1. Correction to « Sleep problems in autism: Sex differences in the school-age population ». Autism Res;2024 (Jan 14)

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2. Al Awaji NN, Al-Taleb SM, Albagawi TO, Alshammari MT, Sharar FA, Mortada EM. Evaluating Parents’ Concerns, Needs, and Levels of Satisfaction with the Services Provided for ASD Children in Saudi Arabia. J Multidiscip Healthc;2024;17:123-146.

BACKGROUND: Supporting children with autism spectrum disorder (ASD) and their parents is vital in improving their children’s abilities and their parents’ ability to care for them. Thus, parents’ perceptions of and levels of satisfaction with the services provided for their children must be assessed. AIM: This study aimed to understand parents’ perceptions of and satisfaction with the speech-language services (SLS) provided for ASD children in different health facilities in Saudi Arabia. METHODS: This cross-sectional study included 109 parents of ASD children. The survey included five sections dealing with (1) general information about the child; (2) assessment of the child’s ASD characteristics (including their age when diagnosed, when they first noticed symptoms, and their speech, language, and communication abilities); (3) the reasons for enrollment in SLS sessions; (4) questions about SLS; and (5) parents’ perceptions of SLS, satisfaction with the service, descriptions of their children’s progress, and the respect and support they received. RESULTS: Parents’ satisfaction levels were significantly higher when they had easy access to SLS, sufficient information and support, proper training in applying therapy exercises at home, and perceived respect and support from speech and language pathologists (SLPs). The reasons for discontinuing SLS included high session costs, the need for initial behavioral sessions, the lack of qualified SLPs, the end of the sessions, the lack of improvement, the nonavailability of specialized centers, and parents’ dependence on home training only. They also sought opportunities for work and education, continuous and intensive SLS sessions, reduced costs, centers for adults with ASD, and accessible schools. Parents’ main concerns were their children’s poor speech and language skills, independence, and social acceptance. CONCLUSION AND IMPLICATIONS: The study highlighted the importance of understanding parents’ experiences with SLS, identifying the factors that enhance SLS use by ASD children, and improving parents’ satisfaction with such services.

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3. Albekairi TH, Alanazi MM, Ansari MA, Nadeem A, Attia SM, Bakheet SA, Al-Mazroua HA, Aldossari AA, Almanaa TN, Alwetaid MY, Alqinyah M, Alnefaie HO, Ahmad SF. Cadmium exposure exacerbates immunological abnormalities in a BTBR T(+) Itpr3(tf)/J autistic mouse model by upregulating inflammatory mediators in CD45R-expressing cells. J Neuroimmunol;2024 (Jan 15);386:578253.

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by behavior, learning, communication, and social interaction abnormalities in various situations. Individuals with impairments usually exhibit restricted and repetitive actions. The actual cause of ASD is yet unknown. It is believed, however, that a mix of genetic and environmental factors may play a role in its development. Certain metals have been linked to the development of neurological diseases, and the prevalence of ASD has shown a positive association with industrialization. Cadmium chloride (Cd) is a neurotoxic chemical linked to cognitive impairment, tremors, and neurodegenerative diseases. The BTBR T(+) Itpr3(tf)/J (BTBR) inbred mice are generally used as a model for ASD and display a range of autistic phenotypes. We looked at how Cd exposure affected the signaling of inflammatory mediators in CD45R-expressing cells in the BTBR mouse model of ASD. In this study, we looked at how Cd affected the expression of numerous markers in the spleen, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. Furthermore, we investigated the effect of Cd exposure on the expression levels of numerous mRNA molecules in brain tissue, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. The RT-PCR technique was used for this analysis. Cd exposure increased the number of CD45R(+)IFN-γ(+), CD45R(+)IL-6(+), CD45R(+)NF-κB p65(+), CD45R(+)GM-CSF(+), CD45R(+)GM-CSF(+), CD45R(+)iNOS(+), and CD45R(+)Notch1(+) cells in the spleen of BTBR mice. Cd treatment also enhanced mRNA expression in brain tissue for IFN-γ, IL-6, NF-κB, GM-CSF, iNOS, MCP-1, and Notch1. In general, Cd increases the signaling of inflammatory mediators in BTBR mice. This study is the first to show that Cd exposure causes immune function dysregulation in the BTBR ASD mouse model. As a result, our study supports the role of Cd exposure in the development of ASD.

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4. Azizi M, Imannezhad S, Moradpoor M, Alaghbandian E, Saeidi P, Sobhani M, Maleki MM, Jahangiri S, Shojaei B, Mohammadi Y. Increasing the tolerance of mothers with children with autism: the effectiveness of cognitive therapy based on mindfulness – experimental research. Ann Med Surg (Lond);2024 (Jan);86(1):207-211.

INTRODUCTION AND IMPORTANCE: Autism spectrum disorder significantly impacts the life and psychosocial health of the family, resulting in high levels of anxiety, stress, isolation, and indecisiveness among parents. This study aimed to determine the effectiveness of cognitive therapy based on mindfulness in increasing the tolerance of mothers of children with autism. CASE PRESENTATION: The study used a semi-experimental pre-test-post-test design with a control group. The study population comprised mothers referred to autism centers in Tehran. Eighty mothers were randomly divided into two groups, with 40 in each group. The Connor and Davidson Resilience Scale was used to measure the level of tolerance in both groups in the pre-test and post-test stages. The experimental group underwent cognitive therapy group therapy based on mindfulness, comprising eight sessions of 120 min. On the other hand, the control group did not receive any intervention. CLINICAL DISCUSSION: The results of the study showed that the tolerance scores of the experimental group significantly increased after the intervention, in both the post-test and follow-up stages. CONCLUSION: Therefore, the results of this research emphasize the importance of using this intervention in increasing the tolerance of mothers of children with autism spectrum disorder and creating new horizons in the clinical interventions of these people.

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5. Brown KA, Donise KR, Cancilliere MK, Aluthge DP, Chen ES. Characterizing Autism Spectrum Disorder and Predicting Suicide Risk for Pediatric Psychiatric Emergency Services Encounters. AMIA Annu Symp Proc;2023;2023:864-873.

Individuals diagnosed with autism spectrum disorder (ASD) are at a higher risk for mental health concerns including suicidal thoughts and behaviors (STB). Limited studies have focused on suicidal risk factors that are more prevalent or unique to the population with ASD. This study sought to characterize and classify youth presenting to the psychiatric emergency department (ED) for a chief complaint of STB. The results of this study validated that a high number of patients with ASD present to the ED with STB. There were important differences in clinical characteristics to those with ASD versus those without. Clinical features that showed important impact in predicting high suicide risk in the ASD cases include elements of the mental status exam such as affect, trauma symptoms, abuse history, and auditory hallucinations. Focused attention is needed on these unique differences in ASD cases so that suicide risk level can be appropriately and promptly addressed.

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6. Cardon G, Cate M, Cordingley S, Bown B. Auditory Brainstem Response in Autistic Children: Implications for Sensory Processing. Hearing Balance Commun;2023;21(3):224-232.

PURPOSE: Autistic individuals frequently experience sensory processing difficulties. Such difficulties can significantly impact important functions and quality of life. We are only beginning to understand the neural mechanisms of atypical sensory processing. However, one established way to measure aspects of auditory function is the auditory brainstem response (ABR). While ABR has been primarily hypothesized thus far as a means of early detection/diagnosis in autism, it has the potential to aid in examining sensory processing in this population. METHOD: Thus, we investigated standard ABR waveform characteristics in age-matched groups of autistic and typically developing children during various stimulus and intensity conditions. We also examined within ear waveform cross correlations and inter-aural cross correlations (IACC) to assess replicability and synchrony of participants’ ABRs, which was a novel approach to ABR analysis in this population. RESULTS: We observed longer peak latencies (esp. wave III and V) and interpeak latencies in the autism and typically developing groups in different conditions. There were no statistically significant results in cross correlation or IACC. CONCLUSIONS: These results suggest that brainstem auditory function may differ slightly, but is mostly similar, between autistic and typically developing children. We discuss these findings in terms of their implications for sensory processing and future utility.

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7. Chadwick W, Angulo-Herrera I, Cogram P, Deacon RJM, Mason DJ, Brown D, Roberts I, O’Donovan DJ, Tranfaglia MR, Guilliams T, Thompson NT. A novel combination treatment for fragile X syndrome predicted using computational methods. Brain Commun;2024;6(1):fcad353.

Fragile X syndrome is a neurodevelopmental disorder caused by silencing of the fragile X messenger ribonucleotide gene. Patients display a wide spectrum of symptoms ranging from intellectual and learning disabilities to behavioural challenges including autism spectrum disorder. In addition to this, patients also display a diversity of symptoms due to mosaicism. These factors make fragile X syndrome a difficult syndrome to manage and suggest that a single targeted therapeutic approach cannot address all the symptoms. To this end, we utilized Healx’s data-driven drug discovery platform to identify a treatment strategy to address the wide range of diverse symptoms among patients. Computational methods identified the combination of ibudilast and gaboxadol as a treatment for several pathophysiological targets that could potentially reverse multiple symptoms associated with fragile X syndrome. Ibudilast is an approved broad-spectrum phosphodiesterase inhibitor, selective against both phosphodiesterase 4 and phosphodiesterase 10, and has demonstrated to have several beneficial effects in the brain. Gaboxadol is a GABA(A) receptor agonist, selective against the delta subunit, which has previously displayed encouraging results in a fragile X syndrome clinical trial. Alterations in GABA and cyclic adenosine monophosphate metabolism have long since been associated with the pathophysiology of fragile X syndrome; however, targeting both pathways simultaneously has never been investigated. Both drugs have a good safety and tolerability profile in the clinic making them attractive candidates for repurposing. We set out to explore whether the combination of ibudilast and gaboxadol could demonstrate therapeutic efficacy in a fragile X syndrome mouse model. We found that daily treatment with ibudilast significantly enhanced the ability of fragile X syndrome mice to perform a number of different cognitive assays while gaboxadol treatment improved behaviours such as hyperactivity, aggression, stereotypy and anxiety. Importantly, when ibudilast and gaboxadol were co-administered, the cognitive deficits as well as the aforementioned behaviours were rescued. Moreover, this combination treatment showed no evidence of tolerance, and no adverse effects were reported following chronic dosing. This work demonstrates for the first time that by targeting multiple pathways, with a combination treatment, we were able to rescue more phenotypes in a fragile X syndrome mouse model than either ibudilast or gaboxadol could achieve as monotherapies. This combination treatment approach holds promise for addressing the wide spectrum of diverse symptoms in this heterogeneous patient population and may have therapeutic potential for idiopathic autism.

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8. Cui J, Zhai Z, Wang S, Song X, Qiu T, Yu L, Zhai Q, Zhang H. The role and impact of abnormal vitamin levels in autism spectrum disorders. Food Funct;2024 (Jan 15)

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder with a predominance of social behavioral disorders, has increased dramatically in various countries in recent decades. The interplay between genetic and environmental factors is believed to underlie ASD pathogenesis. Recent analyses have shown that abnormal vitamin levels in early life are associated with an increased risk of autism. As essential substances for growth and development, vitamins have been shown to have significant benefits for the nervous and immune systems. However, it is unknown whether certain vitamin types influence the emergence or manifestation of ASD symptoms. Several studies have focused on vitamin levels in children with autism, and neurotypical children have provided different insights into the types of vitamins and their intake. Here, we review the mechanisms and significance of several vitamins (A, B, C, D, E, and K) that are closely associated with the development of ASD in order to prevent, mitigate, and treat ASD. Efforts have been made to discover and develop new indicators for nutritional assessment of children with ASD to play a greater role in the early detection of ASD and therapeutic remission after diagnosis.

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9. Dell’Osso L, Amatori G, Giovannoni F, Massimetti E, Cremone IM, Carpita B. Rumination and altered reactivity to sensory input as vulnerability factors for developing post-traumatic stress symptoms among adults with autistic traits. CNS Spectr;2024 (Jan 15):1-31.

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10. Evans MM, Kim J, Abel T, Nickl-Jockschat T, Stevens HE. Developmental Disruptions of the Dorsal Striatum in Autism Spectrum Disorder. Biol Psychiatry;2024 (Jan 15);95(2):102-111.

Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental condition characterized by social and communication deficits as well as patterns of restricted, repetitive behavior. Abnormal brain development has long been postulated to underlie ASD, but longitudinal studies aimed at understanding the developmental course of the disorder have been limited. More recently, abnormal development of the striatum in ASD has become an area of interest in research, partially due to overlap of striatal functions and deficit areas in ASD, as well as the critical role of the striatum in early development, when ASD is first detected. Focusing on the dorsal striatum and the associated symptom domain of restricted, repetitive behavior, we review the current literature on dorsal striatal abnormalities in ASD, including studies on functional connectivity, morphometry, and cellular and molecular substrates. We highlight that observed striatal abnormalities in ASD are often dynamic across development, displaying disrupted developmental trajectories. Important findings include an abnormal trajectory of increasing corticostriatal functional connectivity with age and increased striatal growth during childhood in ASD. We end by discussing striatal findings from animal models of ASD. In sum, the studies reviewed here demonstrate a key role for developmental disruptions of the dorsal striatum in the pathogenesis of ASD. Directing attention toward these findings will improve our understanding of ASD and of how associated deficits may be better addressed.

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11. Gao J, Xu Y, Li Y, Lu F, Wang Z. Comprehensive exploration of multi-modal and multi-branch imaging markers for autism diagnosis and interpretation: insights from an advanced deep learning model. Cereb Cortex;2024 (Jan 13)

Autism spectrum disorder is a complex neurodevelopmental condition with diverse genetic and brain involvement. Despite magnetic resonance imaging advances, autism spectrum disorder diagnosis and understanding its neurogenetic factors remain challenging. We propose a dual-branch graph neural network that effectively extracts and fuses features from bimodalities, achieving 73.9% diagnostic accuracy. To explain the mechanism distinguishing autism spectrum disorder from healthy controls, we establish a perturbation model for brain imaging markers and perform a neuro-transcriptomic joint analysis using partial least squares regression and enrichment to identify potential genetic biomarkers. The perturbation model identifies brain imaging markers related to structural magnetic resonance imaging in the frontal, temporal, parietal, and occipital lobes, while functional magnetic resonance imaging markers primarily reside in the frontal, temporal, occipital lobes, and cerebellum. The neuro-transcriptomic joint analysis highlights genes associated with biological processes, such as « presynapse, » « behavior, » and « modulation of chemical synaptic transmission » in autism spectrum disorder’s brain development. Different magnetic resonance imaging modalities offer complementary information for autism spectrum disorder diagnosis. Our dual-branch graph neural network achieves high accuracy and identifies abnormal brain regions and the neuro-transcriptomic analysis uncovers important genetic biomarkers. Overall, our study presents an effective approach for assisting in autism spectrum disorder diagnosis and identifying genetic biomarkers, showing potential for enhancing the diagnosis and treatment of this condition.

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12. Ghosh S, Kaushik JS. Evolution in Diagnostics of Intellectual Developmental Disorders. Indian Pediatr;2024 (Jan 15);61(1):75-77.

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13. Gonçalves CL, Doifode T, Rezende VL, Costa MA, Rhoads JM, Soutullo CA. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sci;2024 (Jan 15);337:122357.

The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.

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14. Green J, Shaughnessy N. Autistic phenomenology: past, present, and potential future. Front Psychol;2023;14:1287209.

We are now at a transition point in autism conceptualisation, science, and clinical practise, where phenomenology could play a key role. This paper takes a broad view of the history of phenomenological perspectives on the autism concept and how this has evolved over time, including contemporaneous theory and methods. Early inquiry from a clinical perspective within the tradition of classical continental phenomenology, linked closely to the consideration of schizophrenia, is contrasted with emerging observations of child development and a period in the second half of the twentieth century of scientific inquiry into a behavioural autistic phenotype where there was little or no phenomenological aspect; a phenotype that has determined the recent scientific and clinical conceptualisation of autism within current nosology. We then mark a more recent reawakening of interdisciplinary interest in subjective experience and phenomenological inquiry, which itself coincides with the increasing prominence and salience of the neurodiversity movement, autistic advocacy, and critical autism studies. We review this emerging phenomenological work alongside a contemporaneous clinical phenomenology perspective and representations of autistic experience from within the extensive literature (including life writing) from autistic people themselves; all perspectives that we argue need now be brought into juxtaposition and dialogue as the field moves forward. We argue from this for a future which could build on such accounts at a greater scale, working toward a more co-constructed, systematic, representative, and empirical autistic phenomenology, which would include citizen and participatory science approaches. Success in this would not only mean that autistic experience and subjectivity would be re-integrated back into a shared understanding of the autism concept, but we also argue that there could be the eventual goal of an enhanced descriptive nosology, in which key subjective and phenomenological experiences, discriminating for autism, could be identified alongside current behavioural and developmental descriptors. Such progress could have major benefits, including increased mutual empathy and common language between professionals and the autistic community, the provision of crucial new foci for research through aspects of autistic experience previously neglected, and potential new supportive innovations for healthcare and education. We outline a programme and methodological considerations to this end.

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15. Hnoonual A, Plong-On O, Worachotekamjorn J, Charalsawadi C, Limprasert P. Clinical and molecular characteristics of FMR1 microdeletion in patient with fragile X syndrome and review of the literature. Clin Chim Acta;2024 (Jan 15);553:117728.

BACKGROUND: Fragile X syndrome (FXS) is mainly caused by FMR1 CGG repeat expansions. Other types of mutations, particularly deletions, are also responsible for FXS phenotypes, however these mutations are often missed by routine clinical testing. MATERIALS AND METHODS: Molecular diagnosis in cases of suspected FXS was a combination of PCR and Southern blot. Measurement of the FMRP protein level was useful for detecting potentially deleterious impact. RESULTS: PCR analysis and Southern blot revealed a case with premutation and suspected deletion alleles. Sanger sequencing showed that the deletion involved 313 bp upstream of repeats and some parts of CGG repeat tract, leaving transcription start site. FMRP was detected in 5.5 % of blood lymphocytes. CONCLUSION: According to our review of case reports, most patients carrying microdeletion and full mutation had typical features of FXS. To our knowledge, our case is the first to describe mosaicism of a premutation and microdeletion in the FMR1 gene. The patient was probably protected from the effects of the deletion by mosaicism with premutation allele, leading to milder phenotype. It is thus important to consider appropriate techniques for detecting FMR1 variants other than repeat expansions which cannot be detected by routine FXS diagnosis.

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16. Kauley N, John JR, Barr KR, Wu WT, Grove R, Masi A, Eapen V. Predicting Communication Skills Outcomes for Preschool Children with Autism Spectrum Disorder Following Early Intervention. Neuropsychiatr Dis Treat;2024;20:35-48.

PURPOSE: This study aims to assess changes in the receptive and expressive language skills and to determine if the baseline characteristics such as communication, cognitive and motor skills, predict outcomes in preschool children with Autism Spectrum Disorder (ASD) following early intervention. METHODS: We recruited 64 children participating in the Early Start Denver Model (ESDM) early intervention program at an Autism Specific Early Learning and Care Center (ASELCC) in Australia. Baseline characteristics across various developmental domains was measured using the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd Edition (VABS-II), and the ESDM Curriculum Checklist. Linear mixed-effects models were used to examine the effects of the intervention on outcomes. Fixed-effects such as time, groups (verbal and minimally verbal), and time-by-group interactions were assessed whilst adjusting for covariates. Further, multiple linear regression models were used to determine if the baseline characteristics were significant predictors of the outcomes following the early intervention. RESULTS: Among the 64 children who participated in this study, 38 children were verbal, whereas 26 were deemed to have minimal verbal skills. The mean age of the sample was 4.1 years with a significant male predilection (83%) and from a culturally and linguistically diverse (CALD) background (64%). Findings of the linear mixed effects model showed significant within and between group differences in the ESDM subscales, indicating higher magnitude of changes in the verbal group compared to the minimally verbal group. Finally, the multiple linear regression models suggested that baseline MSEL visual reception and expressive language scores were predictive of changes in the ESDM receptive and expressive communication scores. CONCLUSION: Understanding a child’s baseline skill levels may provide valuable clues regarding what interventions would work best, or which interventions may be less suitable for individual preschool-aged children with ASD.

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17. Kolhe PD, Sharath HV, Thakre VM, Ankar P. Multimodal Physiotherapy Approach for Autism With Speech Impairment and Attention Deficit: A Case Report. Cureus;2023 (Dec);15(12):e50547.

Autism is a disorder distinguished by significant challenges in social interaction and communication coupled with repetitive and stereotypical patterns of behavior and activities. Deficits in social interaction and language development become apparent before age three. In children, this condition is referred to as autism spectrum disorder (ASD). Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity. Individuals with ADHD may struggle with sustaining attention, organizing tasks, and completing assignments. They may exhibit hyperactive behaviors such as fidgeting, difficulty staying seated, and impulsive actions like interrupting others. ADHD can significantly impact daily functioning and is often diagnosed in childhood, with symptoms potentially persisting into adulthood. The disorder has three main subtypes: predominantly inattentive, predominantly hyperactive-impulsive, and combined presentation. Treatment typically involves a combination of behavioral interventions, psychoeducation, and, in some cases, medication, aiming to provide support and strategies for individuals to manage their symptoms effectively in various aspects of life. Cognitive impairment in ASD varies, meaning it could be at the sensory perception level of cognitive processing, learning, and memory. The goal of the training intervention was to control physiological arousal, enhance awareness, keep annoyance from getting worse, and encourage self-regulation abilities. In this case report, we discuss the approach of multimodal physiotherapy for autism with speech impairment and attention deficit. Furthermore, physiotherapy needs to find a position in the new mental health care paradigm in order to contribute to mental health care.

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18. Lee JK. Mapping the Intrinsic Structural Connectivity Landscape in Autism. Biol Psychiatry;2024 (Jan 15);95(2):100-101.

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19. Leyhausen J, Schäfer T, Gurr C, Berg LM, Seelemeyer H, Pretzsch CM, Loth E, Oakley B, Buitelaar JK, Beckmann CF, Floris DL, Charman T, Bourgeron T, Banaschewski T, Jones EJH, Tillmann J, Chatham C, Murphy DG, Ecker C. Differences in Intrinsic Gray Matter Connectivity and Their Genomic Underpinnings in Autism Spectrum Disorder. Biol Psychiatry;2024 (Jan 15);95(2):175-186.

BACKGROUND: Autism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs. METHODS: Here, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group differences were assessed using a general linear model. A gene expression decoding analysis based on the Allen Human Brain Atlas was performed to link neuroanatomical differences to putative underpinnings. RESULTS: Group differences in global and local wiring costs were predominantly observed in medial and lateral prefrontal brain regions, in inferior temporal regions, and at the left temporoparietal junction. The resulting neuroanatomical patterns were enriched for genes that had been previously implicated in the etiology of autism at genetic and transcriptomic levels. CONCLUSIONS: Based on intrinsic gray matter connectivity, the current study investigated the complex neuroanatomy of autism and linked between-group differences to putative genomic and/or molecular mechanisms to parse the heterogeneity of autism and provide targets for future subgrouping approaches.

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20. Lin F, Jun L, Ziqi W, Zhang T, Lu T, Jiang M, Yang K, Jia M, Zhang D, Wang L. Replication of previous autism-GWAS hits suggests the association between NAA1, SORCS3, and GSDME and autism in the Han Chinese population. Heliyon;2024 (Jan 15);10(1):e23677.

BACKGROUND: Autism is a severe neurodevelopmental disorder characterized by social interaction deficits, impairments in communication, and restricted and repetitive stereotyped behavior and activities. Family and twin studies suggested an essential role of genetic factors in the etiology of autism spectrum disorder (ASD). Also, other studies found SORCS3 and GSDME (DFNA5) might be involved in brain development and susceptible to ASD. METHODS: In this study, 17 genome-wide significant SNPs reported in previous ASD genome-wide association studies (GWAS) and 7 SNPs in strong linkage disequilibrium with known ASD GWAS hits were selected to investigate the association between these SNPs and autism in the Han Chinese population. Then, 10 tagSNPs in SORCS3 and 11 tagSNPs in GSDME were selected to analyze the association between these SNPs and autism. The selected 24 SNPs and tagSNPs were genotyped using the Agena MassARRAY SNP genotyping assay in 757 Han Chinese autism trios. RESULTS: Rs1484144 in NAA11 was significantly associated with autism; significance remained after the Bonferroni correction (P < 0.0022). Also, rs79879286, rs12154597, and rs12540919 near GSDME, as well as rs9787523 and rs3750261 in SORCS3, were nominally associated with autism. CONCLUSION: Our study suggests that rs1484144 in NAA11 is a significant SNP for autism in the Han Chinese population, while SORCS3 and GSDME might be the susceptibility genes for autism in this population.

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21. Luyster R, Leiwant I, Arunachalam S. Frequency, Form and Function of Dyadic Questions in Children with Autism: A CHILDES corpus study. Commun Disord Q;2023 (May);44(3):163-172.

Children’s questions to their caregivers – and caregivers’ questions to their children – play an important role in child development. For children on the autism spectrum, who often experience cognitive, linguistic and social difficulties, prior research on questions has resulted in inconsistent and incomplete findings. The present study characterized the frequency, form, and function of queries posed by children on the autism spectrum (n = 12), non-spectrum peers (n =20), and parents using the Nadig ASD English Corpus in the Child Language Data Exchange System (CHILDES). Results suggested that children on the autism spectrum and their caregivers produced fewer questions than non-spectrum dyads; however, whereas wh- questions were under-represented in the repertoire of children on the spectrum, they were over-represented in the repertoire of their parents. Finally, question function was similarly diverse for parents and children across groups. These findings offer important clinical implications for question-asking interventions targeting this population.

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22. Mariano V, Kanellopoulos AK, Ricci C, Di Marino D, Borrie SC, Dupraz S, Bradke F, Achsel T, Legius E, Odent S, Billuart P, Bienvenu T, Bagni C. Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization. Biol Psychiatry;2024 (Jan 15);95(2):161-174.

BACKGROUND: 15q11.2 deletions and duplications have been linked to autism spectrum disorder, schizophrenia, and intellectual disability. Recent evidence suggests that dysfunctional CYFIP1 (cytoplasmic FMR1 interacting protein 1) contributes to the clinical phenotypes observed in individuals with 15q11.2 deletion/duplication syndrome. CYFIP1 plays crucial roles in neuronal development and brain connectivity, promoting actin polymerization and regulating local protein synthesis. However, information about the impact of single nucleotide variants in CYFIP1 on neurodevelopmental disorders is limited. METHODS: Here, we report a family with 2 probands exhibiting intellectual disability, autism spectrum disorder, spastic tetraparesis, and brain morphology defects and who carry biallelic missense point mutations in the CYFIP1 gene. We used skin fibroblasts from one of the probands, the parents, and typically developing individuals to investigate the effect of the variants on the functionality of CYFIP1. In addition, we generated Drosophila knockin mutants to address the effect of the variants in vivo and gain insight into the molecular mechanism that underlies the clinical phenotype. RESULTS: Our study revealed that the 2 missense variants are in protein domains responsible for maintaining the interaction within the wave regulatory complex. Molecular and cellular analyses in skin fibroblasts from one proband showed deficits in actin polymerization. The fly model for these mutations exhibited abnormal brain morphology and F-actin loss and recapitulated the core behavioral symptoms, such as deficits in social interaction and motor coordination. CONCLUSIONS: Our findings suggest that the 2 CYFIP1 variants contribute to the clinical phenotype in the probands that reflects deficits in actin-mediated brain development processes.

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23. Piri F, Salmani ME, Sepehri H. Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of orexin receptor. Ann Med Surg (Lond);2024 (Jan);86(1):166-171.

INTRODUCTION: Autism spectrum disorder (ASD) is a disabling psychiatric disease characterized by impairments in communication and social skills. The pathophysiology of autism is complex and not fully known. Considering the incidence of sleep disorders in individuals with ASD and the important role of orexin in sleep, it is possible to hypothesize that an alteration of the orexinergic system could be implicated in the pathogenesis of autism symptoms. The present study was conducted to investigate the effect of suvorexant [dual orexin receptor antagonists (DORAs)] on autism-like behavior in prenatally valproic acid (VPA)-exposed rats]. METHODS: Wistar female rats were administered VPA [600 mg/kg, intraperitoneally (i.p.)] or normal saline (10 ml/kg, i.p.; vehicle control) on gestational day 12.5. Thirty-two male offspring were divided into four groups: Control, VPA, Suvorexant+VPA, and VPA+Risperidone. The pups were given suvorexant [20 ml/kg, by mouth/orally (p.o.)] or risperidone (1 ml/kg, p.o.) daily from postnatal day (PND) (40-54). The offspring were tested for repetitive behaviors and cognitive ability with a Y-maze task on PND 55, and social interaction was assessed by play behavior in the open field on PND 56. And anxiety with using the three-chamber social assay on PND 56. RESULTS: In the Y-maze apparatus, spontaneous alteration significantly decreased in the prenatal VPA-treated rats compared to control rats showing autistic-like behavior, and 2-week suvorexant increased the alternation, indicating the beneficial effect of suvorexant. Prenatal treatment with VPA, impaired play behavior (sniffing, grooming, and darting), and increased anxiety-related behavior. Suvorexant treatment attenuated the problems in male offspring’s social behavior. CONCLUSION: Our results showed that suvorexant improved ASD-associated behaviors in the VPA-treated rats, and the orexinergic system may be associated with the pathogenesis of autism symptoms.

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24. Procyshyn TL, Tsompanidis A, Baron-Cohen S. Embracing evolutionary theories of autism: Implications for psychiatry. Acta Psychiatr Scand;2024 (Feb);149(2):85-87.

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25. Rojas-Velazquez D, Kidwai S, Kraneveld AD, Tonda A, Oberski D, Garssen J, Lopez-Rincon A. Methodology for biomarker discovery with reproducibility in microbiome data using machine learning. BMC Bioinformatics;2024 (Jan 15);25(1):26.

BACKGROUND: In recent years, human microbiome studies have received increasing attention as this field is considered a potential source for clinical applications. With the advancements in omics technologies and AI, research focused on the discovery for potential biomarkers in the human microbiome using machine learning tools has produced positive outcomes. Despite the promising results, several issues can still be found in these studies such as datasets with small number of samples, inconsistent results, lack of uniform processing and methodologies, and other additional factors lead to lack of reproducibility in biomedical research. In this work, we propose a methodology that combines the DADA2 pipeline for 16s rRNA sequences processing and the Recursive Ensemble Feature Selection (REFS) in multiple datasets to increase reproducibility and obtain robust and reliable results in biomedical research. RESULTS: Three experiments were performed analyzing microbiome data from patients/cases in Inflammatory Bowel Disease (IBD), Autism Spectrum Disorder (ASD), and Type 2 Diabetes (T2D). In each experiment, we found a biomarker signature in one dataset and applied to 2 other as further validation. The effectiveness of the proposed methodology was compared with other feature selection methods such as K-Best with F-score and random selection as a base line. The Area Under the Curve (AUC) was employed as a measure of diagnostic accuracy and used as a metric for comparing the results of the proposed methodology with other feature selection methods. Additionally, we use the Matthews Correlation Coefficient (MCC) as a metric to evaluate the performance of the methodology as well as for comparison with other feature selection methods. CONCLUSIONS: We developed a methodology for reproducible biomarker discovery for 16s rRNA microbiome sequence analysis, addressing the issues related with data dimensionality, inconsistent results and validation across independent datasets. The findings from the three experiments, across 9 different datasets, show that the proposed methodology achieved higher accuracy compared to other feature selection methods. This methodology is a first approach to increase reproducibility, to provide robust and reliable results.

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26. Slater H, Yin Z, Walsh CG. Characterization of Adult Patients with Autism Spectrum Disorder that Use Patient Portal. AMIA Annu Symp Proc;2023;2023:1267-1276.

Patients with autism spectrum disorder (ASD) access healthcare frequently, yet little is known about their interactions with patient portals. To describe adults with ASD using patient portal, we conducted regression analyses of visit history, demographics, co-occurring conditions and diagnoses, and patient portal use to determine factors most indicative of whether a patient 1) has sent at least one message (via patient or proxy) and 2) has at least one message sent on their behalf via a proxy account after they turned 18 years old. The 2,412-person cohort had 996 (41.3%) patients who had sent at least one message on their account with 129 (5.3%) of patients having at least one proxy message. This study found that adults with ASD are less likely to use messaging functionality and more likely to have a message sent via proxy than other patient populations. Comorbid mental illness was correlated with using messaging functionality.

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27. Sługocka A, Przybyła MA, Barski JJ. Early development of the Tsc1 Purkinje cell specific mouse knockouts. Acta Neurobiol Exp (Wars);2023 (Dec 12);83(4):404-413.

Tsc1 is a gene which expression results in hamartin, a protein involved in regulation of the mTOR1 pathway. Inactivation of Tsc1 gives rise to hyperactivation of the mTOR1 machinery, increased proliferation and growth of cells with subsequent cell degeneration and cell death. In humans, mutations of Tsc1 result in an inherited disorder ‑ tuberous sclerosis complex (TSC) with the concomitant multiorgan non‑malignant tumors (tubers), epileptic seizures and autistic‑like manifestations. General mouse knock‑outs, homozygous for the inactivated Tsc1 alleles do not survive and die at early embryonal stages. To circumvent this problem, we utilized the Cre/loxP system and removed Tsc1 specifically in Purkinje cells using the pcp2/L7Cre mouse strain and the Tsc1tmDjk/J strains. Because of the published results showing the autistic‑like symptoms after the same crossbred, we have decided to look closer at the early postnatal period of these mutants. Surprisingly no evidence of any behavioral alterations were found, including the ultrasonic vocalizations of newborns. We decided to focus more attention on the interpretation of data, including a more detailed statistical evaluation of our results.

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