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Abstract Autism spectrum disorder (ASD) is a complex neurobiological disorder characterized by neuropsychological and behavioral deficits. Cognitive impairment, lack of social skills, and stereotyped behavior are the major autistic symptoms, visible after a certain age. It is one of the fastest growing disabilities. Its current prevalence rate in t...
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Background:
Autism spectrum disorder (ASD) is a group of childhood pervasive neurodevelopmental disorders characterized predominantly by persistent moderate to severe impairment in social skills, communication, and associated with restricted repetitive or stereotyped behaviors. Early diagnosis of this disorder is paramount, which then allows for a...
Citations
... ASD has been associated with abnormalities in the cerebral cortex and subsequently affected cognitive functions (i.e. communication, interaction and learning) [23] and multiple pathologies in cortical areas [24][25][26]. ...
The neuronal cell adhesion molecule contactin-4 (CNTN4) is genetically associated with autism spectrum disorder (ASD) and other psychiatric disorders. Cntn4-deficient mouse models have previously shown that CNTN4 plays important roles in axon guidance and synaptic plasticity in the hippocampus. However, the pathogenesis and functional role of CNTN4 in the cortex has not yet been investigated. Our study found a reduction in cortical thickness in the motor cortex of Cntn4 −/− mice, but cortical cell migration and differentiation were unaffected. Significant morphological changes were observed in neurons in the M1 region of the motor cortex, indicating that CNTN4 is also involved in the morphology and spine density of neurons in the motor cortex. Furthermore, mass spectrometry analysis identified an interaction partner for CNTN4, confirming an interaction between CNTN4 and amyloid-precursor protein (APP). Knockout human cells for CNTN4 and/or APP revealed a relationship between CNTN4 and APP. This study demonstrates that CNTN4 contributes to cortical development and that binding and interplay with APP controls neural elongation. This is an important finding for understanding the physiological function of APP, a key protein for Alzheimer’s disease. The binding between CNTN4 and APP, which is involved in neurodevelopment, is essential for healthy nerve outgrowth.
... The identi cation of reliable biomarkers is crucial for the elucidating the pathogenesis and early diagnosis of ASD [7,8]. Metabolic factors, which integrate genetic vulnerability and environmental factors, are promising potential ASD biomarkers [9]. ...
Background
The etiology and pathogenic mechanism of autism spectrum disorder (ASD) remain unclear. To provide data on the etiology and biomarkers of ASD, our study evaluated serum lipid levels and nutrition profiles of Chinese children with ASD.
Methods
A total of 32 ASD childrenand 59 healthychildren were enrolled in this study. We assessed thirteen biochemical indicators that reflect serum lipids and nutritional status. Univariate and multivariate analysis, spearman correlation analysis, and receiver operating characteristic (ROC) curves were used to assess differential indicator between the ASD and control groups and the diagnostic value for ASD.
Results
TG (odds ratio [OR] = 2.187, 95% confidence interval [CI]: 1.299-3.682), CHOL (OR = 1.808, 95% CI: 1.055-3.097) and ALB (OR = 4.709, 95% CI: 1.294-17.135) were the main factors that led to a diagnosis of ASD. Each of the differential indicators provided significant diagnostic value for ASD, including TG (AUC=0.6504, P=0.0182), CHOL (AUC=0.7055, P=0.0013), and ALB (AUC=0.7587, P<0.0001).
Conclusion
Impaired lipid metabolism may be related to the pathogenesis of ASD. TG, CHOL and ALB were important influencing factors that led to ASD and may be potential biomarkers for early diagnosis and treatment.
... The clinical symptoms of ASD vary among patients. Their severity also differs, both in the area of social communication and cognitive functioning [4]. The most characteristic symptoms of ASD are deficits in social interactions, including empathy deficits, limited vocabulary, inability to adhere to accepted norms and behaviors, and difficulties maintaining eye contact [5,6]. ...
... The prevalence of ASD is increasing globally, highlighting the need for early diagnosis and intervention. 21 However, the lack of early symptoms and limitations in current diagnostic methods pose challenges in this regard. Therefore, identifying specific biomarkers for ASD that enable early diagnosis and intervention holds significant clinical and research value. ...
Autism spectrum disorder (ASD) presents a significant risk to human well‐being and has emerged as a worldwide public health concern. Twenty‐eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9‐O‐18:0), DL‐2‐hydroxystearic acid, and 7(S),17(S)‐dihydroxy‐8(E),10(Z),13(Z),15(E),19(Z)‐docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three‐biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.
... Deprived contact eye, controlling, grappling by expressing or comprehending emotions and exaggerated attention or delayed speech are some of the earlier signs of having ASD [1,2]. ASD is termed as the most general developmental disorder [3,4]. For meeting the clinical treatment criterion of ASD, each person should have common deficits in social interface and social interaction and confirmation of constrained and cyclic structures of interest, behaviors and activities [5,6]. ...
... EEG signals are generally used for detecting ASD and brain diseases that include autism [4,13], depression [14], epilepsy [15], Parkinson's disease [2,16] and schizophrenia [17]. Different models to read the activities of the brain are used with functional near-infrared spectroscopy (fNIRS), EEG, functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). ...
Autism spectrum disorder (ASD) is a disorder in neurological growth, which includes cognitive and behavioral impairment and it starts from infancy. However, the reason for ASD is still vague and no effective medical ways are used for its discovery. Earlier discovery of ASD is extensively beneficial for children’s health sustainability. The classical detection models rely on expertise analysis which tends to be expensive and inaccurate. Thus, this paper presents an effectual autism diagnostic model with electroencephalogram (EEG) signals that are produced through the electrical activities of the brain for detecting ASD. The Gaussian filter is employed to abandon the noise. Various statistical features signal and spectral-based features are extracted and provided to DRN for enhanced efficiency. The ASD detection is undergone using Chronological Sewing Training Optimization-Deep Residual Network (CSTO-DRN) wherein DRN is pre-trained using CSTO algorithm by tuning finest weights. The CSTO is built by incorporating the Chronological concept with Sewing Training-Based Optimization (STBO). The CSTO-DRN provided finest accuracy of 88.6%, Negative Predictive Value (NPV) of 87.8%, Positive Predictive Value (PPV) of 89.4%, True negative rate (TNR) of 85%, True positive rate (TPR) of 88.9%, and F-Measure of 87.5%. Its execution can enhance the efficiency of detection and minimize cost and human intervention.
... Many mental diseases associated with these regions have been reported, such as major depression and bipolar disorder [39]. The posterior cingulate cortex has an important role in cognition, while cognitive developmental impairment is one of the major autistic symptoms [41]. The region also shows abnormalities in other neurological and psychiatric disorders including Alzheimer's disease, schizophrenia, autism, depression, attention deficit hyperactivity disorder, and aging [42]. ...
Background
Alterations in surface area (SA) in specific regions of the cortex have been reported in many individuals with autism spectrum disorder (ASD), however, the genetic background between ASD and SA is still unclear. This study estimated the genetic correlation and causal effect of ASD and cortical SA.
Methods
Summarized data of genome-wide association studies (GWAS) were separately downloaded from the Psychiatric Genomics Consortium (18,381 cases of ASD, and 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 participants of Europeans). We used Linkage disequilibrium score regression (LDSC) and Heritability Estimation from Summary Statistics (HESS) to calculate the heritability of each trait. As for the genetic correlation between ASD and SA, LDSC was used for global correlation and HESS was used to examine the local genetic covariance further. We used three Mendelian randomization (MR) methods, Inverse-variance weighted, MR-Egger, and weighted median to estimate the causal relationship.
Results
LDSC observed a nominal significant genetic correlation (rg = 0.1229, P-value = 0.0346) between ASD and SA of the rostral anterior cingulate gyrus whereas analysis through HESS did not reveal any significant loci having genetic covariance. Based on MR results, statistically meaningful estimations were found in the following areas, postcentral cortex (β (SE) = 21.82 (7.84) mm, 95% CI: 6.46 to 37.19 mm, PIVW = 5.38 × 10− 3, PFDR = 3.09 × 10− 2), posterior cingulate gyrus (β (SE) = 6.23 (2.69) mm, 95% CI: 0.96 to 11.49 mm, PIVW = 2.05 × 10− 2, PFDR = 4.26 × 10− 2), supramarginal gyrus (β (SE) = 19.25 (8.43) mm, 95% CI: 29.29 to 35.77 mm, PIVW = 2.24 × 10− 2, PFDR = 4.31 × 10− 2).
Conclusion
Our results provided genetic evidence to support the opinion that individuals with ASD tend to develop differences in cortical SA of special areas. The findings contributed to understanding the genetic relationship between ASD and cortical SA.
... Studies reveal increased cortical thinning in the frontal lobe, parietal lobe, occipital lobe, and the entire cortex of individuals with ASD. Neuroimaging techniques highlight abnormal brain connectivity in children with ASD, indicating intrinsic differences in brain connectivity compared to their neurotypical counterparts (Bhat et al., 2014). ...
... 1 (FMRP). FXS patients exhibit a series of cognitive and behavioral deficits, such as intellectual disability, language impairment, social defects, and stereotyped and repetitive behavior [1][2][3]. Currently there is no effective treatment for FXS and it is urgent to identify new targets for therapeutic strategy development. ...
... By crossing Fmr1 ± female mice (FVB background) with Mapt ± male mice (C57BL/6/SV129 background), we acquired the offspring with an FVB;C57BL/6/SV129 mixed background. Because FXS afflicts males much more than females and disease phenotypes are already obvious in pediatric and adolescent patients [1][2][3], we selected the male offspring at 1 month of age, which is roughly equivalent to 3.5-year-old and 12.5-year-old humans based on total life span and based on maturational rate comparisons, respectively (LIFE SPAN AS A BIOMARKER: https:// www. jax. ...
... Since it is reported that FXS patients and animal models also exhibit abnormal circadian behavioral rhythm [28,29], we further studied Per1 mRNA expression by qRT-PCR. Consistent with RNA sequencing data, we found that Per1 mRNA expression was decreased in Fmr1 −/y mice and partially reversed by Mapt deficiency (F (3,12) = 63.12, p < 0.0001 for Fmr1 −/y versus WT, p = 0.0308 for Fmr1 −/ y ;Mapt ± versus Fmr1 −/y , one-way ANOVA followed by Tukey's post hoc test, Fig. 4C). ...
Background
Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown.
Methods
Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1± female mice with Mapt± male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis.
Results
Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice.
Limitations
Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination.
Conclusion
Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment.
... There is a need for more robust and large-scale trials for testing the safety and efficacy of newer medications that can treat specific symptoms of autism without any significant side effects (Yatawara et al., 2015). Other therapies that require more research and study are Musical therapies (Bhat et al., 2014) and the use of Zonisamide. Music is said to improve verbal communication in ASD individuals. ...
... Music is said to improve verbal communication in ASD individuals. At the same time, Zonisamide, which is an anti-epileptic, is thought to increase the influx of cystine and reduce oxidative stress in autistic children (Bhat et al., 2014). Some other interventions with proven benefits are Discrete Trial Training (DITI), Verbal Behavioral Intervention (VBI), and Pivotal response training (PRI). ...
Autism spectrum disorders (ASD) are a collection of neurodevelopmental disabilities, defined by the presence of
social, behavioral and communication deficits, that are typically recognized during the first three years of life.
Autism has emerged as a significant public health concern, yet there are no answers to its increasing rates. Recent
data from the Autism and Developmental Disability Monitoring (ADDM) Network reported that 1 in every 36
(2.8 %) 8-year-old children were found to have autism in 2020. The current research attempts to identify the
major challenges around autism care across the US such as: Inconsistent diagnosis and referral leading to delayed
start of service, unequal availability of trained licensed Applied Behavioral Analysis (ABA) therapist, Inconsistent
implementation of ABA interventions at various settings, Lack of support, education services and vocational
opportunities for children transitioning into adulthood. This article also proposes and discusses possible strategies
for mitigating those challenges.
Keywords:
Autism Autism challenges in the US Behavioral interventions
Implementation science Caregiver support Funding
... ASDs was first described in 1943 and since then, a large increase in the incidence of ASDs worldwide (Baj et al., 2021). ASDs is one of the fastest growing disabilities, accounting for substantial health loss across the lifespan (Bhat et al., 2014). Epidemiological data reveal that there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons in 2010 (Baxter et al., 2015). ...
It is unclear whether the health equity of autism spectrum disorders (ASDs) has changed in different years, regions, and gender. The aims of this study were to provide a comprehensive description of the ASDs burden and provide evidence for improvement in health policies regarding ASDs inequality. This study is a population-based cross-sectional study based on the Global Burden of Disease datasets 1990–2019. We collected detailed information on ASDs between 1990 and 2019 in 204 countries worldwide, derived from the Global Burden of Disease study in 2019. Burden was calculated in terms of the incidence, prevalence and years lived with disability (YLDs). Concentration curves and concentration indices were used to summarize the degree of income-related inequality in the burden of ASDs. The overall age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized YLDs rate (ASYR) of ASDs was 9.3 (95 %UI 7.7–11.1), 369.4 (95 %UI 305.9–441.2), 56.3 (95 %UI 36.8–81.5) per 100,000 people, respectively. The ASIR, ASPR and ASYR of ASDs affected three times as many males as females. The changing trends of age-standardized rates of ASDs showed that the ASIR of ASDs a slow growing trend globally. However, the ASPR and ASYR of ASDs showed a slow decreasing trend globally. All the concentration curves were below the line of equality and statistically significant. There was no significant difference in the age-standardized rate for different years in socio-demographic index-related inequality happened over 29 years (p > 0.05). The global burden of ASDs has remained higher in males and pro-rich, the income-related inequality tended not to change between 1990 and 2019.
