes, as previously reported for those clinically diagnosed with ASD. Therefore, autistic traits may have important health implications. Replicating these findings in samples of autistic people is needed to identify the mechanism of their effect on aging and physical health to improve outcomes for those with ASD diagnoses or high autistic traits. LAY SUMMARY: The role that autistic traits have in relation to health outcomes has not been investigated. We looked at how physical health and aging (measured with self-reported questions and decline in multiple biological measures) were related to autistic traits (measured with a questionnaire, at age 45). We found that higher autistic traits were associated with poorer reports of physical health, and a faster pace of aging. This suggests that both those with autism and those with higher autistic traits may be more likely to experience poorer health outcomes.

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10. Mazumdar A, Banerjee M, Chatterjee B, Saha S, Gupta GS. Mobile application based early educational intervention for children with autism – a pilot trial. Disability and rehabilitation Assistive technology. 2021: 1-8.

PURPOSE: To design and develop a mobile application for pre-school readiness of children with autism and also to identify their learning pattern. METHODOLOGY: Based on strong foundation of functional academics, we have developed a mobile application for providing an early educational intervention program to the children with autism. Three successive software trials have been conducted among 31 children with autism of age group of three to 10 years. The mobile app has been provided to educators and parents and they have been allowed to supervise the children during their learning phase for eight to 10 weeks. The imprint of learning pattern is recorded and learning progress profile is generated for individual child. RESULTS: Data analysis of learning progress profile shows that 90% of the participants preferred drag and drop or simple touch approach over conventional methods practised during classroom teachings. More than 84% of the children are found to adapt pre-requisite skills for writing like scribbling, tracing, dots joining, copying, etc. after using the app on their tablet who are reluctant to hold pencil and paper otherwise. Twenty-five percent of the participants are reported to reciprocate the greeting etiquettes in class such as greeting teachers and their peers. CONCLUSIONS: The mobile application made a valuable contribution to early intervention program for children with autism by imparting appropriate learning opportunities readily available to them. Performance metrics underlying each activity form a strong base of identification of learning patterns and formulation of revised individualized education plan (IEP).Implications for RehabilitationChildren with autism need the mobile application as an educational intervention program for it is readily available and user friendly.Educators need the mobile application to quantify the performance parameters and there by monitor/evaluate the progress of the child.Overall, the present research has aimed to develop an easy reach app by which educating as well as handling challenging behaviour of the children with autism would be easier.

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11. McPartland JC, Lerner MD, Bhat A, Clarkson T, Jack A, Koohsari S, Matuskey D, McQuaid GA, Su WC, Trevisan DA. Looking Back at the Next 40 Years of ASD Neuroscience Research. Journal of autism and developmental disorders. 2021; 51(12): 4333-53.

During the last 40 years, neuroscience has become one of the most central and most productive approaches to investigating autism. In this commentary, we assemble a group of established investigators and trainees to review key advances and anticipated developments in neuroscience research across five modalities most commonly employed in autism research: magnetic resonance imaging, functional near infrared spectroscopy, positron emission tomography, electroencephalography, and transcranial magnetic stimulation. Broadly, neuroscience research has provided important insights into brain systems involved in autism but not yet mechanistic understanding. Methodological advancements are expected to proffer deeper understanding of neural circuitry associated with function and dysfunction during the next 40 years.

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12. Mert S, Köşgeroğlu N. Meeting the care needs of people with intellectual and developmental disabilities and their families through the Model of Nursing Based on Activities of Living. Journal of intellectual disabilities : JOID. 2021: 17446295211010023.

AIM: This study aimed to identify the problems families of people with intellectual and developmental disabilities face in meeting their family members’ care needs, using the Model of Nursing Based on Activities of Living, and planned implemented and evaluated the nursing interventions to fulfill these care needs. METHOD: A cross-sectional screening model was used in the study. One hundred families of people with intellectual and developmental disabilities, who accepted home visits between September 2008 and December 2008, were included in the study. RESULTS: The study revealed a statistically significant difference (p < 0.05) between the Model of Nursing Based on Activities of Living total mean scores of care needs in the pre- (1.69 ± 0.21) and post-nursing intervention (1.50 ± 0.24) periods. Nurse-led interventions for daily life activities of people with intellectual and developmental disabilities and their families were found to be effective (p < 0.05). CONCLUSION: In line with the Model of Nursing Based on Activities of Living, nurse-led collaboration with families and relevant institutions positively contributed to meeting the care needs of people with intellectual and developmental disabilities and their families.

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13. O’Brien MJ, Pelzel KE, Hendrix NM, Schieltz KM, Miller K, Call NA, Tsami L, Lerman DC, Berg WK, Kopelman TG, Wacker DP, Lindgren SD. Parent Ratings of Generalized and Indirect Effects of Functional Communication Training for Children with Autism Spectrum Disorder. Behavior modification. 2021: 1454455211018815.

Functional communication training (FCT) is a behavioral treatment that has been shown to reduce problem behavior and increase appropriate communication in young children with autism spectrum disorder (ASD). In this study, we assessed the effects of FCT on targeted and nontargeted problem behaviors outside of the training context, as well as parent stress, for 30 young children with ASD and their parents. Indirect measures of generalization treatment effects were administered prior to and following FCT treatment delivered via telehealth. Children demonstrated significant improvement on both targeted (measured via observation) and nontargeted (measured via checklist) problem behaviors, both within and outside of the training context, and parent stress was significantly reduced following treatment. These results suggest that the impact of FCT may extend beyond the training context for both the children being treated and the parents delivering treatment, even when generalization is not specifically programmed for during treatment.

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14. Rawsthorne H, Calahorro F, Holden-Dye L, V OC, Dillon J. Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour. PloS one. 2021; 16(5): e0243121.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours. Investigations are well served by experimental approaches that allow tractable investigation of the underpinning genetic basis of circuits that control behaviours that operate in the biological domains that are neuro-atypical in autism. The model organism C. elegans provides an experimental platform to investigate the effect of genetic mutations on behavioural outputs including those that impact social biology. Here we use progeny-derived social cues that modulate C. elegans food leaving to assay genetic determinants of social behaviour. We used the SAFRI Gene database to identify C. elegans orthologues of human ASD associated genes. We identified a number of mutants that displayed selective deficits in response to progeny. The genetic determinants of this complex social behaviour highlight the important contribution of synaptopathy and implicates genes within cell signalling, epigenetics and phospholipid metabolism functional domains. The approach overlaps with a growing number of studies that investigate potential molecular determinants of autism in C. elegans. However, our use of a complex, sensory integrative, emergent behaviour provides routes to enrich new or underexplored biology with the identification of novel candidate genes with a definable role in social behaviour.

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15. Salem AC, MacFarlane H, Adams JR, Lawley GO, Dolata JK, Bedrick S, Fombonne E. Evaluating atypical language in autism using automated language measures. Scientific reports. 2021; 11(1): 10968.

Measurement of language atypicalities in Autism Spectrum Disorder (ASD) is cumbersome and costly. Better language outcome measures are needed. Using language transcripts, we generated Automated Language Measures (ALMs) and tested their validity. 169 participants (96 ASD, 28 TD, 45 ADHD) ages 7 to 17 were evaluated with the Autism Diagnostic Observation Schedule. Transcripts of one task were analyzed to generate seven ALMs: mean length of utterance in morphemes, number of different word roots (NDWR), um proportion, content maze proportion, unintelligible proportion, c-units per minute, and repetition proportion. With the exception of repetition proportion (p [Formula: see text]), nonparametric ANOVAs showed significant group differences (p[Formula: see text]). The TD and ADHD groups did not differ from each other in post-hoc analyses. With the exception of NDWR, the ASD group showed significantly (p[Formula: see text]) lower scores than both comparison groups. The ALMs were correlated with standardized clinical and language evaluations of ASD. In age- and IQ-adjusted logistic regression analyses, four ALMs significantly predicted ASD status with satisfactory accuracy (67.9-75.5%). When ALMs were combined together, accuracy improved to 82.4%. These ALMs offer a promising approach for generating novel outcome measures.

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16. Silva EADJ, Medeiros WMB, Torro N, Sousa JMM, Almeida I, Costa FBD, Pontes KM, Nunes ELG, Rosa MDD, Albuquerque K. Cannabis and cannabinoid use in autism spectrum disorder: a systematic review. Trends in psychiatry and psychotherapy. 2021.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction, associated with the presence of restricted and repetitive patterns of behavior, interests, or activities. Cannabis has been used to alleviate symptoms associated with ASD. METHOD: We carried out a systematic review of studies that investigated the clinical effects of cannabis and cannabinoid use on ASD, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA checklist). The search was carried out in four databases: MEDLINE/PubMed, Scientific Electronic Library Online (SciELO), Scopus, and Web of Science. No limits were established for language during the selection process. Nine studies were selected and analyzed. RESULTS: Some studies showed that cannabis products reduced the number and/or intensity of different symptoms, including hyperactivity, attacks of self-mutilation and anger, sleep problems, anxiety, restlessness, psychomotor agitation, irritability, aggressiveness perseverance, and depression. Moreover, they found an improvement in cognition, sensory sensitivity, attention, social interaction, and language. The most common adverse effects were sleep disorders, restlessness, nervousness and change in appetite. CONCLUSION: Cannabis and cannabinoids may have promising effects in the treatment of symptoms related to ASD, and can be used as a therapeutic alternative in the relief of those symptoms. However, randomized, blind, placebo-controlled clinical trials are necessary to clarify findings on the effects of cannabis and its cannabinoids in individuals with ASD. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO), code 164161.

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17. Sloneem J, Moss J, Powell S, Hawkins C, Fosi T, Richardson H, Aylett S. The prevalence and profile of autism in Sturge-Weber syndrome. Journal of autism and developmental disorders. 2022; 52(5): 1942-55.

A systematic retrospective case note review was undertaken to investigate autism diagnostic factors in 124 individuals with Sturge-Weber syndrome (SWS). Social Responsiveness Scale questionnaires were then analysed to explore the severity and profile of autism characteristics in 70 participants. Thirty-two to forty percent of participants had a clinical diagnosis of autism and half of those without a diagnosis showed significant social communication difficulties. Children had a relative strength in social awareness and social motivation, which are typically much reduced in people with autism. This finding may explain why, to date, the diagnosis has often been overlooked in this population. The research therefore suggests that children with Sturge-Weber should be screened to identify social communications difficulties and provided with timely support.

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18. Stevenson PK, Casenhiser DM, Lau BYB, Krishnan K. Systematic analysis of goal-related movement sequences during maternal behaviour in a female mouse model for Rett syndrome. The European journal of neuroscience. 2021; 54(2): 4528-49.

Rodent dams seek and gather scattered pups back to the nest (pup retrieval), an essential aspect of maternal care. Systematic analysis of the dynamic sequences of goal-related movements that comprise the entire behavioural sequence, which would be ultimately essential for understanding the underlying neurobiology, is not well-characterized. Here, we present such analysis across 3 days in alloparental female mice (Surrogates or Sur) of two genotypes; Mecp2(Heterozygotes) (Het), a female mouse model for Rett syndrome and their wild type (WT) siblings. We analysed CBA/CaJ and C57BL/6J WT surrogates for within-strain comparisons. Frame-by-frame analysis over different phases was performed manually using DataVyu software. We previously showed that surrogate Het are inefficient at pup retrieval, by end-point analysis such as latency index and errors. Here, the sequence of searching, pup-approach and successful retrieval streamlines over days for WT, while Het exhibits variations in this pattern. Goal-related movements between Het and WT are similar in other phases, suggesting context-driven atypical patterns in Het during the pup retrieval phase. We identified proximal pup approach and pup grooming as atypical tactile interactions between pups and Het. Day-by-day analysis showed dynamic changes in goal-related movements in individual animals across genotypes and strains. Overall, our approach (1) highlights natural variation in individual mice on different days, (2) establishes a « gold-standard » manually curated dataset to help build behavioural repertoires using machine learning approaches, and (3) suggests atypical tactile sensory processing and possible regression in a female mouse model for Rett syndrome.

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19. Teskey G, Anagnostou E, Mankad D, Smile S, Roberts W, Brian J, Bowdish DME, Foster JA. Intestinal permeability correlates with behavioural severity in very young children with ASD: A preliminary study. Journal of neuroimmunology. 2021; 357: 577607.

Systemic inflammation is known to alter behaviour, and since it has been reported that individuals with autism spectrum disorder (ASD) have higher levels of circulating cytokines, it has been hypothesized that systemic inflammation may exacerbate behaviours characteristic of ASD. The acute phase proteins α-2-macroglobulin, C-reactive protein, haptoglobin, serum amyloid P, serum amyloid A, ferritin and tissue plasminogen activator, as well as markers of intestinal permeability (intestinal fatty acid binding protein and lipopolysaccharide) were quantitated in the plasma of very young children with ASD. Behaviour severity was measured using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS) and the Vineland Adaptive Behaviour Scale (VABS). An increase in circulating I-FABP correlated with more severe deficits in communication, communication + social interaction as well as maladaptive behaviour. The acute phase protein haptoglobin was associated with more severe social interaction and communication + social interaction. In summary, I-FABP, a marker of intestinal epithelial damage, was associated with more severe behavioural phenotypes in very young children with ASD. In addition, the acute phase protein, haptoglobin, was associated with behaviour.

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20. Zalosnik MI, Fabio MC, Bertoldi ML, Castañares CN, Degano AL. MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge. Scientific reports. 2021; 11(1): 10997.

Rett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene. It has been suggested that immune alterations may play an active role in the generation and/or maintenance of RTT phenotypes. However, there is no clear consensus about which pathways are regulated in vivo by MeCP2 in the context of immune activation. In the present work we set to characterize the role of MeCP2 during the progression of Experimental Autoimmune Encephalomyelitis (EAE) using the MeCP2(308/y) mouse model (MUT), which represents a condition of « MeCP2 function deficiency ». Our results showed that MeCP2 deficiency increased the susceptibility to develop EAE, along with a defective induction of anti-inflammatory responses and an exacerbated MOG-specific IFNγ expression in immune sites. In MUT-EAE spinal cord, we found a chronic increase in pro-inflammatory cytokines gene expression (IFNγ, TNFα and IL-1β) and downregulation of genes involved in immune regulation (IL-10, FoxP3 and CX3CR1). Moreover, our results indicate that MeCP2 acts intrinsically upon immune activation, affecting neuroimmune homeostasis by regulating the pro-inflammatory/anti-inflammatory balance in vivo. These results are relevant to identify the potential consequences of MeCP2 mutations on immune homeostasis and to explore novel therapeutic strategies for MeCP2-related disorders.

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