1. Benli ET, Babur E, Dursun N, Saray H, Barutçu Ö, Süer C. Genetic machinery which accompanies metaplasticity operates differentially in experimental model of autism. Int J Dev Neurosci;2024 (Dec 1)

The present study investigated metaplasticity-related mRNA expressions in valproic acid (VPA)-rats, focusing on the PI3K/AKT pathway. Wistar dams were treated with a single intraperitoneal injection of 600 mg/kg VPA or saline on embryonic day E12.5 or an equal volume of saline solution. Three behavioral tests were conducted on these males’ offspring: grid-walking test, negative geotaxis test, and three-chamber social interaction test. Metaplasticity was induced in 60-day-old male progeny by giving high-frequency stimulation for 5 minutes following low-frequency stimulation to the perforant pathway. For the baseline stimulation protocol (n = 6), stimulation was delivered to the dentate gyrus at the previously determined stimulation intensity (0.33 Hz 0.175 msec 30 s) for 75 min. The percent change of slope of field excitatory postsynaptic potential (fEPSP) and amplitude of population spike were calculated 55-60 min after induction protocol. The mRNA levels of PI3K, PTEN, AKT, GSK-3β, and MAPT were measured in the hippocampus by using quantitative rt-PCR. We found that offspring of VPA-treated rats showed significantly impaired sensorimotor coordination, decreased sociability, impaired preference for social novelty, and reduced input-output curve of fEPSP slope, compared to control animals. Despite a similar metaplastic response, mRNA levels of genes of interest were similar but considerably down-regulated after induction in offspring of VPA-treated dams. Our study provides evidence that the induced expression of autism-related genes has evolved to enable an adaptation mechanism during metaplastic control of long-term potentiation.

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2. Chen YF, Tsao CY, Chen YT, Chang HC, Li WY, Chiang JL, Chen CF, Chen CH, Gau SS, Lee KY, Lee LJ, Wang YC. Altered odor perception in Dlgap2 mutant mice, a mouse model of autism spectrum disorder. Behav Brain Res;2024 (Dec 2);480:115365.

Olfactory dysfunction has been observed in patients with Autism Spectrum Disorder (ASD). A microdeletion at the 8p23 terminal regions of chromosome 8p23 was identified in a Taiwanese patient with ASD, suggesting a potential association with mutations in the DLGAP2 gene. DLGAP2 is expressed in the olfactory bulb in rodents. The current study investigated olfactory phenotypes of Dlgap2 mutant mice. The results indicated that odor detection capabilities were comparable between wild-type (WT) and Dlgap2 mutant mice. However, homozygous mutant (Homo) mice showed less interest in sniffing odors of banana and almond but greater sniffing activity in response to bedding from unfamiliar cages. Notably, exposure to banana odor elicited significant c-fos expression in most olfaction-related brain regions of WT mice, while Homo mice did not show much increase in c-fos levels in major olfactory areas, which may correlate with their diminished sniffing behavior. Bedding stimuli induced pronounced c-fos expression in WT brains and some olfaction-related regions, including the olfactory bulb, amygdala, hypothalamus, and medial prefrontal cortex, in Homo mice. These mutants may still process olfactory signals from the bedding through a relatively narrow channel, which might elicit their interest, leading to increased sniffing behaviors that may compensate for their olfactory deficits. The DLGAP2 protein was absent in the olfactory bulb of Homo mice, and the levels of PSD95 and CaMKIIβ were also affected, indicating alterations in synaptic transmission and signaling within the olfactory system. This study evaluated olfactory perception in a mouse model of ASD, which may advance diagnostic and therapeutic strategies.

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3. Choi JW, Oh J, Bennett DH, Kannan K, Tancredi DJ, Miller M, Schmidt RJ, Shin HM. Corrigendum to ‘Gestational exposure to organophosphate esters and autism spectrum disorder and other non-typical development in a cohort with elevated familial likelihood’ [Environ. Res. 263 (2024) 120141]. Environ Res;2024 (Dec 2):120492.

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4. Du Y, Fan X, Song C, Chang W, Xiong J, Deng L, Ji WK. Sec23IP recruits VPS13B/COH1 to ER exit site-Golgi interface for tubular ERGIC formation. J Cell Biol;2024 (Dec 2);223(12)

VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES-Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B-VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconventional cargo carrier that expedites ER-to-Golgi transport. In addition, depletion of VPS13B or Sec23IP delays ER export of procollagen, suggesting a link between procollagen secretion and joint laxity in patients with Cohen disease. Together, our study reveals a crucial role of VPS13B-Sec23IP interaction at the ERES-Golgi interface in the pathogenesis of Cohen syndrome.

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5. Elmakhzen B, Bouguenouch L, Oussama K, Ali El Asri Y, Askander O. Atypical presentation of Dyggve-Melchior-Clausen disease in a Moroccan child without developmental delay and intellectual disabilities. Mol Biol Rep;2024 (Dec 2);52(1):32.

BACKGROUND: Dyggve-Melchior-Clausen (DMC) disease is a rare autosomal recessive disorder primarily characterized by spondylo-epimetaphyseal dysplasia, intellectual disability, and distinctive facial features. Patients typically present with severe developmental delays and cognitive impairments, defining features of the syndrome. METHODS AND RESULTS: This case report examines a 13-year-old Moroccan child diagnosed with DMC disease, presenting classical skeletal abnormalities, including spondylo-epimetaphyseal dysplasia, as confirmed through exome sequencing. Notably, the child exhibited a mutation recurrently identified in the Moroccan population. However, the patient showed no signs of developmental delay or intellectual disability, a marked deviation from the traditionally described phenotype. This finding suggests a broader clinical variability associated with DMC disease, emphasizing the importance of individualized assessments. CONCLUSIONS: This atypical presentation expands the phenotypic spectrum of DMC disease, challenging its conventional diagnostic criteria. Further research is required to elucidate the factors influencing phenotypic variability in DMC and to explore potential genotype-phenotype correlations. Early identification and documentation of such atypical cases are critical for refining diagnostic and management strategies for rare disorders.

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6. Fussell JJ, Stein REK, Friedman S, Hansen R, Roizen N, Sideridis G, Vanderbilt D, Barbaresi W. Characteristics of Young Children Associated with Diagnostic Utility of the Autism Diagnostic Observation Schedule: A DBPNet Study. J Dev Behav Pediatr;2024 (Nov 26)

OBJECTIVE: The aim of this study is to identify characteristics of children for whom a developmental-behavioral pediatrician’s (DBP) diagnostic impressions of autism spectrum disorder (ASD) or non-ASD were changed by Autism Diagnostic Observation Schedule (ADOS) results. METHOD: A prospective study of children 1½ to <6 years consecutively referred to 8 sites for possible ASD. Cognitive/developmental, language, and adaptive testing varied, as each site followed its usual clinical approach. DBPs documented diagnosis as ASD or non-ASD and their degree of diagnostic certainty (1-10) pre- and post-ADOS. Cases where DBP diagnostic impression did not change after ADOS administration ("Stable Group," n = 314) were compared with those for whom it did change ("Changed Group," n = 35), followed by matched random sample comparisons. RESULTS: There were no significant differences in child characteristics (age, gender, race, ethnicity, insurance, caregiver education) between the Stable and Changed groups. DBPs' diagnostic certainty was significantly lower, both pre- and post-ADOS, in the Changed versus Stable group. Change was associated with milder symptoms of ASD and less impaired language. In an age- and gender-matched comparison, significant differences remained for diagnostic certainty and severity of social communication impairments. Cognitive scores were significantly higher in the Changed Group. Because of significantly higher caregiver education and a trend toward more privately insured children among the Changed Group, samples (n = 35 each) were then matched on those characteristics, revealing the same differences for diagnostic certainty, severity of ASD symptoms, and language skills. CONCLUSION: Young children with milder ASD symptoms and less impaired language may benefit most from the administration of the ADOS.

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7. Holt JM, Siekman K, Fairbanks M, Fairbanks M, Stern N. The impact of art, storytelling, and STEAM-based approaches on creativity development in autistic youth and young adults: A mixed methods study protocol. PLoS One;2024;19(12):e0313506.

There are contradicting perspectives regarding autistics’ ability to be creative. Some researchers cite autistics’ underlying social communication and interaction differences, fixated interests, and inflexible patterns as fundamentally inhibiting creativity. However, many autistics refute this mindset and produce creative works as painters, sculptors, photographers, and graphic artists. This protocol describes a mixed methods study that aims to determine the impact of art, storytelling, and STEAM-based approaches to develop autistic youth and young adult participants’ creative self-efficacy, psychological empowerment, and design thinking traits. The primary research question is: How does a 120-minute workshop intervention impact the creative self-efficacy of autistic participants? We hypothesize that autistic participants’ creative self-efficacy scores would linearly increase from the baseline measure. Exploratory research questions include: How does the workshop intervention affect the psychological empowerment and design thinking traits of the autistic participants? We hypothesize that autistic participants’ psychological empowerment and design thinking traits scores would linearly increase from the baseline measure. We will use a design-based implementation research approach that values the collaboration between the researchers and educators who design interventions to understand when, how, and why learning happens. Recruitment began on 10 November 2023 and ended on 9 August 2024. The study’s results are expected to be published in mid-2025. The study will provide crucial empirical evidence on the effects of an arts-based program on creative self-efficacy, psychological empowerment, and design thinking traits in autistic youth and young adults. We will use qualitative descriptive thematic analysis methods to analyze the digital images, stop motion videos, and participant presentations. Digital artifacts of the participants’ creative process and the study team’s analysis of the autistic youth’s presentations will provide additional data to understand the study phenomenon’s depth, meaning, and context. A mixed methods design is advantageous when exploring complex issues that require empirical evidence and contextual understanding.

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8. Lam XR, Cheng LJ, Leo CSY, Toh ZA, He HG. Global prevalence of depression in caregivers of children with autism: A systematic review and meta-analysis. J Pediatr Nurs;2024 (Dec 2)

PROBLEM: Depression is reported as the most common disorder among caregivers, especially for caregivers of children with autism. However, limited systematic reviews have investigated the prevalence of depressive symptoms among these caregivers. This systematic review and meta-analysis aim to synthesize the prevalence of global depressive symptoms among caregivers of children with autism and identify associated factors. ELIGIBILITY CRITERIA: Articles were limited to English language and reported on the prevalence of depressive symptoms among formal or informal caregivers, aged 18 or older, of children with ASD, with no publication year restrictions. SAMPLE: A total of 40 included studies involving 13,853 caregivers of children with autism were included. RESULTS: Meta-analysis of 40 included studies involving 13,853 caregivers of children with autism showed a pooled prevalence estimate of 45 % (95 % CI: 39.0-51.0). Depressive symptoms were most prevalent in European studies, with a rate of 54 % (N: 980), closely followed by the Eastern Mediterranean region at 53 % (N:1071). The South-East Asia and Western Pacific region exhibited a prevalence of 40 % (N: 5719), while the Americas reported a rate of 38 % (N: 6083). CONCLUSION: This review presents compelling evidence of a high global prevalence rate of 45 % for depressive symptoms among caregivers of children with ASD. IMPLICATIONS: To enhance nursing support for caregivers of children with ASD, specific interventions are needed. Nurses should integrate mental health screenings into regular check-ups, link caregivers to community resources, and receive specialized training. Promoting respite care and collaborating with stakeholders can further address caregiver stress and mental health stigma.

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9. Mgaieth F, Palmer M, Charman T, Simonoff E. Facing Change and Uncertainty: Lessons Learned from Autistic Children and their Families During the COVID-19 Pandemic. J Autism Dev Disord;2024 (Dec 2)

The COVID-19 pandemic presented a great challenge for individuals around the globe, and particularly for vulnerable populations such as autistic children. This qualitative study explored the experience of autistic children (both verbal and minimally verbal) and their families during the pandemic in August-October 2020 through the lens of 18 parents recruited from an opportunistic follow-up of a randomized controlled trial. Findings revealed that the pandemic was detrimental to the mental health of most parents. School closures, disrupted routines and concerns of the virus were believed by parents to be particularly responsible for increased in their child’s behaviour that challenges and anxiety, resulting in changes in acquired skills and development of tics for some. However, other parents reported that increased one-to-one interaction with their child improved their social interaction and communication. Additionally, families felt more able to cope with the situation when supported by their partner, support services and schools. The findings highlight the challenges and benefits experienced by families with an autistic child during the pandemic. They provide valuable insights into potential areas that warrant attention when preparing for future emergencies. Enhancing our ability to respond to the needs of autistic children and their families, and establishing policies that can support their well-being should be prioritised to effectively address future challenges.

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10. Pickles K, Houdmont J, Smits F, Hill B. ‘Part of the team as opposed to watching from the outside’: Critical incident study of autistic veterinary surgeons’ workdays. Vet Rec;2024 (Dec 2):e4957.

BACKGROUND: Autistic individuals experience differences in sensory processing, communication and executive function, which may affect their experience of the workplace. We investigated UK-based autistic clinical veterinary surgeons’ experiences to establish contributing factors to a good or difficult workday. METHODS: Purposive sampling was used to conduct semi-structured qualitative interviews with 15 autistic veterinary surgeons. A critical incident technique was applied to explore the characteristics of a good and a difficult workday. Reflexive thematic analysis was used to identify recurrent themes and sub-themes in the narratives. RESULTS: Five major themes were identified as contributing to a difficult workday for autistic veterinarians: professional interactions, feeling out of control, the physical environment, role-specific challenges and self-doubt. Four overarching themes were identified as being associated with a good workday: positive interactions, feeling in control, having enough time and a sense of achievement. LIMITATIONS: As this is a qualitative study with a small number of participants, the extent to which these findings reflect the experience of the wider autistic veterinary surgeon community is unclear. CONCLUSION: Strategies to mitigate the effect of the most cited factors leading to difficult workdays, centring around neurodiversity awareness of colleagues and control of work, are likely to be helpful to autistic veterinary surgeons.

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11. Qiu Z, Du A. Revisiting the genetic architecture of autism spectrum disorders in the genomic era: Insights from East Asian studies. Curr Opin Neurobiol;2024 (Nov 30);90:102936.

This review delves into the genetic landscape of Autism Spectrum Disorder (ASD) in the genomic era, with a special focus on insights from East Asian populations. We analyze a spectrum of genetic research, including whole-exome and whole-genome sequencing, to elucidate both the challenges and advancements in comprehending the genetic foundations of ASD. Critical findings from this review highlight the identification of de novo variants, particularly noting the significant role of rare variants that differ from the common variants identified in earlier research. The review emphasizes the importance of large, diverse, and meticulously maintained ASD cohorts, which are essential for advancing genetic studies and developing potential therapeutic interventions. Through collaborative international efforts, we argue for a global perspective necessary to grasp the intricate genetic factors underlying ASD.

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12. Reid M, Clawson A, Ratto A, Rich BA. No Way Out? Cognitive Rigidity and Depressive Symptoms Associated with Suicidal Thoughts and Behaviors in Autistic Youth. Child Psychiatry Hum Dev;2024 (Dec 2)

Research has found increased premature mortality among autistic individuals, with suicide being one of the most common causes of premature death in autistic youth. This study aimed to fill literature gaps related to suicidal thoughts and behaviors (STB) in autistic youth by exploring the clinical predictors of suicidal ideation (SI) and suicidal and/or self-injurious behavior (SSIB) in 404 autistic youth from a clinic database. Consistent with prior literature, STB were elevated in autistic youth compared to general population rates. Self-reported suicidal ideation and behaviors were increased in autistic youth assigned female at birth. Caregivers reported greater SI in older autistic youth as compared to younger youth. Logistic regression analyses showed that elevated depressive symptoms and greater cognitive rigidity significantly increased the likelihood of SI in autistic youth. Results have important implications for understanding factors that increase the risk for suicidal ideation and behaviors in autistic youth and informing the development of responsive interventions.

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13. Schafer EC, Gopal KV, Mathews L, Miller S, Lam BPW. Impact of an Auditory Processing Training Program on Individuals With Autism Spectrum Disorder. Am J Audiol;2024 (Dec 2);33(4):1221-1236.

PURPOSE: Children and young adults diagnosed with autism spectrum disorder (ASD) often report and exhibit significant auditory processing difficulties, particularly in background noise. This study extends our previous work by examining the potential benefits of a 12-week auditory processing training (APT) program designed to address the auditory processing difficulties in individuals with ASD via auditory training and the use of remote-microphone technology. Effect sizes of training benefits also were calculated, and principal component analysis (PCA) was used to consolidate performance across various tests into fewer meaningful constructs related to auditory processing in this population. METHOD: Twenty-eight children and young adults with ASD participated in a 12-week APT program that included one-on-one speech-in-noise training, computerized dichotic training, and use of remote-microphone technology at home and at school. Before and after training, each participant completed tests of speech recognition in noise, spatial processing, binaural integration, and general auditory processing skills. RESULTS: Significant performance improvements and medium-to-large effect sizes were found across most test measures after the participants completed the APT program and when using the remote-microphone system. PCA identified strong relationships among all test measures as well as documented the relationships between behavioral performance, training duration, and training improvements. CONCLUSIONS: The APT program significantly improved spatial processing, binaural integration, phonological processing, auditory memory, auditory cohesion, and speech recognition in noise in individuals with ASD when the remote-microphone system was used. PCA analysis of pre- and posttraining data showed a strong relationship among all test measures, suggesting an abbreviated auditory processing test battery may be feasible for individuals with ASD. Training duration (minutes) and training improvements were associated with performance outcomes measured by the test battery.

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14. Yang L, Fang F, Jin H, Wu Y. [Clinical characterisation of creatine transporter deficiency associated with SLC6A8 gene variants]. Zhonghua Er Ke Za Zhi;2024 (Dec 2);62(12):1202-1207.

Objective: To analyze the clinical features of creatine transporter(CRTR) deficiency associated with SLC6A8 gene variants. Methods: The clinical data (clinical presentation, brain imaging, creatine metabolism test and gene variants) of 5 patients admitted to Beijing Children’s Hospital, Capital Medical University and diagnosed with CRTR deficiency associated with SLC6A8 gene variants from January 2016 to June 2024 were retrospectively analyzed. Results: A total of 5 patients, all male, presented with the onset of the disease at 1 year and 1 month old to 1 year and 10 months old, and diagnosis at 1 year and 3 months to 9 years old. All patients exhibited varying degrees of intellectual and physical developmental deficits, with autistic-like behaviors present in 2 patients and convulsive episodes present in 4 patients. The brain magnetic resonance imaging, of all 5 patients showed either poor or slightly delayed myelination. Additionally, the brain magnetic resonance spectroscopy (MRS) imaging of 5 patients all showed decreased creatine peaks, and 4 patients had elevated urinary creatine levels indicated by blood and (or) urine creatine metabolism tests. There were 3 patients completed blood creatinine tests, all indicating reduction. Whole-exome sequencing was conducted on all 5 patients, and 4 unreported novel variants were identified: c.371G>C, c.1017-1G>A, c.912+1G>T and c.1016+2T>A. Following treatment with creatine, arginine, and glycine supplementation, no significant advancement was observed in motor and language development. Conclusions: CRTR deficiency associated with SLC6A8 gene variants manifests as developmental delay with or without seizures, with atypical clinical features, the presence of decreased blood creatinine levels and elevated urinary creatine levels. Combined with brain MRS and genetic testing results, patients can be diagnosed.

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15. Zarhin D, Asher N. Orchestrating rhythms in autism care: enacting parental expertise in and through time. Health Sociol Rev;2024 (Dec 2):1-17.

This article delves into the underexplored relationship between lay expertise and temporality by analysing semi-structured interviews with parents who treat their autistic children using complementary and alternative medicine (CAM). The analysis indicates that time and temporalities play a significant role in how parents construct and enact their expertise. Faced with uncertainty, urgency, and inadequate support from medical and educational systems, parents assumed crucial responsibilities in managing their children’s therapies. Over time, they acquired knowledge and skills, ultimately claiming expertise in caring for their children, making therapy decisions and administering treatments. Parents engaged in complex time work as they attempted to orchestrate everyday, developmental, therapeutic, and social rhythms, alternating their focus between future and present. They endeavoured to synchronise their children’s rhythms with those of peers by using CAM therapies not yet adopted into conventional medicine, which they perceived as slow and outdated. This study contributes novel insights into autism care, temporalities of care, and the under-examined nexus between lay expertise and temporality.

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