Prevalence Of Autism Spectrum Disorder Research Articles

The role and impact of abnormal vitamin levels in autism spectrum disorders.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder with a predominance of social behavioral disorders, has increased dramatically in various countries in recent decades. The interplay between genetic and environmental factors is believed to underlie ASD pathogenesis. Recent analyses have shown that abnormal vitamin levels in early life are associated with an increased risk of autism. As essential substances for growth and development, vitamins have been shown to have significant benefits for the nervous and immune systems. However, it is unknown whether certain vitamin types influence the emergence or manifestation of ASD symptoms. Several studies have focused on vitamin levels in children with autism, and neurotypical children have provided different insights into the types of vitamins and their intake. Here, we review the mechanisms and significance of several vitamins (A, B, C, D, E, and K) that are closely associated with the development of ASD in order to prevent, mitigate, and treat ASD. Efforts have been made to discover and develop new indicators for nutritional assessment of children with ASD to play a greater role in the early detection of ASD and therapeutic remission after diagnosis.

The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits.

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

Mothers' experiences: A missing puzzle piece in caring for children with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social relationships, communication, and restricted and repetitive behavioral patterns [1]. In recent years, epidemiological studies have shown a rapid increase in the prevalence of ASD. According to the report from the Center for Disease Control and Prevention in the United States, the prevalence was estimated to be 1 in 59 individuals in 2014 and 1 in 54 individuals in 2016 among 8-year-old children [2]. ASD is a complex developmental condition that is accompanied by persistent challenges in social interaction, speech, and nonverbal communication, significantly affecting mother-child interactions [3]. One of the most significant concerns for mothers of these children is how to care for them. The exact cause of this disorder remains largely unknown, and lack of awareness about autism often leads to delayed recognition of the child's difficulties by families [4]. As a result, the golden time for early intervention may be missed, and life in society becomes more challenging for both these children and their caregivers. Additionally, these children require care and support from their families and community institutions from birth throughout their growth and development, making caregiving a stressful process for mothers. Therefore, caring for these children necessitates the adoption of specialized caregiving and parenting approaches [5, 6]. The literature review indicates that the majority of studies conducted in the field of caring for children with autism have primarily been quantitative studies with a traditional intervention approach, focusing on the effectiveness of cognitive-behavioral therapy play therapy, storytelling therapy, supportive counseling, psychotherapy, and teaching coping skills [7-9]. While quantitative research methods have their benefits in many areas, they alone cannot provide a comprehensive examination of the deep dimensions of the phenomenon from the perspective of individuals' first-hand experiences [10].

A novel autism-associated UBLCP1 mutation impacts proteasome regulation/activity

The landscape of autism spectrum disorder (ASD) in Lebanon is unique because of high rates of consanguinity, shared ancestry, and increased remote consanguinity. ASD prevalence in Lebanon is 1 in 68 with a male-to-female ratio of 2:1. This study aims to investigate the impact of an inherited deletion in UBLCP1 (Ubiquitin-Like Domain-Containing CTD Phosphatase 1) on the ubiquitin-proteasome system (UPS) and proteolysis. Whole exome sequencing in a Lebanese family with ASD without pathogenic copy number variations (CNVs) uncovered a deletion in UBLCP1. Functional evaluation of the identified variant is described in fibroblasts from the affected. The deletion in UBLCP1 exon 10 (g.158,710,261CAAAG > C) generates a premature stop codon interrupting the phosphatase domain and is predicted as pathogenic. It is absent from databases of normal variation worldwide and in Lebanon. Wild-type UBLCP1 is widely expressed in mouse brains. The mutation results in decreased UBLCP1 protein expression in patient-derived fibroblasts from the autistic patient compared to controls. The truncated UBLCP1 protein results in increased proteasome activity decreased ubiquitinated protein levels, and downregulation in expression of other proteasome subunits in samples from the affected compared to controls. Inhibition of the proteasome by using MG132 in proband cells reverses alterations in gene expression due to the restoration of protein levels of the common transcription factor, NRF1. Finally, treatment with gentamicin, which promotes premature termination codon read-through, restores UBLCP1 expression and function. Discovery of an ASD-linked mutation in UBLCP1 leading to overactivation of cell proteolysis is reported. This, in turn, leads to dysregulation of proteasome subunit transcript levels as a compensatory response.

Exploring the autism “diagnostic odyssey” in the Greater Accra region of Ghana

Introduction: Despite the increasing global prevalence of autism spectrum disorders (ASD), there is limited information about ASD in Africa. Existing research on ASD in Africa shows that autistic children are diagnosed relatively late or not at all. The purpose of this study was to understand the barriers to an autism diagnosis and to engage key stakeholders to action plan steps to reduce the barriers. Methods: We conducted a participatory, mixed methods study using semi-structured interviews, a survey, photo elicitation, and focus groups with 11 participants (four parents and seven health professionals) in the Greater Accra region of Ghana. Findings: Neuro-paediatricians in our study reported that it takes, on average, two to six visits over two weeks to two years or more to diagnose a child. Our thematic qualitative analysis yielded three overarching themes, with barriers and facilitators for each: 1) Systemic, 2) Community, and 3) Parent/Family factors that influence the diagnostic process. The action plan of our stakeholder focus group prioritizes community education to dispel myths and encourage autism acceptance within the Ghanaian community. Conclusion: Knowledge about the diagnostic odyssey can help facilitate early diagnosis and intervention. Implications for practice This research study confirmed known challenges to the autism diagnostic process. It contributed nuanced insights into the role of culture, the importance of education, and the need for community involvement in improving the diagnostic process, early occupational therapy intervention, and autism acceptance within the community.

From Data to Insights: Machine Learning Empowers Prognostic Biomarker Prediction in Autism.

Autism Spectrum Disorder (ASD) poses significant challenges to society and science due to its impact on communication, social interaction, and repetitive behavior patterns in affected children. The Autism and Developmental Disabilities Monitoring (ADDM) Network continuously monitors ASD prevalence and characteristics. In 2020, ASD prevalence was estimated at 1 in 36 children, with higher rates than previous estimates. This study focuses on ongoing ASD research conducted by Erciyes University. Serum samples from 45 ASD patients and 21 unrelated control participants were analyzed to assess the expression of 372 microRNAs (miRNAs). Six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) exhibited significant downregulation in all ASD patients compared to healthy controls. The current study endeavors to identify dependable diagnostic biomarkers for ASD, addressing the pressing need for non-invasive, accurate, and cost-effective diagnostic tools, as current methods are subjective and time-intensive. A pivotal discovery in this study is the potential diagnostic value of miR-126-3p, offering the promise of earlier and more accurate ASD diagnoses, potentially leading to improved intervention outcomes. Leveraging machine learning, such as the K-nearest neighbors (KNN) model, presents a promising avenue for precise ASD diagnosis using miRNA biomarkers.

The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interactions, restrictive and repetitive behavior, and a wide range of cognitive impediments. The prevalence of ASD tripled in the last 20 years and now affects 1 in 44 children. Although ASD's etiology is not yet elucidated, a growing body of evidence shows that it stems from a complex interplay of genetic and environmental factors. In recent years, there has been increased focus on the role of gut microbiota and their metabolites, as studies show that ASD patients show a significant shift in their gut composition, characterized by an increase in specific bacteria and elevated levels of short-chain fatty acids (SCFAs), especially propionic acid (PPA). This review aims to provide an overview of the role of microbiota and SCFAs in the human body, as well as possible implications of microbiota shift. Also, it highlights current studies aiming to compare the composition of the gut microbiome of ASD-afflicted patients with neurotypical control. Finally, it highlights studies with rodents where ASD-like symptoms or molecular hallmarks of ASD are evoked, via the grafting of microbes obtained from ASD subjects or direct exposure to PPA.

The early life growth of head circumference, weight, and height in infants with autism spectrum disorders: a systematic review

BackgroundsThe Autism spectrum disorder (ASD) prevalence has increased significantly over the past two decades. This review summarizes the current knowledge of the association between the early life growth of head circumference (HC), weight, and height with ASD in infants.MethodsPubMed, Scopus, Science Direct, and Google Scholar databases were searched up to November 2021 using relevant keywords. All original articles are written in English evaluating the early life growth of HC, weight, and height in infants with ASD were eligible for the present review.ResultsTotally, 23 articles involving 4959 infants were included in this review. Of 13 studies that evaluated HC of infants at birth, 10 studies (83.33%) showed that the HC at the birth of autistic children was similar to that of the average found in the control group. Among 21 studies that evaluated the HC and weight status in infants, 19 studies (90.47%) showed that autistic children had larger HC and weight than the control group or abnormal acceleration of head growth during infancy. Height growth of infants was investigated in 13 studies, of which 10 cases (76.92%) reported that infants with ASD were significantly longer than control groups. Most of he included studies had a good quality.ConclusionsThe findings suggest that in infants with ASD, without the contribution of birth growth factors and sex of the child, the growth of HC, weight, and height probably was faster than in infants with normal development, in early life. Therefore, these measurements might be useful as initial predictive biomarkers for the risk of developing ASD.

The Risk of Autism in Children Relevance of Age of Father & Genetics During Pregnancy Clinical Observation

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by difficulties in social interaction and communication alongside stereotypic, repetitive behavior and narrow interests. The reported prevalence of ASD in children has increased during the last two decades. The current prevalence of ASD is estimated to be approximately 1% (1–3). At least part of the explanation for the increasing ASD prevalence is likely to be related to factors such as changing diagnostic criteria, greater awareness, improved case identification, and changes in age of diagnosis.

Cadmium exposure exacerbates immunological abnormalities in a BTBR T+ Itpr3tf/J autistic mouse model by upregulating inflammatory mediators in CD45R-expressing cells

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by behavior, learning, communication, and social interaction abnormalities in various situations. Individuals with impairments usually exhibit restricted and repetitive actions. The actual cause of ASD is yet unknown. It is believed, however, that a mix of genetic and environmental factors may play a role in its development. Certain metals have been linked to the development of neurological diseases, and the prevalence of ASD has shown a positive association with industrialization. Cadmium chloride (Cd) is a neurotoxic chemical linked to cognitive impairment, tremors, and neurodegenerative diseases. The BTBR T+ Itpr3tf/J (BTBR) inbred mice are generally used as a model for ASD and display a range of autistic phenotypes. We looked at how Cd exposure affected the signaling of inflammatory mediators in CD45R-expressing cells in the BTBR mouse model of ASD. In this study, we looked at how Cd affected the expression of numerous markers in the spleen, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. Furthermore, we investigated the effect of Cd exposure on the expression levels of numerous mRNA molecules in brain tissue, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. The RT-PCR technique was used for this analysis. Cd exposure increased the number of CD45R+IFN-γ+, CD45R+IL-6+, CD45R+NF-κB p65+, CD45R+GM-CSF+, CD45R+GM-CSF+, CD45R+iNOS+, and CD45R+Notch1+ cells in the spleen of BTBR mice. Cd treatment also enhanced mRNA expression in brain tissue for IFN-γ, IL-6, NF-κB, GM-CSF, iNOS, MCP-1, and Notch1. In general, Cd increases the signaling of inflammatory mediators in BTBR mice. This study is the first to show that Cd exposure causes immune function dysregulation in the BTBR ASD mouse model. As a result, our study supports the role of Cd exposure in the development of ASD.

Preclinical Evidence for the Role of the Yin/Yang Angiotensin System Components in Autism Spectrum Disorder: A Therapeutic Target of Astaxanthin.

Autism spectrum disorder (ASD) prevalence is emerging with an unclear etiology, hindering effective therapeutic interventions. Recent studies suggest potential renin-angiotensin system (RAS) alterations in different neurological pathologies. However, its implications in ASD are unexplored. This research fulfills the critical gap by investigating dual arms of RAS and their interplay with Notch signaling in ASD, using a valproic acid (VPA) model and assessing astaxanthin's (AST) modulatory impacts. Experimentally, male pups from pregnant rats receiving either saline or VPA on gestation day 12.5 were divided into control and VPA groups, with subsequent AST treatment in a subset (postnatal days 34-58). Behavioral analyses, histopathological investigations, and electron microscopy provided insights into the neurobehavioral and structural changes induced by AST. Molecular investigations of male pups' cortices revealed that AST outweighs the protective RAS elements with the inhibition of the detrimental arm. This established the neuroprotective and anti-inflammatory axes of RAS (ACE2/Ang1-7/MasR) in the ASD context. The results showed that AST's normalization of RAS components and Notch signaling underscore a novel therapeutic avenue in ASD, impacting neuronal integrity and behavioral outcomes. These findings affirm the integral role of RAS in ASD and highlight AST's potential as a promising treatment intervention, inviting further neurological research implications.

Glial cells are affected more than interneurons by the loss of Engrailed 2 gene in the mouse cerebellum.

Glial cells play a pivotal role in the inflammatory processes, which are common features of several neurodevelopmental and neurodegenerative disorders. Their major role in modulating neuroinflammation underscores their significance in these conditions. Engrailed-2 knockout mice (En2-/- ) are considered a valuable model for autism spectrum disorder (ASD) due to their distinctive neuroanatomical and behavioral traits. Given the higher prevalence of ASD in males, our objective was to investigate glial and interneuron alterations in the cerebellum of En2-/- mice compared with wild-type (WT) mice in both sexes. We employed immunohistochemical analysis to assess cell density for all cell types studied and analyzed the area (A) and shape factor (SF) of microglia cell bodies. Our findings revealed the following: (a) In WT mice, the density of microglia and astrocytes was higher in females than in males, while interneuron density was lower in females. Notably, in En2-mutant mice, these differences between males and females were not present. (b) In both male and female En2-/- mice, astrocyte density exceeded that in WT mice, with microglia density being greater only in females. (c) In WT females, microglia cell bodies exhibited a larger area and a lower shape factor compared to WT males. Remarkably, the En2 mutation did not appear to influence these sex-related differences. (d) In both male and female En2-/- mice, we observed a consistent pattern: microglia cell bodies displayed a larger area and a smaller shape factor. Given the ongoing debate surrounding the roles of glia and sex-related factors in ASD, our observations provide valuable insights into understanding how an ASD-associated gene En2 affects specific cell types in the cerebellum.

Environmental Influences on Individuals with Autistic Spectrum Disorders with Special Emphasis on Seasonality: An Overview.

This paper offers an in-depth exploration of the intricate relationship between environmental factors and autism spectrum disorder (ASD), with a special emphasis on seasonality. It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of several environmental factors influencing the etiology of ASD. The discussion encompasses various elements, including birth months, maternal health, dietary choices, and vitamin D deficiency, delving into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how environmental factors, particularly seasonality, may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.

Screening and Bioinformatics Analysis of Differential Genes in Autism Spectrum Disorder Based on GEO Database.

The prevalence of autism spectrum disorder (ASD) in children has been increasing year by year, which has seriously affected the quality of life of children. There are many theories about the cause of ASDs, with some studies suggesting that it may be related to gene expression levels or inflammation and immune system dysfunction. But the exact mechanism is not fully understood. profile of gene expression The protein interaction network (PPI) of differentially expressed genes was created using the STRING web tool and GSE77103, which was chosen from the gene expression omnibus (GEO) database. Using the CytoHubba plugin of Cytoscape program, the hub genes were examined. The hub gene regulatory network for miRNA-mRNA was then built. We identified 551 differentially expressed genes(DEGs) in 8 children with ASD and normal children. In addition, we screened out 10 hub genes (MX1, ISG15, IRF7, DDX58, IFIT1, BCL2L1, HPGDS, CTSD, PTGS2 and CD68) that were most associated with the development of ASDs. Then, microRNAs (miRNAs) closely related to hub genes (such as has-miR-27a-5p) were screened, and the miRNA-mRNA regulatory network was constructed. In this study, a total of 10 hub genes were identified, including MX1, ISG15, IRF7, DDX58, IFIT1, BCL2L1, HPGDS, CTSD, PTGS2 and CD68, which are closely related to ASD. These genes may play a key role in the occurrence and progression of ASD. In addition, we also revealed some miRNAs that regulate the hub genes of ASD. These results may deepen our understanding of ASD and provide potential biomarkers and targets for future treatment of patients with ASD.

Mechanism of Polygala-Acorus in Treating Autism Spectrum Disorder Based on Network Pharmacology and Molecular Docking

Background:: Recent epidemic survey data have revealed a globally increasing prevalence of autism spectrum disorders (ASDs). Currently, while Western medicine mostly uses a combination of comprehensive intervention and rehabilitative treatment, patient outcomes remain unsatisfactory. Polygala–Acorus, used as a pair drug, positively affects the brain and kidneys, and can improve intelligence, wisdom, and awareness; however, the underlying mechanism of action is unclear. background: Recent epidemic survey data revealed a globally increasing prevalence of autism spectrum disorders (ASDs). Currently, Western medicine mostly uses a combination of comprehensive intervention and rehabilitative treatment, but patient outcomes remain unsatisfactory. Polygala–Acorus, used as a pair drug, positively affects the brain and kidneys and can improve intelligence, wisdom, and awareness. However, the underlying mechanism is unclear. Objective:: We performed network pharmacology analysis of the mechanism of Polygala– Acorus in treating ASD and its potential therapeutic effects to provide a scientific basis for the pharmaceutical’s clinical application. Methods:: The chemical compositions and targets corresponding to Polygala–Acorus were obtained using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform, ChemSource.com, and PharmMapper database. Disease targets in ASD were screened using the DisGeNET, DrugBank, and GeneCards databases. Gene Ontology functional analysis and metabolic pathway analysis (Kyoto Encyclopedia of Genes and Genomes) were performed using the Metascape database and validated via molecular docking using AutoDock Vina and PyMOL software. Results:: Molecular docking analysis showed that the key active components of Polygala- Acorus interacted with the following key targets: EGFR, SRC, MAPK1, and ALB. Thus, the key active components of Polygala-Acorus (sibiricaxanthone A, sibiricaxanthone B tenuifolin, polygalic acid, cycloartenol, and 8-isopentenyl-kaempferol) have been found to bind to EGFR, SRC, MAPK1, and ALB. Conclusion:: This study has preliminarily revealed the active ingredients and underlying mechanism of Polygala-Acorus in the treatment of ASD, and our predictions need to be proven by further experimentation.

A Scoping Review of Studies on Assistive Technology Interventions and Their Impact on Individuals with Autism Spectrum Disorder in Arab Countries.

To review the current literature on the AT interventions and outcomes reported for individuals with ASD in Arab countries. A scoping review adhering to PRISMA guidelines was undertaken to explore the utilization of AT, segmented into three categories: low-technology (low-tech), mid-technology (mid-tech), and high-technology (high-tech) devices. Twelve studies had a pooled sample of 1547 participants, primarily male school-aged children with ASD. The AT applications evaluated ranged from low-tech visual schedules and support to high-tech virtual reality systems. Studies have reported the potential benefits of AT in improving communication, social, academic, adaptive, and functional abilities; however, comparative evidence between AT interventions is limited. The identified barriers to the adoption of AT included caregiver uncertainty about the use of AT and a lack of awareness of AT among professionals and the Arab community in general. Available studies suggest that the adoption of AT can enhance the skills of individuals with ASD in Arab countries. However, more rigorous studies across diverse demographic groups and Arab national regions are needed to strengthen the evidence base and provide appropriate recommendations.

First-episode psychosis and autism spectrum disorder: a scoping review and a guide to overcome diagnostic challenges

Background Undiagnosed Autism Spectrum Disorder (ASD) may represent a diagnostic challenge in people who refer to specialized services for first-episode psychosis (FEP). Similarly, individuals with ASD can present newly-onset psychotic symptoms. Aims The present review aimed to summarize the literature available on ASD and FEP to guide differential diagnosis between the two conditions and discuss the impact of ASD-FEP comorbidity on recovery. Methods The PRISMA-ScR guidelines were followed. After conducting a comprehensive literature search, we screened 204 papers including participants with: (1) a comorbid diagnosis of FEP and ASD; (2) FEP and autistic traits; (3) separate groups of FEP and ASD. Results A total of 18 studies were discussed and confirmed the high prevalence of ASD or autistic traits in people referring to FEP services (up to 9% and 35% of FEP, respectively), which could negatively impact pathways to care, clinical presentation, and outcomes. Due to some similarities in ASD and FEP presentation (e.g., difficulties in social functioning), a differential diagnosis could be challenging. The features more suggestive of ASD rather than a primary FEP include illogical and concrete thinking, and a longstanding social interaction difficulty. Aberrant salience and suspiciousness can manifest in ASD, but are usually more transient, and stress-related than in FEP. Also, perceptual abnormalities are due to altered sensory processing rather than pathological hallucinations. The co-occurrence of ASD symptoms is associated with a reduced probability of clinical and functional recovery in FEP, a higher risk of suicidal behaviors, and higher unemployment rates. Conclusions The kaleidoscopic manifestations of FEP require an adequate differential diagnosis that should include ASD. FEP services ought to be equipped for an adequate assessment and diagnostic formulation, which can result particularly challenging should symptoms of autism be present in adult patients.

Associations of Atopic Dermatitis with Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Background: Atopic dermatitis (AD) shares similarities with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) regarding pathogenesis involving neuroinflammation and genetics. Nevertheless, evidence on the associations of AD with ADHD and/or ASD is inconclusive. This study aimed to systematically examine the existing evidence on the associations between AD, ADHD, and ASD. Methods: The Meta-Analysis of Observational Studies in Epidemiology guideline was followed. We searched MEDLINE, Embase, Cochrane Library, and Web of Science databases from their respective inceptions to March 4, 2022. Observational studies providing adjusted estimates and/or prevalences for ADHD and ASD in patients with AD were enrolled. A random-effects model meta-analysis was conducted to calculate pooled odds ratios (ORs) and confidence intervals (CIs). Subgroup analyses according to AD severity, age, geographic location, and study design were performed. Results: Overall, a total of 24 studies with 71,373,639 subjects were enrolled. Our meta-analysis demonstrated significant associations of AD with ADHD (pooled OR: 1.28; 95% CI: 1.18–1.40) and ASD (pooled OR: 1.87; 95% CI: 1.30–2.68). Subgroup analyses revealed that the associations for ADHD were the most prominent in studies evaluating severe AD patients as well as in studies focusing on school-age children and adolescents. Among patients with AD, the pooled prevalence of ADHD was 6.6%, and the respective prevalence of ASD was 1.6%. Conclusion: The evidence to date suggests significant associations of AD with ADHD and ASD. Psychiatric consultation and an interdisciplinary approach would benefit patients with AD presented with behavioral symptoms suggestive of ADHD or ASD.

39 Neurodevelopmental Complexity of a Patient with Perinatal Right Middle Cerebral Artery Stroke and Infantile Spasms

Objective:A rich literature exists on cognitive changes related to focal injury in the adult brain. In contrast, the developing brains of children are less understood. In contrast to adult cases, 20% to 25% of perinatal strokes result in language disorder regardless of lesion lateralization. Existing literature suggests children with perinatal stroke may present with a range of executive functioning and visuospatial processing difficulties. Gross and fine motor challenges are also likely to occur. Furthermore, these children have an increased prevalence of autism spectrum disorder (ASD) and carry the highest risk for epilepsy. Despite growing research on neurodevelopmental profiles in patients with perinatal stroke, published literature is limited.Participants and Methods:Our study examines neurodevelopment of a 2-year-old, right-handed male with a history of perinatal ischemic right middle cerebral artery (MCA) stroke, infantile spasms, and left hemiparesis following right hemispherectomy for seizure management who underwent two neurodevelopmental evaluations at our medical center over approximately 3 years.Results:Findings from the patient’s evaluation with the Mullen Scales of Early Learning revealed overall cognitive ability in the low average range (SS = 89, 23rd percentile); however, notable variability was seen in his performance. His receptive language was average (SS = 98, 45th %tile) and consistent with previous evaluation results, and he has made gains in visual reception (from SS = 75, 5th %tile to SS = 91, 27th %tile) and expressive language (from SS = 55, 0.1st %tile to SS = 70, 2nd %tile). In addition, his gross motor was exceptionally low (SS = 55, 0.1st %tile) and consistent with previous evaluation results. Fine motor was low average (SS = 84, 14th %tile).Conclusions:Our patient showed cognitive gains in language and visual reception since his prior evaluation despite history of right MCA stroke and right hemispherectomy. Improvements are likely due to a combination of early brain plasticity and intensive therapies he has received. Consistent with published findings in this population, he experienced seizures associated with his stroke. Our results add to the limited literature on neurodevelopmental challenges associated with perinatal stroke and progress that can be made when appropriate supports are provided early and consistently.

Role of the Autism Risk Gene Shank3 in the Development of Atherosclerosis: Insights from Big Data and Mechanistic Analyses.

Increased medical attention is needed as the prevalence of autism spectrum disorder (ASD) rises. Both cardiovascular disorder (CVD) and hyperlipidemia are closely associated with adult ASD. Shank3 plays a key genetic role in ASD. We hypothesized that Shank3 contributes to CVD development in young adults with ASD. In this study, we investigated whether Shank3 facilitates the development of atherosclerosis. Using Gene Set Enrichment Analysis software (Version No.: GSEA-4.0.3), we analyzed the data obtained from Shank3 knockout mice (Gene Expression Omnibus database), a human population-based study cohort (from Taiwan's National Health Insurance Research Database), and a Shank3 knockdown cellular model. Shank3 knockout upregulated the expression of genes of cholesterol homeostasis and fatty acid metabolism but downregulated the expression of genes associated with inflammatory responses. Individuals with autism had higher risks of hyperlipidemia (adjusted hazard ratio (aHR): 1.39; p < 0.001), major adverse cardiac events (aHR: 2.67; p < 0.001), and stroke (aHR: 3.55; p < 0.001) than age- and sex-matched individuals without autism did. Shank3 downregulation suppressed tumor necrosis factor-α-induced fatty acid synthase expression; vascular cell adhesion molecule 1 expression; and downstream signaling pathways involving p38, Jun N-terminal kinase, and nuclear factor-κB. Thus, Shank3 may influence the development of early-onset atherosclerosis and CVD in ASD. Furthermore, regulating Shank3 expression may reduce inflammation-related disorders, such as atherosclerosis, by inhibiting tumor necrosis factor-alpha-mediated inflammatory cascades.