1. Brunoni AR, Santos JM. Anodal transcranial direct-current stimulation for autism spectrum disorder: A promising approach?. Dev Med Child Neurol;2024 (Feb 15)

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2. Chaki HB, Faran Y. The Effect of Family Characteristics on the Functioning of a Child with an Autistic Spectrum Disorder in Bedouin Society in Israel. J Autism Dev Disord;2024 (Feb 15)

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by difficulties in communication and social-emotional interaction. It is associated with an increase of parental stress and poor family functioning, both of which are harmful for a child’s functioning and adaptive behavior. An important source of support to parents are grandparents, especially in traditional populations. One such population is the Bedouin population. The present study tested the association between emotional support from mother and mother-in-law to the adaptive behavior of children with ASD, and whether this relation is serially mediated by family functioning and satisfaction in life as reported by Bedouin mothers of children with ASD. 100 mothers of children with ASD fulfilled a questionnaire about emotional support from their mothers and mother-in-law, family functioning, satisfaction in life and child’s adaptive behavior. We found that indeed, family functioning and satisfaction in life serially mediated the relations between emotional support from mother and mother-in-law and child adaptive behavior. These findings indicate that intergenerational solidarity between women can improve not only the functioning of the nuclear family and wife’s satisfaction with life, but also, indirectly, the adaptive behavior of a child with ASD. It highlights the importance of women solidarity, especially in traditional society, where women are kept marginal.

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3. Chaves TF, Ocampos M, Barbato IT, de Camargo Pinto LL, de Luca GR, Barbato Filho JH, Bernardi P, Costa Netto Muniz Y, Francesca Maris A. A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD. Sci Rep;2024 (Feb 14);14(1):3762.

Chromosomal microarray (CMA) is the reference in evaluation of copy number variations (CNVs) in individuals with neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and/or autism spectrum disorder (ASD), which affect around 3-4% of the world’s population. Modern platforms for CMA, also include probes for single nucleotide polymorphisms (SNPs) that detect homozygous regions in the genome, such as long contiguous stretches of homozygosity (LCSH). These regions result from complete or segmental chromosomal homozygosis and may be indicative of uniparental disomy (UPD), inbreeding, population characteristics, as well as replicative DNA repair events. In this retrospective study, we analyzed CMA reading files requested by geneticists and neurologists for diagnostic purposes along with available clinical data. Our objectives were interpreting CNVs and assess the frequencies and implications of LCSH detected by Affymetrix CytoScan HD (41%) or 750K (59%) platforms in 1012 patients from the south of Brazil. The patients were mainly children with NDDs and/or congenital anomalies (CAs). A total of 206 CNVs, comprising 132 deletions and 74 duplications, interpreted as pathogenic, were found in 17% of the patients in the cohort and across all chromosomes. Additionally, 12% presented rare variants of uncertain clinical significance, including LPCNVs, as the only clinically relevant CNV. Within the realm of NDDs, ASD carries a particular importance, owing to its escalating prevalence and its growing repercussions for individuals, families, and communities. ASD was one clinical phenotype, if not the main reason for referral to testing, for about one-third of the cohort, and these patients were further analyzed as a sub-cohort. Considering only the patients with ASD, the diagnostic rate was 10%, within the range reported in the literature (8-21%). It was higher (16%) when associated with dysmorphic features and lower (7%) for « isolated » ASD (without ID and without dysmorphic features). In 953 CMAs of the whole cohort, LCSH (≥ 3 Mbp) were analyzed not only for their potential pathogenic significance but were also explored to identify common LCSH in the South Brazilians population. CMA revealed at least one LCSH in 91% of the patients. For about 11.5% of patients, the LCSH suggested consanguinity from the first to the fifth degree, with a greater probability of clinical impact, and in 2.8%, they revealed a putative UPD. LCSH found at a frequency of 5% or more were considered common LCSH in the general population, allowing us to delineate 10 regions as potentially representing ancestral haplotypes of neglectable clinical significance. The main referrals for CMA were developmental delay (56%), ID (33%), ASD (33%) and syndromic features (56%). Some phenotypes in this population may be predictive of a higher probability of indicating a carrier of a pathogenic CNV. Here, we present the largest report of CMA data in a cohort with NDDs and/or CAs from the South of Brazil. We characterize the rare CNVs found along with the main phenotypes presented by each patient and show the importance and usefulness of LCSH interpretation in CMA results that incorporate SNPs, as well as we illustrate the value of CMA to investigate CNV in ASD.

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4. Cho WM, Hsu TW, Cheng CM, Chang WH, Tsai SJ, Bai YM, Su TP, Chen TJ, Chen MH, Liang CS. Cause-specific mortality and comorbid neurodevelopmental disorder in 167,515 patients with bipolar disorder: An entire population longitudinal study. J Affect Disord;2024 (Feb 15);347:463-468.

OBJECTIVE: Studies addressing premature mortality in bipolar disorder (BD) patients are limited by small sample sizes. Herein, we used almost 99 % of the population of Taiwan to address this issue, and its association with comorbid neurodevelopmental disorders and severe BD. METHODS: Between 2003 and 2017, we enrolled 167,515 individuals with BD and controls matched 1:4 for sex and birth year from the National Health Insurance Database linked to the Database of National Death Registry in Taiwan. Time-dependent Cox regression models were used to examine cause-specific mortality (all-cause, natural, and unnatural causes [accidents or suicide]). RESULTS: With adjustments of sex, age, income, urbanization, and physical conditions, suicide was associated with the highest risk of mortality (reported as hazard ratio with 95 % confidence interval: 9.15; 8.53-9.81) among BD patients, followed by unnatural (4.94; 4.72-5.17), accidental (2.15; 1.99-2.32), and natural causes (1.02; 1.00-1.05). Comorbid attention-deficiency hyperactivity disorder did not contribute to the increased risk of cause-specific mortality; however, comorbid autism spectrum disorder (ASD) increased such risks, particularly for natural (3.00; 1.85-4.88) and accidental causes (7.47; 1.80-31.1). Cause-specific mortality revealed a linear trend with the frequency of psychiatric hospitalization (all, p for trend <0.001), and BD patients hospitalized twice or more each year had 34.63-fold increased risk of suicide mortality (26.03-46.07). CONCLUSIONS: BD patients with a higher frequency of psychiatric hospitalization have the highest risk of suicide mortality, and comorbid ASD was associated with an increased risk of natural and accidental causes of mortality.

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5. Clin E, Miller E, Kissine M. Similar social attention, physiological arousal, and familiarity effect in autistic and neurotypical children: A real-life recreational eye-tracking paradigm. J Exp Psychol Gen;2024 (Feb 15)

Social attention is reported to be crucial for the development of social skills, and, according to the social cognitive developmental theory, is fostered by social interactions. Autism is of central importance to the study of social attention, as autism is characterized by atypical social interactions and low social attention, both linked according to the social motivation theory to diminished social interest. Much evidence for positing low social interest in autism comes from eye-tracking studies, which, however, lack ecological validity. Our study documents social attention and physiological arousal, within close to real-life settings, in autistic children, as well as in their neurotypical peers, matched on gender and mental or chronological age. To explore the potential influence of partner familiarity or of the conversational topic, children gaze and electrodermal activity were recorded while they engaged in watercolor activities with, first a familiar and, next, an unfamiliar adult experimenter, who both introduced various topics. Autistic and neurotypical children exhibited comparable attention to their partners’ eyes. Notably, across all groups, heightened visual attention was directed to familiar rather than unfamiliar partners. Moreover, parallel arousal patterns emerged, with all children displaying increased skin conductance responses during more engaging topics and when looking at their interactional partner’s eyes. These findings underscore the task- and context-dependent nature of social attention and highlight the role of familiarity in an ecologically valid context. The absence of group differences challenges the universality of the social cognitive developmental theory and questions the scope of the social motivation theory of autism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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6. Deng S, Gao Q, Zhang L, Xie J, Chen Y, Peng X. Prefabricated Zirconia Crowns and Preformed Metal Crowns in the Treatment of Severely Childhood Caries and Anterior Crossbite in a Child with Autistic Spectrum Disorder. Case Rep Dent;2024;2024:5556502.

Crowns have been recommended to treat decayed teeth and rebuild teeth function. The dental management of children with autism is a tremendous challenge for pediatric dentists due to the impaired behaviors and communication disorders. In this context, a 5-year-old boy with autism was treated to solve carious lesions under the assistance of general anesthesia. The posterior occlusal function was restored, and the crossbite existing in the primary anterior teeth was approached merely by NuSmile® zirconia crowns (ZCs) rather than orthodontic intervention. We conducted an 18-month period. Throughout the long-term follow-up, the boy’s masticatory efficiency was remarkably improved and the anterior teeth had transferred into the correct position with adequate overbite to maintain the new relationship, thus ameliorating the appearance of tissue on the labial surface and enhancing his quality of life and oral health.

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7. Escudero SC, Sepúlveda EM. Pragmatic competence in people with dual diagnosis: down syndrome and autism spectrum disorder. BMC Psychol;2024 (Feb 15);12(1):74.

BACKGROUND: Pragmatics is an area that can be affected in a wide variety of disorders. In this sense, Syndromic Autism is defined as a disorder in which a causal link is established between an associated syndrome and Autism Spectrum Disorder (ASD). Likewise, Down Syndrome (DS) is one of the main genetically based syndromes in which ASD is described as one of its possible manifestations. In this direction, people with DS are described as social beings whereas in ASD there seems to be a specific alteration of this domain. METHODS: In this study, pragmatic performance was analysed in a sample of 72 participants, where comparisons were made between the scores obtained by children with ASD (n = 24), with DS (n = 24) and with DS + ASD (n = 24). RESULTS: The Social Communication Questionnaire (SCQ), the Block Objective and Criterial Language Battery (BLOC-SR) and the Neuropsychology subtest (NEPSY-II) aimed at Theory of Mind (ToM) identified significant differences between the groups. However, two-to-two comparisons reported no significant differences between DS and DS + ASD. CONCLUSIONS: Although several studies report differences between the three proposed groups, our data seem to suggest that ASD symptomatology in DS is associated with Intellectual Developmental Disorder (IDD). However, the lack of solid scientific evidence regarding comorbid diagnosis makes further research along these lines indispensable. TRIAL REGISTRATION: This study was approved by the Ethics Committee for Social Research at UCLM with reference CEIS-704,511-L8M4.

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8. Eva C, Anna J, Mark L. Interorganisational collaboration to improve accessibility of diagnostic evaluations for children with a developmental disability. Health Serv Insights;2024;17:11786329241232531.

INTRODUCTION: A timely integrated diagnostic and care trajectory for children with a developmental disability may prevent severe problems in later life. In Flanders, Belgium, different types of governmental regulated and subsidised settings offer diagnostic evaluations, as (part of) their mission. However, they operate in a non-coordinated way inducing severe accessibility problems for the public. This article studies the factors impacting on interorganisational collaboration and proposes an interorganisational conceptual model improving accessibility. METHODS: Focus groups were performed per type of organisation. Qualitative data were categorised thematically in an iterative process of data- and researcher triangulation. A member check validation was organised. RESULTS: Fifty-nine individuals participated in 6 focus groups. Structural and agency-related barriers for interorganisational collaboration were identified at micro, meso and macro level. Participants provided suggestions for better interorganisational collaboration. DISCUSSION: To improve accessibility adapted to patients’ needs, a patient-centred, integrated and interorganisational network model grounded in a stepped care logic is proposed to adapt the current organisation-centred model. CONCLUSION: A timely, integrated, diagnostic and care trajectory for children with a developmental disability preventing severe problems in later life requires an integration of services during the overall care trajectory of children by means of interorganisational collaboration.

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9. Gerik-Celebi HB, Unsel-Bolat G, Bolat H. Association of ABCA13 Gene Variants with Autism Spectrum Disorder and Other Neuropsychiatric Disorders. Mol Syndromol;2024 (Feb);15(1):22-29.

INTRODUCTION: Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by impaired social skills and limited or repetitive behaviors. In this study, we investigated the role of the ABCA13 gene in the etiopathogenesis of ASD. METHODS: Single-nucleotide variants were evaluated in 79 ASD patients (59 males +20 females) with no established genetic etiology associated with ASD using whole-exome sequencing/clinical exome sequencing method. Family segregation analysis was performed using Sanger sequencing. We presented the clinical and genetic findings of these cases and their parents in detail. RESULTS: We presented 10 different ABCA13 gene variants in cases with ASD and 10 parents carrying the same ABCA13 gene variant. There of these variants were likely pathogenic and seven variants were classified as variant of uncertain significance. Our cases had a comorbidity rate for attention deficit hyperactivity disorder (ADHD) as 70%. Various types of neuropsychiatric symptoms and diagnoses were detected including ADHD, anxiety disorder, intellectual disability, delay in speech, and febrile convulsion among the parents. CONCLUSION: To date, very few variants have been reported in the ABCA13 gene. Our findings enrich the role of ABCA13 gene may play a common role in the landscape of neuropsychiatric disorders.

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10. Kiehl I, Pease R, Hackmann C. The adult experience of being diagnosed with autism spectrum disorder: A qualitative meta-synthesis. Autism;2024 (Feb 15):13623613231220419.

There is little research looking at the experience of individuals diagnosed with autism spectrum disorder as adults. Adults diagnosed with autism spectrum disorder face different challenges than children, and more research is needed to better understand those challenges. For this review, autistic and non-autistic researchers looked at research on the experience of receiving a diagnosis of autism spectrum disorder as an adult. We looked for themes in people’s experience leading up to diagnosis, going through the diagnostic process, and living their life after diagnosis. We analyzed 24 studies and found three overarching themes that captured thirty-two themes describing the experience of diagnosis. The three overarching themes expressed issues with identity and relationships before and after the diagnosis and identified that the diagnosis of autism spectrum disorder in adulthood impacted people’s adaptation to and assimilation (i.e. the making sense of and internalizing the diagnosis) of autism spectrum disorder. While the diagnostic process itself was confusing and disappointing for many, it often led to a sense of relief and clarity regarding past experiences and had effects on identity and self-esteem. It created opportunities to connect with other autistic individuals and to access services, though appropriate supports were widely lacking. Recommendations are made that the impact of the diagnosis on people’s identity and choices about telling others about their diagnosis, and whether and how people want to make adaptations, should be discussed and thought through in the process of diagnosis.

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11. Ko CL, Lin CK, Lin CL. Relationship between executive function and autism symptoms in preschoolers with autism spectrum disorder. Res Dev Disabil;2024 (Feb 13);147:104692.

Executive dysfunction and other symptomatology could have links in preschoolers with autism spectrum disorder (ASD). This study contains three objectives: to explore the difference in executive function between preschoolers with ASD and typically developing individuals (TD), to investigate correlations between executive function and multiple domains of autism symptoms in preschoolers with ASD, and to examine the impact of executive function on symptoms of autism. Participants of this study included preschoolers (4-6 years) with ASD (24 boys, 20 girls) according to DSM-5-TR criteria and TD (24 boys, 20 girls). BRIEF-P (Behavior Rating Inventory of Executive Function-Preschool Version) and CASD-C (Checklist for Autism Spectrum Disorder-Chinese Version) were used as measurement tools. Data were analyzed using MANOVA, ANOVA, Pearson correlations, and simple regression. For the results, the study found results of executive function were significantly lower in preschoolers with ASD than in preschoolers without ASD; the greater the executive dysfunction, the greater the autistic symptomatology, and executive dysfunction predicted 57 % of the variability of autism symptoms. In conclusion, preschoolers with ASD had more executive dysfunction than those without ASD. Based on our findings, the study recommends incorporating executive function into clinical assessment programs to understand how executive function is related to autism symptoms.

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12. Li ST, Chien WC, Chung CH, Tzeng NS. Increased risk of acute stress disorder and post-traumatic stress disorder in children and adolescents with autism spectrum disorder: a nation-wide cohort study in Taiwan. Front Psychiatry;2024;15:1329836.

INTRODUCTION: Children and adolescents with autism spectrum disorder (ASD) may be particularly vulnerable to the impact of traumatic events, yet the association between ASD and the risk of developing acute stress disorder and post-traumatic stress disorder (PTSD) remains uncertain. This study aims to investigate this association, addressing the gap in large-scale evidence on the subject. METHODS: Conducted as a retrospective and matched cohort study, data was sourced from the National Health Insurance Research Database (NHIRD) in Taiwan, spanning from January 1, 2000, to December 31, 2015. The study included patients aged 18 years or under newly diagnosed with ASD (n=15,200) and compared them with a matched control group (n=45,600). The Cox proportional regression model was employed to assess the risk of acute stress disorder and PTSD. RESULTS: Over the 15-year follow-up period, a total of 132 participants developed either acute stress disorder or PTSD. Among them, 105 cases (0.691% or 64.90 per 100,000 person-years) were in the ASD group, while 27 cases (0.059% or 5.38 per 100,000 person-years) were in the control group. The adjusted hazard ratio for the ASD group was significantly higher compared to the control group (25.661 with 95% CI = 15.913-41.232; P < .001). DISCUSSION: This study provides compelling evidence that individuals with ASD face an elevated risk of developing acute stress disorder and PTSD. The findings underscore the importance of clinicians recognizing and addressing this vulnerability in ASD individuals exposed to traumatic events. This emphasizes the need for heightened attention to the risk of PTSD and acute stress disorder in the ASD population.

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13. Maillard AM, Romascano D, Villalón-Reina JE, Moreau CA, Almeida Osório JM, Richetin S, Junod V, Yu P, Misic B, Thompson PM, Fornari E, Gygax MJ, Jacquemont S, Chabane N, Rodríguez-Herreros B. Pervasive alterations of intra-axonal volume and network organization in young children with a 16p11.2 deletion. Transl Psychiatry;2024 (Feb 14);14(1):95.

Reciprocal Copy Number Variants (CNVs) at the 16p11.2 locus confer high risk for autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs). Morphometric MRI studies have revealed large and pervasive volumetric alterations in carriers of a 16p11.2 deletion. However, the specific neuroanatomical mechanisms underlying such alterations, as well as their developmental trajectory, are still poorly understood. Here we explored differences in microstructural brain connectivity between 24 children carrying a 16p11.2 deletion and 66 typically developing (TD) children between 2 and 8 years of age. We found a large pervasive increase of intra-axonal volume widespread over a high number of white matter tracts. Such microstructural alterations in 16p11.2 deletion children were already present at an early age, and led to significant changes in the global efficiency and integration of brain networks mainly associated to language, motricity and socio-emotional behavior, although the widespread pattern made it unlikely to represent direct functional correlates. Our results shed light on the neuroanatomical basis of the previously reported increase of white matter volume, and align well with analogous evidence of altered axonal diameter and synaptic function in 16p11.2 mice models. We provide evidence of a prevalent mechanistic deviation from typical maturation of brain structural connectivity associated with a specific biological risk to develop ASD. Future work is warranted to determine how this deviation contributes to the emergence of symptoms observed in young children diagnosed with ASD and other NDDs.

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14. Matsushima T, Izumi T, Vallortigara G. The domestic chick as an animal model of autism spectrum disorder: building adaptive social perceptions through prenatally formed predispositions. Front Neurosci;2024;18:1279947.

Equipped with an early social predisposition immediately post-birth, humans typically form associations with mothers and other family members through exposure learning, canalized by a prenatally formed predisposition of visual preference to biological motion, face configuration, and other cues of animacy. If impaired, reduced preferences can lead to social interaction impairments such as autism spectrum disorder (ASD) via misguided canalization. Despite being taxonomically distant, domestic chicks could also follow a homologous developmental trajectory toward adaptive socialization through imprinting, which is guided via predisposed preferences similar to those of humans, thereby suggesting that chicks are a valid animal model of ASD. In addition to the phenotypic similarities in predisposition with human newborns, accumulating evidence on the responsible molecular mechanisms suggests the construct validity of the chick model. Considering the recent progress in the evo-devo studies in vertebrates, we reviewed the advantages and limitations of the chick model of developmental mental diseases in humans.

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15. Mendez AI, McQueen E, Gillespie S, Klin A, Klaiman C, Pickard K. Access to Part C, Early Intervention for children younger than 4 years evaluated for autism spectrum disorder. Autism;2024 (Feb 15):13623613241229150.

Health disparities are defined as preventable differences in the opportunities to achieve optimal health outcomes experienced by marginalized and underrepresented communities. For families with autistic children, health disparities limit accessing early intervention services-which have been found to improve quality of life and other outcomes. One specific early intervention service in the United States is Individuals with Disabilities Education Act, Part C Early Intervention programs, which are federally funded interventions for children birth-to-three with developmental delays. This study adds to this topic by examining which factors impact accessing Part C, Early Intervention services for children who were evaluated for autism. Results showed that only half of the sample received these services despite there being concerns about development for all children. In addition, results showed that those who identified as Black had decreased odds of having accessed Part C, Early Intervention compared to those who identified as White. These results suggest that there are disparities when it comes to accessing important early intervention services that may be negatively impacting the Black autistic community.

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16. O’Connor M, Qiao H, Odamah K, Cerdeira PC, Man HY. Heterozygous Nexmif female mice demonstrate mosaic NEXMIF expression, autism-like behaviors, and abnormalities in dendritic arborization and synaptogenesis. Heliyon;2024 (Feb 15);10(3):e24703.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic basis. ASDs are commonly characterized by impairments in language, restrictive and repetitive behaviors, and deficits in social interactions. Although ASD is a highly heterogeneous disease with many different genes implicated in its etiology, many ASD-associated genes converge on common cellular defects, such as aberrant neuronal morphology and synapse dysregulation. Our previous work revealed that, in mice, complete loss of the ASD-associated X-linked gene NEXMIF results in a reduction in dendritic complexity, a decrease in spine and synapse density, altered synaptic transmission, and ASD-like behaviors. Interestingly, human females of NEXMIF haploinsufficiency have recently been reported to demonstrate autistic features; however, the cellular and molecular basis for this haploinsufficiency-caused ASD remains unclear. Here we report that in the brains of Nexmif(±) female mice, NEXMIF shows a mosaic pattern in its expression in neurons. Heterozygous female mice demonstrate behavioral impairments similar to those of knockout male mice. In the mosaic mixture of neurons from Nexmif(±) mice, cells that lack NEXMIF have impairments in dendritic arborization and spine development. Remarkably, the NEXMIF-expressing neurons from Nexmif(±) mice also demonstrate similar defects in dendritic growth and spine formation. These findings establish a novel mouse model of NEXMIF haploinsufficiency and provide new insights into the pathogenesis of NEXMIF-dependent ASD.

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17. Patel N, Berggren KN, Hung M, Bates K, Dixon MM, Bax K, Adams H, Butterfield RJ, Campbell C, Johnson NE. Neurobehavioral Phenotype of Children With Congenital Myotonic Dystrophy. Neurology;2024 (Mar 12);102(5):e208115.

BACKGROUND AND OBJECTIVES: To describe the neurobehavioral phenotype of congenital myotonic dystrophy. Congenital myotonic dystrophy (CDM) is the most severe form of myotonic dystrophy, characterized by symptom presentation at birth and later, cognitive impairment, autistic features, and disordered sleep. METHODS: The neurobehavioral phenotype was assessed in this cross-sectional study by a neuropsychological battery consisting of the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Weschler Intelligence Scale for Children, Fourth Edition, Vineland Adaptive Behavior Scale, Second Edition (Vineland-II), Behavior Rating Inventory of Executive Function including preschool and teacher reports, Autism Spectrum Screening Questionnaire, Social Communication Scale, and Repetitive Behavior Scale-Revised. Sleep quality was evaluated with the Pediatric Sleep Questionnaire and Pediatric Daytime Sleepiness Scale. RESULTS: Fifty-five children with CDM, ages 5 weeks to 14 years, were enrolled. The mean age and (CTG)(n) repeats (±SD) were 6.4 ± 3.8 years and 1,263 ± 432, respectively. The mean IQ was 64.1 ± 14.9 on the Weschler scales with 65.6% of participants falling in the extremely low range for IQ. Adaptive functioning was significantly low for 57.1% of participants (n = 20). Caregiver report of executive functioning indicated 23.1% (9/39) of participants had clinically elevated levels of dysfunction, though teacher report was discrepant and indicated 53.3% of participants with CDM fell in this range (8/15). Spearman correlations were strongly positive (p ≤ 0.05) for estimated full scale IQ, overall adaptive functioning and with daily living and socialization domain standard scores on the Vineland-II ranging from r = 0.719 to r = 0.849 for all ages. Aspects of executive function were directly related to features of autism and sleep quality. Social communication was inversely related to all aspects of daily functioning, except communication, and directly related to aspects of autism behavior. DISCUSSION: Depressed IQ, adaptive skills, and executive functioning, poor sleep quality, and features of autism and altered social functioning individually describe different aspects of the neurobehavioral phenotype in CDM. These neurobehavioral and sleep measures could help quantitatively measure and assess the burden of cognitive impairment in CDM.

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18. Rexrode LE, Hartley J, Showmaker KC, Challagundla L, Vandewege MW, Martin BE, Blair E, Bollavarapu R, Antonyraj RB, Hilton K, Gardiner A, Valeri J, Gisabella B, Garrett MR, Theoharides TC, Pantazopoulos H. Molecular profiling of the hippocampus of children with autism spectrum disorder. Mol Psychiatry;2024 (Feb 14)

Several lines of evidence point to a key role of the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits in memory for person and emotion related stimuli have been reported, along with enhanced ability for declarative memories. Mouse models have demonstrated a critical role of the hippocampus in social memory dysfunction, associated with ASD, together with decreased synaptic plasticity. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix molecules, represent a potential key link between neurodevelopment, synaptic plasticity, and immune system signaling. There is a lack of information regarding the molecular pathology of the hippocampus in ASD. We conducted RNAseq profiling on postmortem human brain samples containing the hippocampus from male children with ASD (n = 7) and normal male children (3-14 yrs old), (n = 6) from the NIH NeuroBioBank. Gene expression profiling analysis implicated molecular pathways involved in extracellular matrix organization, neurodevelopment, synaptic regulation, and immune system signaling. qRT-PCR and Western blotting were used to confirm several of the top markers identified. The CSPG protein BCAN was examined with multiplex immunofluorescence to analyze cell-type specific expression of BCAN and astrocyte morphology. We observed decreased expression of synaptic proteins PSD95 (p < 0.02) and SYN1 (p < 0.02), increased expression of the extracellular matrix (ECM) protease MMP9 (p < 0.03), and decreased expression of MEF2C (p < 0.03). We also observed increased BCAN expression with astrocytes in children with ASD, together with altered astrocyte morphology. Our results point to alterations in immune system signaling, glia cell differentiation, and synaptic signaling in the hippocampus of children with ASD, together with alterations in extracellular matrix molecules. Furthermore, our results demonstrate altered expression of genes implicated in genetic studies of ASD including SYN1 and MEF2C.

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19. Santos TCD, Obando JMC, Leite PEC, Pereira MR, Leitão MF, Abujadi C, Pimenta LFL, Martins RCC, Cavalcanti DN. Approaches of marine compounds and relevant immune mediators in Autism Spectrum Disorder: Opportunities and challenges. Eur J Med Chem;2024 (Feb 15);266:116153.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects social skills, language, communication, and behavioral skills, significantly impacting the individual’s quality of life. Recently, numerous works have centered on the connections between the immune and central nervous systems and the influence of neuroinflammation on autism symptomatology. Marine natural products are considered as important alternative sources of different types of compounds, including polysaccharides, polyphenols, sterols, carotenoids, terpenoids and, alkaloids. These compounds present anti-inflammatory, neuroprotective and immunomodulatory activities, exhibiting a potential for the treatment of many diseases. Although many studies address the marine compounds in the modulation of inflammatory mediators, there is a gap regarding their use in the regulation of the immune system in ASD. Thus, this review aims to provide a better understanding regarding cytokines, chemokines, growth factors and immune responses in ASD, as well as the potential of bioactive marine compounds in the immune regulation in ASD. We expect that this review would contribute to the development of therapeutic alternatives for controlling immune mediators and inflammation in ASD.

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20. Tschida JE, Lee JD, Pomales-Ramos A, Koo V. Reported quality indicators and implementation outcomes of community partnership in autism intervention research: A systematic review. Autism Res;2024 (Feb);17(2):215-233.

There is minimal research on the quality of community partnerships in studies of interventions for autistic children. However, building high quality community engagement in autism intervention research may improve implementation outcomes. This systematic review examined studies that report community partnership in autism intervention research. A total of 135 articles were identified and 11 of these articles were included in the final review. Community partnership data were extracted using indicators from the conceptual framework for assessing research-practice partnerships (RPP; Henrick et al., Henrick et al., Assessing research-practice partnerships: Five dimensions of effectiveness, William T. Grant Foundation, 2017) and implementation outcomes data were extracted using the taxonomy of distinct implementation outcomes (Proctor et al., Administration and Policy in Mental Health and Mental Health Services Research, 38:65-76, 2011). Quality of studies were appraised using JBIs critical appraisal tools (Munn et al., JBI Evidence Synthesis, 18:2127-2133, 2020). RPP indicators and implementation outcomes were variably reported across studies. RPP indicators and implementation outcomes more likely to be reported were related to building trust, cultivating partnership relationships, conducting rigorous research to inform action, acceptability, and feasibility. RPP indicators and implementation outcomes less likely to be reported were related to building capacity to engage in partnership work, sustainability, cost, and penetration. Together, these results may suggest the need for increased sustainability and capacity building efforts in partnerships and increased guidelines for reporting outcomes.

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21. Voldsbekk I, Kjelkenes R, Frogner ER, Westlye LT, Alnaes D. Testing the sensitivity of diagnosis-derived patterns in functional brain networks to symptom burden in a Norwegian youth sample. Hum Brain Mapp;2024 (Feb 15);45(3):e26631.

Aberrant brain network development represents a putative aetiological component in mental disorders, which typically emerge during childhood and adolescence. Previous studies have identified resting-state functional connectivity (RSFC) patterns reflecting psychopathology, but the generalisability to other samples and politico-cultural contexts has not been established. We investigated whether a previously identified cross-diagnostic case-control and autism spectrum disorder (ASD)-specific pattern of RSFC (discovery sample; aged 5-21 from New York City, USA; n = 1666) could be validated in a Norwegian convenience-based youth sample (validation sample; aged 9-25 from Oslo, Norway; n = 531). As a test of generalisability, we investigated if these diagnosis-derived RSFC patterns were sensitive to levels of symptom burden in both samples, based on an independent measure of symptom burden. Both the cross-diagnostic and ASD-specific RSFC pattern were validated across samples. Connectivity patterns were significantly associated with thematically appropriate symptom dimensions in the discovery sample. In the validation sample, the ASD-specific RSFC pattern showed a weak, inverse relationship with symptoms of conduct problems, hyperactivity and prosociality, while the cross-diagnostic pattern was not significantly linked to symptoms. Diagnosis-derived connectivity patterns in a developmental clinical US sample were validated in a convenience sample of Norwegian youth, however, they were not associated with mental health symptoms.

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22. Wong LC, Hsu CJ, Wu YT, Chu HF, Lin JH, Wang HP, Hu SC, Tsai YC, Tsai WC, Lee WT. Investigating the impact of probiotic on neurological outcomes in Rett syndrome: A randomized, double-blind, and placebo-controlled pilot study. Autism;2024 (Feb 15):13623613231225899.

Rett syndrome often involves gastrointestinal symptoms and gut microbiota imbalances. We conducted a study to explore the feasibility of probiotic Lactobacillus plantarum PS128 and the impact on neurological functions in Rett syndrome. The results of our investigation demonstrated that the supplementation of probiotic L. plantarum PS128 was feasible and well tolerated, with 100% retention rate and 0% withdrawal rate. In addition, there was only one participant who had loose stool after taking L. plantarum PS128. Further, there was a tendency to enhance overall cognitive developmental level, as assessed using Mullen Scales of Early Learning. In addition, it significantly improved dystonia, as assessed using the Burke-Fahn-Marsden Movement Scale, in comparison with the placebo group. This study provides a strong foundation for future research and clinical trials exploring the potential of L. plantarum PS128 probiotics as a complementary therapy for individuals with Rett syndrome.

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23. Xue H, Liu S, Zeng L, Fan W. Causal effect of systemic lupus erythematosus on psychiatric disorders: A two-sample Mendelian randomization study. J Affect Disord;2024 (Feb 15);347:422-428.

BACKGROUND: This study aims to investigate the association between systemic lupus erythematosus (SLE) and the risk of seven psychiatric disorders through the application of Mendelian randomization (MR) analysis due to previous observational studies that have suggested a potential link between SLE and psychiatric disorders. METHODS: We collected genetic instruments for SLE from a genome-wide association study (GWAS) involving 23,210 individuals. Seven psychiatric traits were enrolled from the recent largest GWAS, including major depression disorder (MDD), generalized anxiety disorder (GAD), schizophrenia (SCZ), bipolar disorder (BID), autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and insomnia. Summary statistics for psychiatric disorders were obtained from different GWAS meta-analysis studies. The inverse variance weighted (IVW) method was used as the main MR analysis. RESULTS: The IVW method indicated that SLE is associated with a higher risk of GAD (OR = 1.072, 95 % CI [1.017-1.129], P = 0.008) and SCZ (OR = 3.242, 95 % CI [1.578-6.660], P = 0.007). However, no evidence was found for the causal associations between SLE and other psychiatric disorders. Further analyses found no evidence of pleiotropy and heterogeneity. CONCLUSIONS: This two-sample MR analysis provides evidence that genetically predicted SLE may increase the risk of GAD and SCZ in a European population. Future studies are needed to elucidate and investigate the mechanisms underlying these causal relationships. Considering the existence of racial genomic heterogeneity, our findings must be viewed with caution.

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24. Yang C, Wang XK, Ma SZ, Lee NY, Zhang QR, Dong WQ, Zang YF, Yuan LX. Abnormal functional connectivity of the reward network is associated with social communication impairments in autism spectrum disorder: A large-scale multi-site resting-state fMRI study. J Affect Disord;2024 (Feb 15);347:608-618.

BACKGROUND: The social motivation hypothesis proposes that the social deficits of autism spectrum disorder (ASD) are related to reward system dysfunction. However, functional connectivity (FC) patterns of the reward network in ASD have not been systematically explored yet. METHODS: The reward network was defined as eight regions of interest (ROIs) per hemisphere, including the nucleus accumbens (NAc), caudate, putamen, anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), amygdala, and insula. We computed both the ROI-wise resting-state FC and seed-based whole-brain FC in 298 ASD participants and 348 typically developing (TD) controls from the Autism Brain Imaging Data Exchange I dataset. Two-sample t-tests were applied to obtain the aberrant FCs. Then, the association between aberrant FCs and clinical symptoms was assessed with Pearson’s correlation or Spearman’s correlation. In addition, Neurosynth Image Decoder was used to generate word clouds verifying the cognitive functions of the aberrant pathways. Furthermore, a three-way multivariate analysis of variance (MANOVA) was conducted to examine the effects of gender, subtype and age on the atypical FCs. RESULTS: For the within network analysis, the left ACC showed weaker FCs with both the right amygdala and left NAc in ASD compared with TD, which were negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total scores and Social Responsiveness Scale (SRS) total scores respectively. For the whole-brain analysis, weaker FC (i.e., FC between the left vmPFC and left calcarine gyrus, and between the right vmPFC and left precuneus) accompanied by stronger FC (i.e., FC between the left caudate and right insula) were exhibited in ASD relative to TD, which were positively associated with the SRS motivation scores. Additionally, we detected the main effect of age on FC between the left vmPFC and left calcarine gyrus, of subtype on FC between the right vmPFC and left precuneus, of age and age-by-gender interaction on FC between the left caudate and right insula. CONCLUSIONS: Our findings highlight the crucial role of abnormal FC patterns of the reward network in the core social deficits of ASD, which have the potential to reveal new biomarkers for ASD.

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25. Zhou L, Jiang P, Zhao L, Fei X, Tang Y, Luo Y, Gong H, Wang X, Li X, Li S, Zhang C, Yang H, Fan X. Ligustilide inhibits Purkinje cell ferritinophagy via the ULK1/NCOA4 pathway to attenuate valproic acid-induced autistic features. Phytomedicine;2024 (Feb 15);126:155443.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in which social impairment is the core symptom. Presently, there are no definitive medications to cure core symptoms of ASD, and most therapeutic strategies ameliorate ASD symptoms. Treatments with proven efficacy in autism are imminent. Ligustilide (LIG), an herbal monomer extracted from Angelica Sinensis and Chuanxiong, is mainly distributed in the cerebellum and widely used in treating neurological disorders. However, there are no studies on its effect on autistic-like phenotypes and its mechanism of action. PURPOSE: Investigate the efficacy and mechanism of LIG in treating ASD using two Valproic acid(VPA)-exposed and BTBR T + Itpr3tf/J (BTBR) mouse models of autism. METHODS: VPA-exposed mice and BTBR mice were given LIG for treatment, and its effect on autistic-like phenotype was detected by behavioral experiments, which included a three-chamber social test. Subsequently, RNA-Sequence(RNA-Seq) of the cerebellum was performed to observe the biological changes to search target pathways. The autophagy and ferroptosis pathways screened were verified by WB(Western Blot) assay, and the cerebellum was stained by immunofluorescence and examined by electron microscopy. To further explore the therapeutic mechanism, ULK1 agonist BL-918 was used to block the therapeutic effect of LIG to verify its target effect. RESULTS: Our work demonstrates that LIG administration from P12-P14 improved autism-related behaviors and motor dysfunction in VPA-exposed mice. Similarly, BTBR mice showed the same improvement. RNA-Seq data identified ULK1 as the target of LIG in regulating ferritinophagy in the cerebellum of VPA-exposed mice, as evidenced by activated autophagy, increased ferritin degradation, iron overload, and lipid peroxidation. We found that VPA exposure-induced ferritinophagy occurred in the Purkinje cells, with enhanced NCOA4 and Lc3B expressions. Notably, the therapeutic effect of LIG disappeared when ULK1 was activated. CONCLUSION: LIG treatment inhibits ferritinophagy in Purkinje cells via the ULK1/NCOA4-dependent pathway. Our study reveals for the first time that LIG treatment ameliorates autism symptoms in VPA-exposed mice by reducing aberrant Purkinje ferritinophagy. At the same time, our study complements the pathogenic mechanisms of autism and introduces new possibilities for its therapeutic options.

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