1. Abbasi DA, Berry-Kravis E, Zhao X, Cologna SM. Proteomics insights into fragile X syndrome: Unraveling molecular mechanisms and therapeutic avenues. Neurobiol Dis. 2024; 194: 106486.

Fragile X Syndrome (FXS) is a neurodevelopment disorder characterized by cognitive impairment, behavioral challenges, and synaptic abnormalities, with a genetic basis linked to a mutation in the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene that results in a deficiency or absence of its protein product, Fragile X Messenger Ribonucleoprotein (FMRP). In recent years, mass spectrometry (MS) – based proteomics has emerged as a powerful tool to uncover the complex molecular landscape underlying FXS. This review provides a comprehensive overview of the proteomics studies focused on FXS, summarizing key findings with an emphasis on dysregulated proteins associated with FXS. These proteins span a wide range of cellular functions including, but not limited to, synaptic plasticity, RNA translation, and mitochondrial function. The work conducted in these proteomic studies provides a more holistic understanding to the molecular pathways involved in FXS and considerably enhances our knowledge into the synaptic dysfunction seen in FXS.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bitektine E, Hintermayer MA, Chen A, Ko A, Rodriguez C. Medical students’ perceptions on preparedness and care delivery for patients with autism or intellectual disability. Can Med Educ J. 2024; 15(1): 37-47.

INTRODUCTION: To provide competent care to patients with autism spectrum disorder (ASD) or intellectual developmental disorder (IDD), healthcare professionals must recognize the needs of neurodivergent populations and adapt their clinical approach. We assessed the perceived preparedness of medical students to adapt care delivery for patients with ASD/IDD, as well as their perceptions on neurodiversity education. METHODS: We conducted a sequential explanatory mixed-methods study on undergraduate medical students at McGill University during the academic year 2020-2021. We administered an online survey, followed by semi-structured interviews. We analyzed data using descriptive statistics and thematic analysis. We integrated findings at the interpretation level. RESULTS: We included two-hundred-ten survey responses (~29% of class), and 12 interviews. Few students felt prepared to adjust care for patients with ASD/IDD despite most indicating doing so was important. Ninety-seven percent desired more training regarding care accommodation for neurodivergent patients. Thematic analysis unveiled the perception of current insufficient education, and the value of experiential learning. DISCUSSION/CONCLUSIONS: This study highlights low perceived preparedness of medical students to accommodate care for neurodivergent patients, and a desire for more instruction. Incorporating interactive training in medical school curricula regarding modifying care delivery for neurodivergent individuals may improve the perceived preparedness of medical trainees to work with these patients and care quality.

Lien vers le texte intégral (Open Access ou abonnement)

3. Boesen K, Gøtzsche PC, Ioannidis JPA. Requesting conflicts of interest declarations from the European Medicines Agency: 3-year follow-up status. Epidemiol Psychiatr Sci. 2024; 33: e17.

AIMS: We have previously described the European Medicines Agency’s (EMA) and the US Food and Drug Administration’s guidelines, each for a specific psychiatric indication, on how to design pivotal drug trials used in new drug applications. Here, we report on our efforts over 3 years to retrieve conflicts of interest declarations from EMA. We wanted to assess potential internal industry influence judged as the proportion of guideline committee members with industry conflicts of interest. METHODS: We submitted Freedom of Information requests in February 2020 to access EMA’s lists of committee members (and their declared conflicts of interest) involved in drafting the 13 ‘Clinical efficacy and safety’ guidelines available on EMA’s website pertaining to psychiatric indications. In our request, we did not specify the exact EMA committees. Here, we describe the received documents and report the proportion of members with industry interests (i.e. defined as any financial industry relationship). It is a follow-up paper to our first report (http://doi.org/10.1017/S2045796021000147). RESULTS: After 2 years and 9 months (November 2022), the EMA sent us member lists and corresponding conflicts of interest declarations from the Committee for Medicinal Products for Human use (CHMP) from 2012, 2013 and 2017. These member lists pertained to 3 of the 13 requested guidelines (schizophrenia, depression and autism spectrum disorder). The 10 remaining guidelines were published before 2011 and EMA stated that they needed to require permission from their expert members (with unknown retrieval rate) and foresaw excessive workload and long wait. Therefore, we withdrew our request. The CHMPs from 2012, 2013 and 2017 had from 34 to 36 members; 39%-44% declared any interests and we judged 14%-18% as having industry interests. For the schizophrenia guideline, we identified two members with industry interests to companies who submitted feedback on the guideline. We did not receive declarations from the Central Nervous System (CNS) Working Party, the CHMP appointed expert group responsible for drafting and incorporating feedback into the guidelines. CONCLUSIONS: After almost 3 years, we received information, which only partly addressed our request. We recommend EMA to improve transparency by publishing the author names and their corresponding conflicts of interest declarations directly in the ‘Clinical efficacy and safety’ guidelines and to not remove conflicts of interest declarations after 1 year from their website to reduce the risk of stealth corporate influence during the development of these influential guidelines.

Lien vers le texte intégral (Open Access ou abonnement)

4. Curie A, Lion-François L, Valayannopoulos V, Perreton N, Gavanon M, Touil N, Brun-Laurisse A, Gheurbi F, Buchy M, Halep H, Cheillan D, Mercier C, Brassier A, Desnous B, Kassai B, De Lonlay P, Des Portes V. Clinical Characteristics, Developmental Trajectory, and Caregiver Burden of Patients With Creatine Transporter Deficiency (SLC6A8). Neurology. 2024; 102(8): e209243.

BACKGROUND AND OBJECTIVES: Creatine transporter deficiency (CTD) is a rare X-linked genetic disorder characterized by intellectual disability (ID). We evaluated the clinical characteristics and trajectory of patients with CTD and the impact of the disease on caregivers to identify relevant endpoints for future therapeutic trials. METHODS: As part of a French National Research Program, patients with CTD were included based on (1) a pathogenic SLC6A8 variant and (2) ID and/or autism spectrum disorder. Families and patients were referred by the physician who ordered the genetic analysis through Reference Centers of ID from rare causes and inherited metabolic diseases. After we informed the patients and their parents/guardians about the study, all of them gave written consent and were included. A control group of age-matched and sex-matched patients with Fragile X syndrome was also included. Physical examination, neuropsychological assessments, and caregiver impact were assessed. All data were analyzed using R software. RESULTS: Thirty-one patients (27 male, 4 female) were included (25/31 aged 18 years or younger). Most of the patients (71%) had symptoms at <24 months of age. The mean age at diagnosis was 6.5 years. Epilepsy occurred in 45% (mean age at onset: 8 years). Early-onset behavioral disorder occurred in 82%. Developmental trajectory was consistently delayed (fine and gross motor skills, language, and communication/sociability). Half of the patients with CTD had axial hypotonia during the first year of life. All patients were able to walk without help, but 7/31 had ataxia and only 14/31 could walk tandem gait. Most of them had abnormal fine motor skills (27/31), and most of them had language impairment (30/31), but 12/23 male patients (52.2%) completed the Peabody Picture Vocabulary Test. Approximately half (14/31) had slender build. Most of them needed nursing care (20/31), generally 1-4 h/d. Adaptive assessment (Vineland) confirmed that male patients with CTD had moderate-to-severe ID. Most caregivers (79%) were at risk of burnout, as shown by Caregiver Burden Inventory (CBI) > 36 (significantly higher than for patients with Fragile X syndrome) with a high burden of time dependence. DISCUSSION: In addition to clinical endpoints, such as the assessment of epilepsy and the developmental trajectory of the patient, the Vineland scale, PPVT5, and CBI are of particular interest as outcome measures for future trials. TRIAL REGISTRATION INFORMATION: ANSM Registration Number 2010-A00327-32.

Lien vers le texte intégral (Open Access ou abonnement)

5. De La Fuente DC, Tamburini C, Stonelake E, Andrews R, Hall J, Owen MJ, Linden DEJ, Pocklington A, Li M. Impaired oxysterol-liver X receptor signaling underlies aberrant cortical neurogenesis in a stem cell model of neurodevelopmental disorder. Cell Rep. 2024; 43(3): 113946.

The mechanisms by which genomic risks contribute to the onset of neuropsychiatric conditions remain a key challenge and a prerequisite for successful development of effective therapies. 15q11.2 copy number variation (CNV) containing the CYFIP1 gene is associated with autism and schizophrenia. Using stem cell models, we show that 15q11.2 deletion (15q11.2del) and CYFIP1 loss of function (CYFIP1-LoF) lead to premature neuronal differentiation, while CYFIP1 gain of function (CYFIP1-GoF) favors neural progenitor maintenance. CYFIP1 dosage changes led to dysregulated cholesterol metabolism and altered levels of 24S,25-epoxycholesterol, which can mimic the 15q11.2del and CYFIP1-LoF phenotypes by promoting cortical neuronal differentiation and can restore the impaired neuronal differentiation of CYFIP1-GoF neural progenitors. Moreover, the neurogenic activity of 24S,25-epoxycholesterol is lost following genetic deletion of liver X receptor (LXRβ), while compound deletion of LXRβ in CYFIP1(-/-) background rescued their premature neurogenesis. This work delineates LXR-mediated oxysterol regulation of neurogenesis as a pathological mechanism in neural cells carrying 15q11.2 CNV and provides a potential target for therapeutic strategies for associated disorders.

Lien vers le texte intégral (Open Access ou abonnement)

6. Denomme MM, McCallie BR, Haywood ME, Parks JC, Schoolcraft WB, Katz-Jaffe MG. Paternal aging impacts expression and epigenetic markers as early as the first embryonic tissue lineage differentiation. Hum Genomics. 2024; 18(1): 32.

BACKGROUND: Advanced paternal age (APA) is associated with adverse outcomes to offspring health, including increased risk for neurodevelopmental disorders. The aim of this study was to investigate the methylome and transcriptome of the first two early embryonic tissue lineages, the inner cell mass (ICM) and the trophectoderm (TE), from human blastocysts in association with paternal age and disease risk. High quality human blastocysts were donated with patient consent from donor oocyte IVF cycles from either APA (≥ 50 years) or young fathers. Blastocysts were mechanically separated into ICM and TE lineage samples for both methylome and transcriptome analyses. RESULTS: Significant differential methylation and transcription was observed concurrently in ICM and TE lineages of APA-derived blastocysts compared to those from young fathers. The methylome revealed significant enrichment for neuronal signaling pathways, as well as an association with neurodevelopmental disorders and imprinted genes, largely overlapping within both the ICM and TE lineages. Significant enrichment of neurodevelopmental signaling pathways was also observed for differentially expressed genes, but only in the ICM. In stark contrast, no significant signaling pathways or gene ontology terms were identified in the trophectoderm. Despite normal semen parameters in aged fathers, these significant molecular alterations can adversely contribute to downstream impacts on offspring health, in particular neurodevelopmental disorders like autism spectrum disorder and schizophrenia. CONCLUSIONS: An increased risk for neurodevelopmental disorders is well described in children conceived by aged fathers. Using blastocysts derived from donor oocyte IVF cycles to strategically control for maternal age, our data reveals evidence of methylation dysregulation in both tissue lineages, as well as transcription dysregulation in neurodevelopmental signaling pathways associated with APA fathers. This data also reveals that embryos derived from APA fathers do not appear to be compromised for initial implantation potential with no significant pathway signaling disruption in trophectoderm transcription. Collectively, our work provides insights into the complex molecular mechanisms that occur upon paternal aging during the first lineage differentiation in the preimplantation embryo. Early expression and epigenetic markers of APA-derived preimplantation embryos highlight the susceptibility of the future fetus to adverse health outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

7. Fok AHK, Huang Y, So BWL, Zheng Q, Tse CSC, Li X, Wong KK, Huang J, Lai KO, Lai CSW. KIF5B plays important roles in dendritic spine plasticity and dendritic localization of PSD95 and FMRP in the mouse cortex in vivo. Cell Rep. 2024; 43(3): 113906.

Kinesin 1 (KIF5) is one major type of motor protein in neurons, but its members’ function in the intact brain remains less studied. Using in vivo two-photon imaging, we find that conditional knockout of Kif5b (KIF5B cKO) in CaMKIIα-Cre-expressing neurons shows heightened turnover and lower stability of dendritic spines in layer 2/3 pyramidal neurons with reduced spine postsynaptic density protein 95 acquisition in the mouse cortex. Furthermore, the RNA-binding protein fragile X mental retardation protein (FMRP) is translocated to the proximity of newly formed spines several hours before the spine formation events in vivo in control mice, but this preceding transport of FMRP is abolished in KIF5B cKO mice. We further find that FMRP is localized closer to newly formed spines after fear extinction, but this learning-dependent localization is disrupted in KIF5B cKO mice. Our findings provide the crucial in vivo evidence that KIF5B is involved in the dendritic targeting of synaptic proteins that underlies dendritic spine plasticity.

Lien vers le texte intégral (Open Access ou abonnement)

8. Greene RK, Rutter TM, Phelps RA, Olsen EK, Harmon R, Moyer DN. Diagnostic assessment of autism spectrum disorder in transgender and gender diverse youth. Clin Neuropsychol. 2024: 1-22.

Objective: Higher prevalence of autism spectrum disorder (ASD) diagnosis and associated traits has been observed among transgender and gender diverse (TGD) youth, and the number of TGD youth requesting evaluation for autism is growing. This study explored the demographic and clinical profiles of TGD youth evaluated in a specialty autism clinic. Method: Retrospective autism evaluation results for 41 TGD youth aged 5-18 years and 67 cisgender-matched controls were included in the study. Results: Approximately, half of TGD youth were diagnosed with autism (TGDASD+; n = 19 vs. TGDASD-; n = 22). There were no group differences in sex assigned at birth, gender identity, FSIQ, race, or ethnicity. Compared to TGDASD- (allistic) youth, TGD autistics had significantly lower adaptive functioning and were more likely to have an IEP eligibility of ASD. Anxiety and mood disorders were more common in TGD youth, whereas language disorders were more prevalent in cisgender controls. Attention-Deficit/Hyperactivity Disorder (ADHD) was more common among TGDASD- youth (72%) than TGDASD+ youth (47%), though not significantly. Conclusions: TGD youth with school-based IEP eligibilities of ASD and lower adaptive functioning are more likely to be diagnosed with ASD upon medical evaluation. The combination of identifying as TGD and having ADHD may heighten suspicion for ASD. Asking about gender identity during autism evaluations for children middle school-aged and older is recommended.

Lien vers le texte intégral (Open Access ou abonnement)

9. Gubbiotti M, Balzarro M, Zoccante L, Di Gennaro G, Marchiafava M, Bedetti C, Rubilotta E. National Survey on bladder and bowel dysfunctions in Autism Spectrum Disorder population. Front Psychiatry. 2024; 15: 1140113.

INTRODUCTION: To evaluate lower urinary tract symptoms (LUTS) and bowel disorders in a population of young subjects with autism spectrum disorder (ADS) by a national survey and to assess the relationship between the occurrence, frequency, and type of LUTS and the severity of behavioral and neuropsychiatric characteristics. MATERIALS AND METHODS: A survey on LUTS and bowel disorders in the ASD population was sent by mail and social media through the main Italian Associations of ASD between February and September 2022. The correlation between LUTS and ASD severity was also assessed. RESULTS: The survey was completed by 502 subjects with a mean age of 16.6 years ± 10 years: male participants were 413 (mean age: 16.5 years ± 9.8 years), while female participants 89 (mean age: 17.2 years ± 10.9 years). ADS severity was found low in 29.9%, moderate in 27.1%, and severe in 43%. LUTS were reported by 77.1%, storage symptoms in 51.4%, and voiding symptoms in 60.6%. Urinary incontinence was reported by 12.5%. Enuresis was reported by 14.3% (72/502) of the respondents: primary enuresis in 70.8% (51/72), secondary in the remaining. Pads were used by 40 subjects with a median of 2.9 pads/day (range, 0-8). A toilet training program was performed by 61 of the respondents, with satisfactory results in 40/61 (65.6%). A significant correlation was found between greater ASD severity and higher LUTS rates. The mean VAS score on the impact of LUTS on family relationships was 2 ± 2.9. Regular bowel function was reported by 57.4% (288/502) of the respondents, while increased daily defecations were present in 11.2% (56/502), constipation in 31.5% (158/502), and fecal incontinence in 7.9% (40/502). CONCLUSION: This survey demonstrated that LUTS are very common in the young ASD population and that the prevalence of urinary symptoms is related to higher severity of the ASD condition. Bowel disorders are often associated with urinary symptoms and dysfunctions. Urologists should be aware of the frequent occurrence of urological disorders and symptoms in individuals with ASD and should be involved in their clinical management in a multidisciplinary team that cares for these people.

Lien vers le texte intégral (Open Access ou abonnement)

10. Honybun E, Cockle E, Malpas CB, O’Brien TJ, Vajda FJ, Perucca P, Rayner G. Neurodevelopmental and Functional Outcomes Following In Utero Exposure to Antiseizure Medication: A Systematic Review. Neurology. 2024; 102(8): e209175.

BACKGROUND AND OBJECTIVES: To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal neurodevelopmental outcomes, focusing on social, emotional, behavioral, and adaptive domains of human function, and the frequency of neurodevelopmental and psychiatric disorders in ASM-exposed offspring. METHODS: Electronic searches of MEDLINE, PsychINFO, and EMBASE were conducted and limited to studies published between 1990 and 2023 in English. Studies were eligible if they prospectively or retrospectively reported neurodevelopmental outcomes of ASM-exposed offspring. The Newcastle-Ottawa scale was used to conduct methodologic quality assessments of included studies, and a narrative synthesis integrated the review findings. RESULTS: Forty-three studies were included. Valproate has been consistently associated with a 2- to 4-fold increased risk of autism spectrum disorder (ASD), 2- to 5-fold increased risk of intellectual disability (ID), and poor adaptive functioning. Growing evidence indicates that topiramate is associated with a 2-fold increased risk of ASD and 3- to 4-fold increased risk of ID. The risks of adverse neurodevelopmental outcomes for valproate and topiramate seem to be dose dependent. Phenobarbital has been suggested to be associated with deleterious neurodevelopmental effects, but data are limited. Levetiracetam has recently been linked with an increased risk of attention deficit hyperactivity disorder and anxiety disorders in a single study. Carbamazepine has been associated with variable neurodevelopmental outcomes. Lamotrigine seems to be « safe » in terms of postnatal neurodevelopment. Data for oxcarbazepine, phenytoin, and clonazepam are limited but seem to have little-to-no risk of adverse outcomes. Evidence for the remaining ASMs, including gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is lacking. Several methodologic limitations impeded data synthesis, including heterogeneity in outcome measures and small samples of monotherapy exposures. DISCUSSION: The findings of this review support the conclusion that valproate and topiramate use during pregnancy is associated with a significantly increased risk of neurodevelopmental effects on the fetus. Apart from lamotrigine, which seems to be free of adverse neurodevelopmental effects, data for the other ASMs are mixed or inadequate to draw definite conclusions. Further research into the neurodevelopmental effects of prenatal exposure to ASMs, including most newer agents, is much needed.

Lien vers le texte intégral (Open Access ou abonnement)

11. Hu Q, Feng L, Yang MH, Yang F. Letter to the editor on « A novel frameshift mutation of FOXG1-induced congenital variant of Rett syndrome: A case report ». Asian J Surg. 2024.

Lien vers le texte intégral (Open Access ou abonnement)

12. Libster N, Harwood R, Meacham K, Kasari C. « I do my best to do right by her »: Autistic motherhood and the experience of raising a non-autistic adolescent daughter. Autism. 2024: 13623613241241577.

Little is known about the parenting experiences of autistic mothers, especially those who have daughters who are not on the autism spectrum. In this study, we interviewed seven autistic mothers who have raised or are currently raising non-autistic teenage daughters. Mothers were asked to describe what parenting was/is like during their daughters’ teenage years. We analyzed the transcripts of the interviews and found several common themes. Mothers described their relationships with their daughters to be loving, safe, and empathetic. Mothers described several strengths when it came to parenting, such as helping their daughters solve problems and using positive strategies to handle conflict with their daughters. Mothers also described challenges they faced when interacting with other non-autistic people and when trying to form relationships with them. Mothers tried to build their daughters’ social skills so that they would not experience the same challenges. This study shows that autistic mothers have close, loving relationships with their non-autistic teenage daughters but have trouble forming relationships with other non-autistic people. It is, therefore, important that non-autistic parents are more understanding and welcoming of autistic mothers.

Lien vers le texte intégral (Open Access ou abonnement)

13. Nakamura T, Yoshihara T, Tanegashima C, Kadota M, Kobayashi Y, Honda K, Ishiwata M, Ueda J, Hara T, Nakanishi M, Takumi T, Itohara S, Kuraku S, Asano M, Kasahara T, Nakajima K, Tsuboi T, Takata A, Kato T. Transcriptomic dysregulation and autistic-like behaviors in Kmt2c haploinsufficient mice rescued by an LSD1 inhibitor. Mol Psychiatry. 2024.

Recent studies have consistently demonstrated that the regulation of chromatin and gene transcription plays a pivotal role in the pathogenesis of neurodevelopmental disorders. Among many genes involved in these pathways, KMT2C, encoding one of the six known histone H3 lysine 4 (H3K4) methyltransferases in humans and rodents, was identified as a gene whose heterozygous loss-of-function variants are causally associated with autism spectrum disorder (ASD) and the Kleefstra syndrome phenotypic spectrum. However, little is known about how KMT2C haploinsufficiency causes neurodevelopmental deficits and how these conditions can be treated. To address this, we developed and analyzed genetically engineered mice with a heterozygous frameshift mutation of Kmt2c (Kmt2c(+/fs) mice) as a disease model with high etiological validity. In a series of behavioral analyses, the mutant mice exhibit autistic-like behaviors such as impairments in sociality, flexibility, and working memory, demonstrating their face validity as an ASD model. To investigate the molecular basis of the observed abnormalities, we performed a transcriptomic analysis of their bulk adult brains and found that ASD risk genes were specifically enriched in the upregulated differentially expressed genes (DEGs), whereas KMT2C peaks detected by ChIP-seq were significantly co-localized with the downregulated genes, suggesting an important role of putative indirect effects of Kmt2c haploinsufficiency. We further performed single-cell RNA sequencing of newborn mouse brains to obtain cell type-resolved insights at an earlier stage. By integrating findings from ASD exome sequencing, genome-wide association, and postmortem brain studies to characterize DEGs in each cell cluster, we found strong ASD-associated transcriptomic changes in radial glia and immature neurons with no obvious bias toward upregulated or downregulated DEGs. On the other hand, there was no significant gross change in the cellular composition. Lastly, we explored potential therapeutic agents and demonstrate that vafidemstat, a lysine-specific histone demethylase 1 (LSD1) inhibitor that was effective in other models of neuropsychiatric/neurodevelopmental disorders, ameliorates impairments in sociality but not working memory in adult Kmt2c(+/fs) mice. Intriguingly, the administration of vafidemstat was shown to alter the vast majority of DEGs in the direction to normalize the transcriptomic abnormalities in the mutant mice (94.3 and 82.5% of the significant upregulated and downregulated DEGs, respectively, P < 2.2 × 10(-16), binomial test), which could be the molecular mechanism underlying the behavioral rescuing. In summary, our study expands the repertoire of ASD models with high etiological and face validity, elucidates the cell-type resolved molecular alterations due to Kmt2c haploinsufficiency, and demonstrates the efficacy of an LSD1 inhibitor that might be generalizable to multiple categories of psychiatric disorders along with a better understanding of its presumed mechanisms of action.

Lien vers le texte intégral (Open Access ou abonnement)

14. Ohtsubo T, Mizoguchi Y, Aita C, Imamura Y, Kobayashi M, Kunitake Y, Tateishi H, Ueno T, Monji A. Relationship between serum cortisol levels, stereotypies, and the presence of autism spectrum disorder in patients with severe intellectual disability. Sci Rep. 2024; 14(1): 7139.

Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.

Lien vers le texte intégral (Open Access ou abonnement)

15. Pantalone G, Mancardi MM, Rossi A, Romanelli R, Marasco E, Carla M. A de novo frameshift variant in MED13 gene in a patient with autism spectrum disorder and magnetic resonance imaging abnormalities mimicking tuberous sclerosis. Am J Med Genet A. 2024: e63611.

The mediator complex subunit 13 (MED13) gene is implicated in neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability, and speech delay with varying severity and course. Additional, extra central nervous system, features include eye or vision problems, hypotonia, congenital heart abnormalities, and dysmorphisms. We describe a 7-year- and 4-month-old girl evaluated for ASD whose brain magnetic resonance imaging was suggestive of multiple cortical tubers. The exome sequencing (ES – trio analysis) uncovered a unique, de novo, frameshift variant in the MED13 gene (c.4880del, D1627Vfs*17), with a truncating effect on the protein. This case report thus expands the phenotypic spectrum of MED13-related disorders to include brain abnormalities.

Lien vers le texte intégral (Open Access ou abonnement)

16. Robinson Williams A, Amoakohene E, Maenner MJ, Zahorodny W, DiRienzo M, Grzybowski A, Hall-Lande J, Pas ET, Bakian AV, Lopez M, Patrick M, Shenouda J, Shaw KA. Community testing practices for autism within the autism and developmental disabilities monitoring network. Paediatr Perinat Epidemiol. 2024.

BACKGROUND: No data exist at the population level on what tests are used to aid in the diagnosis of autism spectrum disorder in community practice. OBJECTIVES: To describe autism spectrum disorder testing practices to inform autism spectrum disorder identification efforts. METHODS: Data are from the Autism and Developmental Disabilities Monitoring Network, a multi-site surveillance system reporting prevalence estimates and characteristics of 8-year-old children with autism spectrum disorder. Percentages of children with autism spectrum disorder who received any autism spectrum disorder test or a ‘gold standard’ test were calculated by site, sex, race, median household income, and intellectual ability status. Risk ratios were calculated to compare group differences. RESULTS: Of 5058 8-year-old children with autism spectrum disorder across 11 sites, 3236 (64.0%) had a record of any autism spectrum disorder test and 2136 (42.2%) had a ‘gold standard’ ADOS or ADI-R test. Overall, 115 children (2.3%) had both the ADOS and ADI-R in their records. Differences persisted across race, median household income, and intellectual ability status. Asian/Pacific Islander children had the highest percent receiving any ASD test (71.8%; other groups range: 57.4-66.0%) and White children had the highest percent receiving ‘gold standard’ tests (46.4%; other groups range: 35.6-43.2%). Children in low-income neighbourhoods had a lower percent of any test (62.5%) and ‘gold standard’ tests (39.4%) compared to medium (70.2% and 47.5%, respectively) and high (69.6% and 46.8%, respectively) income neighbourhoods. Children with intellectual disability had a lower percent of any ASD test (81.7%) and ‘gold standard’ tests (52.6%) compared to children without intellectual disability (84.0% and 57.6%, respectively). CONCLUSIONS: Autism spectrum disorder testing practices vary widely by site and differ by race and presence of co-occurring intellectual disability, suggesting opportunities to standardise and/or improve autism spectrum disorder identification practices.

Lien vers le texte intégral (Open Access ou abonnement)

17. Tan C, Song H, Ma S, Liu X, Zhao Y. Autistic Traits and Aggressive Behavior in Chinese College Students: A Serial Mediation Model and the Gender Difference. Psychol Res Behav Manag. 2024; 17: 1385-97.

BACKGROUND: The existence of aggressive behavior in autism spectrum disorders (ASD) raises questions about whether cognitive and emotional factors in social information processing play a role between autistic traits (ATs) and aggressive behavior in the general population, especially in the context of Chinese culture. Moreover, given a possible gender difference in these variables, the study aimed to examine the effect of ATs on aggressive behavior, and the potential mediating role of hostile attribution bias and alexithymia on this association, as well as gender difference. METHODS: 850 Chinese college students participated in the assessment, including their ATs, hostile attribution bias, alexithymia, and aggressive behavior. Pearson correlation, mediation effects analyses, and multiple-group comparison were conducted. RESULTS: The results indicated that ATs indirectly predicted increased aggressive behavior through attribution bias and alexithymia. Gender difference in mediating effects was revealed: ATs indirectly predicted increased aggressive behavior through the serial mediating effect only in males. CONCLUSION: Hostile attribution bias and alexithymia completely mediated the association between ATs and aggressive behavior, which contained the separate mediating effects of (a) hostile attribution bias and (b) alexithymia and the serial mediating effect of (c) hostile attribution bias and alexithymia. Gender differences in mediating effects were found only in the serial mediating effect, which was significant in males but not in females. The findings revealed the internal mechanism of ATs affecting aggressive behavior and gender difference, which have implications for the intervention of aggressive behavior of individuals with autism and those with high levels of ATs.

Lien vers le texte intégral (Open Access ou abonnement)

18. Thompson BAD, Gilmore R, Barfoot J, Sakzewski L. A systematic review of the efficacy of group social skills interventions on social functioning and social participation in children with acquired brain injury or cerebral palsy. Child Care Health Dev. 2024; 50(2): e13242.

AIM: The aim of this study was to evaluate the efficacy of Group social skills interventions (GSSIs) versus any comparator on social functioning in children aged 5-12 years with acquired brain injury or cerebral palsy. BACKGROUND: GSSIs are an evidence-based approach to foster social skills development in children with autism spectrum disorder. Currently, limited literature exploring GSSIs in children with acquired brain injury and cerebral palsy is available. RESULTS: MEDLINE, SCOPUS, Embase, CINAHL, Cochrane Library, PsycINFO, clinicaltrials.gov, ICTRP and ProQuest Dissertations and Theses were systematically searched. Study screening, risk-of-bias, Grading of Recommendations Assessment, Development and Evaluation and data extraction were performed in duplicate. Six studies were included in the narrative synthesis (one randomised controlled trial and five nonrandomised studies). Results indicate that GSSIs may increase children’s social skills as measured on the Social Skills Rating System and Social Skills Questionnaire. Very low certainty evidence was found for improvements in social functioning and competence. CONCLUSIONS: There is low certainty evidence that participation in GSSI may lead to gains in social functioning for children with acquired brain injury or cerebral palsy. Given the certainty of the evidence, these results must be interpreted with caution. Only one randomised controlled trial of GSSIs for children with acquired brain injury was identified, underscoring the need for additional high-quality studies.

Lien vers le texte intégral (Open Access ou abonnement)