1. Arslan R, Yanık D, Pekşen Akça R. Investigation of Menstrual Hygiene and Self-Care Skills of Adolescent Girls with Autism Spectrum Disorder: Mother Views. J Autism Dev Disord. 2024.

PURPOSE: Puberty a period of transition from childhood to adulthood, poses problems that are difficult to manage for typically developing adolescents, but even more difficult for adolescents with autism. It is vital that girls with autism spectrum disorder (ASD), like their typically developing peers, are able to manage these physiological processes in a healthy way and learn self-care and hygiene behaviours without being dependent on others. Given the contribution of mothers to the menstrual hygiene and self-care skills of adolescent girls, this study aims to explore the views of mothers. METHODS: The study is a case study designed in the qualitative research model. The research was carried out with the participation of 10 mothers met the necessary criteria and agreed to take part in the study voluntarily. The data obtained were subjected to descriptive and thematic analysis. Codes, sub-themes and main themes were created. RESULTS: The research identifies the themes of self-care and menstrual hygiene, preparations made during menstruation, behavioral problems in adolescents, the person who carries out hygiene and self-care, and situations that tire/strain mothers during menstruation. CONCLUSION: At the end of the research, it was concluded that the adolescent girls with ASD are mostly unable to perform their self-care and hygiene adequately, and that the mothers do nothing to prepare their daughters for adolescence. It was also concluded that the most stressful situation for mothers during adolescence is usually the difficulty their daughters have in using sanitary pads, cleaning armpits and genital hair, and bathing.

Lien vers le texte intégral (Open Access ou abonnement)

2. Chen L, Liu LM, Guo M, Du Y, Chen YW, Xiong XY, Cheng Y. Altered leptin level in autism spectrum disorder and meta-analysis of adipokines. BMC Psychiatry. 2024; 24(1): 479.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

Lien vers le texte intégral (Open Access ou abonnement)

3. DeSpenza T, Jr., Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina ML, Desmet N, Dang HQ, Fields J, Nelson-Williams C, Zhang J, Mekbib KY, Dennis E, Mehta NH, Duy PQ, Shimelis H, Walsh LK, Marlier A, Deniz E, Lake EMR, Constable RT, Hoffman EJ, Lifton RP, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper SL, Jin SC, Kahle KT, Luikart BW. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proc Natl Acad Sci U S A. 2024; 121(27): e2314702121.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.

Lien vers le texte intégral (Open Access ou abonnement)

4. Friedman C, Luxama CM. Mental and Behavioral Health, and Crisis Services for People with Intellectual and Developmental Disabilities in Medicaid Home- and Community-Based Services. J Autism Dev Disord. 2024.

People with intellectual and developmental disabilities (IDD) often have higher rates of comorbid mental health conditions compared to the general population. Yet, many people with IDD also have unmet needs for mental and behavioral health services. The aim of this study was to examine how states provided mental and behavior health, and crisis services to people with IDD in their Home- and Community-Based Services (HCBS) programs, the largest funding mechanism for Long-Term Services and Supports (LTSS) for people with IDD in the United States. We analyzed fiscal year (2021) Medicaid HCBS waivers for people with IDD from across the United States to examine if and how they provided mental and behavior health, and crisis services. States projected spending $968.9 million for mental and behavior health, and crisis services for 190,299 people with IDD. Applied behavior analysis services were provided at greater rates than positive behavior supports and other forms of behavior interventions. While most states provided mental and behavior health, and crisis services in their waivers, there were vast inconsistencies in how they did so, across states, waivers, and services. HCBS are a crucial safety net to ensure people with IDD, especially those who also have mental health disabilities, can live and thrive in their communities.

Lien vers le texte intégral (Open Access ou abonnement)

5. Gallegos E, Gevarter C, Binger C, Hartley M. An Interprofessional Graduate Student and Family Coaching Program in Naturalistic Communication Techniques. Semin Speech Lang. 2024; 45(3): 171-93.

Researchers implemented a short-term cascading coaching model focusing on naturalistic developmental behavioral intervention with three participant triads. Triads consisted of a graduate student clinician, a minimally verbal child with autism spectrum disorder, and the child’s parent. Coaching and intervention occurred during an interprofessional summer clinic that included graduate student clinicians from special education and speech and hearing sciences departments. The efficacy of short-term instruction, researcher coaching for student clinicians, and student clinician coaching of parents was evaluated using a multiple baseline across participants’ design. The dependent variables were student clinician’s and parent’s use of elicitation techniques (creating communication temptations, waiting, and prompting) and response techniques (naturally reinforcing children’s communication and providing spoken language models). Following coaching, parents and student clinicians from all triads increased their use of elicitation and response techniques, with very large effect sizes across all variables. Visual analysis findings suggest individualized differences and variability across triads. Implications for graduate education and parent coaching programs are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

6. Gatica-Bahamonde G, Mendez-Fadol A, Sánchez-Sepúlveda F, Peñailillo-Diaz C, van Kessel R, Czabanowska K, Roman-Urrestarazu A. Testing an online screening for autism in the COVID-19 pandemic: a psychometric study of the Q-CHAT-24 in Chilean toddlers. Front Psychiatry. 2024; 15: 1363976.

BACKGROUND: The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18-24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile. METHODS: An intentional non-probabilistic sampling was used. Three hundred and thirteen toddlers were examined. Participants completed an online version of the Q-CHAT-24 which was disseminated through the REDCap platform. Evidence of reliability through internal consistency and evidence of predictive validity through ROC curve analysis were realized. RESULTS: The mean age of the children evaluated was 21.16 months. The Shapiro-Wilk test revealed that Q-CHAT-24 scores was normally distributed. 71 cases (23.12%) scored 38 points or more on the Q-CHAT-24, qualifying as Autistic Risk. 48 cases (15.63%) were confirmed as autistic through the ADOS-2 Module T. All items were positively correlated with Q-CHAT-24 total score. All items were positively correlated with Q-CHAT-24 total score. Internal consistency was acceptable for the Q-CHAT-24 (Cronbach ´s α=0.78). The internal consistencies were analyzed for the Q-CHAT-24 Factors, and they were good for factor 1 « Communication and Social Interaction » (Cronbach ´s α=0.85) and acceptable for factor 2 « Restrictive and Repetitive Patterns » (Cronbach ´s α=0.74). Receiver operating characteristic (ROC) curve analyses were performed. The AUC values were 0.93 with statistical significance (p<0.01). For the cut-off point of 38, the Sensitivity, Specificity and Youden index values were 0.89, 0.8 and 0.7, respectively. The Positive Predictive Value (PPV) was 86% and the Negative Predictive Value (NPV) was 85%. CONCLUSIONS: In accordance with the objectives of this study, evidence of reliability and predictive validity was demonstrated for the Q-CHAT-24 in this Chilean population. More importantly, this study provides Sensitivity and Specificity data for a remote application version of an autism screening tool already validated in Chile. The implications of this have to do with the possibility of establishing a remote assessment system for children at risk of autism on a population scale.

Lien vers le texte intégral (Open Access ou abonnement)

7. Ivanova DV, Khabirov RA, Ziganshin AU. Ectonucleotidase Activity in Smooth Muscle Tissues of Rats with a Valproate Model of Autism. Bull Exp Biol Med. 2024.

Ectonucleotidases play an important role in regulating the level of extracellular nucleotides and nucleosides and are an important part of the regulation of the effects of adenosine and ATP on adenosine and P2 receptors, respectively. We have previously established the ambiguous effect of P2 receptor agonists on the contractile activity of smooth muscle tissue in rats with the valproate model of autism. In this work, HPLC was used to evaluate the activity of ectonucleotidases in the smooth muscle tissues of the internal organs of rats with a valproate model of autism. The activity of ectonucleotidases was significantly higher in the smooth muscle tissues of the duodenum, vas deferens, and bladder, but lower in the ileum and uterus. The results obtained make it possible to compare the activity of ectonucleotidases identified here with changes in P2 receptor-mediated contractility of smooth muscle tissues revealed in our previous experiments.

Lien vers le texte intégral (Open Access ou abonnement)

8. Khound M, Ghosh S, Kaushik JS. Enhancing Skills for Early Detection and Management of Autism in Schools. Indian J Pediatr. 2024.

Lien vers le texte intégral (Open Access ou abonnement)

9. Kourdougli N, Nomura T, Wu M, Heuvelmans A, Dobler Z, Contractor A, Portera-Cailliau C. The NKCC1 inhibitor bumetanide restores cortical feedforward inhibition and lessens sensory hypersensitivity in early postnatal fragile X mice. Biol Psychiatry. 2024.

BACKGROUND: Exaggerated responses to sensory stimuli, a hallmark of Fragile X syndrome (FXS), contribute to anxiety and learning challenges. Sensory hypersensitivity is recapitulated in the Fmr1 knockout (KO) mouse model of FXS. Recent studies in Fmr1 KO mice have demonstrated differences in activity of cortical interneurons and a delayed switch in the polarity of GABA signaling during development. Previously, we reported that blocking the chloride transporter NKCC1 with the diuretic bumetanide, could rescue synaptic circuit phenotypes in primary somatosensory cortex (S1) of Fmr1 KO mice. However, it remains unknown whether bumetanide can rescue earlier circuit phenotypes or sensory hypersensitivity in Fmr1 KO mice. METHODS: We used acute and chronic systemic administration of bumetanide in Fmr1 KO mice and performed in vivo 2-photon calcium imaging to record neuronal activity, while tracking mouse behavior with high-resolution videos. RESULTS: We demonstrate that layer (L) 2/3 pyramidal neurons in S1 of Fmr1 KO mice show a higher frequency of synchronous events at postnatal day (P) 6 compared to wild-type controls. This was reversed by acute administration of bumetanide. Furthermore, chronic bumetanide treatment (P5-P14) restored S1 circuit differences in Fmr1 KO mice, including reduced neuronal adaptation to repetitive whisker stimulation, and ameliorated tactile defensiveness. Bumetanide treatment also rectified the reduced feedforward inhibition of L2/3 neurons in S1 and boosted the circuit participation of parvalbumin interneurons. CONCLUSIONS: This further supports the notion that synaptic, circuit, and sensory behavioral phenotypes in Fmr1 KO can be mitigated by inhibitors of NKCC1, such as the FDA-approved diuretic bumetanide.

Lien vers le texte intégral (Open Access ou abonnement)

10. Leoncini S, Boasiako L, Di Lucia S, Beker A, Scandurra V, Vignoli A, Canevini MP, Prato G, Nobili L, Nicotera AG, Di Rosa G, Chiarini MBT, Cutrera R, Grosso S, Lazzeri G, Tongiorgi E, Morano P, Botteghi M, Barducci A, De Felice C. 24-h continuous non-invasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: evidence of an overlooked chronic fatigue status. Front Neurol. 2024; 15: 1388506.

BACKGROUND: Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients. METHODS: A total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7-35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L’Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients’ contributions to the surrounding water vapor partial pressure [P(H2O) (pt)] and carbon dioxide [P(CO2) (pt)] were indirectly estimated. RESULTS: Of the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing. CONCLUSION: Our findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression.

Lien vers le texte intégral (Open Access ou abonnement)

11. Liloia D, Zamfira DA, Tanaka M, Manuello J, Crocetta A, Keller R, Cozzolino M, Duca S, Cauda F, Costa T. Disentangling the role of gray matter volume and concentration in autism spectrum disorder: A meta-analytic investigation of 25 years of voxel-based morphometry research. Neurosci Biobehav Rev. 2024; 164: 105791.

Despite over two decades of neuroimaging research, a unanimous definition of the pattern of structural variation associated with autism spectrum disorder (ASD) has yet to be found. One potential impeding issue could be the sometimes ambiguous use of measurements of variations in gray matter volume (GMV) or gray matter concentration (GMC). In fact, while both can be calculated using voxel-based morphometry analysis, these may reflect different underlying pathological mechanisms. We conducted a coordinate-based meta-analysis, keeping apart GMV and GMC studies of subjects with ASD. Results showed distinct and non-overlapping patterns for the two measures. GMV decreases were evident in the cerebellum, while GMC decreases were mainly found in the temporal and frontal regions. GMV increases were found in the parietal, temporal, and frontal brain regions, while GMC increases were observed in the anterior cingulate cortex and middle frontal gyrus. Age-stratified analyses suggested that such variations are dynamic across the ASD lifespan. The present findings emphasize the importance of considering GMV and GMC as distinct yet synergistic indices in autism research.

Lien vers le texte intégral (Open Access ou abonnement)

12. Martin P, Szkop KJ, Robert F, Bhattacharyya S, Beauchamp RL, Brenner J, Redmond NE, Huang S, Erdin S, Larsson O, Ramesh V. TSC2 loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts in an mTORC1- and MNK1/2-reversible fashion. bioRxiv. 2024.

Tuberous sclerosis complex (TSC) is an inherited neurodevelopmental disorder (NDD) with frequent manifestations of epilepsy and autism spectrum disorder (ASD). TSC is caused by inactivating mutations in TSC1 or TSC2 tumor suppressor genes, with encoded proteins hamartin (TSC1) and tuberin (TSC2) forming a functional complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. This has led to treatment with allosteric mTORC1 inhibitor rapamycin analogs (« rapalogs ») for TSC tumors; however, rapalogs are ineffective for treating neurodevelopmental manifestations. mTORC1 signaling controls protein synthesis by regulating formation of the eIF4F complex, with further modulation by MNK1/2 kinases via phosphorylation of the eIF4F subunit eIF4E. While both these pathways modulate translation, comparing their impact on transcriptome-wide mRNA translation, as well as effects of inhibiting these pathways in TSC has not been explored. Here, employing CRISPR-modified, isogenic TSC2 patient-derived neural progenitor cells (NPCs), we have examined transcriptome-wide changes in mRNA translation upon TSC2 loss. Our results reveal dysregulated translation in TSC2 -Null NPCs, which significantly overlaps with the translatome from TSC1 -Null NPCs. Interestingly, numerous non-monogenic ASD-, NDD-and epilepsy-associated genes identified in patients harboring putative loss-of-function mutations, were translationally suppressed in TSC2 -Null NPCs. Importantly, translation of these ASD- and NDD-associated genes was reversed upon inhibition of either mTORC1 or MNK1/2 signaling using RMC-6272 or eFT-508, respectively. This study establishes the importance of mTORC1-eIF4F- and MNK-eIF4E-sensitive mRNA translation in TSC, ASD and other neurodevelopmental disorders laying the groundwork for evaluating drugs in clinical development that target these pathways as a treatment strategy for these disorders.

Lien vers le texte intégral (Open Access ou abonnement)

13. Mazurek MO, Nevill RE, Orlando K, Page K, Howard M, Davis BE. Integration of Family Navigation into ECHO Autism for Pediatric Primary Care in Underserved Communities. J Autism Dev Disord. 2024.

Children with autism from underserved communities face complex system-, provider-, and family-level barriers to accessing timely diagnosis and early intervention. The current study evaluated the preliminary effects and feasibility of a new program (ECHO Autism LINKS) that integrated pediatric primary care provider (PCP) training with family navigation (FN) to bridge the gaps between screening, referral, and service access. Three cohorts of PCPs (n = 42) participated in the program, which consisted of 60-minute sessions delivered by Zoom twice per month for 12 months. Each session included didactics, case-based learning, and collaborative discussion with participants and an interdisciplinary team of experts. Family navigators were members of the expert team and provided FN services to families referred by PCP participants. Program attendance and engagement were strong, with 40 cases presented and 258 families referred for FN services, most of whom (83%) needed help accessing and connecting with services, and 13% required ongoing support due to complex needs. PCPs demonstrated significant improvements in self-efficacy in providing best-practice care for children with autism, reported high satisfaction, and observed improved knowledge and practice as a result of the program. The results of this initial pilot provide support for the feasibility, acceptability, and preliminary efficacy of the ECHO Autism LINKS program. The model holds promise in addressing complex barriers to healthcare access by providing both PCPs and families with the knowledge and support they need. Future research is needed to evaluate the efficacy and effectiveness of the program in improving child and family outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

14. Megari K, Frantzezou CK, Polyzopoulou ZA, Tzouni SK. Neurocognitive features in childhood & adulthood in autism spectrum disorder: A neurodiversity approach. Int J Dev Neurosci. 2024.

OBJECTIVES: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a diverse profile of cognitive functions. Heterogeneity is observed among both baseline and comorbid features concerning the diversity of neuropathology in autism. Symptoms vary depending on the developmental stage, level of severity, or comorbidity with other medical or psychiatric diagnoses such as intellectual disability, epilepsy, and anxiety disorders. METHOD: The neurodiversity movement does not face variations in neurological and cognitive development in ASD as deficits but as normal non-pathological human variations. Thus, ASD is not identified as a neurocognitive pathological disorder that deviates from the typical, but as a neuro-individuality, a normal manifestation of a neurobiological variation within the population. RESULTS: In this light, neurodiversity is described as equivalent to any other human variation, such as ethnicity, gender, or sexual orientation. This review will provide insights about the neurodiversity approach in children and adults with ASD. Using a neurodiversity approach can be helpful when working with children who have autism spectrum disorder (ASD). DISCUSSION: This method acknowledges and values the various ways that people with ASD interact with one another and experience the world in order to embrace the neurodiversity approach when working with children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

15. Nutor C, Dickerson AS, Hsu T, Al-Jadiri A, Camargo CA, Schweitzer JB, Shuster CL, Karagas MR, Madan JC, Restrepo B, Schmidt RJ, Lugo-Candelas C, Neiderhiser J, Sathyanarayana S, Dunlop AL, Brennan PA. Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program. Autism Res. 2024.

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

Lien vers le texte intégral (Open Access ou abonnement)

16. O’Loghlen J, McKenzie M, Lang C, Paynter J. Correction: Repetitive Behaviors in Autism and Obsessive-Compulsive Disorder: A Systematic Review. J Autism Dev Disord. 2024.

Lien vers le texte intégral (Open Access ou abonnement)

17. Papastamou F, Dumont C, Destrebecqz A, Kissine M. Predictive Processing During Cue-Outcome Associative Learning in Autistic Children. J Autism Dev Disord. 2024.

PURPOSE: Predictive coding theories posit that autism is characterized by an over-adjustment to prediction errors, resulting in frequent updates of prior beliefs. Atypical weighting of prediction errors is generally considered to negatively impact the construction of stable models of the world, but may also yield beneficial effects. In a novel associative learning paradigm, we investigated whether unexpected events trigger faster learning updates in favour of subtle but fully predictive cues in autistic children compared to their non-autistic counterparts. We also explored the relationship between children’s language proficiency and their predictive performances. METHODS: Anticipatory fixations and explicit predictions were recorded during three associative learning tasks with deterministic or probabilistic contingencies. One of the probabilistic tasks was designed so that a fully predictive but subtle cue was overshadowed by a less predictive salient one. RESULTS: Both autistic and non-autistic children based their learning on the salient cue, and, contrary to our predictions, showed no signs of updating in favour of the subtle cue. While both groups demonstrated associative learning, autistic children made less accurate explicit predictions than their non-autistic peers in all tasks. Explicit prediction performances were positively correlated with language proficiency in non-autistic children, but no such correlation was observed in autistic children. CONCLUSION: These results suggest no over-adjustment to prediction errors in autistic children and highlight the need to control for general performance in cue-outcome associative learning in predictive processing studies. Further research is needed to explore the nature of the relationship between predictive processing and language development in autism.

Lien vers le texte intégral (Open Access ou abonnement)

18. Rahdar M, Davoudi S, Dehghan S, Javan M, Hosseinmardi N, Behzadi G, Janahmadi M. Reversal of electrophysiological and behavioral deficits mediated by 5-HT7 receptor upregulation following LP-211 treatment in an autistic-like rat model induced by prenatal valproic acid exposure. Neuropharmacology. 2024; 257: 110057.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations and imbalances in multiple brain neurochemical systems, particularly the serotonergic neurotransmission. This includes changes in serotonin (5-HT) levels, aberrations in 5-HT transporter activity, and decreased synthesis and expression of 5-HT receptors (5-HT7Rs). The exact role of the brain 5-HT system in the development of ASD remains unclear, with conflicting evidence on its involvement. Recently, we have reported research has shown a significant decrease in serotonergic neurons originating from the raphe nuclei and projecting to the CA1 region of the dorsal hippocampus in autistic-like rats. Additionally, we have shown that chronic activation of 5-HT7Rs reverses the effects of autism induction on synaptic plasticity. However, the functional significance of 5-HT7Rs at the cellular level is still not fully understood. This study presents new evidence indicating an upregulation of 5-HT7R in the CA1 subregion of the hippocampus following the induction of autism. The present account also demonstrates that activation of 5-HT7R with its agonist LP-211 can reverse electrophysiological abnormalities in hippocampal pyramidal neurons in a rat model of autism induced by prenatal exposure to VPA. Additionally, in vivo administration of LP-211 resulted in improvements in motor coordination, novel object recognition, and a reduction in stereotypic behaviors in autistic-like offspring. The findings suggest that dysregulated expression of 5-HT7Rs may play a role in the pathophysiology of ASD, and that agonists like LP-211 could potentially be explored as a pharmacological treatment for autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

19. Sakamoto N, Oe M, Ozone M. An Exploratory Study of the Associations Between Sensory Processing Patterns and Emotional/Behavioral Problems in Children with Autism Spectrum Disorder. Kurume Med J. 2024; 70(1.2): 47-52.

AIM: In autism spectrum disorder (ASD), abnormal sensory processing patterns are observed in various sensory modalities, including visual, auditory, touch, olfactory, taste, vestibular, and proprioceptive senses. Few studies have examined the relationship between sensory processing patterns and emotions, or their effects on daily life. We investigated the relationship between sensory processing patterns and emotional/behavioral problems in children with ASD. PARTICIPANTS AND METHODS: A retrospective chart review was conducted. Forty-three children with ASD (33 boys, 10 girls, median age 9 years) in the outpatient clinic of a psychiatric hospital participated; their parent (s) were invited to complete the Sensory Profile 2 (SP2) and the Child Behavior Checklist (CBCL) questionnaires. The participants’ teachers were invited to complete the Teacher’s Report Form (TRF). RESULTS: In the correlation analyses, each of the four quadrants of the SP2 (low registration, sensory seeking, hypersensitivity, and sensory avoiding) had significant positive correlations with different types of emotional and behavioral problems measured by the CBCL. Focusing on emotion, ‘anxious/depressed’ was correlated with low registration (r = 0.41) and sensory avoiding (r = 0.60), while ‘withdrawal/depressed’ was correlated with sensory avoiding (r = 0.46). Only one significant correlation was revealed between the SP2 and the TRF. CONCLUSION: Our results suggest a link between sensory processing patterns and emotional/behavioral problems. In school settings, the relationship between sensory processing patterns and emotional/behavioral problems may be easily overlooked.

Lien vers le texte intégral (Open Access ou abonnement)

20. Shakhawat AMD, Foltz JG, Nance AB, Bhateja J, Raymond JL. Systemic pharmacological suppression of neural activity reverses learning impairment in a mouse model of Fragile X syndrome. Elife. 2024; 12.

The enhancement of associative synaptic plasticity often results in impaired rather than enhanced learning. Previously, we proposed that such learning impairments can result from saturation of the plasticity mechanism (Nguyen-Vu et al., 2017), or, more generally, from a history-dependent change in the threshold for plasticity. This hypothesis was based on experimental results from mice lacking two class I major histocompatibility molecules, MHCI H2-K(b) and H2-D(b) (MHCI K(b)D(b-/-)), which have enhanced associative long-term depression at the parallel fiber-Purkinje cell synapses in the cerebellum (PF-Purkinje cell LTD). Here, we extend this work by testing predictions of the threshold metaplasticity hypothesis in a second mouse line with enhanced PF-Purkinje cell LTD, the Fmr1 knockout mouse model of Fragile X syndrome (FXS). Mice lacking Fmr1 gene expression in cerebellar Purkinje cells (L7-Fmr1 KO) were selectively impaired on two oculomotor learning tasks in which PF-Purkinje cell LTD has been implicated, with no impairment on LTD-independent oculomotor learning tasks. Consistent with the threshold metaplasticity hypothesis, behavioral pre-training designed to reverse LTD at the PF-Purkinje cell synapses eliminated the oculomotor learning deficit in the L7-Fmr1 KO mice, as previously reported in MHCI K(b)D(b-/-)mice. In addition, diazepam treatment to suppress neural activity and thereby limit the induction of associative LTD during the pre-training period also eliminated the learning deficits in L7-Fmr1 KO mice. These results support the hypothesis that cerebellar LTD-dependent learning is governed by an experience-dependent sliding threshold for plasticity. An increased threshold for LTD in response to elevated neural activity would tend to oppose firing rate stability, but could serve to stabilize synaptic weights and recently acquired memories. The metaplasticity perspective could inform the development of new clinical approaches for addressing learning impairments in autism and other disorders of the nervous system.

Lien vers le texte intégral (Open Access ou abonnement)

21. Singh B. In women with epilepsy, use of valproate in the second half of pregnancy was linked to autism in offspring. Ann Intern Med. 2024.

Hernández-Díaz S, Straub L, Bateman BT, et al. Risk of autism after prenatal topiramate, valproate, or lamotrigine exposure. N Engl J Med. 2024;390:1069-1079. 38507750.

Lien vers le texte intégral (Open Access ou abonnement)

22. Stahmer AC, Yu Y, Suhrheinrich J, Melgajaro M, Schetter P. The Role of Implementation Climate in Moderating Educator Use of Evidence-Based Practices and Outcomes for Autistic Students. J Autism Dev Disord. 2024.

Ensuring effective use of evidence-based practice (EBP) for autism in schools is imperative due to the significantly increasing number of autistic students receiving school services each year. High-quality EBP use has proven challenging in schools. Research indicates implementation climate, or how EBP are supported, rewarded, and valued, and EBP resources are related to successful implementation. However, limited understanding of system-level contextual factors that impact EBP implementation for school-based providers makes development of appropriate implementation supports challenging. Understanding these factors is crucial for selecting and tailoring implementation strategies to support EBP scale up. In this observational study, California school-based providers (n = 1084) completed surveys related to implementation climate, leadership, autism experience and EBP implementation (use, competence, knowledge). Student outcomes included state level academic and behavioral indicators. Using an implementation science framework (Aarons et al., in Administration and Policy in Mental Health and Mental Health Services Research 38:4-23, 2011) and multilevel modeling, we examined the relationship between EBP Implementation and student outcomes and the moderation effects of provider and district level factors. Higher implementation climate predicted better EBP implementation outcomes, and proved more impactful when provider hands-on autism experience was low. Greater EBP resources predicted a higher percentage of students who met math standards only when district poverty level was high. Our findings suggested moderating effects on EBP implementation from both provider and system level factors. Implementation climate and resources may be especially key in addressing equity issues related to high poverty schools in which teachers often have less autism experience.

Lien vers le texte intégral (Open Access ou abonnement)

23. Stein Elger R, Chowdhury SK, Pacheco Garrillo M, Sauls R, Sundaramurugan S, Rozen E, Puri H, Brice DJ, Liu J, Bakour C, Kirby RS. The Role of Adverse Childhood Experience in the Relationship Between Autism Severity and Early Intervention and Special Education Plan. J Autism Dev Disord. 2024.

The purpose of this study is to examine the association between autism spectrum disorder (ASD) severity and having a special education or early intervention plan and the impact of adverse childhood experiences (ACEs) on this association. This study used the 2020-2021 National Survey of Children’s Health (NSCH) and included 2,537 children aged 3-17 years old who currently have ASD. Multivariable logistic regression, controlling for demographic and family characteristics and health status, was used to explore the association between autism severity and having an early intervention plan. The analysis was stratified by the number of ACEs to explore their role in the association. Children with moderate or severe ASD were more likely to have a special education or early intervention plan than those with mild ASD in the crude and adjusted models. This association continued to be true for children who experienced 1 ACE (aOR: 2.28, 95%CI: 1.09-4.77) but not true for those who experienced no ACEs (aOR: 1.16, 95%CI: 0.70-1.94) and 2 or more ACEs (aOR: 1.84, 95%CI: 0.92-3.69). Results demonstrate that children with moderate or severe autism were more likely to receive early intervention or special education. This association changed depending on the number of ACEs experiences.

Lien vers le texte intégral (Open Access ou abonnement)

24. Xiao J, Zhu H, Kong W, Jiang X, Wu C, Chen JG, Li X. Stabilizing axin leads to optic nerve hypoplasia in a mouse model of autism. Exp Eye Res. 2024; 245: 109988.

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

Lien vers le texte intégral (Open Access ou abonnement)

25. Yang F, Wang M. Effect of the OPHN1 novel variant c.1025+1 G>A on RNA splicing: insights from a minigene assay. BMC Med Genomics. 2024; 17(1): 175.

This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient’s mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene’s mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.

Lien vers le texte intégral (Open Access ou abonnement)