1. Bahrami L, Miller CT, Miller H, Carlson KL, Foster TE, Ganesh A, Johnson D, Patterson BL, Hine JF. Enhancing Diagnostic Follow-up and Care Coordination for Children with Autism in a Busy Resident Continuity Clinic: Leveraging the Electronic Health Record. J Autism Dev Disord;2024 (Jan 30)

PURPOSE: A high-quality primary care clinic should provide clear action points and important care coordination for a child receiving a new diagnosis of autism spectrum disorder (ASD). Unfortunately, a substantial proportion of caregivers report little-to-no post-diagnosis support from their home clinics and primary care providers often report lack of training and resources in providing these supports. METHODS: We implemented an intervention package to investigate the impact on the frequency and quality of follow-up care for children with ASD in a busy, high-volume resident continuity clinic. The package consisted of a care coordination scheduling pathway and a standardized clinical template-embedded in the electronic health record (EHR)-that guided providers through best-practice recommendations and patient resources. RESULTS: As a result of these interventions, 74% of patients had ASD-specific follow-up, a more than threefold increase from baseline with a majority of providers using the EHR-embedded template to guide their visit. Providers also indicated a high degree of usability for the system and that it aided them in following best-practice guidelines for ASD care. CONCLUSION: Through explicit scheduling pathways and a novel EHR template, we saw a significant increase in ASD-specific follow-up visits and implementation of best practices for ASD care, demonstrating a new process for training and engaging primary care providers in clear action steps for post-diagnostic care without having to rely on tertiary referrals.

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2. Bui DT, Ton ANV, Nguyen CTD, Nguyen SH, Tran HK, Nguyen XT, Nguyen HT, Pham GLT, Tran DS, Harrington J, Pham HN, Pham TNV, Cao TA. Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform. Sci Rep;2024 (Jan 29);14(1):2360.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

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3. Cao Z, Min X, Xie X, Huang M, Liu Y, Sun W, Xu G, He M, He K, Li Y, Yuan J. RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT. Proc Natl Acad Sci U S A;2024 (Feb 6);121(6):e2320383121.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (Mecp2) gene. Here, we found that inhibition of Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) kinase ameliorated progression of motor dysfunction after onset and prolonged the survival of Mecp2-null mice. Microglia were activated early in myeloid Mecp2-deficient mice, which was inhibited upon inactivation of RIPK1 kinase. RIPK1 inhibition in Mecp2-deficient microglia reduced oxidative stress, cytokines production and induction of SLC7A11, SLC38A1, and GLS, which mediate the release of glutamate. Mecp2-deficient microglia release high levels of glutamate to impair glutamate-mediated excitatory neurotransmission and promote increased levels of GluA1 and GluA2/3 proteins in vivo, which was reduced upon RIPK1 inhibition. Thus, activation of RIPK1 kinase in Mecp2-deficient microglia may be involved both in the onset and progression of RTT.

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4. Chang JC, Lai MC, Chang SS, Gau SS. Factors mediating pre-existing autism diagnosis and later suicidal thoughts and behaviors: A follow-up cohort study. Autism;2024 (Jan 30):13623613231223626.

Autistic people are more likely to experience suicidal thoughts and behaviors. The underlying relationships between potential risk factors and suicidal thoughts and behaviors in autistic individuals remain unclear. To understand this, we investigated whether specific factors in childhood/youth explain the effects of pre-existing autism spectrum disorder (ASD) diagnoses on later suicidal thoughts and behaviors in adolescence/adulthood. We assessed internalizing and externalizing problems, bullying experiences, and executive functions (including cognitive flexibility, sustained attention, and spatial working memory) at an average baseline age of 13.4 years and suicidal thoughts and behaviors at an average follow-up age of 19.2 years among 129 autistic and 121 typically developing (TD) individuals. During the follow-up period in adolescence/adulthood, autistic individuals were more likely to report suicidal thoughts than TD individuals. Being bullied partially accounted for the relationship between a pre-existing ASD diagnosis and later-reported higher suicidal thoughts. Contrary to our hypothesis, higher (instead of lower) cognitive flexibility in some autistic young people appeared to partially explain their higher rates of suicidal thoughts compared with typically developing young people. The findings imply that school bullying prevention and tailored intervention programs for autistic people, especially those with higher cognitive flexibility, are warranted to reduce their risks of experiencing suicidal thoughts.

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5. Chang YT, Lee YJ, Haque M, Chang HC, Javed S, Lin YC, Cho Y, Abramovitz J, Chin G, Khamis A, Raja R, Murai KK, Huang WH. Comparative analyses of the Smith-Magenis syndrome protein RAI1 in mice and common marmoset monkeys. J Comp Neurol;2024 (Jan);532(1):e25589.

Retinoic acid-induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith-Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate-specific cell types, including intralaminar astrocytes and MEIS2-expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate-specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.

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6. Chezan LC, Bauer A, Drasgow E, Garcia H, Warman A. Generalization and Discrimination of Positively Reinforced Explicit Mands in Young Children with Autism Spectrum Disorder. Behav Modif;2024 (Jan 30):1454455241228768.

Many children with autism spectrum disorder (ASD) exhibit generalization errors following mand training. In this study, we extended the literature on the generalization of positively reinforced explicit mands in three young children with ASD and complex communication needs. First, we used mand training to teach a new, socially appropriate, positively reinforced explicit mand to request preferred toys. Second, we assessed the discriminated generalization of the newly acquired mand by using untrained examples and nonexamples. Results suggest that our mand training resulted in acquisition of a discriminated positively reinforced explicit mand in all three children. Overgeneralization was documented for one of the three children included in the study. We discuss implications for researchers and practitioners related to the importance of assessing for generalization errors following mand training.

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7. Czerwonka B, Johnston J, Smith-Steinert R. Anesthesia Management for Electroconvulsive Therapy. Aana j;2024 (Feb);92(1):51-56.

Electroconvulsive therapy (ECT) was first introduced in the late 1930s. In 2016, 1.4 million people worldwide were treated with ECT, a procedure that differs from any other. Indications for ECT include schizophrenia, schizoaffective disorder, catatonia, neuroleptic malignant syndrome, and bipolar disorder. Additionally, ECT can be beneficial for patients with autism spectrum disorder, specifically those with self-injurious behaviors and severe behaviors related to agitated or excited catatonia. As indications for ECT have grown, the results of therapy have proven beneficial. The anesthesia care for these patients has a direct impact on the initiation of a seizure, the duration and quality of which determines whether the procedure is successful. The anesthetic nuances of the procedure make it imperative that anesthesia providers not only understand the procedure, but also how the medications chosen and comorbidities of the patient can alter the outcome. This can ensure that providers utilize the most up to date practices while ensuring that care is delivered in a systematic approach providing safer, more effective patient care.

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8. Dionísio A, Espírito A, Pereira AC, Mouga S, d’Almeida OC, Oliveira G, Castelo-Branco M. Neurochemical differences in core regions of the autistic brain: a multivoxel (1)H-MRS study in children. Sci Rep;2024 (Jan 29);14(1):2374.

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy ((1)H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

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9. Goldblum JE, McFayden TC, Bristol S, Putnam OC, Wylie A, Harrop C. Correction: Autism Prevalence and the Intersectionality of Assigned Sex at Birth, Race, and Ethnicity on Age of Diagnosis. J Autism Dev Disord;2024 (Jan 30)

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10. Hayward BA. A job analysis of mental health nursing in a school for students with intellectual and developmental disabilities. Int J Ment Health Nurs;2024 (Jan 30)

While schools have become settings for the delivery of mental health supports to students, mental health nursing has not yet described its practice in schools. In the absence of this mental health nursing literature, a quantitative self-reporting job analysis methodology was used to describe the tasks of mental health nursing in a specialist school as an observant-participator in a single-case holistic case study. Additional aims were to compare the results with the general school nursing and the disability nursing literatures and interpret these findings for mental health nursing. Categories of tasks from general school nursing were used to deductively interpret the results. Tasks were recorded across all categories of school nursing. The greatest number of tasks were recorded in the professional performance category, followed by planning, then personnel. The least number of tasks were recorded in the health education and promotion category, followed by practice and treatments, assessment and diagnosis, and management. These results differ from tasks in general school nursing but share similarities with intellectual and developmental disability nursing, particularly related to relationships and communication. Practising effectively as a mental health nurse in a specialist school requires capabilities for working with people with disability, particularly communicating and establishing relationships, in addition to clinical mental health skills. Mental health nursing in schools is an area of practice that requires further exploration to capitalise on emerging policy developments to support student mental health.

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11. Holyfield C, MacNeil S, Caldwell N, O’Neill Zimmerman T, Lorah E, Dragut E, Vucetic S. Leveraging Communication Partner Speech to Automate Augmented Input for Children on the Autism Spectrum Who Are Minimally Verbal: Prototype Development and Preliminary Efficacy Investigation. Am J Speech Lang Pathol;2024 (Jan 30):1-19.

PURPOSE: Augmentative and alternative communication (AAC) technology innovation is urgently needed to improve outcomes for children on the autism spectrum who are minimally verbal. One potential technology innovation is applying artificial intelligence (AI) to automate strategies such as augmented input to increase language learning opportunities while mitigating communication partner time and learning barriers. Innovation in AAC research and design methodology is also needed to empirically explore this and other applications of AI to AAC. The purpose of this report was to describe (a) the development of an AAC prototype using a design methodology new to AAC research and (b) a preliminary investigation of the efficacy of this potential new AAC capability. METHOD: The prototype was developed using a Wizard-of-Oz prototyping approach that allows for initial exploration of a new technology capability without the time and effort required for full-scale development. The preliminary investigation with three children on the autism spectrum who were minimally verbal used an adapted alternating treatment design to compare the effects of a Wizard-of-Oz prototype that provided automated augmented input (i.e., pairing color photos with speech) to a standard topic display (i.e., a grid display with line drawings) on visual attention, linguistic participation, and (for one participant) word learning during a circle activity. RESULTS: Preliminary investigation results were variable, but overall participants increased visual attention and linguistic participation when using the prototype. CONCLUSIONS: Wizard-of-Oz prototyping could be a valuable approach to spur much needed innovation in AAC. Further research into efficacy, reliability, validity, and attitudes is required to more comprehensively evaluate the use of AI to automate augmented input in AAC.

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12. Lobl M. Fragile X Syndrome and Premutation Disorders: New Developments and Treatments. J Dev Behav Pediatr;2024 (Jan 30)

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13. MacKenzie KT, Beck KB, Eack SM, Zeglen KN, Conner CM, Mazefsky CA. Developing a Measure of Key Adult Outcomes in Adults with Developmental Disabilities: Conceptual Model and Item Generation of the REALS (Relationships, Employment, Autonomy, and Life Satisfaction). J Autism Dev Disord;2024 (Jan 30)

Employment, social relationships, and autonomy are priorities to people with intellectual and developmental disabilities (IDDs). However, few validated measures exist to systematically assess these key adult outcomes in this population. This research includes first steps to develop self- and proxy report measures of life outcomes for adults with IDDs-the Relationships, Employment, Autonomy, and Life Satisfaction (REALS). A literature search identified existing adult outcome measures, and comparison of their domains informed initial conceptual model development. External consultants revised the model, and items were generated. Autistic adults (n = 15), adults with other IDDs (n = 7), caregivers of autistic adults (n = 13), and caregivers of adults with other IDDs (n = 10) completed in-depth cognitive interviews to assess comprehension of items and response categories, factors influencing how participants respond to items, and the inclusiveness of the item pool. A final conceptual model was generated with three subdomains (social relationships, employment, and autonomy), including assessment of life satisfaction within each domain. Cognitive interviews revealed that response set restructuring and item-level revisions were needed to capture the complexity of adult life and make the measure more accessible across a range of abilities. This study developed a conceptual model of relationships, work, and autonomy specific to adults with IDDs. Future work will involve collecting data from 800 + self-reporters with IDDs and 800 + caregivers of adults with IDDs to conduct psychometric analyses. Improving measurement in this area is critical to better understanding the needs of adults with IDDs and improving services available to them.

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14. Mohamed Z, Russell A, Palmer M, Simonoff E, Hollocks MJ. Co-designing behavioural activation for depression for autistic adolescents: A case series. Clin Child Psychol Psychiatry;2024 (Jan 29):13591045241229583.

Autistic youth are at high risk of depression, but there are few psychological interventions that have been specifically designed for use with this population. Behavioural activation (BA) is a particularly promising approach for autistic adolescents, having an established evidence-base for the treatment of depression in non-autistic people, and with a strong focus on behavioural, rather than cognitive change, which is a challenge for some autistic people. In this study, we worked with autistic adolescents and clinicians to co-design a BA-informed intervention to be delivered in an online format. We then conducted a pilot case-series with seven autistic adolescents with depression. Our focus was on establishing the acceptability and feasibility of the intervention but clinical outcomes on both self- and parent-reported symptoms of depression and anxiety are also presented. Our results indicate the intervention to be acceptable and feasible for autistic adolescents, with six out of seven participants being retained to the end of the intervention. Qualitative feedback indicated that all participants found the intervention a positive experience and would recommend it to others. Similarly, all participants found the online format acceptable, with 64% preferring this format to face-to-face therapy. Qualitative feedback and suggestions for refinement will also be discussed. Autistic youth are at high risk of depression, but there are few psychological interventions that have been specifically designed for use with this population. Behavioural activation (BA) is a particularly promising approach for autistic adolescents, which has been used previously with non-autistic people. BA-focusses on improving mood through increasing engagement in positive activities and is well suited to being adapted to meet the needs of autistic youth. In this study, we worked with autistic adolescents and clinicians to co-design a BA-informed intervention to be delivered in an online format. We then conducted a pilot case-series with seven autistic adolescents with depression. Our focus was on establishing the acceptability (can participants complete the intervention) and feasibility (can this be done again on a larger scale) of the intervention. Our results indicated that the intervention was acceptable and feasible for autistic adolescents, with six out of seven participants being retained to the end of the intervention. Feedback from young people and their parents indicated that all participants both found the intervention a positive experience and would recommend it to others. Similarly, all participants found the online format acceptable, with 64% preferring this format to face-to-face therapy. Qualitative feedback and suggestions for refinement will also be discussed. eng

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15. Patel K, Fogler J, Sideridis G, Soares N. Profiles of Autistic Youth with and Without Co-occurring Behavioral Health and Neurodevelopmental Disorders: A Latent Class Analysis. J Dev Behav Pediatr;2024 (Jan 30)

OBJECTIVE: Autism spectrum disorder (ASD) diagnosis relies on clinical observation and documentation, but the presence of comorbidities can affect diagnostic validity across clinicians and exacerbate access to timely care. This study used latent class analysis to optimize subgroup identification based on functional level and associated comorbidities using the Behavioral Assessment System for Children, Third Edition (BASC-3), and Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), in a pediatric population referred for autism evaluation. METHODS: This retrospective study reviewed clinical data extracted over a 3-year period (2018-2021). A latent class analysis was used to explore the presence of latent groups guided by the likelihood ratio test and fit indices. Additional analyses contrasted ASD and non-ASD groups on the BASC-3 and Vineland-3 variables. RESULTS: There were 191 included participants (mean age 65.9 months, 76.4% male), of whom over half (60.7%) had an ASD diagnosis. Using 185 cases, the exploratory latent class analysis showed the emergence of 4 distinct subgroups. Composition of classes varied on ASD diagnosis, neurodevelopmental difficulties, behavioral health concerns, and intellectual disability. When contrasting ASD and non-ASD groups, significant between-group differences were observed across Vineland-3 variables and BASC-3 adaptive skills subscales indicating poorer social and adaptive functioning. CONCLUSION: Latent class analysis of commonly used behavioral and adaptive measures can help distinguish between subgroups of pediatric patients referred for ASD evaluations and assist in triage of cases based on severity.

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16. Shim S, Ha S, Choi J, Kwon HK, Cheon KA. Alterations in Plasma Cytokine Levels in Korean Children with Autism Spectrum Disorder. Yonsei Med J;2024 (Feb);65(2):70-77.

PURPOSE: Numerous studies have supported the role of the immune dysfunction in the pathogenesis of autism spectrum disorder (ASD); however, to our knowledge, no study has been conducted on plasma cytokine levels in children with ASD in South Korea. In this study, we aimed to analyze the immunological characteristics of Korean children with ASD through plasma cytokine analysis. MATERIALS AND METHODS: Blood samples were collected from 94 ASD children (mean age 7.1; 81 males and 13 females) and 48 typically developing children (TDC) (mean age 7.3; 30 males and 18 females). Plasma was isolated from 1 mL of blood by clarifying with centrifugation at 8000 rpm at 4℃ for 10 min. Cytokines in plasma were measured with LEGENDplex HU Th cytokine panel (BioLegend, 741028) and LEGENDplex HU cytokine panel 2 (BioLegend, 740102). RESULTS: Among 25 cytokines, innate immune cytokine [interleukin (IL)-33] was significantly decreased in ASD children compared with TDC. In acute phase proteins, tumor necrosis factor α (TNF-α) was significantly increased, while IL-6, another inflammation marker, was decreased in ASD children compared with TDC. The cytokines from T cell subsets, including interferon (IFN)-γ, IL-5, IL-13, and IL-17f, were significantly decreased in ASD children compared to TDC. IL-10, a major anti-inflammatory cytokine, and IL-9, which modulates immune cell growth and proliferation, were also significantly decreased in ASD children compared to TDC. CONCLUSION: We confirmed that Korean children with ASD showed altered immune function and unique cytokine expression patterns distinct from TDC.

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17. Song Y, Zhao Y, Baranova A, Cao H, Yue W, Zhang F. Causal association of attention-deficit/hyperactivity disorder and autism spectrum disorder with post-traumatic stress disorder. Psychiatr Genet;2024 (Jan 23)

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two neurodevelopmental disorders that often result in individuals experiencing traumatic events. However, little is known about the connection between ADHD/ASD and post-traumatic stress disorder (PTSD). This study aimed to investigate the genetic associations between these disorders. METHODS: Genetic correlation analysis was used to examine the genetic components shared between ADHD (38 691 cases and 275 986 controls), ASD (18 381 cases and 27 969 controls) and PTSD (23 212 cases and 151 447 controls). Two-sample Mendelian randomization analyses were employed to explore the bidirectional causal relationships between ADHD/ASD and PTSD. RESULTS: The results of the genetic correlation analysis revealed significant positive correlations of PTSD with ADHD(rg = 0.70) and ASD (rg = 0.34). Furthermore, the Mendelian randomization analysis revealed that genetic liabilities to ADHD [odds ratio (OR) = 1.14; 95% confidence interval (CI), 1.06-1.24; P = 7.88 × 10-4] and ASD (OR = 1.04; CI, 1.01-1.08; P = 0.014) were associated with an increased risk of developing PTSD later in life. However, no evidence supported that genetic liability to PTSD could elevate the risk of ADHD or ASD. CONCLUSION: The findings of this study supported that ADHD and ASD may increase the risk of PTSD, but not vice versa.

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18. Tessarech M, Friocourt G, Marguet F, Lecointre M, Le Mao M, Muñoz Díaz R, Mignot C, Keren B, Héron B, De Bie C, Van Gassen K, Loisel D, Delorme B, Syrbe S, Klabunde-Cherwon A, Jamra RA, Wegler M, Callewaert B, Dheedene A, Zidannes-Marinnes M, Guichet A, Bris C, Van Bogaert P, Biquard F, Lenaers G, Marcorelles P, Ferec C, Gonzalez B, Procaccio V, Vitobello A, Bonneau D, Laquerriere A, Khiati S, Colin E. De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity. Genet Med;2024 (Jan 27):101087.

PURPOSE: Interneuronopathies are a group of neurodevelopmental disorders characterized by deficient migration and differentiation of GABAergic interneurons resulting in a broad clinical spectrum, including autism spectrum disorders, early-onset epileptic encephalopathy, intellectual disability, and schizophrenic disorders. SP9 is a transcription factor belonging to the Krüppel-like factor and specificity protein family, the members of which harbor highly conserved DNA binding domains. SP9 plays a central role in interneuron development and tangential migration, but it has not yet been implicated in a human neurodevelopmental disorder. METHODS: Cases with SP9 variants were collected through international data-sharing networks. To address the specific impact of SP9 variants in silico and in vitro assays were carried out. RESULTS: De novo heterozygous variants in SP9 cause a novel form of interneuronopathy. SP9 missense variants affecting the Glutamate 378 amino acid result in severe epileptic encephalopathy due to hypomorphic and neomorphic DNA-binding effects, whereas SP9 loss-of-function variants result in a milder phenotype with epilepsy, developmental delay, and autism spectrum disorder. CONCLUSION: De novo heterozygous SP9 variants are responsible for a neurodevelopmental disease. Interestingly, variants located in conserved DNA-binding domains of KLF/SP family transcription factors may lead to neomorphic DNA-binding functions resulting in a combination of loss- and gain-of-function effects.

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19. Wang S, Xu Y. RNA structure promotes liquid-to-solid phase transition of short RNAs in neuronal dysfunction. Commun Biol;2024 (Jan 29);7(1):137.

In nucleotide expansion disorders, RNA foci are reportedly associated with neurodegenerative disease pathogeneses. Characteristically, these RNAs exhibit long poly-RNA repeats, such as 47 × CAG, 47 × CUG, or 29 × GGGGCC, usually becoming abnormal pathological aggregations above a critical number of nucleotide repeats. However, it remains unclear whether short, predominantly cellular RNA molecules can cause phase transitions to induce RNA foci. Herein, we demonstrated that short RNAs even with only two repeats can aggregate into a solid-like state via special RNA G-quadruplex structures. In human cells, these solid RNA foci could not dissolve even when using agents that disrupt RNA gelation. The aggregation of shorter RNAs can be clearly observed in vivo. Furthermore, we found that RNA foci induce colocalization of the RNA-binding protein Sam68, a protein commonly found in patients with fragile X-associated tremor/ataxia syndrome, suppressing cell clonogenicity and eventually causing cell death. Our results suggest that short RNA gelation promoted by specific RNA structures contribute to the neurological diseases, which disturb functional cellular processes.

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20. Zeng Z, Wang Z, Yu P, Wang Y, Pei Y, Dai Y, Liu Y, Yang Y. The Association between Assisted Reproductive Technologies and Neurodevelopmental Disorders in Offspring: An Overview of Current Evidence. J Integr Neurosci;2024 (Jan 16);23(1):15.

The utilization of assisted reproductive technologies (ART) is on the rise, resulting in a growing population of ART-conceived offspring. The health concerns of this unique population have attracted significant attention. During ART procedures, gametes and early-stage embryos are exposed to various non-physiological conditions, such as manipulation, culture media, and cryopreservation, which may disrupt embryonic development and potentially impact the health of offspring. Notably, the potential impact of ART on neurodevelopment and its association with an increased risk of neurodevelopmental disorders (NDD) later in life remains a subject of debate. This review aims to summarize the current research advancements concerning the effects of ART on neurodevelopment, specifically focusing on the evidence of the relationship between ART, epigenetic modifications, and NDD, including autism spectrum disorder, intellectual disability, attention deficit hyperactivity disorder, and cerebral palsy. Future studies should prioritize large sample sizes, rigorous adjustment for confounding factors, and the use of interdisciplinary approaches to effectively monitor the neurodevelopmental outcomes of ART-conceived children.

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21. Zhang S, Han F, Wang Q, Fan F. Probiotics and Prebiotics in the Treatment of Autism Spectrum Disorder: A Narrative Review. J Integr Neurosci;2024 (Jan 22);23(1):20.

More than half of the patients with autism spectrum disorder (ASD) have gastrointestinal (GI) comorbidities, such as constipation, indigestion, abdominal pain, and diarrhea. Recent studies suggest prescribing probiotics and prebiotics in ASD could relieve GI disturbances and behavioral issues. This narrative review generalizes the research progress on probiotic and prebiotic therapies for ASD over the past 5 years and further discusses the underlying mechanisms of interaction between probiotics and prebiotics with ASD. Preliminary evidence has demonstrated the beneficial effects of probiotics and prebiotics on GI problems, autism-related behavioral disorders, and gut microbiome composition; the mechanism of probiotics and prebiotics in the treatment of ASD is mediated through inflammatory signaling pathways, metabolic pathways, neuronal signaling pathways, and the involvement of the vagus nerve. However, the results are inconclusive and mainly generated by animal experiments. Overall, the present review recommends further standardization of clinical studies to draw more robust evidence for prescribing probiotics and prebiotics in ASD.

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