1. Al-Ayadhi L, Abualnaja A, AlZarroug A, Alharbi T, Alhowikan AM, Halepoto DM, Al-Mazidi S. A Disintegrin and Metalloproteinase Protein 8 (ADAM 8) in Autism Spectrum Disorder: Links to Neuroinflammation. Neuropsychiatr Dis Treat;2023;19:1771-1780.

BACKGROUND: Converging lines of evidence confirmed neuroinflammation’s role in autism spectrum disorder (ASD) etiological pathway. A disintegrin and metalloproteinase 8 (ADAM8) play major roles in inflammatory and allergic processes in various diseases. AIM: This study aimed to investigate ADAM8 plasma levels in autistic children compared to healthy controls. Also, to discover the association between ADAM8, disease severity, and neuroinflammation in ASD. METHODOLOGY: This case-control study included children with ASD (n=40) and aged-matched healthy controls (n=40). The plasma levels of the ADAM 8 were determined using enzyme-linked immunosorbent assay (ELISA). The assessment of ASD severity and social and sensory behaviors were categorized as mild, moderate and severe. Correlations among ADAM8 plasma levels and ASD severity scores [Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS) and Short Sensory Profile (SSP)] were obtained by Spearman correlation coefficient (r). RESULTS: ASD children (n=40), including severe autism (n=21) and mild-to-moderate autism (n=19), showed significantly (p ≤ 0.05) lower plasma levels of ADAM8 [4683 (2885-5229); 4663 (4060-5000); 4632 (2885-5229)], respectively, than those of healthy controls [5000 (4047-5000)] [median (IQR) pg/mL]. However, there was no significant difference between the ADAM8 levels of children with severe and mild-to-moderate autism (p = 0.71). Moreover, ADAM8 plasma levels were not significantly correlated with the severity of ASD measured by behavioral scales [CARS (r= -0.11, p=0.55), SRS (r=0.11, p= 0.95), SSP (r=-0.23, p=0.23)]. CONCLUSION: The low ADAM8 plasma levels in children with ASD possibly indicated that ADAM8 might be implicated in the pathogenesis of ASD but not in the severity of the disease. These results should be interpreted with caution until additional studies are carried out with larger populations to decide whether the reduction in plasma ADAM8 levels is a mere consequence of ASD or if it plays a pathogenic role in the disease.

Lien vers le texte intégral (Open Access ou abonnement)

2. Annamneedi A, Gora C, Dudas A, Leray X, Bozon V, Crepieux P, Pellissier LP. Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders. Br J Pharmacol;2023 (Aug 13)

Autism spectrum disorders (ASD) are diagnosed in 1/100 children worldwide, based on two core symptoms, deficits in social interaction and communication and stereotyped behaviours. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors that transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR, vasopressin V(1A) , V(1B) , metabotropic glutamate mGlu(5) , mGlu(7) , GABA(B2) , dopamine D(1) , D(2) , D(3) , serotoninergic 5-HT(1B) , β(2) -adrenoceptor, cholinergic M(3) , adenosine A(2A) , A(3) , angiotensin AT(2) , cannabinoid CB(1) , chemokine CX(3) CR1, orphan GPR37, GPR85 and olfactory OR1C1, OR2M4, OR2T10, OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, 5-HT(2A) and 5-HT(7) for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight that D(2) , 5-HT(2A) , CB(1) , OTR and V(1A) are the most promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD.

Lien vers le texte intégral (Open Access ou abonnement)

3. Brown RL, Epel EE, Lin J, Dubal DB, Prather AA. Associations between klotho and telomere biology in high stress caregivers. Aging (Albany NY);2023 (Aug 14);15(15):7381-7396.

Aging biomarkers may be related to each other through direct co-regulation and/or through being regulated by common processes associated with chronological aging or stress. Klotho is an aging regulator that acts as a circulating hormone with critical involvement in regulating insulin signaling, phosphate homeostasis, oxidative stress, and age-related inflammatory functioning. Both klotho and telomere length are biomarkers of biological aging and decrease with age; however, the relationship between them is not well understood. Here we test the association between klotho levels and the telomere length of specific sorted immune cells among a healthy sample of mothers caregiving for a child with autism spectrum disorder (ASD; i.e., experiencing higher caregiving stress) or a child without ASD, covarying age and body mass index, in order to understand if high stress associated with caregiving for a child with an ASD may be involved in any association between these aging biomarkers. In 178 caregiving women (n = 90 high-stress mothers of children with ASD, n = 88 low-stress mothers of neurotypical children), we found that klotho levels were positively associated with telomere length in PBMCs (an effect driven by CD4+ and CD8+CD28- T cells) among high-stress mothers of children with an ASD but not among low-stress mothers of neurotypical children. There were no significant associations between klotho and telomerase activity in either group, across cell types assessed here. Our results suggest that klotho levels and telomere length may be associated through a coordinated downregulation of longevity factors occurring under higher stress caregiving conditions.

Lien vers le texte intégral (Open Access ou abonnement)

4. Cha WJ, Kim K. Diminished emotion recognition with reduced face gaze in complex situation in individuals with broad autism phenotype. Int J Clin Health Psychol;2023 (Oct-Dec);23(4):100399.

BACKGROUND/OBJECTIVE: Individuals with broad autism phenotype (BAP) showed a diminished ability to recognize emotion. This study aims to examine whether their decline in emotion recognition ability could be more clearly identified as task complexity increased and whether their decline could be influenced by their eye-gaze patterns. METHOD: 41 individuals with BAP and 40 healthy controls performed two types of emotion recognition tasks. After confirming conditions wherein the BAP group did not perform well compared to the control group, we compared gaze proportion on faces and context between groups when performing the conditions. RESULTS: The more difficult the task, the clearer the significant relationships between the level of autistic traits and emotion recognition ability. The BAP group showed lower accuracy compared to the control group when a face with mild emotional intensity was presented with context. In terms of gaze proportion, the BAP group looked less at faces when recognizing emotions compared to the control group. CONCLUSION: These findings indicate that diminished emotion recognition ability in individuals with BAP may be influenced by face gaze.

Lien vers le texte intégral (Open Access ou abonnement)

5. Chavoshnejad P, Vallejo L, Zhang S, Guo Y, Dai W, Zhang T, Razavi MJ. Mechanical hierarchy in the formation and modulation of cortical folding patterns. Sci Rep;2023 (Aug 14);13(1):13177.

The important mechanical parameters and their hierarchy in the growth and folding of the human brain have not been thoroughly understood. In this study, we developed a multiscale mechanical model to investigate how the interplay between initial geometrical undulations, differential tangential growth in the cortical plate, and axonal connectivity form and regulate the folding patterns of the human brain in a hierarchical order. To do so, different growth scenarios with bilayer spherical models that features initial undulations on the cortex and uniform or heterogeneous distribution of axonal fibers in the white matter were developed, statistically analyzed, and validated by the imaging observations. The results showed that the differential tangential growth is the inducer of cortical folding, and in a hierarchal order, high-amplitude initial undulations on the surface and axonal fibers in the substrate regulate the folding patterns and determine the location of gyri and sulci. The locations with dense axonal fibers after folding settle in gyri rather than sulci. The statistical results also indicated that there is a strong correlation between the location of positive (outward) and negative (inward) initial undulations and the locations of gyri and sulci after folding, respectively. In addition, the locations of 3-hinge gyral folds are strongly correlated with the initial positive undulations and locations of dense axonal fibers. As another finding, it was revealed that there is a correlation between the density of axonal fibers and local gyrification index, which has been observed in imaging studies but not yet fundamentally explained. This study is the first step in understanding the linkage between abnormal gyrification (surface morphology) and disruption in connectivity that has been observed in some brain disorders such as Autism Spectrum Disorder. Moreover, the findings of the study directly contribute to the concept of the regularity and variability of folding patterns in individual human brains.

Lien vers le texte intégral (Open Access ou abonnement)

6. Cui M, Ni Q, Wang Q. Review of intervention methods for language and communication disorders in children with autism spectrum disorders. PeerJ;2023;11:e15735.

In recent years, the number of patients-particularly children-with autism spectrum disorder (ASD) has been continually increasing. ASD affects a child’s language communication and social interaction to a certain extent and has an impact on behavior, intelligence level, and other aspects of the child. Data indicates that 40% to 70% of children with ASD experience language developmental delays, which are mainly manifested as lack of language or language developmental delay, self-talk, use of stereotyped language, parroting, et cetera. A language communication disorder is a major symptom of ASD and is the most common reason for patients to visit a doctor. Therefore, language intervention training and communication skills have been made a cornerstone of autism intervention. However, a literature search has revealed that most studies only examine certain intervention methods or a combination of two or three intervention methods, which cannot be used by therapists or rehabilitation teachers. Therefore, this article summarizes relevant literature on language communication training for ASD children at home and abroad and briefly introduces the characteristics and training methods of language disorders in children with ASD in order to provide some ideas and references for relevant researchers and practitioners.

Lien vers le texte intégral (Open Access ou abonnement)

7. Di Luzio M, Guerrera S, Pontillo M, Lala MR, Casula L, Valeri G, Vicari S. Autism spectrum disorder, very-early onset schizophrenia, and child disintegrative disorder: the challenge of diagnosis. A case-report study. Front Psychiatry;2023;14:1212687.

BACKGROUND: Autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) contains several disorders previously present as distinct diagnoses in the DSM Revised Fourth Edition (DSM-IV-TR). These include child disintegrative disorder (CDD). The latter presents typical features, such as a late regression of developmental acquisitions. However, it also shows symptoms similar to ASD, and psychotic symptoms, such as very-early onset schizophrenia (VEOS), are described in the literature. CASE REPORT: In this case report we deepen the case of P., a child who presents a late regression, at 7 years old, associated with psychotic symptoms in the absence of organic alterations. The child was treated with antipsychotic drug therapy and cognitive behavioral therapy. P. was diagnosed with ASD with acute and late regression associated with psychotic symptoms. During the follow-up, there was a gradual improvement in the clinical conditions. Improvements were possible due to therapeutic intervention (pharmacological and psychotherapeutic) and/or the natural course of the disorder. CONCLUSION: The diagnostic difficulty of this case reflects a clinical complexity in which it is not easy to distinguish between neurodevelopmental and psychiatric aspects. Clinical cases such as that of P. emphasize the theme of the neurodevelopment continuum model in which neurodevelopmental and psychiatric disturbances can be considered within a pattern of pathological continuity.

Lien vers le texte intégral (Open Access ou abonnement)

8. Gasser B, Escher G, Calin AE, Deppeler M, Marchon M, Kurz J, Mohaupt M. Are steroid hormones and autistic traits affected by metformin? First insights from a pilot. Compr Psychoneuroendocrinol;2023 (Nov);16:100196.

BACKGROUND: Different lines of evidence imply that metformin could alter steroid hormone homeostasis and thereby improve social impairment. Here, we tried to correlate the impact of metformin treatment on alterations in steroid hormones and autism spectrum traits before versus after treatment with metformin. MATERIAL & METHODS: Urine steroid hormones were measured using gas chromatography mass spectrometry in 12 male subjects (54.2 ± 9.1 years, 177.3 ± 4.1 cm, 80 ± 10.4 kg) and 7 female subjects (64.14 ± 18.0 years, 162.7 ± 4.1 cm, 76.1 ± 10.4 kg). Furthermore, a questionnaire on autism spectrum traits (Autism Spectrum Questionnaire]) was administered prior to and after metformin treatment. RESULTS: Overall, a decrease of steroid hormones were detected, which were most pronounced in the metabolites of corticosterone, deoxycortisol, cortisol, as well as androgens. These remained after Bonferroni correction (three classes: glucocorticoid, mineralocorticoid, androgens). No effect on autism spectrum traits (social skills, attention switching skills, attention to detail skills, communication skills, imagination skills), was identified pre versus post metformin treatment. DISCUSSION: The decreased steroid hormone levels are based on different mechanisms; one effect is likely via mitochondria, another effect via activated protein kinase prior to post treatment. The finding on autistic traits must be taxed as negative and do not directly provide an argument for using metformin in the treatment of autism.

Lien vers le texte intégral (Open Access ou abonnement)

9. Han L, Guan L, Zhang Z, Li W, Li J, Bao C, Ye M, Tang M, Ke X. Risk factors and clinical characteristics of autism spectrum disorder with regression in China. Autism Res;2023 (Aug 14)

Autism spectrum disorder with regression (ASD-R) is characterized by the loss of previously acquired skills during the initial year of life. This study aimed to investigate the clinical characteristics, patterns of regression, and potential risk factors associated with ASD-R in the Chinese Han population. A case-control study was conducted between September 2020 and March 2022. A total of 186 children were enrolled, including 58 children with ASD-R, 70 with ASD without regression (ASD-NR), and 58 typically developing children. Demographic information, clinical characteristics, and potential risk factors related to ASD-R were assessed using a combination of questionnaires, interviews, and physician assessments. The results revealed that children with ASD-R exhibited more severe impairments in social communication and stereotyped behaviors compared with those with ASD-NR. Language regression, constituting 40% of cases within the ASD-R group, was found to be the most common type of regression. Furthermore, our analysis revealed that fever (OR = 4.01, 95% CI: 1.26-12.76) and diarrhea (OR = 6.32, 95% CI: 1.38-29.03) were identified as significant risk factors for ASD-R. These findings contribute to our understanding of the heterogeneity of ASD and highlight the importance of considering immune responses and gastrointestinal factors in the etiology of ASD-R.

Lien vers le texte intégral (Open Access ou abonnement)

10. Kanina A, Larsson H, Sjölander A, Butwicka A, Taylor MJ, Martini MI, Lichtenstein P, Lundberg FE, Onofrio BM, Rosenqvist MA. Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study. Transl Psychiatry;2023 (Aug 14);13(1):282.

Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53-1.58] to 2.65 [ ≥ 4 adversities; 1.98-3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59-1.84] to 1.37 [1.30-1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

Lien vers le texte intégral (Open Access ou abonnement)

11. Lerner MD, Gurba AN, Gassner DL. A framework for neurodiversity-affirming interventions for autistic individuals. J Consult Clin Psychol;2023 (Sep);91(9):503-504.

Despite being targets of intervention practice and research for over 60 years, autistic people have been left out of the conversation. Until recently, nearly no research or implementation work has sought the input of autistic people in regard to the design of interventions and, more importantly, how the goals for such interventions are prioritized and determined. This reframe has profound implications for autism-focused interventions and research, most of which have aimed to reduce or eliminate autism symptoms, with variable empirical support (Bottema-Beutel, 2023). These outcomes are practically and ethically incompatible with a neurodiversity perspective. Most prominently, applied behavior analysis (ABA), which was the first intervention approach widely applied to autistic people, has come under increasing scrutiny and criticism for failing to include autistic people in the design of intervention elements and consideration of goals; moreover, autistic people are increasingly identifying iatrogenic effects they have experienced when receiving ABA (Bottema-Beutel, 2023), with these concerns often being met with minimization rather than an endorsement of their validity and willingness to hear them out. Thus, there is a pressing need for a neurodiversity-affirming interventions (NAI) framework for autism. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Lien vers le texte intégral (Open Access ou abonnement)

12. Liu J, Yan J, Qu F, Mo W, Yu H, Hu P, Zhang Z. A pilot study on glutamate receptor and carrier gene variants and risk of childhood autism spectrum. Metab Brain Dis;2023 (Aug 14)

Imbalanced glutamate signaling has been implicated in the development of autism spectrum disorder (ASD). This case-control study was to examine single nucleotide polymorphisms (SNPs) in glutamate receptor and carrier genes and determine their association with childhood ASD in a Chinese Han population. A total of 12 SNPs in genes encoding glutamate receptors (GRM7 and GRM8) and carriers (SLC1A1 and SLC25A12) were examined in 249 autistic children and 353 healthy controls. The Childhood Autism Rating Scale (CARS) and its verbal communication domain were applied to evaluate the severity of the disease and language impairment, respectively. The T allele of rs2292813 in the SLC25A12 gene was significantly associated with an increased risk of ASD (odds ratio (OD) = 1.7, 95% confidence interval (CI): 1.1-2.6, P = 0.0107). Neither the genotypes nor allele distributions of other SNPs were associated with the risk of ASD. Notably, rs1800656 and rs2237731 in the GRM8 gene, but not other SNPs, were related to the severity of language impairment. All SNPs were not correlated with the overall severity of ASD. Our findings support associations between the SLC25A12 gene variant and the risk of childhood ASD, and between the GRM8 gene variant and the severity of language impairment in the Chinese Han population.

Lien vers le texte intégral (Open Access ou abonnement)

13. Magaña S, Errisuriz VL, Yu AP, Heydaria N, Zeng W, Mirza M, Vanegas S, Brown S, Parra-Medina D, Suarez-Balcazar Y. Associations between parenting strategies and BMI percentile among Latino children and youth with intellectual and developmental disabilities. Front Pediatr;2023;11:1189686.

INTRODUCTION: Maintaining healthy weight is a challenge for all children, and particularly for children with IDD compared to nondisabled children and for Latino children compared to non-Latino White children. Parenting practices related to food intake and physical activity have been found to be important in maintaining children’s weight. In this study, we describe the prevalence of overweight and obesity status among Latino children with IDD and their maternal caregivers and determine the relationship between food and physical activity parenting practices and childhood obesity among Latino children with IDD. METHODS: We interviewed 94 Latino parent/child dyads and collected information about parenting practices, home environment, and parent and child height and weight using standardized measures. Parent body mass index (BMI) and child BMI percentile were calculated from height and weight. RESULTS: The combined overweight/obesity status for children in our sample was high (60.3%) compared to national rates among nondisabled Latino children (56%) and non-Latino White children with autism (37%). Contrary to research on nondisabled children, we found that greater parental use of controlling dietary strategies was associated with lower BMI percentile in Latino children with IDD. These findings may be indicative of the fact that children with IDD tend to have unique dietary behaviors that warrant more disability and culturally sensitive strategies. DISCUSSION: Our findings suggest that overweight and obesity is especially prevalent for Latino children with IDD and that more research is needed on family factors that promote health in Latino families of children with IDD.

Lien vers le texte intégral (Open Access ou abonnement)

14. Meng C, Li T, Wang J. Temporal course of attention bias toward emotional faces in individuals with autistic traits: an eye-movement study. Front Neurosci;2023;17:1218595.

INTRODUCTION: Similar attention patterns have been found in individuals with autism spectrum disorder (ASD) and autistic traits (ATs). The Intense World Theory and previous studies suggest that individuals with ASD may demonstrate a vigilance-avoidance attention pattern toward emotional faces. However, the attention patterns in individuals with ATs remain unclear. Therefore, this study employs eye-tracking technology to examine the characteristics and temporal course of attention bias toward emotional faces in individuals with ATs. METHODS: The Autism-spectrum Quotient (AQ) was used to evaluate the level of ATs among 2,502 college students. A total of 50 participants were selected from the 2,502 college students: 25 high-AQ group participants were randomly selected from the 10% of individuals with the highest AQ scores. Similarly, 25 low-AQ group participants were randomly selected from the 10% of participants with the lowest AQ scores. All selected participants completed an eye-tracking study while performing a dot-probe task with emotional faces (positive-neutral, negative-neutral, and negative-positive). By analyzing data from different time periods, the attention bias and time course of individuals with ATs toward emotional faces were investigated. RESULTS: The results show that compared to the low-AQ group, the high-AQ group detected negative faces faster in the early stages of emotional face processing. As the presentation time of emotional faces increased (at the 2-3 s mark), the fixation scores for negative-neutral faces of the high-AQ group were less than 0.5, which was significantly lower than those of the low-AQ group. Meanwhile, the high-AQ group showed brief attentional avoidance toward positive emotion at 3-4 s in the positive-neutral trials, indicating that the high-AQ group exhibited attention avoidance to both negative and positive faces during the middle and later stages of emotional processing. CONCLUSION: This study suggests that individuals with ATs display a vigilance-avoidance pattern toward emotional faces. It contributes to a deeper understanding of the mechanisms of attention in persons with ATs and further supports the Intense World Theory.

Lien vers le texte intégral (Open Access ou abonnement)

15. Muroke V, Jalanko M, Ruotsalainen S, Perola M, Helle E, Sinisalo J. Phenotype of ASDs Associated With 4p16 Risk Locus and Novel Genome-Wide Associations of ASD Patients in the Finnish Population. Circ Genom Precis Med;2023 (Aug 14):e004070.

Lien vers le texte intégral (Open Access ou abonnement)

16. Rabie AH, Saleh AI. A new diagnostic autism spectrum disorder (DASD) strategy using ensemble diagnosis methodology based on blood tests. Health Inf Sci Syst;2023 (Dec);11(1):36.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disease that impacts a child’s way of behavior and social communication. In early childhood, children with ASD typically exhibit symptoms such as difficulty in social interaction, limited interests, and repetitive behavior. Although there are symptoms of ASD disease, most people do not understand these symptoms and therefore do not have enough knowledge to determine whether or not a child has ASD. Thus, early detection of ASD children based on accurate diagnosis model based on Artificial Intelligence (AI) techniques is a critical process to reduce the spread of the disease and control it early. Through this paper, a new Diagnostic Autism Spectrum Disorder (DASD) strategy is presented to quickly and accurately detect ASD children. DASD contains two layers called Data Filter Layer (DFL) and Diagnostic Layer (DL). Feature selection and outlier rejection processes are performed in DFL to filter the ASD dataset from less important features and incorrect data before using the diagnostic or detection method in DL to accurately diagnose the patients. In DFL, Binary Gray Wolf Optimization (BGWO) technique is used to select the most significant set of features while Binary Genetic Algorithm (BGA) technique is used to eliminate invalid training data. Then, Ensemble Diagnosis Methodology (EDM) as a new diagnostic technique is used in DL to quickly and precisely diagnose ASD children. In this paper, the main contribution is EDM that consists of several diagnostic models including Enhanced K-Nearest Neighbors (EKNN) as one of them. EKNN represents a hybrid technique consisting of three methods called K-Nearest Neighbors (KNN), Naïve Bayes (NB), and Chimp Optimization Algorithm (COA). NB is used as a weighed method to convert data from feature space to weight space. Then, COA is used as a data generation method to reduce the size of training dataset. Finally, KNN is applied on the reduced data in weight space to quickly and accurately diagnose ASD children based on new training dataset with small size. ASD blood tests dataset is used to test the proposed DASD strategy against other recent strategies [1]. It is concluded that the DASD strategy is superior to other strategies based on many performance measures including accuracy, error, recall, precision, micro_average precision, macro_average precision, micro_average recall, macro_average recall, F1-measure, and implementation-time with values equal to 0.93, 0.07, 0.83, 0.82, 0.80, 0.83, 0.79, 0.81, 0.79, and 1.5 s respectively.

Lien vers le texte intégral (Open Access ou abonnement)

17. Silva APD, Cáceres-Assenço AM. Telemonitoring of children with risk indicators for Autism Spectrum Disorder: preliminary findings. Codas;2023;35(5):e20210308.

PURPOSE: monitor the development of pragmatic skills in children with clinical risk indicators for autism spectrum disorder (ASD) before and after the application of an integrated parental guidance protocol. METHODS: Seven families who had children with clinical risk indicators for autism spectrum disorder and were in the diagnostic process participated in this study. The study was divided into three moments: (1) structured interview with parents and assessment of children’s pragmatic skills, (2) virtual sessions with guidance to parents related to the characteristics of the condition and skills that can be developed to favor their development, and (3) reassessment of children’s pragmatic skills. Statistical analysis considered occupation of communicative space, use of functions and communicative means at ground zero and post-monitoring. RESULTS: There was no significant difference between the two evaluation moments, but a greater number was observed in the use of communicative acts and more interactive communicative functions as an outcome. CONCLUSION: The monitoring of children’s pragmatic skills suggests that they present discrete evolution, especially the more interactive ones, after the application of the integrated parental guidance protocol.

Lien vers le texte intégral (Open Access ou abonnement)

18. Thompson CH, Potet F, Abramova TV, DeKeyser JM, Ghabra NF, Vanoye CG, Millichap JJ, George AL. Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties. J Gen Physiol;2023 (Oct 2);155(10)

Pathogenic variants in voltage-gated sodium (NaV) channel genes including SCN2A, encoding NaV1.2, are discovered frequently in neurodevelopmental disorders with or without epilepsy. SCN2A is also a high-confidence risk gene for autism spectrum disorder (ASD) and nonsyndromic intellectual disability (ID). Previous work to determine the functional consequences of SCN2A variants yielded a paradigm in which predominantly gain-of-function variants cause neonatal-onset epilepsy, whereas loss-of-function variants are associated with ASD and ID. However, this framework was derived from a limited number of studies conducted under heterogeneous experimental conditions, whereas most disease-associated SCN2A variants have not been functionally annotated. We determined the functional properties of SCN2A variants using automated patch-clamp recording to demonstrate the validity of this method and to examine whether a binary classification of variant dysfunction is evident in a larger cohort studied under uniform conditions. We studied 28 disease-associated variants and 4 common variants using two alternatively spliced isoforms of NaV1.2 expressed in HEK293T cells. Automated patch-clamp recording provided a valid high throughput method to ascertain detailed functional properties of NaV1.2 variants with concordant findings for variants that were previously studied using manual patch clamp. Many epilepsy-associated variants in our study exhibited complex patterns of gain- and loss-of-functions that are difficult to classify by a simple binary scheme. The higher throughput achievable with automated patch clamp enables study of variants with greater standardization of recording conditions, freedom from operator bias, and enhanced experimental rigor. This approach offers an enhanced ability to discern relationships between channel dysfunction and neurodevelopmental disorders.

Lien vers le texte intégral (Open Access ou abonnement)

19. Wu M, Joubran E, Kumar D, Assadi ND, Nguyen H. Variations in Anxiety and Related Psychiatric Comorbidity Levels Among Youths With Individual Diagnoses of Autism Spectrum Disorder or Attention Deficit Hyperactivity Disorder and Those With Both Diagnoses. Cureus;2023 (Jul);15(7):e41759.

Children with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) individually and those with co-occurring ADHD and ASD experience higher rates of total anxiety and psychiatric comorbidities such as gender dysphoria and locomotor skills compared to their typically developing (TD) peers. In this study, it was hypothesized that youth with comorbid ADHD and ASD would experience higher levels of overall anxiety, specifically separation, generalized, and social anxiety. A literature review of relevant studies published from 2007 to 2020 was performed, with a search involving key terms such as « Anxiety, » « ADHD » and « ASD' ». It was discovered that individuals with ADHD or ASD had higher levels of anxiety compared to their peers. Furthermore, children who have co-occurring ADHD and ASD had more serve levels of anxiety than children with an individual diagnosis of ADHD or ASD. Children with ASD, ADHD, and co-occurring ADHD and ASD had a higher prevalence of gender dysphoria and impaired locomotor skills, which lead to higher levels of psychiatric comorbidities seen in this population. It can be hypothesized psychiatric comorbidities could also have implications for the high anxiety levels seen in this population but further research is needed to confirm this.

Lien vers le texte intégral (Open Access ou abonnement)

20. Yu X, Mostafijur Rahman M, Carter SA, Lin JC, Zhuang Z, Chow T, Lurmann FW, Kleeman MJ, Martinez MP, van Donkelaar A, Martin RV, Eckel SP, Chen Z, Levitt P, Schwartz J, Hackman D, Chen JC, McConnell R, Xiang AH. Prenatal air pollution, maternal immune activation, and autism spectrum disorder. Environ Int;2023 (Aug 14);179:108148.

BACKGROUND: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM(2.5)) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children. OBJECTIVES: This study examined interactions between MIA-related conditions and prenatal PM(2.5) or major PM(2.5) components on ASD risk. METHODS: In a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM(2.5) and four PM(2.5) components, black carbon (BC), organic matter (OM), nitrate (NO(3)(-)), and sulfate (SO(4)(2-)), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates. RESULTS: ASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM(2.5) [1.07; 1.03-1.12 per interquartile (3.73 μg/m(3)) increase] and with all four PM(2.5) components. However, there were no interactions of each category of MIA-related conditions with PM(2.5) or its components on either multiplicative or additive scales. CONCLUSIONS: MIA-related conditions and pregnancy PM(2.5) were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM(2.5) exposure with ASD risk.

Lien vers le texte intégral (Open Access ou abonnement)

21. Zhao P, Chen X, Bellafard A, Murugesan A, Quan J, Aharoni D, Golshani P. Accelerated social representational drift in the nucleus accumbens in a model of autism. bioRxiv;2023 (Aug 5)

Impaired social interaction is one of the core deficits of autism spectrum disorder (ASD) and may result from social interactions being less rewarding. How the nucleus accumbens (NAc), as a key hub of reward circuitry, encodes social interaction and whether these representations are altered in ASD remain poorly understood. We identified NAc ensembles encoding social interactions by calcium imaging using miniaturized microscopy. NAc population activity, specifically D1 receptor-expressing medium spiny neurons (D1-MSNs) activity, predicted social interaction epochs. Despite a high turnover of NAc neurons modulated by social interaction, we found a stable population code for social interaction in NAc which was dramatically degraded in Cntnap2 (-/-) mouse model of ASD. Surprisingly, non-specific optogenetic inhibition of NAc core neurons increased social interaction time and significantly improved sociability in Cntnap2 (-/-) mice. Inhibition of D1- or D2-MSNs showed reciprocal effects, with D1 inhibition decreasing social interaction and D2 inhibition increasing interaction. Therefore, social interactions are preferentially, specifically and dynamically encoded by NAc neurons and social representations are degraded in this autism model.

Lien vers le texte intégral (Open Access ou abonnement)