1. Balboni G, Widaman KF, Esposito G. Enhancing research practice in developmental disabilities. Research in developmental disabilities. 2023; 137: 104499.

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2. Cho S, Cola M, Knox A, Pelella MR, Russell A, Hauptmann A, Covello M, Cieri C, Liberman M, Schultz RT, Parish-Morris J. Sex differences in the temporal dynamics of autistic children’s natural conversations. Molecular autism. 2023; 14(1): 13.

BACKGROUND: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification. METHODS: Forty-five school-aged children with autism (29 boys and 16 girls) and 47 non-autistic/neurotypical (NT) children (23 boys and 24 girls) engaged in a 5-min « get-to-know-you » conversation with a young adult confederate that was unaware of children’s diagnostic status. Groups were matched on IQ estimates. Recordings were time-aligned and orthographically transcribed by trained annotators. Several speech and pause measures were calculated. Groups were compared using analysis of covariance models, controlling for age. RESULTS: Autistic girls used significantly more words than autistic boys, and produced longer speech segments than all other groups. Autistic boys spoke more slowly than NT children, whereas autistic girls did not differ from NT children in total word counts or speaking rate. Autistic boys interrupted confederates’ speech less often and produced longer between-turn pauses (i.e., responded more slowly when it was their turn) compared to other children. Within-turn pause duration did not differ by group. LIMITATIONS: Our sample included verbally fluent children and adolescents aged 6-15 years, so our study results may not replicate in samples of younger children, adults, and individuals who are not verbally fluent. The results of this relatively small study, while compelling, should be interpreted with caution and replicated in a larger sample. CONCLUSION: This study investigated the temporal dynamics of everyday conversations and demonstrated that autistic girls and boys have distinct natural language profiles. Specifying differences in verbal communication lays the groundwork for the development of sensitive screening and diagnostic tools to more accurately identify autistic girls, and could inform future personalized interventions that improve short- and long-term social communication outcomes for all autistic children.

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3. Cordani R, Tobaldini E, Rodrigues GD, Giambersio D, Veneruso M, Chiarella L, Disma N, De Grandis E, Toschi-Dias E, Furlan L, Carandina A, Prato G, Nobili L, Montano N. Cardiac autonomic control in Rett syndrome: Insights from heart rate variability analysis. Frontiers in neuroscience. 2023; 17: 1048278.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS.

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4. Davis A, Van Eck K, Copeland-Linder N, Phuong K, Belcher HME. Hospitalization and Mortality for Insured Patients in the United States with COVID-19 with and without Autism Spectrum Disorder. Journal of autism and developmental disorders. 2023: 1-8.

Autism spectrum disorder (ASD) is a neuropsychiatric condition that may be associated with negative health outcomes. This retrospective cohort study reveals the odds of hospitalization and mortality based on ASD for a population of insured patients with COVID-19. The odds of hospitalization and mortality for people with ASD were found to be greater than individuals without ASD when adjusted for sociodemographic characteristics. Hospitalization and mortality was associated with a dose-response increase to comorbidity counts (1 to 5+). Odds of mortality remained greater for those with ASD when adjusting for comorbid health conditions. ASD is a risk factor for COVID-19 mortality. Comorbid health conditions play a particular role in increasing the odds of COVID-19 related hospitalization and death for ASD patients.

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5. Dominguez-Alonso S, Carracedo A, Rodriguez-Fontenla C. The non-coding genome in Autism Spectrum Disorders. European journal of medical genetics. 2023; 66(6): 104752.

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders (NDDs) characterized by difficulties in social interaction and communication, repetitive behavior, and restricted interests. While ASD have been proven to have a strong genetic component, current research largely focuses on coding regions of the genome. However, non-coding DNA, which makes up for ∼99% of the human genome, has recently been recognized as an important contributor to the high heritability of ASD, and novel sequencing technologies have been a milestone in opening up new directions for the study of the gene regulatory networks embedded within the non-coding regions. Here, we summarize current progress on the contribution of non-coding alterations to the pathogenesis of ASD and provide an overview of existing methods allowing for the study of their functional relevance, discussing potential ways of unraveling ASD’s « missing heritability ».

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6. Frame NW, Allas MJ, Pequegnat B, Vinogradov E, Liao VC, Al-Abdul-Wahid S, Arroyo L, Allen-Vercoe E, Lowary TL, Monteiro MA. Structure and synthesis of a vaccine and diagnostic target for Enterocloster bolteae, an autism-associated gut pathogen – Part II. Carbohydrate research. 2023; 526: 108805.

Enterocloster bolteae (formerly known as Clostridium bolteae) is a gastro-intestinal pathogenic bacterium often detected in the fecal microbiome of children in the autism spectrum. E. bolteae excretes metabolites that are thought to act as neurotoxins. This study is an update of our first E. bolteae investigation that discovered an immunogenic polysaccharide. Through a combination of chemical derivatizations/degradations, spectrometry and spectroscopy techniques, a polysaccharide composed of disaccharide repeating blocks comprised of 3-linked β-d-ribofuranose and 4-linked α-l-rhamnopyranose, [→3)-β-D-Ribf-(1 → 4)-α-L-Rhap-(1→](n), was identified. To confirm the structure, and to provide material for subsequent investigations, the chemical synthesis of a corresponding linker-equipped tetrasaccharide, β-D-Ribf-(1 → 4)-α-L-Rhap-(1 → 3)-β-D-Ribf-(1 → 4)-α-L-Rhap-(1→O(CH(2))(8)N(3), is also described. Research tools based on this immunogenic glycan structure can form the foundation for serotype classification, diagnostic/vaccine targets and clinical studies into the hypothesized role of E. bolteae in the onset/augmentation of autism related conditions in children.

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7. Gosling CJ, Cartigny A, Stevanovic D, Moutier S, Delorme R, Attwood T. Known-groups and convergent validity of the theory of mind task battery in children with autism spectrum disorder. The British journal of clinical psychology. 2023.

OBJECTIVES: One of the most promising Theory of Mind (ToM) tests developed for children with ASD is the Theory of Mind Task Battery (ToM-TB). Still, additional psychometric properties of this tool need to be assessed. The main objective of this preregistered study was to investigate the known-groups and convergent validities of the ToM-TB compared to a well-established test used to assess ToM in children with ASD (the Strange Stories Test; SST). METHODS: A total of 68 school-aged children were recruited (34 children with ASD and 34 children with typical development). The groups were matched on sex and age, and on both receptive language abilities and overall cognitive functioning. RESULTS: Regarding the known-groups validity, we found group differences in the performance on the ToM-TB and SST. Additional analyses revealed that this result tended to be more robust for the ToM-TB than for the SST. Regarding convergent validity, we showed that the ToM-TB and SST correlated strongly, for children with ASD and children with typical development. In contrast, we found small correlations of these two tests with social competence in daily life. No evidence was found for greater known-groups or convergent validity of one test compared to the other. CONCLUSION: Our data confirmed the relevance of the ToM-TB and the SST for the assessment of ToM in school-aged children. Future studies should continue to assess the psychometric qualities of various ToM tests to provide reliable information to best guide researchers and clinicians when choosing optimal neuropsychological tools.

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8. Greenlee JL, Stelter CR, Hickey E, Burton C, Carlson M, Winter MA. Using the Three-Minute Speech Sample to Examine the Parent-Adolescent Relationship in Autistic Youth: A Qualitative Analysis. Journal of autism and developmental disorders. 2023.

PURPOSE: This qualitative study examines autistic adolescents’ perception of the quality of their relationship with their parent using the Three Minute Speech Sample. METHODS: Twenty autistic youth (13-17 years; 83% male) spoke, uninterrupted, for three minutes about their thoughts and feelings regarding their mothers. Audio-recorded speech samples were transcribed and coded for emergent themes. RESULTS: Adolescents highlighted emotional support and acceptance in the context of their relationship, support mothers provide for mental health, love and caring, efforts to build the relationship through shared activities, and areas of adolescent-parent conflict. CONCLUSION: The TMSS is a low cost, low burden method by which autistic adolescents can comfortably and effectively self-report the quality of their relationship with their parent/caregiver.

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9. Grönniger B, Danzer A, Kimpe K, Singh A, Sadowski G. Viscoelastic Behavior of Supercooled and Glassy ASDs at Humid Conditions Can Be Predicted. Molecular pharmaceutics. 2023.

Amorphous solid dispersions (ASDs) are commonly used to increase the dissolution rate of poorly soluble active pharmaceutical ingredients (APIs). Unfortunately, most ASDs are thermodynamically unstable and, even though kinetically stabilized, will thus eventually crystallize. The crystallization kinetics is determined by the thermodynamic driving force and by molecular mobility, which in turn depend on the drug load, temperature, and relative humidity (RH) at which the ASDs are stored. This work focuses on viscosity as an indicator for the molecular mobility in ASDs. The viscosity and shear moduli of ASDs consisting of the polymer poly(vinylpyrrolidone-co-vinyl acetate) or hydroxypropyl methylcellulose acetate succinate and the API nifedipine or celecoxib were studied using an oscillatory rheometer. The effects of temperature, drug load, and RH on the viscosity were investigated. With the knowledge of how much water is absorbed by the polymer or ASD and thereby also the knowledge of the glass-transition temperature of the wet polymer or ASD, the viscosity of dry and wet ASDs was predicted to be in very good agreement with experimental data just based on the viscosity of neat polymers and the glass-transition temperatures of wet ASDs.

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10. Kim SA, Kasari C. Brief Report: Longitudinal Trajectory of Working Memory in School-Aged Children on the Autism Spectrum: Period of High Plasticity and « Late Bloomers ». Journal of autism and developmental disorders. 2023.

PURPOSE: While working memory (WM) is a powerful predictor for children’s school outcomes, autistic children are more likely to experience delays. This study compared autistic children and their neurotypical peers’ WM development over their elementary school years, including relative growth and period of plasticity. METHODS: Using a nationally-representative dataset, latent growth models were built to examine periods of high plasticity and the relationship between children’s performance upon school entry and their relative growth. RESULTS: While both groups made steeper gains during the early school years, autistic children’s period of highest plasticity was prolonged by 1 year, which suggests a larger window for interventions. Further, autistic children who started kindergarten with poorer WM were more likely to make rapid growth during the last 3 years of elementary school, which is when their neurotypical peers’ development started to plateau. CONCLUSION: Findings should prompt various stakeholders to examine interventions and instructions to maximize autistic children’s growth in WM. Further, the continued support and monitoring by educators throughout autistic children’s late childhood can be particularly beneficial for the « late-bloomers. ».

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11. Kramer JM, Guerrero F, Caoili A, Beasley JB, Kalb L, Klein A, Goode TD. Telehealth information and communication technology access for family caregivers of people with intellectual and developmental disabilities and mental health needs. Disability and health journal. 2023: 101463.

BACKGROUND: Telehealth is increasingly used to deliver mental health services. However, the potential benefits of telehealth for people with intellectual and developmental disabilities and mental health needs (IDD-MH) may not be fully realized. This study addresses gaps in knowledge about access to information and communication technologies (ICTs) for individuals with IDD-MH from the perspective of their family caregivers. OBJECTIVE: What factors are associated with access to ICTs among family caregivers of people with IDD-MH who use START services? METHODS: Retrospective analysis of cross-sectional interview data gathered for START use at the onset of COVID-19. START is a crisis prevention and intervention evidence-based model for people with IDD-MH implemented across the USA. To assess needs during COVID-19, START coordinators conducted interviews with 1455 family caregivers between March and July 2020. A multinomial regression model examined correlates of ICT access, as indicated by an index (poor, limited, and optimal access). Correlates included the level of IDD, age, gender, race, ethnicity, rural setting of the person with IDD-MH, and caregiver status. RESULTS: Age (ages 23-30 years) and sole caregiver status were significantly associated with limited access (both p ≤ .001). Age (ages 23-30 years and ≥31 years, p < .001), race (Black or African American, p = .001), ethnicity (Hispanic, p = .004), and sole caregiver status (p < .001) were significantly associated with poor access. CONCLUSIONS: Disparities existed in ICT access for adults, specific racial/ethnic groups, and sole caregiver households. Healthcare policy related to telehealth must consider how ICT access can be equitable for all users with IDD-MH.

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12. Kriegel G, Paul S, Leonard KH, Sandor P. Prevalence of Autism Spectrum Disorder (ASD) in Inpatient Adolescent Psychiatric Population. Journal of autism and developmental disorders. 2023.

The prevalence of autism spectrum disorder (ASD) has increased in recent decades, much of which is related to changes in diagnostic criteria, and greater awareness among professionals and parents. Using a prospective cross-sectional study design, this study explores the prevalence of ASD among 173 adolescents admitted to two psychiatric facilities in Canada, and its association with some early pre and perinatal risk factors. The overall prevalence of ASD in the psychiatric population was 11.56% compared to 1.52% in children and youth in Canada. While prenatal and perinatal factors were not significantly associated with ASD, we found a frequent association of ASD with different comorbid psychiatric conditions. These findings further our knowledge in planning and management of ASD among this population.

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13. Kumar M, Hiremath C, Khokhar SK, Bansal E, Sagar KJV, Padmanabha H, Girimaji AS, Narayan S, Kishore MT, Yamini BK, Jac Fredo AR, Saini J, Bharath RD. Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: evidence from toddlers. Journal of translational medicine. 2023; 21(1): 246.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social and communication skills, narrow interests, and repetitive behavior. It is known that the cerebellum plays a vital role in controlling movement and gait posture. However, recently, researchers have reported that the cerebellum may also be responsible for other functions, such as social cognition, reward, anxiety, language, and executive functions. METHODS: In this study, we ascertained volumetric differences from cerebellar lobular analysis from children with ASD, ASD siblings, and typically developing healthy controls. In this cross-sectional study, a total of 30 children were recruited, including children with ASD (N = 15; mean age = 27.67 ± 5.1 months), ASD siblings (N = 6; mean age = 17.5 ± 3.79 months), and typically developing children (N = 9; mean age = 17.67 ± 3.21 months). All the MRI data was acquired under natural sleep without using any sedative medication. We performed a correlation analysis with volumetric data and developmental and behavioral measures obtained from these children. Two-way ANOVA and Pearson correlation was performed for statistical data analysis. RESULTS: We observed intriguing findings from this study, including significantly increased gray matter lobular volumes in multiple cerebellar regions including; vermis, left and right lobule I-V, right CrusII, and right VIIb and VIIIb, respectively, in children with ASD, compared to typically developing healthy controls and ASD siblings. Multiple cerebellar lobular volumes were also significantly correlated with social quotient, cognition, language, and motor scores with children with ASD, ASD siblings, and healthy controls, respectively. CONCLUSIONS: This research finding helps us understand the neurobiology of ASD and ASD-siblings, and critically advances current knowledge about the cerebellar role in ASD. However, results need to be replicated for a larger cohort from longitudinal research study in future.

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14. Madigand J, Rio M, Vandevelde A. Equine assisted services impact on social skills in autism spectrum disorder: A meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry. 2023; 125: 110765.

Many studies focus on the impact of equine assisted services (EAS) on social skills in autism spectrum disorder (ASD) but existing data are not consensual and the only available meta-analysis included only three studies and did not consider the social responsiveness scale (SRS). This meta-analysis aims to measure the impact of EAS on social skills in ASD. Using Pubmed, Embase, Web of Science and the Cochrane Library, the means and standard deviations of every available SRS post-intervention scores in each participant group were collected from the five selected randomised controlled trials with 240 participants. An EAS significant beneficial impact was found for the total SRS score, social communication and social cognition. A tendency to a significant impact was found for social awareness and social motivation. No significant difference was shown for autistic mannerisms. This meta-analysis shows a significant beneficial impact of EAS for several social skills in ASD. Further randomised controlled trials are required to complement these results and expand the knowledge on the field of possibilities of this care in ASD.

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15. Martín R, Suárez-Pinilla AS, García-Font N, Laguna-Luque ML, López-Ramos JC, Oset-Gasque MJ, Gruart A, Delgado-García JM, Torres M, Sánchez-Prieto J. The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome. Molecular autism. 2023; 14(1): 14.

BACKGROUND: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. METHODS: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. RESULTS: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by β adrenergic receptors. A reduction in extracellular Ca(2+) concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, β adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. LIMITATIONS: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. CONCLUSIONS: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS.

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16. Mykins M, Layo-Carris D, Dunn LR, Skinner DW, McBryar AH, Perez S, Shultz TR, Willems A, Lau BYB, Hong T, Krishnan K. Wild-type MeCp2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome. Journal of neuroscience research. 2023.

Rett syndrome is characterized by an early period of typical development and then, regression of learned motor and speech skills in girls. Loss of MECP2 protein is thought to cause Rett syndrome phenotypes. The specific underlying mechanisms from typical developmental trajectory to regression features throughout life are unclear. Lack of established timelines to study the molecular, cellular, and behavioral features of regression in female mouse models is a major contributing factor. Due to random X-chromosome inactivation, female patients with Rett syndrome and female mouse models for Rett syndrome (Mecp2(Heterozygous) , Het) express a functional copy of wild-type MeCp-2 protein in approximately half of all cells. As MeCp2 expression is regulated during early postnatal development and experience, we characterized the expression of wild-type MeCp2 in the primary somatosensory cortex of female Het mice. Here, we report increased MeCp2 levels in non-parvalbumin-positive neurons of 6-week-old adolescent Het relative to age-matched wild-type controls, while also displaying typical levels of perineuronal net expression in the barrel field subregion of the primary somatosensory cortex, mild tactile sensory perception deficits, and efficient pup retrieval behavior. In contrast, 12-week-old adult Het express MeCp2 at levels similar to age-matched wild-type mice, show increased perineuronal net expression in the cortex, and display significant tactile sensory perception deficits. Thus, we have identified a set of behavioral metrics and the cellular substrates to study regression during a specific time in the female Het mouse model, which coincides with changes in wild-type MeCp2 expression. We speculate that the precocious increase in MeCp2 expression within specific cell types of adolescent Het may provide compensatory benefits at the behavioral level, while the inability to further increase MeCp2 levels leads to regressive behavioral phenotypes over time.

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17. Qian M, Lin S, Tan Y, Chen Q, Wang W, Li J, Mu C. A nonsense mutation in the CUL3 gene in a Chinese patient with autism spectrum disorder and epilepsy: A case report. Medicine. 2023; 102(14): e33457.

RATIONALE: CUL3 (OMIM: 603136) encodes cullin-3, a core component of ubiquitin E3 ligase. Existing medical research suggests that CUL3 mutations are closely related to neurodevelopmental disorder with or without autism or seizures (neurodevelopmental disorder with autism and seizures, OMIM: 619239). However, the number of published case reports of autism spectrum disorder due to CUL3 gene mutations is limited. PATIENT CONCERN: A four-year-old Chinese girl presented with generalized epilepsy, and then exhibited developmental regression, including loss of her speaking ability, eye contact aversion, and stereotyped behavior. DIAGNOSES: Whole-exome sequencing identified a nonsense mutation in the CUL3 gene, being c.2065A > T (p.Lys689*); no previous similar case was reported. The final diagnosis was autism, epilepsy, and motor growth retardation. INTERVENTION: In order to improve quality of life of the patient, she was provided with exercise rehabilitation training and autism behavioral guidance therapy for 3 months. OUTCOMES: The patient’s exercise capacity had improved, and improvements in autism symptoms were not obvious. LESSONS: For clinicians, patients with developmental regression accompanied with concurrent epilepsy and autism spectrum disorder should be advised that relevant genetic tests are necessary to clarify the diagnosis.

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18. Shaker E, Agami OE, Salamah A. Bumetanide, a Diuretic That Can Help Children with Autism Spectrum Disorder. CNS & neurological disorders drug targets. 2023.

BACKGROUND: Autism Spectrum Disorder (ASD) is a common child neurodevelopmental disorder, whose pathogenesis is not completely understood. Until now, there is no proven treatment for the core symptoms of ASD. However, some evidence indicates a crucial link between this disorder and GABAergic signals which are altered in ASD. Bumetanide is a diuretic that reduces chloride, shifts gamma-amino-butyric acid (GABA) from excitation to inhibition, and may play a significant role in the treatment of ASD. OBJECTIVE: The objective of this study is to assess the safety and efficacy of bumetanide as a treatment for ASD. METHODS: Eighty children, aged 3-12 years, with ASD diagnosed by Childhood Autism Rating Scale (CARS), ⩾30 were included in this double-blind, randomized, and controlled study. Group 1 received Bumetanide, Group 2 received a placebo for 6 months. Follow-up by CARS rating scale was performed before and after 1, 3, and 6 months of treatment. RESULTS: The use of bumetanide in group 1 improved the core symptoms of ASD in a shorter time with minimal and tolerable adverse effects. There was a statistically significant decrease in CARS and most of its fifteen items in group 1 versus group 2 after 6 months of treatment (p-value <0.001). CONCLUSION: Bumetanide has an important role in the treatment of core symptoms of ASD.

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19. Smith JR, York T, Warn S, Borodge D, Pierce DL, Fuchs DC. Another Option for Aggression and Self-Injury, Alternative Benzodiazepines for Catatonia in Profound Autism. Journal of child and adolescent psychopharmacology. 2023; 33(3): 109-17.

Introduction: Individuals with profound autism often present for inpatient care due to aggression. Diagnostic and treatment options are limited. Agitated catatonia is a treatable comorbidity in autism, which should be considered in cases of aggression. Preliminary data report high clinical response rates of catatonia in autism when treated with electroconvulsive therapy (ECT), with poor response to lorazepam. However, access to ECT is often limited, especially in pediatric populations. Methods: We conducted a retrospective chart review to identify cases of hyperactive catatonia with partial response to lorazepam in profoundly autistic children presenting to the pediatric medical hospital. Five cases were identified, all of whom were followed by the child and adolescent psychiatry consult-liaison service during admission and treated without the use of ECT. Data from the medical record were obtained after institutional review board (IRB) approval including the following: (1) treatment course, (2) Bush-Francis Catatonia Rating Scale (BFCRS) scores, and (3) Kanner Catatonia Rating Scale (KCRS) severity scores. The Clinical Global Impressions-Improvement (CGI-I) Scale was applied retrospectively to each case. Results: All five patients demonstrated clinically significant improvements. The average CGI-I score was 1.2. The average percentage reduction in the BFCRS and KCRS severity scores was 63% and 59%, respectively. Two of five patients were first stabilized with infusions midazolam and dexmedetomidine due to the symptom severity and then transitioned to long-acting oral benzodiazepines. Overall, four of five patients were stabilized with oral clonazepam and one of five with oral diazepam. Notably, four of five patients experienced an acute worsening of aggression, self-injury, and other catatonic symptoms with escalating dosages of antipsychotic treatment, which occurred before inpatient admission. All patients experienced resolution of physical aggression toward self and/or others, experienced improvement in their communicative abilities, and were able to return home or enter residential level of care upon discharge. Conclusions: Given the limited availability of ECT and the unclear utility of lorazepam for hyperactive catatonia in autism, the use of long-acting benzodiazepines and/or midazolam infusion may offer a safe and readily available treatment alternative.

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20. Sumiya M, Senju A. Brief Reports: Influence of Friendship on Loneliness Among Adolescents with Autism Spectrum Disorders in Japan. Journal of autism and developmental disorders. 2023.

PURPOSE: Previous studies have reported that people with autism spectrum disorder (ASD) have higher levels of loneliness than neurotypical (NTP) people, most likely because of their difficulties in social communication with their predominantly NTP peers. However, direct investigations on the causal influence of friendship on their feelings of loneliness is scarce. METHODS: In the current study, using the causal mediation analysis, we investigated whether friendship among ASD individuals influences their feelings of loneliness, especially during adolescence when the importance of friendship is typically most elevated. Furthermore, we examined whether individual differences in autistic behavioral features or age affect feelings of loneliness or the qualities of friendship with linear regression analyses. RESULTS: The results demonstrated that the higher levels of loneliness in adolescents with ASD were mediated by one aspect of friendship, companionship. We also found that positive aspects of friendship, but not negative aspects, influence the feelings of loneliness in both ASD and NTP populations. One subcategory of the measured autistic trait, difficulty in imagination, which is associated the ability to consider another’s perspective, had a negative relationship with the positive aspects of friendship in the ASD group, but not in the NTP group. CONCLUSION: These findings indicate that the quality of the positive aspects of friendship is similarly important for both adolescents with ASD and NTP adolescents, but the autistic behavioral features could interfere with the experience of such positive friendships.

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21. Wall CA, Roberts JE. Negative affect and respiratory sinus arrhythmia are differentially related to social anxiety and autism features in autistic preschoolers contrasted to fragile X syndrome. Frontiers in psychiatry. 2023; 14: 1151263.

INTRODUCTION: Autism spectrum disorder (ASD) is a highly heterogeneous and complex disorder with co-occurring disorders commonplace. This presents tremendous diagnostic challenges given the phenotypic overlap between autism and other diagnoses, including social anxiety, as well as variance in specific genetic disorders like fragile X syndrome (FXS). Biobehavioral measurement approaches integrate behavioral and biological data, and by so doing have the potential to address diagnostic challenges and shed light on the mechanisms underlying social impairments. METHODS: The present study utilized a biobehavioral approach to evaluate how biologically based indices of baseline respiratory sinus arrhythmia (RSA) and temperamental negative affect differ and predict autism and anxiety in a sample of 120 preschoolers with non-syndromic autism (nsASD) with co-occurring intellectual impairment, FXS, and neurotypical (NT) development. RESULTS: Results indicated that children with nsASD display elevated negative affect compared to both FXS and NT controls which did not differ from each other and females exhibited more negative affect relative to males. Interestingly, elevated negative affect predicted social anxiety, but not ASD in FXS. Baseline RSA did not differ across the groups; however, reduced RSA predicted elevated autism severity for the nsASD group but not those with FXS or NT development. DISCUSSION: Taken together, biobehavioral markers differentiated the groups in discrete ways that advance our understanding of autism and promote improved diagnostic clarity using objective measurement.

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22. Wehrle S, Cangemi F, Janz A, Vogeley K, Grice M. Turn-timing in conversations between autistic adults: Typical short-gap transitions are preferred, but not achieved instantly. PloS one. 2023; 18(4): e0284029.

The organisation of who speaks when in conversation is perhaps the most fundamental aspect of human communication. Research on a wide variety of groups of speakers has revealed a seemingly universal preference for between-speaker transitions consisting of very short silent gaps. Previous research on conversational turn-taking in Autism Spectrum Disorder (ASD) consists of only a handful of studies, most of which are limited in scope and based on the non-spontaneous speech of children and adolescents. No previous studies have investigated dialogues between autistic adults. We analysed the conversational turn-taking behaviour of 28 adult native German speakers in two groups of dyads, in which both interlocutors either did or did not have a diagnosis of ASD. We found no clear difference in turn-timing between the ASD and the control group overall, with both groups showing the same preference for very short silent-gap transitions that has been described for many other groups of speakers in the past. We did, however, find a clear difference between groups specifically in the earliest stages of dialogue, where ASD dyads produced considerably longer silent gaps than controls. We discuss our findings in the context of the previous literature, the implications of diverging behaviour specifically in the early stages of conversation, and the general importance of studying the neglected aspect of interactions between autistic adults.

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23. Whelan M, McGillivray J, Rinehart NJ. Using Life Course Theory to Explore the Association Between Autistic Traits, Child, Family, and School Factors and the Successful Transition to Secondary School. Journal of autism and developmental disorders. 2023.

Life Course Theory contends that school transitions can interrupt academic and wellbeing trajectories, depending on child, family, and school factors. Hierarchical regression analyses examined how autistic traits were associated with school transition outcomes. Autistic traits explained 12% of the variance in Quality of Life (QOL), 24% of the variance in mental health and 9% of the variance in school belonging. When autistic traits were accounted for, gender was a significant predictor of changes in QOL whereas changes in school belonging were predicted by cognitive functioning, parent education, school attendance and school refusal. Changes in mental health after transition were mostly predicted by family factors including family structure, family functioning and parent education but were also significantly predicted by sleep problems.

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24. Xiong Y, Chen J, Li Y. Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder. Frontiers in neuroscience. 2023; 17: 1125428.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with onset in childhood. The mechanisms underlying ASD are unclear. In recent years, the role of microglia and astrocytes in ASD has received increasing attention. Microglia prune the synapses or respond to injury by sequestrating the injury site and expressing inflammatory cytokines. Astrocytes maintain homeostasis in the brain microenvironment through the uptake of ions and neurotransmitters. However, the molecular link between ASD and microglia and, or astrocytes remains unknown. Previous research has shown the significant role of microglia and astrocytes in ASD, with reports of increased numbers of reactive microglia and astrocytes in postmortem tissues and animal models of ASD. Therefore, an enhanced understanding of the roles of microglia and astrocytes in ASD is essential for developing effective therapies. This review aimed to summarize the functions of microglia and astrocytes and their contributions to ASD.

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