1. Akkus N, Cubuk PO. Diagnostic yield of the chromosomal microarray analysis in turkish patients with unexplained development delay/ıntellectual disability(ID), autism spectrum disorders and/or multiple congenital anomalies and new clinical findings. Mol Biol Rep. 2024; 51(1): 577.

BACKGROUND: Chromosomal microarray analysis is an essential tool for copy number variants detection in patients with unexplained developmental delay/intellectual disability, autism spectrum disorders, and multiple congenital anomalies. The study aims to determine the clinical significance of chromosomal microarray analysis in this patient group. Another crucial aspect is the evaluation of copy number variants detected in terms of the diagnosis of patients. METHODS AND RESULTS: A Chromosomal microarray analysis was was conducted on a total of 1227 patients and phenotype-associated etiological diagnosis was established in 135 patients. Phenotype-associated copy number variants were detected in 11% of patients. Among these, 77 patients 77 (57%, 77/135) were diagnosed with well-recognized genetic syndromes and phenotype-associated copy number variants were found in 58 patients (42.9%, 58/135). The study was designed to collect data of patients in Kocaeli Derince Training and Research Hospital retrospectively. In our study, we examined 135 cases with clinically significant copy number variability among all patients. CONCLUSIONS: In this study, chromosomal microarray analysis revealed pathogenic de novo copy number variants with new clinical features. Chromosomal microarray analysis in the Turkish population has been reported in the largest patient cohort to date.

Lien vers le texte intégral (Open Access ou abonnement)

2. Alwetaid MY, Almanaa TN, Bakheet SA, Ansari MA, Nadeem A, Attia SM, Hussein MH, Attia MS, Ahmad SF. Aflatoxin B(1) Exposure Exacerbates Chemokine Receptor Expression in the BTBR T(+) Itpr3(tf)/J Mouse Model, Unveiling Insights into Autism Spectrum Disorder: A Focus on Brain and Spleen. Reprod Toxicol. 2024: 108599.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant difficulties in social interaction, communication, and repeated stereotypic behaviour. Aflatoxin B(1) (AFB(1)) is the most potent and well-known mycotoxin in various food sources. Despite its propensity to generate significant biochemical and structural changes in human and animal tissues, the influence of AFB(1) on ASD has yet to be thoroughly studied. Mounting evidence indicates that chemokine receptors play a crucial function in the central nervous system and are implicated in developing several neuroinflammatory disorders. Chemokine receptors in individuals with ASD were elevated in the anterior cingulate gyrus astrocytes, cerebellum, and brain. METHODS: The BTBR T(+)Itpr3(tf/)J (BTBR) mice are inbred strains that exhibit strong and consistently observed deficits in social interactions, characterized by excessive self-grooming and limited vocalization in social contexts. We examined the impact of AFB(1) on CCR3-, CCR7-, CCR9-, CXCR3-, CXCR4-, and CXCR6-expressing I-A/I-E(+) cells in the spleen of the BTBR mouse model of autism. We evaluated the mRNA levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 chemokine receptors in the brain. RESULTS: The exposure to AFB(1) in BTBR mice resulted in a significant rise in the number of I-A/I-E(+)CCR3(+), I-A/I-E(+)CCR7(+), I-A/I-E(+)CCR9(+), I-A/I-E(+)CXCR3(+), I-A/I-E(+)CXCR4(+), and I-A/I-E(+)CXCR6(+) cells. Furthermore, exposure to AFB(1) increased mRNA expression levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 in the brain. CONCLUSIONS: These findings highlight that AFB(1) exposure increases the expression of chemokine receptors in BTBR mice, indicating the necessity for further research into AFB(1)’s role in the development of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

3. Byl M, Morere AC, Fonteyne C. Undiagnosed Autism Spectrum Disorder in a Child With Chronic Pain: A Case Report. Cureus. 2024; 16(3): e56946.

The literature acknowledges the presence of psychiatric comorbidities in pediatric chronic pain populations. Few studies have focused on comorbidity with autism spectrum disorders. We describe the case of a 10-year-old patient at the onset of his care by the chronic pain team. This boy had been experiencing refractory multifocal chronic pain for three years and had undergone multiple medical examinations that had not identified the cause of the pain or provided sufficient pain relief. During our consultations, the behavioral peculiarities (averted gaze, inhibition), the atypical description of this boy’s pain (pain in the hair), and sensory peculiarities (intolerance to noise) led us to suspect an autism spectrum disorder. A multidisciplinary approach, including a thorough developmental history and evaluation by an autism resource center, confirmed this suspicion. The diagnosis of an underlying autism spectrum disorder allowed us to guide our management by integrating the specific sensory aspects of this boy. Concurrently, we facilitated the family’s better understanding of the young boy’s issues and addressed his social and communication difficulties. Through multidisciplinary care and the integration of these various aspects, our patient’s clinical situation improved. Multidisciplinary management is essential in chronic pain teams.

Lien vers le texte intégral (Open Access ou abonnement)

4. Chang JP, Chou WJ, Chiu YN, Tsai WC, Shang CY, Wu YY, Gau SS. Mothering and mother-child interactions in the unaffected siblings of autistic children. Dev Med Child Neurol. 2024.

AIM: To investigate parenting and mother-child interactions in unaffected siblings of autistic children. METHOD: This cross-sectional study enrolled 274 probands with a DSM-5 diagnosis of autism spectrum disorder (ASD) (87.4% male; mean [SD] age = 11 years 4 months [3 years 2 months]), their unaffected siblings (n = 274, 46.72% male; mean [SD] age = 11 years 3 months [3 years 4 months]), and 296 age-balanced and sex-balanced typically developing children (82.77% male; mean [SD] age = 11 years 3 months [2 years 8 months]). Maternal parenting styles and mother-child interactions were assessed using maternal reporting. RESULTS: Regardless of the child’s age, maternal educational level, or presence of attention-deficit/hyperactivity disorder, autistic children received more overprotective and controlling parental behaviour than unaffected children. Correlates for parenting, mother-child interactions, and behavioural problems in the home setting in children with ASD and typically developing children were autistic traits, maternal anxiety and depressive symptoms, and maternal autistic characteristics; those in unaffected siblings were age, autistic traits, maternal educational level, and maternal autistic characteristics. INTERPRETATION: The diagnosis of ASD in a child can significantly influence maternal parenting behaviours, mother-child interactions, and the child’s behavioural problems in the home setting. Furthermore, maternal anxiety or depressive symptoms, along with autistic characteristics in both mother and child, might shape parenting practices and exacerbate behavioural difficulties in autistic children.

Lien vers le texte intégral (Open Access ou abonnement)

5. Golbaghi N, Naeimi S, Darvishi A, Najari N, Cussotto S. Probiotics in autism spectrum disorder: Recent insights from animal models. Autism. 2024: 13623613241246911.

Autism spectrum disorder is a neurodevelopmental disorder characterized by a wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism spectrum disorder, often proving ineffective and accompanied by a multitude of side effects. The gut microbiota is the reservoir of bacteria inhabiting our gastrointestinal tract. The gut microbial alterations observed in individuals with autism spectrum disorder, including elevated levels of Bacteroidetes, Firmicutes, and Proteobacteria, as well as reduced levels of Bifidobacterium, provide a basis for further investigation into the role of the gut microbiota in autism spectrum disorder. Recent preclinical studies have shown favorable outcomes with probiotic therapy, including improvements in oxidative stress, anti-inflammatory effects, regulation of neurotransmitters, and restoration of microbial balance. The aim of this review is to explore the potential of probiotics for the management and treatment of autism spectrum disorder, by investigating insights from recent studies in animals.

Lien vers le texte intégral (Open Access ou abonnement)

6. Jiang X, Shou XJ, Zhao Z, Chen Y, Meng FC, Le J, Song TJ, Xu XJ, Guo W, Ke X, Cai XE, Zhao W, Kou J, Huo R, Liu Y, Yuan HS, Xing Y, Han JS, Han SP, Li Y, Lai H, Zhang L, Jia MX, Liu J, Liu X, Kendrick KM, Zhang R. A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood. Psychoradiology. 2023; 3: kkad005.

BACKGROUND: Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers, particularly in young children at the age when symptoms become fully established. Furthermore, such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level. OBJECTIVE: This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children. METHODS: A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) together with symptom severity and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets. RESULTS: Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification achieved very high accuracy of 96.77% in the discovery dataset, and 91.67% and 88.89% in the two independent validation datasets. CONCLUSIONS: Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

Lien vers le texte intégral (Open Access ou abonnement)

7. King C, Mali I, Strating H, Fangman E, Neyhard J, Payne M, Bossmann SH, Plakke B. Region-Specific Brain Volume Changes Emerge in Adolescence in the Valproic Acid Model of Autism and Parallel Human Findings. Dev Neurosci. 2024.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats. Regional volumes were obtained via magnetic resonance imaging (MRI) at either postnatal day 28 (P28) or postnatal day 40 (P40), which correspond to early and late adolescence, respectively. Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males but not females. These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.

Lien vers le texte intégral (Open Access ou abonnement)

8. La Valle C, Shen L, Shih W, Kasari C, Lord C, Tager-Flusberg H. Real-time coded measures in natural language samples capture change over time in minimally verbal autistic children. Autism Res. 2024.

Prior research supports the use of natural language sampling (NLS) to assess the rate of speech utterances (URate) and the rate of conversational turns (CTRate) in minimally verbal (MV) autistic children. Bypassing time-consuming transcription, previous work demonstrated the ability to derive URate and CTRate using real-time coding methods and provided support for their strong psychometric properties. (1) Unexplored is how URate and CTRate using real-time coding methods capture change over time and (2) whether specific child factors predict changes in URate and CTRate in 50 MV autistic children (40 males; M = 75.54, SD = 16.45 (age in months)). A NLS was collected at Time 1 (T1) and Time 2 (T2) (4.5 months between T1 and T2) and coding was conducted in ELAN Linguistic Annotator software using a real-time coding approach to derive URate and CTRate. Findings from paired samples Wilcoxon tests revealed a significant increase in child URate (not examiner URate) and child and examiner CTRate from T1 to T2. Child chronological age, Mullen expressive language age equivalent scores, and URate and CTRate at T1 were predictive of URate and CTRate at T2. Findings support using NLS-derived real-time coded measures of URate and CTRate to efficiently capture change over time in MV autistic children. Identifying child factors that predict changes in URate and CTRate can help in the tailoring of goals to children’s individual needs and strengths.

Lien vers le texte intégral (Open Access ou abonnement)

9. Lau WKW, Leung MK, Poon K, Zhang R. Early diagnosis of autism spectrum disorder using structural connectivity biomarker. Psychoradiology. 2024; 4: kkae004.

Lien vers le texte intégral (Open Access ou abonnement)

10. Ma X, Zhou W, Zheng H, Ye S, Yang B, Wang L, Wang M, Dong GH. Connectome-based prediction of the severity of autism spectrum disorder. Psychoradiology. 2023; 3: kkad027.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by social and behavioural deficits. Current diagnosis relies on behavioural criteria, but machine learning, particularly connectome-based predictive modelling (CPM), offers the potential to uncover neural biomarkers for ASD. OBJECTIVE: This study aims to predict the severity of ASD traits using CPM and explores differences among ASD subtypes, seeking to enhance diagnosis and understanding of ASD. METHODS: Resting-state functional magnetic resonance imaging data from 151 ASD patients were used in the model. CPM with leave-one-out cross-validation was conducted to identify intrinsic neural networks that predict Autism Diagnostic Observation Schedule (ADOS) scores. After the model was constructed, it was applied to independent samples to test its replicability (172 ASD patients) and specificity (36 healthy control participants). Furthermore, we examined the predictive model across different aspects of ASD and in subtypes of ASD to understand the potential mechanisms underlying the results. RESULTS: The CPM successfully identified negative networks that significantly predicted ADOS total scores [r (df = 150) = 0.19, P = 0.008 in all patients; r (df = 104) = 0.20, P = 0.040 in classic autism] and communication scores [r (df = 150) = 0.22, P = 0.010 in all patients; r (df = 104) = 0.21, P = 0.020 in classic autism]. These results were reproducible across independent databases. The networks were characterized by enhanced inter- and intranetwork connectivity associated with the occipital network (OCC), and the sensorimotor network (SMN) also played important roles. CONCLUSIONS: A CPM based on whole-brain resting-state functional connectivity can predicted the severity of ASD. Large-scale networks, including the OCC and SMN, played important roles in the predictive model. These findings may provide new directions for the diagnosis and intervention of ASD, and maybe could be the targets in novel interventions.

Lien vers le texte intégral (Open Access ou abonnement)

11. Matsuura Y, Fune J, Ngai L. Navigating Multiple Challenges: Malnutrition and Nephrotoxic Drug Effects in a Non-verbal Child With Autism Spectrum Disorder Requiring Dialysis. Cureus. 2024; 16(3): e56951.

Acute kidney injury (AKI) is a common medication adverse event, particularly in patients with pre-existing medical conditions taking nephrotoxic medications. However, little is known about the differences in the risk of nephrotoxic medication-related complications in children with autism spectrum disorder (ASD) compared to the general pediatric population. A nine-year-old non-verbal boy with ASD was hospitalized for scrotal cellulitis requiring vancomycin and piperacillin/tazobactam due to a lack of clinical response to cephalosporins. His history is significant for being an extremely selective eater, and his appetite decreased over four months prior to presentation. Poorly controlled scrotal pain, despite acetaminophen use, was suspected based on his facial expressions and maternal assessment, especially considering his non-verbal status. Consequently, a non-steroidal anti-inflammatory drug was initiated. The hospital course was complicated by the development of a scrotal abscess, minimal enteral intake, hypoalbuminemia-induced intravascular dehydration, oliguria, and generalized edema. His creatinine increased to 5.11 mg/dL from 0.51 mg/dL despite early discontinuation of nephrotoxic medications and fluid resuscitation, which led to hemodialysis due to worsening AKI. Subsequently, urinary output and edema improved. Creatinine improved to <1 mg/dL with careful creatinine monitoring and concomitant furosemide and albumin infusion in the pediatric intensive care unit. Children with comorbidities, such as malnutrition, who require nephrotoxic medications, need extra attention. Implementing clinical decision support tools or quality improvement programs can promote the prevention of nephrotoxic medication exposure and decrease the incidence of AKI. An alert within an electronic health record system for multiple nephrotoxic drugs and daily multidisciplinary huddles during patient-centered rounds could help reduce and eliminate adverse events. In particular, for non-verbal patients or those with limited communication skills, such as children with ASD, rigorous and close monitoring of vital signs, physical condition, pain, medication intake, and lab results, in addition to a nephrotoxic medication screening and notification system, should be key to optimizing patient care.

Lien vers le texte intégral (Open Access ou abonnement)

12. Myers RK, Labows C, McDonald CC, Yerys BE, Sartin EB, Carey ME, Mollen CJ, Curry AE. Preparing to « Live a Life of Possibilities »: Experiences of Healthcare Providers Readying Autistic Adolescents and Their Families for Independent Driving. J Autism Dev Disord. 2024.

Autistic adolescents and their families may experience barriers to transportation, including independent driving, which is critical to supporting quality of life and engagement in social, educational, and employment opportunities. Healthcare providers may feel unprepared to provide guidance to autistic adolescents, although they are among the professionals families turn to for guidance. This study describes providers’ experiences supporting autistic adolescents and families in the decision to pursue licensure and identifies barriers experienced in providing support. We conducted interviews with 15 healthcare providers focused on how they support autistic adolescents and their families in navigating topics related to independence, driving, and transportation. Key themes identified included: importance of understanding adolescents’ perspectives and motivations, approaches to readying caregivers for children to pursue driving, and role of providers in fostering agreement between adolescents and caregivers. Results reflect healthcare providers as intermediaries between autistic adolescents and caregivers making the decision to pursue licensure and bring families to consensus. Our findings emphasize the importance of healthcare providers, in collaboration with community-based providers, in supporting autistic adolescents and their families considering licensure. Improving conversations between providers and families provides opportunity to better support quality of life among autistic adolescents and their caregivers navigating the transition to independence.

Lien vers le texte intégral (Open Access ou abonnement)

13. Ng CSM. Maternal stress, parenting, and mother-child interactions in unaffected siblings of children with autism spectrum disorder in China. Dev Med Child Neurol. 2024.

Lien vers le texte intégral (Open Access ou abonnement)

14. Okabe M, Sato T, Takahashi M, Honjo A, Okawa M, Ishida M, Kukimoto-Niino M, Shirouzu M, Miyamoto Y, Yamauchi J. Autism Spectrum Disorder- and/or Intellectual Disability-Associated Semaphorin-5A Exploits the Mechanism by Which Dock5 Signalosome Molecules Control Cell Shape. Curr Issues Mol Biol. 2024; 46(4): 3092-107.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger’s syndrome, and pervasive developmental disorder. Individuals with ASD may exhibit difficulties in social interactions, communication challenges, repetitive behaviors, and restricted interests. While genetic mutations in individuals with ASD can either activate or inactivate the activities of the gene product, impacting neuronal morphogenesis and causing symptoms, the underlying mechanism remains to be fully established. Herein, for the first time, we report that genetically conserved Rac1 guanine-nucleotide exchange factor (GEF) Dock5 signalosome molecules control process elongation in the N1E-115 cell line, a model line capable of achieving neuronal morphological changes. The increased elongation phenotypes observed in ASD and intellectual disability (ID)-associated Semaphorin-5A (Sema5A) Arg676-to-Cys [p.R676C] were also mediated by Dock5 signalosome molecules. Indeed, knockdown of Dock5 using clustered regularly interspaced short palindromic repeat (CRISPR)/CasRx-based guide(g)RNA specifically recovered the mutated Sema5A-induced increase in process elongation in cells. Knockdown of Elmo2, an adaptor molecule of Dock5, also exhibited similar recovery. Comparable results were obtained when transfecting the interaction region of Dock5 with Elmo2. The activation of c-Jun N-terminal kinase (JNK), one of the primary signal transduction molecules underlying process elongation, was ameliorated by either their knockdown or transfection. These results suggest that the Dock5 signalosome comprises abnormal signaling involved in the process elongation induced by ASD- and ID-associated Sema5A. These molecules could be added to the list of potential therapeutic target molecules for abnormal neuronal morphogenesis in ASD at the molecular and cellular levels.

Lien vers le texte intégral (Open Access ou abonnement)

15. Ouyang Y, Feng J, Wang T, Xue Y, Mohamed ZA, Jia F. Comparison of the efficacy of parent-mediated NDBIs on developmental skills in children with ASD and fidelity in parents: a systematic review and network meta-analysis. BMC Pediatr. 2024; 24(1): 270.

BACKGROUND: Recently, studies on behavioral interventions for autism have gained popularity. Naturalistic Developmental Behavior Interventions (NDBIs) are among the most effective, evidence-based, and widely used behavior interventions for autism. However, no research has been conducted on which of the several NDBI methods is most effective for parents and children with autism spectrum disorders. Therefore, we conducted a network meta-analysis to compare the specific effects of each type of parental-mediated NDBI on children’s developmental skills and parent fidelity. METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), CINAHL, and Wanfang databases were searched from inception to August 30, 2023. A total of 32 randomized controlled trial studies that examined the efficacy of different NDBIs were included. RESULTS: Parents of children with ASD who received Pivotal Response Treatment (PRT) reported significant improvements in their children’s social skills (SUCRA, 74.1%), language skills (SUCRA, 88.3%), and parenting fidelity (SUCRA, 99.5%). Moreover, parents who received Early Start Denver Model (ESDM) reported significant improvements in their children’s language (SMD = 0.41, 95% CI: 0.04, 0.79) and motor skills (SMD = 0.44, 95% CI: 0.09, 0.79). In terms of the efficacy of improving parent fidelity, the results showed that the Improving Parents as Communication Teachers (ImPACT) intervention significantly improved parent fidelity when compared with the treatment-as-usual group (TAU) (SMD = 0.90, 95% CI: 0.39, 1.42) and the parental education intervention (PEI) (SMD = 1.10, 95% CI:0.28, 1.91).There was a difference in parent fidelity among parents who received PRT(SMD = 3.53, 95% CI: 2.26, 4.79) or ESDM(SMD = 1.42, 95% CI: 0.76, 2.09) training compared with PEI. CONCLUSION: In conclusion, this study revealed that parents can achieve high fidelity with the ImPACT intervention, and it can serve as an early first step for children newly diagnosed with ASD. It also showed that parent-mediated ESDM is effective in improving language and motor skills for children with ASD and can be used as part of the second stage of parent training. Parent-mediated PRT can also be used as a third stage of parent training with sufficient training intensity to further improve language, social, and motor skills.

Lien vers le texte intégral (Open Access ou abonnement)

16. Reilly C, Bjurulf B, Hallböök T. Autism and attention-deficit/hyperactivity disorder in children with Dravet syndrome: A population-based study. Dev Med Child Neurol. 2024.

AIM: To identify on a population basis the prevalence of autism and attention-deficit/hyperactivity disorder (ADHD) in children with Dravet syndrome and factors associated with symptoms of autism and ADHD. METHOD: Forty-one of 48 children with Dravet syndrome living in Sweden, born between 1st January 2000 and 31st December 2018 underwent assessment including measures of autism and ADHD. Diagnoses of autism and ADHD were made with respect to DSM-5 criteria. Factors associated with features of autism and ADHD were analysed via regression. RESULTS: Twenty-five of the 41 children fulfilled DSM-5 criteria for autism spectrum disorder and 12 of 37 children considered for an ADHD diagnosis fulfilled DSM-5 criteria for ADHD. Severe intellectual disability was significantly associated with a greater degree of autistic features (p < 0.001) and a DSM-5 diagnosis of autism spectrum disorder (p = 0.029). Younger children had significantly more features of ADHD (p = 0.004) and features of inattention were significantly more common than features of hyperactivity/impulsivity (p < 0.001). INTERPRETATION: Children with Dravet syndrome often have significant features of autism and ADHD, primarily inattentive type. Screening for autism and ADHD should be routine in children with Dravet syndrome.

Lien vers le texte intégral (Open Access ou abonnement)

17. Rein B, Raymond K, Boustani C, Tuy S, Zhang J, St Laurent R, Pomrenze MB, Boroon P, Heifets B, Smith M, Malenka RC. MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens. Sci Adv. 2024; 10(17): eadl6554.

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an « empathogen, » empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA’s action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA’s empathogenic effects.

Lien vers le texte intégral (Open Access ou abonnement)

18. Sánchez-Gómez V, Verdugo M, Crespo M, San Román A. A Pioneer Tool to Reduce Restrictive Practices toward People with Intellectual and Developmental Disabilities. Behav Sci (Basel). 2024; 14(4).

Reducing restrictive practices toward individuals with intellectual and developmental disabilities is a globally recognized imperative and human rights priority. This paper presents a novel tool called LibRe for assessing and reducing restrictive practices. This tool involved an instrumental multistage design and collaboration between professionals, individuals with disabilities, family members, and experts from different fields. It addresses diverse restrictive practices in five key domains: physical or mechanical, chemical or pharmacological, structural, relational, and practices related to contexts and supports. It addresses practices that are pertinent to the Spanish context and that existing tools have not covered. Embedded as a step within an organizational approach, LibRe fosters organizational transformation and provides resources to achieve outcomes within reduction plans for restrictive practices. In total, 156 teams comprising 585 professionals, 64 people with disabilities, and 44 family members responded to the tool. In terms of evidence for internal structure validity, the oblique five-factor model exhibited an adequate fit through confirmatory factor analysis, along with satisfactory reliability indices, according to ordinal alpha and omega. Users positively appraised the tool’s usefulness and identified its strengths and challenges. Although further research is needed, preliminary evidence frames LibRe as a useful resource for practice and research.

Lien vers le texte intégral (Open Access ou abonnement)

19. Sawicki CM, Janal MN, Wade SD. Preoperative Multisensory Room Use in Pediatric Patients With Autism: A Randomized Clinical Trial. Pediatr Dent. 2024; 46(2): 91-8.

Purpose: To evaluate the impact of multisensory room (MSR) use on preoperative anxiety and postoperative outcomes in children with autism spectrum disorder (ASD) undergoing dental treatment with general anesthesia. Methods: Forty children, ages six to 17 years, with ASD re- quiring general anesthesia for dental treatment, participated in this study. Participants were randomized to either the control group (standard pre- operative waiting room) or intervention group (MSR) for 20 minutes prior to general anesthesia induction. Pre- and post-intervention preoperative anxiety were measured. Following surgery, postoperative emergence delirium was assessed. Short- and long-term postoperative pain and adverse behavioral effects were evaluated six hours, 24 hours, one week, and one month post-surgery. Data analysis employed repeated measures analysis of variance with two groups and either two or four time periods. Results: The sample was predominantly male (62.5 percent) and identified as either White or Black (53 percent) and non-Hispanic (60 percent). Preoperative behavioral anxiety levels increased post-intervention in the control group (P<0.05) and decreased in the MSR group (P<0.001). Following surgery, pain intensity was greater in the control group compared to the MSR group at six hours (P<0.05) and 24 hours (P<0.01), and similar at one and four weeks. Pre- and post-intervention measures of preoperative heart rate, postoperative emergence delirium, and behavioral effects were similar between groups and over time. Conclusion: These findings suggest a novel, nonpharmacologic technique that can be utilized by various health care specialties to reduce preoperative anxiety and improve post- operative outcomes in children with autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

20. Strang JF, Fischbach AL, Rao S, Clawson A, Knauss M, Bernstein SN, van der Miesen AIR, Inge AP, Alonzo K, Zeroth J, Kenworthy L, Morgan CI, Brandt A, Moore CC, Ahlers K, Jankowski MK, McClellan LS, Henise SB, Cap CJ, Exley SL, Youmatz A, Song M, McLaren JL, Parchem B. Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults. Clin Neuropsychol. 2024: 1-37.

Objective: Situated in Children’s National Hospital (CNH)’s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP’s feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

Lien vers le texte intégral (Open Access ou abonnement)

21. Suárez-Manzano S, Ruiz-Ariza A, de Loureiro NEM, Martínez-López EJ. Effects of Physical Activity on Cognition, Behavior, and Motor Skills in Youth with Autism Spectrum Disorder: A Systematic Review of Intervention Studies. Behav Sci (Basel). 2024; 14(4).

The aim of this paper was to analyze the acute and chronic effects of physical activity (PA) on cognition, behavior, and motor skill in youth with autism spectrum disorder (ASD), taking into account potential confounders. In addition, it was intended to elaborate a guide of educational applications with strategies for PA use. Studies were identified in four databases from January 2010 to June 2023. A total of 19 interventional studies met the inclusion criteria. PA programs ranged from two weeks to one year in duration, with a frequency of one to five sessions per week. More than 58% of the studies showed positive effects of PA on cognition, and 45.5% on behavior and motor skill. Moderate-vigorous PA for 15-30 min has shown acute effects on cognition, general behavior, and stereotypic/repetitive behaviors in youth with ASD. A total of 9 out of 14 studies showed chronic effects on general behavior and stereotypic behaviors, and only 6 on motor skills.

Lien vers le texte intégral (Open Access ou abonnement)

22. Thom-Jones S, Melgaard I, Gordon CS. Autistic Women’s Experience of Motherhood: A Qualitative Analysis of Reddit. J Autism Dev Disord. 2024.

Autistic mothers remain under-represented in parental and autism research despite the associated physical and psychosocial challenges that accompany the transition to motherhood. Extant literature suggests autistic mothers experience sensory difficulties, communication challenges, stigma, and comorbidities as difficulties, but these studies have focused on autistic women in the perinatal period. The aim of this study was to examine reflections on motherhood from a Reddit community for autistic parents. Identified themes were Autistic Mothering is Different, Autistic Mothers Need Autistic Mothers, Autistic Mothers Experience Stigma, and Learnings from Lockdown. Findings extend existing research by offering insight into the ways autism impacts mothers beyond the perinatal period and have important implications for the future design and delivery of support services for autistic mothers.

Lien vers le texte intégral (Open Access ou abonnement)

23. Vacharasin JM, Ward JA, McCord MM, Cox K, Imitola J, Lizarraga SB. Neuroimmune mechanisms in autism etiology – untangling a complex problem using human cellular models. Oxf Open Neurosci. 2024; 3: kvae003.

Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development.

Lien vers le texte intégral (Open Access ou abonnement)

24. Waas B, Carpenter BS, Franks NE, Merchant OQ, Verhey KJ, Allen BL. Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development. Sci Adv. 2024; 10(17): eade1650.

While the kinesin-2 motors KIF3A and KIF3B have essential roles in ciliogenesis and Hedgehog (HH) signal transduction, potential role(s) for another kinesin-2 motor, KIF17, in HH signaling have yet to be explored. Here, we investigated the contribution of KIF17 to HH-dependent cerebellar development, where Kif17 is expressed in both HH-producing Purkinje cells and HH-responding cerebellar granule neuron progenitors (CGNPs). Germline Kif17 deletion in mice results in cerebellar hypoplasia due to reduced CGNP proliferation, a consequence of decreased HH pathway activity mediated through decreased Sonic HH (SHH) protein. Notably, Purkinje cell-specific Kif17 deletion partially phenocopies Kif17 germline mutants. Unexpectedly, CGNP-specific Kif17 deletion results in the opposite phenotype-increased CGNP proliferation and HH target gene expression due to altered GLI transcription factor processing. Together, these data identify KIF17 as a key regulator of HH-dependent cerebellar development, with dual and opposing roles in HH-producing Purkinje cells and HH-responding CGNPs.

Lien vers le texte intégral (Open Access ou abonnement)

25. Wiggins LD, Daniels J, Overwyk K, Croen L, DiGuiseppi C, Bradley C, Powell P, Dichter G, Moody E, Pazol K. Depressive symptoms and activity engagement in autistic adolescents and those with other developmental disabilities. Disabil Health J. 2024: 101633.

BACKGROUND: Autistic adults and those with other developmental disabilities (DD) have increased depressive symptoms and decreased activity engagement when compared to those with no DD. Few studies explore activities related to depressive symptoms in autistic people and those with other DD during adolescence. OBJECTIVE: The objectives of this analysis were to describe depressive symptoms and activity engagement among autistic adolescents and those with other DD and no DD and explore types of activities associated with depressive symptoms, stratified by study group. METHODS: Parents of adolescents completed a multi-site case-control study of autism and other DD when their child was 2-5 years of age and a follow-up survey when their child was 12-16 years of age. Questions asked about the adolescent’s current diagnoses, depressive symptoms (i.e., diagnosis, medication use, or symptoms), and engagement in club, social, sport, vocational, volunteer, and other organized activities. RESULTS: Autistic adolescents (N = 238) and those with other DD (N = 222) were significantly more likely to have depressive symptoms than adolescents with no DD (N = 406), (31.9 %, 30.6 %, and 15.0 % respectively). Lower percentages of autistic adolescents participated in activities than peers with other DD, who had lower percentages than peers with no DD. Participation in sports was associated with lower likelihood of depressive symptoms in all groups. CONCLUSIONS: Autistic adolescents and those with other DD are at increased risk for depressive symptoms and reduced activity engagement. Participation in sports may be especially important for adolescent mental health regardless of disability status. Implications for public health education and intervention are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

26. Xie X, Zhou R, Fang Z, Zhang Y, Wang Q, Liu X. Seeing beyond words: Visualizing autism spectrum disorder biomarker insights. Heliyon. 2024; 10(9): e30420.

OBJECTIVE: This study employs bibliometric and visual analysis to elucidate global research trends in Autism Spectrum Disorder (ASD) biomarkers, identify critical research focal points, and discuss the potential integration of diverse biomarker modalities for precise ASD assessment. METHODS: A comprehensive bibliometric analysis was conducted using data from the Web of Science Core Collection database until December 31, 2022. Visualization tools, including R, VOSviewer, CiteSpace, and gCLUTO, were utilized to examine collaborative networks, co-citation patterns, and keyword associations among countries, institutions, authors, journals, documents, and keywords. RESULTS: ASD biomarker research emerged in 2004, accumulating a corpus of 4348 documents by December 31, 2022. The United States, with 1574 publications and an H-index of 213, emerged as the most prolific and influential country. The University of California, Davis, contributed significantly with 346 publications and an H-index of 69, making it the leading institution. Concerning journals, the Journal of Autism and Developmental Disorders, Autism Research, and PLOS ONE were the top three publishers of ASD biomarker-related articles among a total of 1140 academic journals. Co-citation and keyword analyses revealed research hotspots in genetics, imaging, oxidative stress, neuroinflammation, gut microbiota, and eye tracking. Emerging topics included « DNA methylation, » « eye tracking, » « metabolomics, » and « resting-state fMRI. » CONCLUSION: The field of ASD biomarker research is dynamically evolving. Future endeavors should prioritize individual stratification, methodological standardization, the harmonious integration of biomarker modalities, and longitudinal studies to advance the precision of ASD diagnosis and treatment.

Lien vers le texte intégral (Open Access ou abonnement)

27. Zhan X, Asmara H, Pfaffinger P, Turner RW. Calcium-dependent regulation of neuronal excitability is rescued in Fragile X Syndrome by a tat-conjugated N-terminal fragment of FMRP. J Neurosci. 2024.

Fragile X Syndrome arises from the loss of Fragile X Messenger Ribonucleoprotein (FMRP) needed for normal neuronal excitability and circuit functions. Recent work revealed that FMRP contributes to mossy fiber LTP by adjusting Kv4 A-type current availability through interactions with a Cav3-Kv4 ion channel complex, yet the mechanism has not yet been defined. In this study using wild-type and Fmr1 knockout (KO) tsA-201 cells and cerebellar sections from male Fmr1 KO mice, we show that FMRP associates with all subunits of the Cav3.1-Kv4.3-KChIP3 complex, and is critical to enabling calcium-dependent shifts in Kv4.3 inactivation to modulate A-type current. Specifically, upon depolarization Cav3 calcium influx activates dual specific phosphatase 1/6 (DUSP1/6) to deactivate ERK1/2 (ERK) and lower phosphorylation of Kv4.3, a signalling pathway that does not function in Fmr1 KO cells. In Fmr1 KO mouse tissue slices cerebellar granule cells exhibit a hyperexcitable response to membrane depolarizations. Either incubating Fmr1 KO cells or in vivo administration of a tat-conjugated FMRP N-terminus fragment (FMRP-N-tat) rescued Cav3-Kv4 function and granule cell excitability, with a decrease in the level of DUSP6. Together these data reveal a Cav3-activated DUSP signalling pathway critical to the function of a FMRP-Cav3-Kv4 complex that is misregulated in Fmr1 KO conditions. Moreover, FMRP-N-tat restores function of this complex to rescue calcium-dependent control of neuronal excitability as a potential therapeutic approach to alleviating the symptoms of Fragile X Syndrome.Significance Statement Changes in neuronal excitability and ion channel functions have been a focus in studies of Fragile X Syndrome. Previous work identified ion channels that are regulated by FMRP through either protein translation or direct protein-protein interactions. The current study reveals FMRP as a constitutive member of a Cav3-Kv4 complex that is required for a Cav3-DUSP-ERK signalling pathway to increase A-type current and reduce cerebellar granule cell excitability. In Fmr1 KO cells, Cav3-Kv4 function and calcium-dependent modulation of A-type current is lost, leading to a hyperexcitable state of cerebellar granule cells. Pretreating with FMRP-N-tat restores all Cav3-Kv4 function and granule cell excitability, providing support for FMRP-tat peptide treatment as a potential therapeutic strategy for Fragile X Syndrome.

Lien vers le texte intégral (Open Access ou abonnement)