Causal Relationship Between Autism Spectrum Disorder and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.

Corrigendum: Diagnosis for autism spectrum disorder children using T1-based gray matter and arterial spin labeling-based cerebral blood flow network metrics.

[This corrects the article DOI: 10.3389/fnins.2024.1356241.].

Biomarkers and pathways in autism spectrum disorder: An individual meta-analysis based on proteomic and metabolomic data.

The utilization of biomarkers for the diagnosis and management of autism spectrum disorders (ASD) remains a relatively unexplored frontier in clinical practice. Proteomics and metabolomics are important tools for revealing key biomarkers and evaluating biological pathways in ASD. We conducted an individual meta-analysis to compare the consistency of biomarkers of ASD from central nervous system (brain and cerebrospinal fluid), circulatory system (blood), and non-invasive samples (urine, saliva, and faeces) and performed pathway enrichment analyses to identify pathways enriched in ASD. After screening 926 proteomics and 619 metabolomics articles, we collected data from 10 studies involving 940 differential proteins and 16 studies assessing a total of 748 differential metabolites. In brain tissue, blood, and urine of ASD cases and controls, flotillin-2 (FLOT2), apolipoprotein E (ApoE), and EH domain-containing protein 3 (EHD3) exhibit differential expression, while vinculin (VCL) displays variations in saliva, blood, and urine. Similarly, in case-control studies, gelsolin (GSN) shows differential expression in brain tissue, saliva, and urine, and malate dehydrogenase 2 (MDH2) in brain tissue, blood, and saliva. Hippuric acid and salicyluric acid were simultaneously found in the brain, blood, urine, and faeces. In terms of pathways, glycolysis/gluconeogenesis, carbon metabolism, and glutathione metabolism were enriched in the brain as well as in saliva or urine. In our study, we identified six shared protein and two metabolic markers in central nervous system, circulatory system, and non-invasive samples, underscoring their potential value for ASD diagnosis and management, warranting further research.

Gastrointestinal Symptoms in Autism Spectrum Disorder: A Case-Control Study.

Background and objectives This study aimed to explore the frequency of gastrointestinal (GI) symptoms and associated risk factors among children with autism spectrum disorder (ASD). Methods This was a retrospective case-control study including children aged 2-14 years diagnosed with ASD by the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria and the assessment card in the ASD center at King Salman Armed Forces Hospital. Data were obtained using a self-developed questionnaire that included demographic features, nutritional and behavioral characteristics, and GI symptoms in the previous six months. The control group consisted of typically developing (TD) children matched to the ASD group for age and gender. Syndromic autism with defined somatic abnormalities and recognized genetic causes (e.g., fragile X syndrome, tuberous sclerosis) were excluded Results A total of 146 ASD children and 114 normal children were included. No significant demographic differences were found between the groups. The ASD group had a higher frequency of low income and a significantly lower rate of exclusive breastfeeding in the first six months. GI symptoms, specifically constipation, abdominal gases and distension, diarrhea, undigested food particles in stool, and mouth ulcers, were significantly more frequent in the ASD group. Weight abnormalities (both increase and decrease) were also more common. Family history of ASD was significantly more in ASD children with GI symptoms while low maternal education was more in those without. Conclusion This study reveals a high prevalence of GI symptoms in ASD children. Family history of ASD and maternal education may influence the GI symptoms reported in ASD children.

Decoding the genetic landscape of autism: A comprehensive review.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings. Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD, influencing both diagnosis and therapeutic strategies. AIM: To explore the genetic architecture of ASD, elucidate mechanistic insights into genetic mutations, and examine gene-environment interactions. METHODS: A comprehensive systematic review was conducted, integrating findings from studies on genetic variations, epigenetic mechanisms (such as DNA methylation and histone modifications), and emerging technologies [including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 and single-cell RNA sequencing]. Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar. RESULTS: Genetic studies have identified numerous risk genes and mutations associated with ASD, yet many cases remain unexplained by known factors, suggesting undiscovered genetic components. Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving. Epigenetic modifications, particularly DNA methylation and non-coding RNAs, also play significant roles in ASD pathogenesis. Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data. CONCLUSION: Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments. Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice. Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies, ultimately enhancing outcomes for individuals affected by ASD.

ProVIA-Kids - outcomes of an uncontrolled study on smartphone-based behaviour analysis for challenging behaviour in children with intellectual and developmental disabilities or autism spectrum disorder.

Introduction: Challenging behaviour (CB) is a common issue among children with autism spectrum disorder or intellectual and developmental disability. Mental health applications are low-threshold cost-effective tools to address the lack of resources for caregivers. This pre-post study evaluated the feasibility and preliminary effectiveness of the smartphone app ProVIA-Kids using algorithm-based behaviour analysis to identify causes of CB and provide individualized practical guidance to manage and prevent CB. Methods: A total of 18 caregivers (M = 38.9 ± 5.0) of children with a diagnosis of autism spectrum disorder (44%), intellectual and developmental disabilities (33%) or both (22%) aged 4-11 years (M = 7.6 ± 1.8) were included. Assessments were performed before and after an 8-week intervention period. The primary outcome was the change in parental stress. Caregiver stress experience due to CB was also rated daily via ecological momentary assessments within the app. Secondary outcomes included the intensity of the child's CB, dysfunctional parenting, feelings of parental competency as well as caregivers' mood (rated daily in the app) and feedback on the app collected via the Mobile Application Rating Scale. Results: We observed increases in parental stress in terms of conscious feelings of incompetence. However, we also saw improvements in parental stress experience due to CB and overreactive parenting, and descriptive improvements in CB intensity and caregiver mood. Discussion: ProVIA-Kids pioneers behaviour analysis in a digital and automated format, with participants reporting high acceptance. Pilot results highlight the potential of the ProVIA-Kids app to positively influence child behaviour and caregiver mental health over a longer intervention period. Registration: The study was registered at https://www.drks.de (ID = DRKS00029039) on May 31, 2022.

CTNND2 moderates the pace of synaptic maturation and links human evolution to synaptic neoteny.

Human-specific genes are potential drivers of brain evolution. Among them, SRGAP2C has contributed to the emergence of features characterizing human cortical synapses, including their extended period of maturation. SRGAP2C inhibits its ancestral copy, the postsynaptic protein SRGAP2A, but the synaptic molecular pathways differentially regulated in humans by SRGAP2 proteins remain largely unknown. Here, we identify CTNND2, a protein implicated in severe intellectual disability (ID) in Cri-du-Chat syndrome, as a major partner of SRGAP2. We demonstrate that CTNND2 slows synaptic maturation and promotes neuronal integrity. During postnatal development, CTNND2 moderates neuronal excitation and excitability. In adults, it supports synapse maintenance. While CTNND2 deficiency is deleterious and results in synaptic loss of SYNGAP1, another major ID-associated protein, the human-specific protein SRGAP2C, enhances CTNND2 synaptic accumulation in human neurons. Our findings suggest that CTNND2 regulation by SRGAP2C contributes to synaptic neoteny in humans and link human-specific and ID genes at the synapse.

Enhancing ensemble classifiers utilizing gaze tracking data for autism spectrum disorder diagnosis.

PROBLEM: Diagnosing Autism Spectrum Disorder (ASD) remains a significant challenge, especially in regions where access to specialists is limited. Computer-based approaches offer a promising solution to make diagnosis more accessible. Eye tracking has emerged as a valuable technique in aiding the diagnosis of ASD. Typically, individuals' gaze patterns are monitored while they view videos designed according to established paradigms. In a previous study, we developed a method to classify individuals as having ASD or Typical Development (TD) by processing eye-tracking data using Random Forest ensembles, with a focus on a paradigm known as joint attention. AIM: This article aims to enhance our previous work by evaluating alternative algorithms and ensemble strategies, with a particular emphasis on the role of anticipation features in diagnosis. METHODS: Utilizing stimuli based on joint attention and the concept of "floating regions of interest" from our earlier research, we identified features that indicate gaze anticipation or delay. We then tested seven class balancing strategies, applied seven dimensionality reduction algorithms, and combined them with five different classifier induction algorithms. Finally, we employed the stacking technique to construct an ensemble model. RESULTS: Our findings showed a significant improvement, achieving an F1-score of 95.5%, compared to the 82% F1-score from our previous work, through the use of a heterogeneous stacking meta-classifier composed of diverse induction algorithms. CONCLUSION: While there remains an opportunity to explore new algorithms and features, the approach proposed in this article has the potential to be applied in clinical practice, contributing to increased accessibility to ASD diagnosis.

Early Behavioural Signs among Nepalese Children with Autism Spectrum Disorder: A Descriptive Cross-sectional Study.

INTRODUCTION: Autism Spectrum Disorder is a complex neurodevelopmental condition. Early identification of symptoms is crucial for timely intervention, yet diagnosing very young children can be challenging due to the variability in symptom presentation and the influence of other developmental factors. This study aimed to find the prevalence of the emergence of early behavioural signs in Nepalese children with Autism Spectrum Disorder. METHODS: A descriptive cross-sectional study was conducted at the Centre for Autism in Kathmandu, Nepal, from January 2023 to June 2023. Ethical approval was obtained, and a sample of 120 children diagnosed with Autism Spectrum Disorder was included in the study. Convenience sampling method was used. Point estimate at 95% Confidence Interval was calculated. RESULTS: Among 120 children with Autism Spectrum Disorder, the prevalence of emergence of early behavioural signs was seen in 112 (93.33%) (88.83-97.77, 95% Confidence Interval) children. CONCLUSIONS: This study provides insights into the emergence of early behavioural signs in Nepalese children with Autism Spectrum Disorder which align with global patterns in prevalence and severity.

A Boy With KIF11-Associated Disorder Along With ADHD and ASD: Collaboration Between Paediatrics and Child Psychiatry.

Kinesin family member 11 (KIF11)-associated disorder, a rare condition caused by autosomal dominant mutations in the KIF11 gene, presents with microcephaly, chorioretinal dysplasia, lymphoedema, and varying degrees of intellectual disability. While intellectual disability is often described in the literature on KIF11 mutations, autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are only mentioned by a few authors but not thoroughly investigated. We present a case report of an 8-year-old boy with KIF11-associated disorder alongside ADHD and ASD but without intellectual disability. Genetic testing confirmed a KIF11 mutation. Cognitive, language, and motor assessments revealed delays in fine motor skills and attention deficits. The diagnosis of ADHD was confirmed by a child neurologist through multidisciplinary investigations, while the ASD diagnosis was established by a child psychiatrist. Despite the challenges of delayed psychiatric assessment, interventions including physiotherapy and medication management were initiated with positive results. We designed a parent support group survey that showed a higher prevalence of neurodevelopmental disorders in children with KIF11 mutations compared to the general population. Therefore, low-threshold referrals to a child psychiatrist have to be made when the potential presence of developmental problems is suspected. Collaboration between ophthalmologists, paediatricians, and child psychiatrists is crucial for early detection and intervention. Addressing developmental disorders promptly improves long-term outcomes and enhances quality of life. Moreover, gaining a deeper understanding of the higher prevalence of ASD and ADHD in individuals with KIF11 mutations could offer valuable insights into the genetic mechanisms underlying neurodevelopmental disorders.

Superior temporal sulcus folding, functional network connectivity, and autistic-like traits in a non-clinical population.

BACKGROUND: Autistic-like traits (ALT) are prevalent across the general population and might be linked to some facets of a broader autism spectrum disorder (ASD) phenotype. Recent studies suggest an association of these traits with both genetic and brain structural markers in non-autistic individuals, showing similar spatial location of findings observed in ASD and thus suggesting a potential neurobiological continuum. METHODS: In this study, we first tested an association of ALTs (assessed with the AQ questionnaire) with cortical complexity, a cortical surface marker of early neurodevelopment, and then the association with disrupted functional connectivity. We analysed structural T1-weighted and resting-state functional MRI scans in 250 psychiatrically healthy individuals without a history of early developmental disorders, in a first step using the CAT12 toolbox for cortical complexity analysis and in a second step we used regional cortical complexity findings to apply the CONN toolbox for seed-based functional connectivity analysis. RESULTS: Our findings show a significant negative correlation of both AQ total and AQ attention switching subscores with left superior temporal sulcus (STS) cortical folding complexity, with the former being significantly correlated with STS to left lateral occipital cortex connectivity, while the latter showed significant positive correlation of STS to left inferior/middle frontal gyrus connectivity (n = 233; all p < 0.05, FWE cluster-level corrected). Additional analyses also revealed a significant correlation of AQ attention to detail subscores with STS to left lateral occipital cortex connectivity. LIMITATIONS: Phenotyping might affect association results (e.g. choice of inventories); in addition, our study was limited to subclinical expressions of autistic-like traits. CONCLUSIONS: Our findings provide further evidence for biological correlates of ALT even in the absence of clinical ASD, while establishing a link between structural variation of early developmental origin and functional connectivity.

Epidemiology and real-world management of childhood epilepsy in Japan: A descriptive study using a health claim database.

INTRODUCTION: The purpose of this epidemiological study was to assess the prevalence, comorbidities, and real-world management of childhood epilepsy to provide insights for enhancing epilepsy management and medical resource planning. MATERIALS AND METHODS: The study encompassed insured individuals aged 0-17 years as of December 2018 who were registered at any point in 2018, for at least part of the year, in a Japanese health claims database spanning January-December 2018. Epilepsy was defined as a diagnosis of epilepsy based on the International Classification of Diseases, 10th Revision codes, and a claimed management fee for epilepsy or an anti-seizure medication (ASM) prescription for longer than 4 weeks. The prevalence of epilepsy, patient characteristics, including comorbidities, and management status, such as prescription of ASMs, were evaluated. RESULTS: Among 1528,905 registered children, 9279 were identified as having epilepsy. The prevalence of epilepsy was the lowest at 1.97 per 1000 population (95 % confidence interval [CI] 1.80-2.15) in the 0-2-year age group and increased with age to 9.34 per 1000 population (95 % CI 8.98-9.72) in the 15-17-year age group, with a significantly higher prevalence in boys than in girls in the ≥12-year age group. ASMs were prescribed to 88.3 %-91.9 % of the patients. Moreover, 27 (0.29 %) patients underwent epilepsy surgery. The frequency of claiming intravenous ASMs and long-term electroencephalogram fees increased with a decrease in age. CONCLUSIONS: Our findings indicate that young children receive more medical resources than adolescents and that epilepsy surgery is underutilized. Further investigations will help improve the management of and develop measures against epilepsy.

A Short-Term Group Telehealth Cognitive Behavioral Therapy Intervention for Youth with Autism and Anxiety: A Pilot Study.

Background: Children with autism often present with comorbid anxiety disorders. Cognitive behavioral therapy (CBT) is an effective, evidence-based approach to treating anxiety, but information on youth with autism and anxiety is limited. Coping Cat is a 16-week CBT intervention for children with anxiety but its use in a group telehealth format in an urban, predominantly Hispanic population is limited. Objectives: (a) To examine the feasibility and preliminary effectiveness of a short-term CBT telehealth group for youth with autism and anxiety disorders in an urban, predominantly Hispanic population and (b) to examine satisfaction with the intervention. Methods: Single-arm pilot study that consisted of a 16-week telehealth CBT group therapy was based on a modified Coping Cat curriculum. Youth with autism and anxiety disorders who were on a waitlist for psychotherapy at an urban developmental center were invited to participate. Anxiety was assessed pre- and posttreatment using the Screen for Child Anxiety Related Emotional Disorders, parent and self-report. Results: Eighteen children were enrolled; 16 children completed the program. Mean age was 11 ± 2.5 years (8-15 years); 89% males, 61% Hispanic. There was a significant reduction in pre-post intervention in symptoms of overall anxiety (parent: 41.0 ± 18.5 to 31.0 ± 16.3 p ≤ 0.003, self: 25.9 ± 12.8 to 14.1 ± 7.8 p ≤ 0.001), panic disorder (parent: 8.1 ± 7.0 to 4.1 ± 4.2 p = 0.013, self: 5.1 ± 4.8 to 0.8 ± 0.9 p = 0.004), and separation anxiety disorder (parent: 7.5 ± 4.8 to 5.7 ± 4.4 p = 0.041, self: 5.8 ± 3.3 to 3.8 ± 2.4 p = 0.018) as per parent and self-reports. Self-report data also revealed a significant reduction in symptoms of social anxiety disorder (6.5 ± 3.5 to 3.9 ± 2.7 p ≤ 0.001). Parents and children reported satisfaction with the group. Conclusion: In this small, predominantly Hispanic population of youth with autism and anxiety disorder, 89% of families were compliant with a group telehealth CBT intervention. Parents and youth reported a significant reduction in anxiety symptoms and program satisfaction. A modified group CBT program via telehealth represents a feasible intervention for youth with autism and anxiety disorders.

Multisession tDCS combined with intrastimulation training improves emotion recognition in adolescents with autism spectrum disorder.

Previous studies indicate that transcranial direct current stimulation (tDCS) is a promising emerging treatment option for autism spectrum disorder (ASD) and its efficacy could be augmented using concurrent training. However, no intrastimulation social cognition training for ASD has been developed so far. The objective of this two-armed, double-blind, randomized, sham-controlled clinical trial is to investigate the effects of tDCS combined with a newly developed intrastimulation social cognition training on adolescents with ASD. Twenty-two male adolescents with ASD were randomly assigned to receive 10 sessions of either anodal or sham tDCS at F3/right supraorbital region together with online intrastimulation training comprising basic and complex emotion recognition tasks. Using baseline magnetic resonance imaging data, individual electric field distributions were simulated, and brain activation patterns of the training tasks were analyzed. Additionally, questionnaires were administered at baseline and following the intervention. Compared to sham tDCS, anodal tDCS significantly improved dynamic emotion recognition over the course of the sessions. This task also showed the highest activations in face processing regions. Moreover, the improvement was associated with electric field density at the medial prefrontal cortex and social awareness in exploratory analyses. Both groups showed high tolerability and acceptability of tDCS, and significant improvement in overall ASD symptoms. Taken together, multisession tDCS improved dynamic emotion recognition in adolescents with ASD using a task that activates brain regions associated with the social brain network. The variability in the electric field might diminish tDCS effects and future studies should investigate individualized approaches.

The function of Mef2c toward the development of excitatory and inhibitory cortical neurons.

Neurodevelopmental disorders (NDDs) are caused by abnormal brain development, leading to altered brain function and affecting cognition, learning, self-control, memory, and emotion. NDDs are often demarcated as discrete entities for diagnosis, but empirical evidence indicates that NDDs share a great deal of overlap, including genetics, core symptoms, and biomarkers. Many NDDs also share a primary sensitive period for disease, specifically the last trimester of pregnancy in humans, which corresponds to the neonatal period in mice. This period is notable for cortical circuit assembly, suggesting that deficits in the establishment of brain connectivity are likely a leading cause of brain dysfunction across different NDDs. Regulators of gene programs that underlie neurodevelopment represent a point of convergence for NDDs. Here, we review how the transcription factor MEF2C, a risk factor for various NDDs, impacts cortical development. Cortical activity requires a precise balance of various types of excitatory and inhibitory neuron types. We use MEF2C loss-of-function as a study case to illustrate how brain dysfunction and altered behavior may derive from the dysfunction of specific cortical circuits at specific developmental times.

Unveiling the role of IGF1R in autism spectrum disorder: a multi-omics approach to decipher common pathogenic mechanisms in the IGF signaling pathway.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.

Psychoeducational and Behavioral Interventions in Autism Spectrum Disorder: is the ABA Method Really the Most Effective?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, social interactions, and repetitive behaviors. Applied Behavior Analysis (ABA) is a prominent intervention aimed at modifying problem behaviors in individuals with ASD. ABA focuses on analyzing environmental contingencies and using operant conditioning to promote functional behaviors. Despite its widespread use, the effectiveness of ABA remains debated, with mixed scientific evidence. Some studies highlight its benefits, while others point out biases and limitations. Further research, including randomized controlled trials, is needed to determine the most effective interventions for ASD, considering the diverse needs of individuals and the potential biases in current studies.

Implementing the Early Start Denver Model in Senegal: Outcomes and Insights from a Low-Resource Context.

BACKGROUND: Autism Spectrum Disorders (ASD) are characterized by significant challenges in social interaction and communication, accompanied by repetitive behaviors. Effective early interventions, such as the Early Start Denver Model (ESDM) are crucial but primarily studied in well-resourced Western countries. This study explores the adaptation and effectiveness of ESDM in Senegal, a low-resource setting, to adress gaps in autism care and intervention accessibility in Africa. SUBJECTS AND METHODS: An observational study was conducted at Diamniadio Children's Hospital, Dakar, Senegal, from January 2019 to July 2021, focusing on children under 10 years suspected of having ASD. Diagnostic assessments were performed using the DSM-5 criteria with tools like the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). Interventions based on ESDM were adapted to local resources and involved regular family and patient engagement. RESULTS: Of the 114 children referred for ASD suspicion, 80 were diagnosed with ASD. Post-diagnosis, 30 children received follow-up care at the day hospital, and another 30 were managed via outpatient care. 20 children did not receive any follow-up care at Diamniadio Children's Hospital. Significant socio-economic disparities were noted, influencing access to and engagement with intervention programs. No significant differences were found in clinical characteristics between groups, but socio-economic factors significantly affected intervention access. CONCLUSION: The adapted ESDM interventions show promise for implementation in resource-limited settings like Senegal, although challenges related to socio-economic disparities and service accessibility persist. Future research should focus on the integration of ASD services into broader health policies to enhance efficacy and accessibility.

Autism spectrum disorder and various mechanisms behind it.

Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition characterized by a range of social, communicative, and behavioral challenges. This comprehensive review delves into key aspects of ASD. Clinical Overview and genetic features provide a foundational understanding of ASD, highlighting the clinical presentation and genetic underpinnings that contribute to its complexity. We explore the intricate neurobiological mechanisms at play in ASD, including structural and functional differences that may underlie the condition's hallmark traits. Emerging research has shed light on the role of the immune system and neuroinflammation in ASD. This section investigates the potential links between immunological factors and ASD, offering insights into the condition's pathophysiology. We examine how atypical functional connectivity and alterations in neurotransmitter systems may contribute to the unique cognitive and behavioral features of ASD. In the pursuit of effective interventions, this section reviews current therapeutic strategies, ranging from behavioral and educational interventions to pharmacological approaches, providing a glimpse into the diverse and evolving landscape of ASD treatment. This holistic exploration of mechanisms in ASD aims to contribute to our evolving understanding of the condition and to guide the development of more targeted and personalized interventions for individuals living with ASD.

The role of gene-environment interactions in social dysfunction: Focus on preclinical evidence from mouse studies.

Human and animal research has demonstrated that genetic and environmental factors can strongly modulate behavioral function, including the expression of social behaviors and their dysfunctionalities. Several genes have been linked to pathologies characterized by alterations in social behaviors, e.g., aggressive/antisocial personality disorder (ASPD), or autism spectrum disorder (ASD). Environmental stimulation (e.g., physical exercise, environmental enrichment) or adversity (e.g., chronic stress, social isolation) may respectively improve or impair social interactions. While the independent contribution of genetic and environmental factors to social behaviors has been assessed in a variety of human and animal studies, the impact of their interactive effects on social functions has been less extensively investigated. Genetic mutations and environmental changes can indeed influence each other through complex mutual effects, e.g., inducing synergistic, antagonistic or interactive behavioral outcomes. This complexity is difficult to be disentangled in human populations, thus encouraging studies in animal models, especially in the mouse species which is the most suitable for genetic manipulations. Here we review the available preclinical evidence on the impact of gene-environment interactions on social behaviors and their dysfunction, focusing on studies in laboratory mice. We included findings combining naturally occurring mutations, selectively bred or transgenic mice with multiple environmental manipulations, including positive (environmental enrichment, physical exercise) and aversive (social isolation, maternal separation, and stress) experiences. The impact of these results is critically discussed in terms of their generalizability across mouse models and social tests, as well as their implications for human studies on social dysfunction.