1. Becker M, Abaev K, Pinhasov A, Ornoy A. S-Adenosyl-Methionine alleviates sociability aversion and reduces changes in gene expression in a mouse model of social hierarchy. Behavioural brain research. 2022; 427: 113866.

Epigenetic changes are an important pathogenic mechanism in many diseases, including a variety of psychiatric disorders such as Autism Spectrum Disorder (ASD) and depression. Methyl donors such as S-Adenosyl-Methionine (SAMe) may cause epigenetic modifications, especially during embryonic development when the epigenetic memory is established. We treated pregnant submissive (Sub) mice exhibiting depressive-like phenotype with SAMe during days 12-14 of gestation aiming to alleviate the depressive – like symptoms in their offspring and normalize the expression in their prefrontal cortex of several genes possibly involved in depression. We also aimed to define possible gender differences of the effects of SAMe on the measured parameters. Treatment of the Dams with SAMe did not affect the early neurodevelopmental milestones in males or females. The results of the behavioral tests showed improvement in some behavioral parameters compared to saline treated Sub mice. Several of these improvements were gender related. Prenatal SAMe treatment mainly improved sociability, as observed in the three chambers social interaction test, in both genders. It also improved the increased locomotion (as observed by the open field test) in the female mice, but not in males. Prenatal SAMe increased the expression of Vegfa and Flt1 in males, but not in females. The expression of IgfII and SynIIb increased in males and decreased in females and the expression of serotonin receptor Htr2A did not change in both genders. In our mouse model of depression, prenatal treatment with SAMe significantly improved some parameters of depressive like behavior and normalized the expression of several genes related to depression. The gender differences observed in our studies may explain the sex related differences in the clinical presentation of depression and the different gender related response to treatment.

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2. Frakking TT, Waugh J, Carty C, Burmeister A, Marozza A, Hobbins S, Kilah M, David M, Kane L, McCormick S, Carter HE. The effect of different service models on quality of care in the assessment of autism spectrum disorder in children: study protocol for a multi-centre randomised controlled trial. BMC pediatrics. 2022; 22(1): 173.

BACKGROUND: There is significant variability in clinical pathways available in the diagnostic assessment of ASD, including the order and timing of allied health assessments in relation to paediatrician consultations. Allied health professionals in first-contact models are increasingly used to improve the timeliness of healthcare access, whilst complementing medical specialty workforce shortages. Anecdotally, the implementation of allied health first-contact models in paediatrics has improved waitlists and timely access to healthcare. However, no rigorous studies have been conducted to evaluate the outcomes of these models. This study aims to determine the impacts of an allied health first-contact model on health service use and costs and patient quality of life and satisfaction. METHODS: An open, semi-blinded, multi-centre randomised controlled trial in paediatric outpatient clinics at two Australian metropolitan public hospitals. 56 children (0-16 years) fulfilling the inclusion criteria will be randomised to one of two clinical pathways for assessment of ASD: (1) allied health first-contact or (2) medical first-contact model. Cost outcomes will be collected from both health service and family perspectives. Caregiver-reported outcome measures include: Pediatric Quality of Life Inventory (PedsQL), the EuroQOL Five Dimension Youth Version (EQ-5D-Y), the Autism Family Experience Questionnaire (AFEQ) and Measure of Processes of Care. DISCUSSION: Evidence of improvements in service and consumer centric outcomes will help inform the development and implementation of high-value, evidenced based models of care for the assessment of ASD in children. The findings from this study are expected to contribute to the evidence base around the costs and consequences of allied health first contact models for the assessment of children with ASD in the Australian setting. Findings of this study may help to inform the allocation of health care resources while maintaining, or potentially improving, patient and family quality of life and experience of care. These findings may be useful in informing the wider adoption of these models in Australia and internationally, particularly in healthcare settings where medical specialist shortages exist. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR) ACTRN12621001433897 . Registered: 25(th) October, 2021.

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3. Kaur R, Boobna T, Kallingal P. Effect of Covid-19 lockdown on indian children with autism. Research in developmental disabilities. 2022; 125: 104230.

BACKGROUND: To prevent the spread of Coronavirus-19 a complete lockdown was enforced in India by March, 2020. The lockdown led to drastic negative effects on the social and communicative life of people. Among these, children and adolescents have been majorly affected. The study aims to investigate the effect of lockdown on Indian children with Autism. METHODS AND PROCEDURES: Thirty parents of children with Autism were given questionnaires to rate the performance of their children, pre- and post-lockdown. The questionnaires were analysed for development across activities of daily living (ADL), language and behavioral characteristics along with school and therapy performance. OUTCOME AND RESULTS: The results revealed a significant regression in performance of children post-lockdown which was evident across all the domains assessed. Various additional issues like changes in sleep patterns, inadequate sitting behavior, attention span, concentration, limited eye contact, mood swings, laziness, clumsiness, hyperactivity and impulsivity were also noted post-lockdown, which were not very prominent before lockdown. CONCLUSIONS AND IMPLICATIONS: The study anticipates to help be better prepared for such situations in future. This includes involvement of better intervention which includes home-based training strategies for these children. Moreover, the study highlights impact of online therapy and schooling for children with Autism.

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4. Li X, Zhao C, Kou H, Zhu F, Yang Y, Lu Y. PDD-guided tumor excision combined with photodynamic therapy in patients with extramammary Paget’s disease. Photodiagnosis and photodynamic therapy. 2022: 102841.

BACKGROUND: In recent years, photodynamic diagnosis (PDD) has been a technique that plays a pivotal role in visualizing tumor size during the assessment of surgery. Photodynamic therapy (PDT) is a developing treatment method apart from surgery, chemotherapy, radiotherapy, and immunotherapy and is approved for several types of tumors and nonmalignant diseases. The purpose of this study was to illustrate the efficiency and safety of PDD-guided tumor excision combined with ALA-PDT in patients with extramammary Paget’s disease (EMPD). METHODS: In our study, 7 cases of EMPD were treated with PDD-guided tumor excision combined with ALA-PDT. After removal of the tumor detected by PDD, each tumor region was irradiated with 177 J/cm(2) using a 635-nm laser for 15 min. Two to four ALA-PDT cycles were applied during and after surgery. EMPD was confirmed by biopsy. RESULTS: PDD may forecast tumor margins in EMPD to guide surgery, and PDT has an inhibitory effect on tumor growth. There was no local recurrence in the follow-up of 2.9 years (range, 0.8-5 years). Only one patient experienced distant recurrence under the armpit. The patients with EMPD were able to complete the treatment protocol, with good results and no significant side effects. CONCLUSIONS: The present study demonstrated an effective protocol using PDD for diagnosis and PDT for multiple therapies, showing potential as an alternative clinical treatment for EMPD.

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5. Liu KY, Teitler JO, Rajananda S, Chegwin V, Bearman PS, Hegyi T, Reichman NE. Elective Deliveries and the Risk of Autism. American journal of preventive medicine. 2022.

INTRODUCTION: Cesarean section and induced deliveries have increased substantially in the U.S., coinciding with increases in autism spectrum disorder. Studies have documented associations between cesarean section deliveries and autism spectrum disorder but have not comprehensively accounted for medical risks. This study evaluates the extent to which cesarean section and induced deliveries are associated with autism spectrum disorder in low-risk births. METHODS: In this retrospective cohort study, California’s birth records (1992-2012) were linked to hospital discharge records to identify low-risk births using a stringent algorithm based on Joint Commission guidelines. Autism spectrum disorder status was based on California Department of Developmental Service data. Logistic regression models were used to estimate associations between autism spectrum disorder and induced vaginal deliveries, cesarean section deliveries not following induction, and cesarean section deliveries following induction, with noninduced vaginal deliveries as the reference category. RESULTS: A total of 1,488,425 low-risk births took place in California from 1992 to 2012. The adjusted odds of autism spectrum disorder were 7% higher for induced vaginal deliveries (AOR=1.07, 95% CI=1.01, 1.14), 26% higher for cesarean section deliveries not following induction (AOR=1.26, 95% CI=1.19, 1.33), and 31% higher for cesarean section deliveries following induction (AOR=1.31, 95% CI=1.18, 1.45) than for noninduced vaginal deliveries. Lower gestational age and neonatal morbidities did not appear to be important underlying pathways. The associations were insensitive to alternative model specifications and across subpopulations. These results suggest that, in low-risk pregnancies, up to 10% of autism spectrum disorder cases are potentially preventable by avoiding cesarean section deliveries. CONCLUSIONS: After accounting for medical risks, elective deliveries-particularly cesarean section deliveries-were associated with a substantially increased risk of autism spectrum disorder.

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6. Roux AM, Tao S, Marcus S, Lushin V, Shea LL. A national profile of substance use disorder among medicaid enrollees on the autism spectrum or with intellectual disability. Disability and health journal. 2022: 101289.

BACKGROUND: Recent research has questioned the assumption that people with intellectual disability (ID) or autism spectrum disorder (ASD) are less at risk of substance use disorders (SUDs). Overall, little is known about SUDs among people with intellectual and developmental disabilities (/IDDs). OBJECTIVE: This study aimed to estimate prevalence of SUD among Medicaid enrollees with ASD, ID, or ASD + ID; characterize these groups and types of SUDs; and identify risk of SUD by demographic and clinical characteristics within groups. METHODS: We used 2008-2012 national Medicaid data to identify enrollees with ASD, ID, ASD + ID and a sample without ASD/ID and identified SUDs within these individuals. We used descriptive statistics to characterize enrollee groups and types of SUDs, calculated SUD prevalence, and used modified Poisson regression to examine adjusted relative risk of SUD within disability groups. RESULTS: SUD prevalence increased yearly across disability groups to 1-2.2%, increasing most quickly among those with ASD. Alcohol abuse was the most common SUD among those with ID-only (57%) versus cannabis abuse among the ASD-only group (41%). Risk of SUD was higher among those with co-occurring psychiatric disorders – notably, depression. CONCLUSIONS: Results highlight increasing prevalence of SUD among Medicaid enrollees with ASD-only and ASD + ID and higher risk of SUD among those with depression and other psychiatric disorders. Understanding access to screening, diagnosis and treatment of SUD among people with I/DDs is a highly important question for future research.

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7. Shan X, Uddin LQ, Xiao J, He C, Ling Z, Li L, Huang X, Chen H, Duan X. Mapping the Heterogeneous Brain Structural Phenotype of Autism Spectrum Disorder Using the Normative Model. Biological psychiatry. 2022.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by substantial clinical and biological heterogeneity. Quantitative and individualized metrics for delineating the heterogeneity of brain structure in ASD are still lacking. Likewise, the extent to which brain structural metrics of ASD deviate from typical development (TD) and whether deviations can be used for parsing brain structural phenotypes of ASD is unclear. METHODS: T1-weighted magnetic resonance imaging data from the Autism Brain Imaging Data Exchange (ABIDE) II (n(TD) = 564) were used to generate a normative model to map brain structure deviations of ABIDE I subjects (n(TD) = 560, n(ASD) = 496). Voxel-based morphometry was used to compute gray matter volume. Non-negative matrix factorization was employed to decompose the gray matter matrix into 6 factors and weights. These weights were used for normative modeling to estimate the factor deviations. Then, clustering analysis was used to identify ASD subtypes. RESULTS: Compared with TD, ASD showed increased weights and deviations in 5 factors. Three subtypes with distinct neuroanatomical deviation patterns were identified. ASD subtype 1 and subtype 3 showed positive deviations, whereas ASD subtype 2 showed negative deviations. Distinct clinical manifestations in social communication deficits were identified among the three subtypes. CONCLUSIONS: Our findings suggest that individuals with ASD have heterogeneous deviation patterns in brain structure. The results highlight the need to test for subtypes in neuroimaging studies of ASD. This study also presents a framework for understanding neuroanatomical heterogeneity in this increasingly prevalent neurodevelopmental disorder.

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8. Singer EV, Niarchou M, Maxwell-Horn A, Hucks D, Johnston R, Sutcliffe JS, Davis LK, Malow BA. Characterizing sleep disorders in an autism-specific collection of electronic health records. Sleep medicine. 2022; 92: 88-95.

OBJECTIVE/BACKGROUND: Sleep problems are common in people on the autism spectrum. This study reviews one detailed approach to querying the electronic health record (EHR) in a large tertiary care center. PATIENTS/METHODS: We developed methods for identifying people on the autism spectrum and defined their sleep problems using the key words, « sleep » or « melatonin », or International Classification of Diseases (ICD) codes. We examined treatment responses of these individuals to melatonin supplementation. RESULTS: Sleep problems were documented in 86% of patients with ages ranging from 6 to 30 years old. Our specific keyword search yielded more patients with sleep diagnoses than ICD codes alone. About two-thirds of patients who received melatonin supplementation reported benefit from its use. CONCLUSIONS: Our study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in people on the autism spectrum. Using specific keywords could be helpful in future work that queries the EHR.

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