Pubmed du 16/08/21
1. Avraham Y, Mankuta D, Lipsker L, Vorobiev L, Patael S, Hassid G, Berry EM, Albeck A. Beta-Carotene derivatives as novel therapy for the prevention and treatment of autistic symptoms. Bioorganic chemistry. 2021; 115: 105224.
Autistic Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction & communication as well as restricted and repetitive behavior. The currently reported incidence of ASD is 1-2%, and it increases dramatically to 10-20% in families predisposed to ASD. To date, there is no effective way to treat or prevent ASD, and only symptomatic treatment with limited efficacy is available. Oxytocin (Oxt) enhances affiliative behavior and improves social cognition. Social deficits characteristic of autism may be related to dysfunctional Oxt neurotransmission. Thus, administration of Oxt may relieve ASD, however it has a short plasma half-life and poor Blood Brain Barrier (BBB) permeability. CD38, a multifunctional ecto-enzyme expressed in brain and immune cells, was found to be critical for social behavior via regulation of Oxt secretion. All-trans retinoic acid (ATRA) is a potent inducer of CD38 and improves social behavior, but it is toxic and teratogenic. We have shown that beta-carotene has a similar therapeutic effect. The present study aimed to investigate the activity of novel beta-carotene derivatives in rescuing low sociability found in BTBR mice, providing an in vivo « proof of principle » that beta-carotene derivatives are potential agents to prevent/ameliorate the reappearance of ASD in high-risk populations for ASD. Beta-carotene and its synthetic analogs were administered orally to newborn BTBR mice with ASD associated like behavior. After 2 months, they were tested (at dosages of 0.1 and 1.0 mg/kg) by cognitive (T-maze spontaneous alteration and neurological score) and behavioral tests (reciprocal social interaction, repetitive grooming / bedding behavior), previously shown as indicators for autistic behavior. The following biochemical and molecular biology parameters were also examined: serum Oxt; gene expression in hippocampus and hypothalamus of CD 38, Oxt, Oxt receptor, BDNF, and retinoic acid receptor. The new compounds were significantly more effective than control. The most effective compounds, both in the behavioral tests and in their biochemical effects, were (3R,3’R)-astaxanthin bis(N-Cbz-l-alanine ester) (3B(and (3S,3’S)-astaxanthin bis(N,N-dimethylglycine ester (5). They did not exert any neurological symptoms. Thus, beta-carotene derivatives may have the potential to prevent and/or ameliorate autistic symptoms when administered orally after birth to newborns of families predisposed to autism.
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2. Courchesne V, Bedford R, Pickles A, Duku E, Kerns C, Mirenda P, Bennett T, Georgiades S, Smith IM, Ungar WJ, Vaillancourt T, Zaidman-Zait A, Zwaigenbaum L, Szatmari P, Elsabbagh M. Non-verbal IQ and change in restricted and repetitive behavior throughout childhood in autism: a longitudinal study using the Autism Diagnostic Interview-Revised. Molecular autism. 2021; 12(1): 57.
BACKGROUND: Restricted and repetitive behavior (RRB) is one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role of each in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development. METHODS: The goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) at age 8 years. RESULTS: The proportion of children showing each RRB tended to diminish with increasing age, except for sensitivity to noise and circumscribed interests, where the proportion increased over time. Although there was no significant main effect of NVIQ, there was a significant interaction between age and NVIQ. This was mainly driven by Difficulties with change in routine, for which higher NVIQ was associated with the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age. LIMITATIONS: The study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children. CONCLUSIONS: These results confirm that specific RRB are differentially linked to age and NVIQ. Studying RRB individually is a promising approach to better understanding how RRB change over the development of autistic children and are linked to other developmental domains.
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3. Stehouwer N, Sawaya A, Shaniuk P, White P. Consultation Needs for Young Adults with Intellectual and Developmental Disabilities Admitted to an Adult Tertiary Care Hospital: Implications for Inpatient Practice. Journal of pediatric nursing. 2021; 60: 288-92.
BACKGROUND: Children with intellectual and developmental disabilities (IDD), particularly those with medical complexity, account for a large proportion of pediatric inpatients and are increasingly surviving to adulthood. However, few studies have evaluated the inpatient care of this population after transition to adult hospitals. This paper describes a Med-Peds Hospitalist service providing inpatient consultation for young adults with childhood conditions and offers a window into issues likely to be faced by young adults with IDD as they face increased admissions to adult hospitals. METHODS: A single center retrospective chart review was performed of adults with intellectual and developmental disabilities referred to the Med-Peds consult service at a large urban adult academic medical center. FINDINGS: The most common medical recommendations provided focused on diagnosis and management of gastrointestinal, neurologic, and respiratory issues. Coordination between pediatric and adult caregivers, disposition planning, communication and family support, and guidance on weight-based dosing were also commonly provided services. DISCUSSION: Young adults with IDD face new challenges when admitted to adult hospitals. In this single-center study, several areas were identified where expert consultation could be helpful. The need for structured coordination of care for this vulnerable patient population was highlighted. Knowledgeable consultative services may be an effective intervention to address the unique needs of hospitalized young adults with IDD. APPLICATION TO PRACTICE: Hospitals should consider structured inpatient programs, care-paths, or consultation from providers knowledgeable in the care of young adults with intellectual disabilities in order to improve the inpatient care of this population.
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4. Uljarević M, Frazier TW, Jo B, Billingham WD, Cooper MN, Youngstrom EA, Scahill L, Hardan AY. Big Data Approach to Characterize Restricted and Repetitive Behaviors in Autism. Journal of the American Academy of Child and Adolescent Psychiatry. 2022; 61(3): 446-57.
OBJECTIVE: Despite being a core diagnostic feature of autism spectrum disorder (ASD), demographic, developmental and clinical correlates of restricted and repetitive behaviors and interests (RRB) remain poorly characterized. This study aimed to utilize the largest available RRB data set to date to provide a comprehensive characterization of how distinct RRB domains vary according to a range of individual characteristics. METHOD: Data were obtained from 17,581 children and adolescents with ASD (mean(age)= 8.24 years, SD(age)= 4.06) from the Simons Foundation Powering Autism Research for Knowledge cohort. Caregivers completed the Repetitive Behavior Scale-Revised questionnaire as a measure of repetitive motor behaviors, self-injurious behaviors, compulsions, insistence on sameness, and circumscribed interests RRB domains. Caregivers also provided information on children’s cognitive functioning, language ability, and social and communication impairments. RESULTS: Male sex was associated with higher severity of repetitive motor behaviors and restricted interests and with lower severity of compulsions and self-injurious behaviors; no sex differences were found for the insistence on sameness domain. Although repetitive motor behaviors showed a mostly linear (negative) association with age, other RRB domains showed more complex and nonlinear pattern of associations. Higher severity of social and communication impairments provided significant independent contribution in predicting higher severity of all RRB domains at the p < .001 level; however, these effects were small (d < 0.25). The strongest of these effects was observed for insistence on sameness (d = 0.24), followed by repetitive motor behaviors (d = 0.21), compulsions (d = 0.17), restricted interests (d = 0.14), and self-injurious behaviors (d = 0.12). CONCLUSION: Findings reported here provide further evidence that RRB subdomains show a somewhat distinct pattern of associations with demographic, developmental, and clinical variables, with a key implication that separate consideration of these domains can help to facilitate efforts to understand diverse ASD etiology and to inform the design of effective interventions.
