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Al-Beltagi M, Saeed NK, Bediwy AS, Alhawamdeh R, Elbeltagi R. Management of critical care emergencies in children with autism spectrum disorder. World J Crit Care Med 2025; 14:99975. [PMID: 40491884 PMCID: PMC11891848 DOI: 10.5492/wjccm.v14.i2.99975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 12/13/2024] [Accepted: 12/30/2024] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Managing critical care emergencies in children with autism spectrum disorder (ASD) presents unique challenges due to their distinct sensory sensitivities, communication difficulties, and behavioral issues. Effective strategies and protocols are essential for optimal care in these high-stress situations. AIM To systematically evaluate and synthesize current evidence on best practices for managing critical care emergencies in children with ASD. The review focuses on key areas, including sensory-friendly environments, communication strategies, behavioral management, and the role of multidisciplinary approaches. METHODS A comprehensive search was conducted across major medical databases, including PubMed, Embase, and Cochrane Library, for studies published between 2000 and 2023. Studies were selected based on their relevance to critical care management in children with ASD, encompassing randomized controlled trials, observational studies, qualitative research, and case studies. Data were extracted and analyzed to identify common themes, successful strategies, and areas for improvement. RESULTS The review identified 50 studies that met the inclusion criteria. Findings highlighted the importance of creating sensory-friendly environments, utilizing effective communication strategies, and implementing individualized behavioral management plans. These findings, derived from a comprehensive review of current evidence, provide valuable insights into the best practices for managing critical care emergencies in children with ASD. Sensory modifications, such as reduced lighting and noise, visual aids, and augmentative and alternative communication tools, enhanced patient comfort and cooperation. The involvement of multidisciplinary teams was crucial in delivering holistic care. Case studies provided practical insights and underscored the need for continuous refinement of protocols. CONCLUSION The review emphasizes the need for a tailored approach to managing critical care emergencies for children with ASD. Sensory-friendly adjustments, effective communication, and behavioral strategies supported by a multidisciplinary team are integral to improving outcomes. Despite progress, ongoing refinement of care practices and protocols is necessary. This ongoing process addresses remaining challenges and engages healthcare professionals in continuous improvement of care for children with ASD in critical settings.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 26671, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
| | - Rawan Alhawamdeh
- Department of Pediatrics Research and Development, Sensoryme Dwc-llc, Dubai 712495, Dubai, United Arab Emirates
- Department of Pediatrics Research and Development, Genomics Sensory Play and Creativity Center, Manama 22673, Manama, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Bahrain, Busiateen 15503, Muharraq, Bahrain
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Bhattacharya B, Toor D, Chatterjee M. Connecting the dots: environmental pollution and Autism Spectrum Disorder. REVIEWS ON ENVIRONMENTAL HEALTH 2025:reveh-2024-0123. [PMID: 40271992 DOI: 10.1515/reveh-2024-0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 03/27/2025] [Indexed: 04/25/2025]
Abstract
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in social communication and repetitive behavior. While the exact etiology of ASD remains elusive, researchers have increasingly turned their attention to the role of environmental factors in its development. Among these factors, environmental pollution has emerged as a potential contributor to the rising prevalence of ASD cases worldwide. This review delves into the growing body of scientific evidence suggesting a significant association between environmental pollution and the risk of ASD. It explores the environmental pollution that have been implicated, including air pollution, water contaminants, heavy metals, pesticides, and endocrine-disrupting chemicals. The detrimental impact of these pollutants on the developing brain, particularly during critical periods of gestation and early childhood has been discussed. This will provide insights into the possible mechanisms by which the various pollutants may influence the neurodevelopmental pathways underlying ASD. Additionally, the potential interplay between genetic susceptibility and environmental exposure is explored to better understand the multifactorial nature of ASD causation. Considering the alarming increase in ASD prevalence and the ubiquity of environmental pollutants, this review emphasizes the urgent need for further investigation and the adoption of comprehensive preventive measures.
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Affiliation(s)
- Bidisha Bhattacharya
- Departments of Molecular Genetics and Molecular Neuroscience, Weizmann Institute of Science, Israel
- Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India
| | - Devinder Toor
- Amity Institute of Virology & Immunology, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India
| | - Mallika Chatterjee
- Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India
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Gonçalves-Ribeiro J, Vaz SH. The IP3R2 Knockout Mice in Behavior: A Blessing or a Curse? J Neurochem 2025; 169:e70062. [PMID: 40172184 DOI: 10.1111/jnc.70062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/19/2025] [Accepted: 03/19/2025] [Indexed: 04/04/2025]
Abstract
The inositol 1,4,5-triphosphate receptor type 2 (IP3R2) plays a critical role in intracellular calcium (Ca2+) signaling, particularly in astrocytes, where it mediates Ca2+ release from the endoplasmic reticulum. This mechanism is vital for astrocytic modulation of neuronal networks, impacting synaptic transmission and broader neural circuit functions. The IP3R2 knockout (IP3R2KO) mouse model has been instrumental in unraveling the nuances of astrocytic somatic Ca2+ dynamics and their implications for brain function. Despite early findings suggesting no significant behavioral or synaptic transmission changes in IP3R2KO mice, further research highlights the model's benefit in exploring cognitive, emotional, and neurodevelopmental processes. IP3R2KO mice revealed key insights into astrocytic Ca2+ signaling diversity, encompassing bulk somatic events and localized microdomain responses, which exhibit temporal and spatial variability. These animals retain alternative Ca2+ mechanisms, likely explaining the absence of severe phenotypes in some contexts. Nevertheless, IP3R2KO mice exhibit impairments in long-term memory retention, working memory, and fear memory, alongside age-related preservation of spatial memory, linking astrocytic IP3R2 signaling to higher-order cognitive functions. Additionally, studies suggest a connection between IP3R2 pathways and depression-like behaviors, with alterations in Brain-Derived Neurotrophic Factor (BDNF) levels and GABAergic signaling, highlighting its relevance to psychiatric conditions. Despite its limitations, such as residual astrocytic Ca2+ activity and inconsistent findings, the IP3R2KO model remains a valuable tool for studying astrocytic contributions to synaptic plasticity and brain function. This underscores the importance of integrating, rather than dismissing, the IP3R2KO model in the development of new methodologies for studying astrocytic Ca2+ dynamics. The use of this model will continue to elucidate the complex interplay between astrocytes and neuronal circuits, fostering advances in understanding astrocytic Ca2+ signaling's role in health and disease.
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Affiliation(s)
- Joana Gonçalves-Ribeiro
- Faculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisboa, Portugal
- Centro Cardiovascular da Universidade de Lisboa, CCUL (CCUL@RISE), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Gulbenkian Institute for Molecular Medicine (GIMM), Lisbon, Portugal
| | - Sandra H Vaz
- Faculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisboa, Portugal
- Centro Cardiovascular da Universidade de Lisboa, CCUL (CCUL@RISE), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Gulbenkian Institute for Molecular Medicine (GIMM), Lisbon, Portugal
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Meguid N, Ismail SR, Anwar M, Hashish A, Semenova Y, Abdalla E, Taha MS, Elsaeid A, Bjørklund G. Gamma-aminobutyric acid and glutamate system dysregulation in a small population of Egyptian children with autism spectrum disorder. Metab Brain Dis 2025; 40:146. [PMID: 40080228 DOI: 10.1007/s11011-025-01557-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 02/09/2025] [Indexed: 03/15/2025]
Abstract
Autism spectrum disorder (ASD) is associated with various symptoms, including repetitive behaviors, restricted interests, and deficits in proper communication. Earlier studies have linked these symptoms to abnormalities in the balance between excitatory (glutamatergic signaling) and inhibitory (GABAergic signaling) neurotransmission. The present study aimed to analyze the levels of different biomarkers in children with ASD compared to neurotypical (NT) controls. The study included 80 children, of whom 40 were cases (children with ASD) and 40 were age- and sex-matched NT controls. Serum levels of GABAA, and GABAB receptors, glutamate, zinc, potassium, and calcium were measured in both groups. ASD diagnosis was verified using the Childhood Autism Rating Scale (CARS) and Autism Diagnostic Interview-Revised (ADI-R). There was a significant decrease (P < 0.001) in the median serum levels of GABAA (0.6) and GABAB receptors (2.03) in children with ASD compared to controls. Additionally, a significant increase in median serum glutamate levels was observed in ASD children (102, P < 0.001) compared to controls. Children with ASD also showed a significant reduction (P < 0.001) in median levels of all studied blood minerals compared to controls, including potassium (3.8 vs. 4.6), calcium (9.0 vs. 9.7), and zinc (57.0 vs. 92.0). The roles of GABAB and zinc as potential pathological biomarkers were investigated due to their highly significant inverse correlations with stereotypic and repetitive behaviors (ADI-R domain), with rho = -0.393 (P = 0.012) and rho = -0.488 (P = 0.001), respectively. Further analysis of pathways regulating these biomarkers may provide deeper insights into the etiology and pathophysiology of ASD, paving the way for potential therapeutic interventions.
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Affiliation(s)
- Nagwa Meguid
- Children with Special Needs Department, National Research Centre, Giza, Egypt
- CONEM Egypt Child Brain Research Group, National Research Centre, Giza, Egypt
| | | | - Mona Anwar
- Children with Special Needs Department, National Research Centre, Giza, Egypt.
- Department of Basic Sciences and Biomechanics, Faculty of Physical Therapy, Heliopolis University, Cairo, Egypt.
| | - Adel Hashish
- Children with Special Needs Department, National Research Centre, Giza, Egypt
| | - Yuliya Semenova
- Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Ebtesam Abdalla
- Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Mohamed S Taha
- Children with Special Needs Department, National Research Centre, Giza, Egypt
| | - Amal Elsaeid
- Children with Special Needs Department, National Research Centre, Giza, Egypt
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), Toften 24, Mo i Rana, 8610, Norway.
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Anindya I, Sekartini R, Ariyanto IA, Wiguna T, Sari NP, Rahayu YS, Soebandrio A. Cytomegalovirus-Reactive IgG Correlates with Increased IL-6 and IL-1β Levels, Affecting Eating Behaviours and Tactile Sensitivity in Children with Autism. Biomedicines 2025; 13:338. [PMID: 40002751 PMCID: PMC11852405 DOI: 10.3390/biomedicines13020338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/06/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Elevated cytokine levels, including IL-6 and IL-1β, can contribute to persistent brain inflammation in children with autism and cytomegalovirus (CMV) infection, exacerbating autism-related behaviours and symptoms. This study evaluates the impact of CMV-induced cytokine increases on the eating behaviours and sensory profiles of children with autism. METHODS A cross-sectional design was employed, involving children aged two to five years (CMV-reactive IgG), with ASD (n= 98) and TD (n = 96). Serological tests using ELISA were conducted to measure IgG CMV, IL-6, and IL-1β biomarkers. Eating behaviours were evaluated using the BAMBI (Brief Autism Mealtime Behaviour Inventory), and sensory profiles were assessed using the SSP (Short Sensory Profile). Statistical analyses were performed using Spearman's rank and chi-square tests. RESULTS The results show that autism significantly affects children's eating behaviours and sensory profiles (p < 0.001), with notable differences found between the groups. Correlation analysis revealed a significant association between IgG CMV and IL-6 (p = 0.026) and IL-1β (p = 0.014) in the ASD group. Additionally, eating behaviours (food refusal and limited variety) in ASD correlated with IL-6 and IL-1β. Sensory characteristics, such as tactile sensitivity, were found to correlate with IL-6 (p = 0.027) and IL-1β (p = 0.002) in the ASD group. CONCLUSIONS These findings suggest that CMV-infected children with autism are at increased risk of IL-6 and IL-1β dysregulation, contributing to sensory processing issues and eating behaviours. Further research is needed to enhance CMV testing protocols and better understand the virus's role in the development of sensory and behavioural issues in children with autism.
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Affiliation(s)
- Isti Anindya
- Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
| | - Rini Sekartini
- Department of Pediatrics, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
| | - Ibnu Agus Ariyanto
- Department of Clinical Microbiology, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
| | - Tjhin Wiguna
- Department of Psychiatry, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
| | - Novika Purnama Sari
- Department Clinical & Developmental Neuropsychology, Faculty of Behavioural and Social Sciences, University of Groningen, 9712 TS Groningen, The Netherlands;
| | | | - Amin Soebandrio
- Department of Clinical Microbiology, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia;
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Zhang Q, Pang X, Guo M, Wang Y, Xu Y, Li Q, Zheng H. Comparison of Gut Microbiota in Two Different Maternal Exposure Models of Autism Spectrum Disorder in Mice. ALPHA PSYCHIATRY 2025; 26:38790. [PMID: 40110373 PMCID: PMC11916071 DOI: 10.31083/ap38790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 08/09/2024] [Accepted: 09/03/2024] [Indexed: 03/22/2025]
Abstract
Background Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with unknown etiology and unclear pathogenesis. Although construction of animal models of ASD using chemical exposure during pregnancy is a mature technique, the gut microbiota of these exposure models induced using different chemicals in mice have not been compared. Methods To compare the effects of exposure to different chemicals during pregnancy on the composition of gut microbiota in offspring, we treated Institute of Cancer Research (ICR) mice with lipopolysaccharide (LPS) and valproic acid (VPA) during pregnancy to construct different offspring ASD mouse models. After successful model construction, the gut microbiota of these models were studied. Results After adjusting for the random effects of the litter, the two groups showed a significant reduction in social time (social deficits) and an increase in self-grooming behaviors (repetitive and stereotyped behaviors). Gut microbiota analysis revealed significant changes, mostly a decrease, in the abundance of four phyla, 52 genera, and 41 species in the two types of ASD models. Several different gut microbes could be related to the development of ASD. Conclusions Chemicals exposure during pregnancy induces ASD-related behavioral abnormalities in offspring mice. Importantly, exposure to different chemicals during pregnancy produces varying degrees of effects on gut microbiota composition in offspring ASD models. This finding can provide a reference for studies on the etiology and pathogenesis of ASD.
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Affiliation(s)
- Qiang Zhang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, Guizhou, China
| | - Xuying Pang
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 200032 Shanghai, China
| | - Min Guo
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 200032 Shanghai, China
| | - Yuezhu Wang
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 200032 Shanghai, China
| | - Yu Xu
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 200032 Shanghai, China
| | - Quan Li
- Department of Obstetrics and Gynecology, Affiliated Hospital of Zunyi Medical University, 563000 Zunyi, Guizhou, China
| | - Huajun Zheng
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 200032 Shanghai, China
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Lee SM, Choi Y, Kim D, Jeong HJ, Do YH, Jung S, Lee B, Choi HJ, Kim S, Oh JM, Jeon S, Han J, Kim Y. Developmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD. Transl Psychiatry 2025; 15:28. [PMID: 39863599 PMCID: PMC11762770 DOI: 10.1038/s41398-024-03201-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 11/20/2024] [Accepted: 12/10/2024] [Indexed: 01/27/2025] Open
Abstract
Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests. Surprisingly, these symptoms were improved by Risperidone treatment, a drug commonly used to treat ASD. RNA sequencing data from mouse neural progenitor cells (mNPCs) showed that the genes regulating trans-synaptic signaling, transmembrane transport, and neuronal projection development were significantly decreased in Clcn4 knockdown (KD) cells compared to wild type (WT). Moreover, Risperidone treatment increased the genes related to the ion transmembrane transport, membrane potential, and neuron projection development in Clcn4 KD. Abnormalities in synaptic plasticity and dendritic spine formation were also observed in Clcn4 KO compared to WT. We observed that phosphorylation of SYNAPSIN, PSD95, ERK and CREB, as well as the expression of CDK5, were reduced in the brains of Clcn4 KO mice. In Clcn4 KO cortical neurons, the phosphorylation of SYNAPSIN and PSD95 expressions also decreased compared to WT, indicating disrupted synaptic function. Additionally, Sholl analysis revealed a reduction in dendritic branching and neuronal projection length in both mouse and human CLCN4 KD neurons. Finally, the decreased phosphorylation of SYNAPSIN and expression of PSD95 along with dendrite abnormalities were restored after Risperidone treatment. These data suggest that dendritic outgrowth and synapse remodeling may serve as endophenotypic targets for drug efficacy in ASD.
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Affiliation(s)
- Seong Mi Lee
- Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea
- Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea
| | - Yura Choi
- Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea
| | - Dayeon Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Ha Jin Jeong
- Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea
- Department of Biomedical Sciences, Center for Glocal Future Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea
| | - Young Ho Do
- Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea
- Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea
| | - Sohee Jung
- Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea
| | - Bomee Lee
- Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea
| | - Hyung Jun Choi
- Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea
| | - Suhyeon Kim
- Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea
| | - Jung-Min Oh
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
| | - Songhee Jeon
- Department of Biomedical Sciences, Center for Glocal Future Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea
| | - Jinju Han
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
| | - Yeni Kim
- Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea.
- Dongguk University International Hospital, Institute of Clinical Psychopharmacology, Goyang, Republic of Korea.
- Department of Child and Adolescent Psychiatry, National Center for Mental Health, Seoul, Republic of Korea.
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Karim A, Alromema N, Malebary SJ, Binzagr F, Ahmed A, Khan YD. eNSMBL-PASD: Spearheading early autism spectrum disorder detection through advanced genomic computational frameworks utilizing ensemble learning models. Digit Health 2025; 11:20552076241313407. [PMID: 39872002 PMCID: PMC11770729 DOI: 10.1177/20552076241313407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 12/18/2024] [Indexed: 01/29/2025] Open
Abstract
Objective Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by various genetic and environmental factors. Currently, there is no definitive clinical test, such as a blood analysis or brain scan, for early diagnosis. The objective of this study is to develop a computational model that predicts ASD driver genes in the early stages using genomic data, aiming to enhance early diagnosis and intervention. Methods This study utilized a benchmark genomic dataset, which was processed using feature extraction techniques to identify relevant genetic patterns. Several ensemble classification methods, including Extreme Gradient Boosting, Random Forest, Light Gradient Boosting Machine, ExtraTrees, and a stacked ensemble of classifiers, were applied to assess the predictive power of the genomic features. TheEnsemble Model Predictor for Autism Spectrum Disorder (eNSMBL-PASD) model was rigorously validated using multiple performance metrics such as accuracy, sensitivity, specificity, and Mathew's correlation coefficient. Results The proposed model demonstrated superior performance across various validation techniques. The self-consistency test achieved 100% accuracy, while the independent set and cross-validation tests yielded 91% and 87% accuracy, respectively. These results highlight the model's robustness and reliability in predicting ASD-related genes. Conclusion The eNSMBL-PASD model provides a promising tool for the early detection of ASD by identifying genetic markers associated with the disorder. In the future, this model has the potential to assist healthcare professionals, particularly doctors and psychologists, in diagnosing and formulating treatment plans for ASD at its earliest stages.
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Affiliation(s)
- Ayesha Karim
- Department of Computer Science, School of Systems and Technology, University of Management and Technology, Lahore, Pakistan
| | - Nashwan Alromema
- Department of Computer Science, Faculty of Computing and Information Technology-Rabigh, King AbdulAziz University, Jeddah, Saudi Arabia
| | - Sharaf J Malebary
- Department of Information Technology, Faculty of Computing and Information Technology, King AbdulAziz University, Rabigh, Saudi Arabia
| | - Faisal Binzagr
- Department of Computer Science, Faculty of Computing and Information Technology-Rabigh, King AbdulAziz University, Jeddah, Saudi Arabia
| | - Amir Ahmed
- College of Information Technology, Information Systems and Security, United Arab Emirates University, Alain, United Arab Emirates
| | - Yaser Daanial Khan
- Department of Computer Science, School of Systems and Technology, University of Management and Technology, Lahore, Pakistan
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Alnakhli AM, Saleh A, Kabel AM, Estfanous RS, Borg HM, Alsufyani KM, Sabry NM, Gomaa FAM, Abd Elmaaboud MA. Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1802. [PMID: 39596986 PMCID: PMC11596946 DOI: 10.3390/medicina60111802] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 10/26/2024] [Accepted: 10/29/2024] [Indexed: 11/29/2024]
Abstract
Background and Objectives: Autism is a developmental disability characterized by impairment of motor functions and social communication together with the development of repetitive or stereotyped behaviors. Neither the exact etiology or the curative treatment of autism are yet completely explored. The goals of this study were to evaluate the possible effects of perindopril on a rat model of autism and to elucidate the possible molecular mechanisms that may contribute to these effects. Materials and Methods: In a rat model of sodium valproate (VPA)-induced autism, the effect of postnatal administration of different doses of perindopril on growth and motor development, social and repetitive behaviors, sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling in the hippocampal tissues were investigated. The histopathological and electron microscopic changes elicited by administration of the different treatments were also investigated. Results: Perindopril dose-dependently combatted the effects of prenatal exposure to VPA on growth and maturation, motor development, and social and repetitive behaviors. In addition, the different doses of perindopril ameliorated the effects of prenatal exposure to VPA on sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling. These effects had a mitigating impact on VPA-induced histopathological and electron microscopic changes in the hippocampal tissues. Conclusions: Perindopril may emerge as a promising agent for amelioration of the pathologic changes of autism spectrum disorders.
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Affiliation(s)
- Anwar M. Alnakhli
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia; (A.M.A.); (A.S.)
| | - Asmaa Saleh
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia; (A.M.A.); (A.S.)
| | - Ahmed M. Kabel
- Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Remon S. Estfanous
- Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
| | - Hany M. Borg
- Physiology Department, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh 33516, Egypt
| | | | - Nesreen M. Sabry
- Clinical Oncology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
| | - Fatma Alzahraa M. Gomaa
- Pharamcognosy and Medicinal Herbs Department, Faculty of Pharmacy, Al-Baha University, AlBaha 65779, Saudi Arabia;
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Sousamli A, Dragioti E, Metallinou D, Lykeridou A, Dourou P, Athanasiadou CR, Anagnostopoulos D, Sarantaki A. Perinatal and Demographic Risk Factors Associated with Autism Spectrum Disorder: A National Survey of Potential Predictors and Severity. Healthcare (Basel) 2024; 12:2057. [PMID: 39451472 PMCID: PMC11507011 DOI: 10.3390/healthcare12202057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/13/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024] Open
Abstract
INTRODUCTION: This study investigates autism spectrum disorders (ASD) in Greece, focusing on estimating prevalence and identifying regional disparities in children aged 4 to 7 years. MATERIALS AND METHODS: Utilizing a quantitative, descriptive, and exploratory methodology, the research employed a structured questionnaire to gather extensive maternal and child health data. RESULTS: The sample consisted of 517 mothers of children diagnosed with ASD from all over Greece, contributing to a nuanced understanding of ASD predictors. This study aims to elucidate the role of prenatal factors in the likelihood of an ASD diagnosis and their impact on the subsequent functionality of children with ASD. The study identified significant predictors of lower functionality in children with ASD, including higher maternal age, delayed ASD diagnosis, lower family income, and higher birth order. Prenatal health issues, such as vaginal bleeding and infections, also influenced functional outcomes. Notably, a family history of neurological or psychiatric conditions appeared protective. DISCUSSION: The regression model demonstrated robust predictive power, underscoring the complexity of genetic, environmental, and socioeconomic factors in ASD development. The findings advocate for early diagnosis and intervention, systematic screening, and addressing socioeconomic disparities to improve functional outcomes. The results support evidence-based service development and policy adjustments to enhance early identification, intervention, and rehabilitation for children with ASD. CONCLUSIONS: Establishing standardized case-recording procedures and an ASD register at national and regional levels is recommended for systematic monitoring and resource evaluation.
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Affiliation(s)
- Aikaterini Sousamli
- Midwifery Department, Faculty of Health and Care Sciences, University of West Attica, 12243 Athens, Greece; (D.M.); (P.D.); (A.S.)
| | - Elena Dragioti
- Research Laboratory Psychology of Patients, Families, and Health Professionals, Department of Nursing, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece;
| | - Dimitra Metallinou
- Midwifery Department, Faculty of Health and Care Sciences, University of West Attica, 12243 Athens, Greece; (D.M.); (P.D.); (A.S.)
| | - Aikaterini Lykeridou
- Midwifery Department, Faculty of Health and Care Sciences, University of West Attica, 12243 Athens, Greece; (D.M.); (P.D.); (A.S.)
| | - Panagiota Dourou
- Midwifery Department, Faculty of Health and Care Sciences, University of West Attica, 12243 Athens, Greece; (D.M.); (P.D.); (A.S.)
| | - Chrysoula Rozalia Athanasiadou
- Midwifery Department, Faculty of Health and Care Sciences, University of West Attica, 12243 Athens, Greece; (D.M.); (P.D.); (A.S.)
| | - Dimitrios Anagnostopoulos
- Section of Social Medicine-Psychiatry-Neurology, School of Medicine, National and Kapodistrian University of Athens, 10559 Athens, Greece;
| | - Antigoni Sarantaki
- Midwifery Department, Faculty of Health and Care Sciences, University of West Attica, 12243 Athens, Greece; (D.M.); (P.D.); (A.S.)
- Research Lab (PEARL)—Perinatal Care and Counseling for Special Populations, Department of Midwifery, University of West Attica, 12243 Athens, Greece
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Al-Beltagi M, Saeed NK, Bediwy AS, Bediwy EA, Elbeltagi R. Decoding the genetic landscape of autism: A comprehensive review. World J Clin Pediatr 2024; 13:98468. [PMID: 39350903 PMCID: PMC11438927 DOI: 10.5409/wjcp.v13.i3.98468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/30/2024] Open
Abstract
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.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Alghrabia, Tanta 31511, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Muharraq, Busaiteen 15503, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Alghrabia, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Eman A Bediwy
- Internal Medicine, Faculty of Medicine, Tanta University, Algharbia, Tanta 31527, Egypt
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Bahrain, Muharraq, Busiateen 15503, Bahrain
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12
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Netto BB, da Silva EP, de Aguiar da Costa M, de Rezende VL, Bolan SJ, Ceretta LB, Aschner M, Dominguini D, Gonçalves CL. Critical period of exposure to mercury and the diagnostic of autism spectrum disorder: A systematic review. J Neurochem 2024; 168:2092-2104. [PMID: 38344837 DOI: 10.1111/jnc.16076] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 01/23/2024] [Accepted: 01/24/2024] [Indexed: 10/04/2024]
Abstract
Autism spectrum disorder (ASD) is characterized by repetitive behaviors and deficits in social interaction. Its etiology is not completely clear, but both genetic and environmental factors contribute to and influence its development and course. The increased number of autism cases in recent years has been strongly associated with increased exposure to heavy metals. Mercury (Hg) has gained prominence in the scientific literature as a result of its presence as an urban pollutant and well-described neurotoxicity. This review assessed the relationship between Hg exposure in the pre- and post-natal period and ASD. The systematic review identified observational clinical studies and pre-clinical trials in journals indexed in the PubMed, Embase, ProQuest, and LILACS databases. The aim of this study was to investigate the association between exposure to Hg and ASD and to define the critical period of exposure. A total of 57 articles were selected for this review, with 35 articles (61.40%) identifying a positive association between ASD and Hg, while 22 articles (38.60%) did not find the same outcome. The biological samples most used to analyze Hg body burdens were hair (36.84%) and blood (36.84%). Most case-control studies found an increase in Hg levels in individuals with ASD who were exposed to a polluted environment in the post-natal period. Taken together, the studies suggest that these patients have a deficient detoxification system, and this could worsen the symptoms of the disorder. However, new studies addressing the influence of Hg on the post-natal nervous system and its relationship with ASD should be carried out.
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Affiliation(s)
- Bruna Bittencourt Netto
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
- Medical School, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | | | - Maiara de Aguiar da Costa
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Victória Linden de Rezende
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Sofia Januário Bolan
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | | | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Diogo Dominguini
- Program in Collective Health, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
- Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, Houston, Texas, USA
| | - Cinara Ludvig Gonçalves
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
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13
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Afshari M, Gharibzadeh S, Pouretemad H, Roghani M. Promising therapeutic effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in addressing autism spectrum disorder induced by valproic acid. Front Neurosci 2024; 18:1385488. [PMID: 39238929 PMCID: PMC11374774 DOI: 10.3389/fnins.2024.1385488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 08/08/2024] [Indexed: 09/07/2024] Open
Abstract
Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects various regions of the brain. Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive method utilized for stimulating different brain areas. Our objective is to alleviate ASD symptoms using high-frequency rTMS (HF-rTMS) in a rat model of ASD induced by valproic acid (VPA). Methods In this investigation, we applied HF-rTMS for ASD treatment, focusing on the hippocampus. Behavioral assessments encompassed core ASD behaviors, as well as memory and recognition tests, alongside evaluations of anxiety and stress coping strategies. Additionally, we analyzed oxidative stress and a related inflammation marker, as well as other biochemical components. We assessed brain-derived neurotrophic factor (BDNF), Microtubule-associated protein-2 (MAP-2), and synaptophysin (SYN). Finally, we examined dendritic spine density in the CA1 area of the hippocampus. Results The results demonstrated that HF-rTMS successfully mitigated ASD symptoms, reducing oxidative stress and improving various biochemical factors, along with an increase in dendritic spine density. Discussion Collectively, our data suggests that HF-rTMS may effectively alleviate ASD symptoms. These findings could be valuable in clinical research and contribute to a better understanding of the mechanisms underlying ASD.
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Affiliation(s)
- Masoud Afshari
- Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran
| | - Shahriar Gharibzadeh
- Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran
| | - Hamidreza Pouretemad
- Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran
| | - Mehrdad Roghani
- Neurophysiology Research Center, Shahed University, Tehran, Iran
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14
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Abu Khait A, Menger A, Hamdan-Mansour AM, Aldalaykeh M, Hamaideh SH, Al-Mrayat YD, Nusair H. The Association Between Coping Strategies and Psychological and Emotional Distress Among Health Care Providers Caring for Autistic Children in Jordan. West J Nurs Res 2024; 46:571-582. [PMID: 38829033 DOI: 10.1177/01939459241254782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
BACKGROUND Health care providers (HCPs) caring for autistic children report more perceived psychological and emotional distress related to their job. However, not much is known about what can be done to mitigate such distress, especially in countries with limited mental health resources, such as Jordan. OBJECTIVE This study aimed to examine the association between coping strategies (problem-focused, emotion-focused, and avoidant) and perceived emotional and psychological distress among HCPs of autistic children in Jordan. METHODS In this cross-sectional study, a convenience sample of 180 HCPs working with autistic children in Jordan were recruited through autism centers and social media using an online self-administered questionnaire. RESULTS The multiple linear regression analysis revealed that 31% of the variability in perceived emotional distress was explained by its significant association with problem-focused coping, emotion-focused coping, and avoidant coping. Likewise, 39% of the variability in perceived psychological distress was explained by its significant association with gender, having an immediate family, area of specialty, problem-focused coping, emotion-focused coping, and avoidant coping. CONCLUSIONS The study shows that problem-focused coping significantly decreases perceived emotional distress, whereas emotion-focused and avoidant coping significantly increase perceived emotional distress. Avoidant coping significantly increases perceived psychological distress. Understanding the association between coping strategies and perceived emotional and psychological distress among HCPs can assist mental health nurses in identifying at-risk providers and providing timely emotional and psychological support.
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Affiliation(s)
- Abdallah Abu Khait
- Department of Community and Mental Health Nursing, Faculty of Nursing, The Hashemite University, Zarqa, Jordan
| | | | - Ayman M Hamdan-Mansour
- Department of Community Health Nursing, School of Nursing, The University of Jordan, Amman, Jordan
| | - Mohammed Aldalaykeh
- Community and Mental Health Nursing Department, College of Nursing, Jordan University of Science and Technology, Irbid, Jordan
| | - Shaher H Hamaideh
- Department of Community and Mental Health Nursing, Faculty of Nursing, The Hashemite University, Zarqa, Jordan
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15
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Shilbayeh SAR, Adeen IS, Alhazmi AS, Ibrahim SF, Al Enazi FAR, Ghanem EH, Binduraihem AM. The Frequency of CYP2D6 and CYP3A4/5 Genotypes and The Impact of Their Allele Translation and Phenoconversion-Predicted Enzyme Activity on Risperidone Pharmacokinetics in Saudi Children with Autism. Biochem Genet 2024; 62:2907-2932. [PMID: 38041757 DOI: 10.1007/s10528-023-10580-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 10/28/2023] [Indexed: 12/03/2023]
Abstract
Data on the role of CYP2D6 and CYP3A4/5 polymorphisms in relation to risperidone (RIS) pharmacokinetics (PK) in children are relatively limited and inconsistent. This is partially attributable to the limited coverage of CYP2D6 and CYP3A4/5 metabolizer phenotypes, particularly those of poor and ultrarapid metabolizers (PMs and UMs), which has led to calls for studies of populations with a non-European background that may carry variants that are less frequent in Europeans. Children ≤ 18 years old with at least 8 weeks of a RIS-based regimen were recruited from three autism centers in Riyadh, Saudi Arabia. The primary outcomes measured were plasma concentrations of RIS and 9-hydroxyrisperidone (9-OH-RIS) and their dose-adjusted (C/D) ratios as a function of phenotypes and activity score (AS). For accurate DNA genotyping, targeted pharmacogenomic testing with the Axiom PharmacoFocus Array was performed via examination of a broad collection of probesets targeting CYP2D6 and CYP3A4/5 variants. The frequency of genotypes/phenotypes and the impact of their allele translation and phenoconversion-predicted enzyme activity were examined. The final cohort included 83 individuals. The most common CYP2D6 phenotype in our population was normal metabolizers (NMs, 66.3%). Inconsistent with some previous studies, the three phenotypes of intermediate metabolizers (IMs), NMs, and UMs were significantly different in terms of RIS concentration, the RIS/9-OH-RIS ratio, the RIS C/D ratio and the 9-OH-RIS C/D ratio. According to AS analyses, there were statistically significant differences in the RIS concentration (P = 0.013), RIS/9-OH-RIS ratio (P < 0.001) and RIS C/D ratio (P = 0.030) when patients were categorized into AS ≤ 1 vs. AS > 1. None of the CYP3A4/5 star allele translated phenotypes revealed a significant influence on any of the RIS PK parameters. Notably, neither CYP2D6 nor CYP3A4/5 phenotyping demonstrated a significant impact on the total active moiety, suggesting that other gene variants could modulate RIS PK. The study confirmed the previously reported partial impact of the CYP2D6 gene on RIS PK. However, future studies using contemporary genotyping techniques targeting a wide range of variants in other candidate genes must be conducted to further examine their interactive effects on RIS PK and the clinical response.
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Affiliation(s)
- Sireen Abdul Rahim Shilbayeh
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University (PNU), P.O. Box 84428, 11671, Riyadh, Saudi Arabia.
| | - Iman Sharaf Adeen
- Department of Pediatric Behavior and Development and Adolescent Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ayman Shawqi Alhazmi
- Department of Pediatric Behavior and Development and Adolescent Medicine, King Saud Medical City, Riyadh, Saudi Arabia
| | - Samah Fathy Ibrahim
- College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Fawwaz Abdul Razaq Al Enazi
- Department of Pediatric Behavior and Development and Adolescent Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ezzeldeen Hasan Ghanem
- Pharmaceutical Analysis Section, King Abdullah International Medical Research Center (KAIMRC), King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
| | - Adel Mohammed Binduraihem
- Health Sciences Research Center, King Abdullah Bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
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16
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Rababa M, Ayasrah S. The effectiveness of a training program based on the assessment of basic language and learning skills- revised tool 'ABLLS-R' in reducing stereotyped behaviors among children with autism spectrum disorder. INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES 2024; 70:1068-1081. [PMID: 39564202 PMCID: PMC11571735 DOI: 10.1080/20473869.2024.2380942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 07/08/2024] [Accepted: 07/08/2024] [Indexed: 11/21/2024]
Abstract
This study investigates the efficiency of a developed training program based on ABLLS-R in reducing stereotypical behaviors among children with autism spectrum disorder (ASD). The experimental approach is employed specifically the single experimental group. The study population consists of 7 children with simple ASD. A measuring stereotypical behaviors was developed which includes two dimensions (motor stereotypical and routine stereotypical behaviors), in addition, a training program based on the ABLLS-R is developed. The findings reveal statistically significant differences between the pre and post treatment of stereotypical behaviors among Jordanian children with ASD in favor of the post-treatment in terms of motor stereotypical behaviors and Routine stereotypical behaviors. The findings indicate that there is an impact and a direct effect on lessen stereotypical motor and routine behaviors among Children with ASD improvement rate (66.6%).
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Affiliation(s)
- Muhammad Rababa
- Faculty of Educational and Psychological Sciences, Amman Arab University, Amman, Jordan
| | - Samer Ayasrah
- Faculty of Educational and Psychological Sciences, Amman Arab University, Amman, Jordan
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17
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Abedini SS, Akhavantabasi S, Liang Y, Heng JIT, Alizadehsani R, Dehzangi I, Bauer DC, Alinejad-Rokny H. A critical review of the impact of candidate copy number variants on autism spectrum disorder. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2024; 794:108509. [PMID: 38977176 DOI: 10.1016/j.mrrev.2024.108509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 04/14/2024] [Accepted: 07/02/2024] [Indexed: 07/10/2024]
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder (NDD) influenced by genetic, epigenetic, and environmental factors. Recent advancements in genomic analysis have shed light on numerous genes associated with ASD, highlighting the significant role of both common and rare genetic mutations, as well as copy number variations (CNVs), single nucleotide polymorphisms (SNPs) and unique de novo variants. These genetic variations disrupt neurodevelopmental pathways, contributing to the disorder's complexity. Notably, CNVs are present in 10 %-20 % of individuals with autism, with 3 %-7 % detectable through cytogenetic methods. While the role of submicroscopic CNVs in ASD has been recently studied, their association with genomic loci and genes has not been thoroughly explored. In this review, we focus on 47 CNV regions linked to ASD, encompassing 1632 genes, including protein-coding genes and long non-coding RNAs (lncRNAs), of which 659 show significant brain expression. Using a list of ASD-associated genes from SFARI, we detect 17 regions harboring at least one known ASD-related protein-coding gene. Of the remaining 30 regions, we identify 24 regions containing at least one protein-coding gene with brain-enriched expression and a nervous system phenotype in mouse mutants, and one lncRNA with both brain-enriched expression and upregulation in iPSC to neuron differentiation. This review not only expands our understanding of the genetic diversity associated with ASD but also underscores the potential of lncRNAs in contributing to its etiology. Additionally, the discovered CNVs will be a valuable resource for future diagnostic, therapeutic, and research endeavors aimed at prioritizing genetic variations in ASD.
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Affiliation(s)
- Seyedeh Sedigheh Abedini
- UNSW BioMedical Machine Learning Lab (BML), The Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW 2052, Australia; School of Biotechnology & Biomolecular Sciences, UNSW Sydney, Sydney, NSW 2052, Australia
| | - Shiva Akhavantabasi
- Department of Molecular Biology and Genetics, Yeni Yuzyil University, Istanbul, Turkey; Ghiaseddin Jamshid Kashani University, Andisheh University Town, Danesh Blvd, 3441356611, Abyek, Qazvin, Iran
| | - Yuheng Liang
- UNSW BioMedical Machine Learning Lab (BML), The Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW 2052, Australia
| | - Julian Ik-Tsen Heng
- Curtin Health Innovation Research Institute, Curtin University, Bentley 6845, Australia
| | - Roohallah Alizadehsani
- Institute for Intelligent Systems Research and Innovation (IISRI), Deakin University, Victoria, Australia
| | - Iman Dehzangi
- Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USA; Department of Computer Science, Rutgers University, Camden, NJ 08102, USA
| | - Denis C Bauer
- Transformational Bioinformatics, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Sydney, Australia; Applied BioSciences, Faculty of Science and Engineering, Macquarie University, Macquarie Park, Australia
| | - Hamid Alinejad-Rokny
- UNSW BioMedical Machine Learning Lab (BML), The Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW 2052, Australia; Tyree Institute of Health Engineering (IHealthE), UNSW Sydney, Sydney, NSW 2052, Australia.
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Metabolomic changes in children with autism. World J Clin Pediatr 2024; 13:92737. [PMID: 38947988 PMCID: PMC11212761 DOI: 10.5409/wjcp.v13.i2.92737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/23/2024] [Accepted: 05/06/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD. AIM To comprehensively explore metabolomic changes in children with ASD, integrating findings from various research articles, reviews, systematic reviews, meta-analyses, case reports, editorials, and a book chapter. METHODS A systematic search was conducted in electronic databases, including PubMed, PubMed Central, Cochrane Library, Embase, Web of Science, CINAHL, Scopus, LISA, and NLM catalog up until January 2024. Inclusion criteria encompassed research articles (83), review articles (145), meta-analyses (6), systematic reviews (6), case reports (2), editorials (2), and a book chapter (1) related to metabolomic changes in children with ASD. Exclusion criteria were applied to ensure the relevance and quality of included studies. RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals. These metabolic biomarkers may serve as objective measures to support clinical assessments, improve diagnostic accuracy, and inform personalized treatment approaches. Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD. CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy, guiding personalized treatment approaches, monitoring treatment response, and improving outcomes. Further research is needed to validate findings, establish standardized protocols, and overcome technical challenges in metabolomic analysis. By advancing our understanding of metabolic dysregulations in ASD, clinicians can improve the lives of affected individuals and their families.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Pediatric, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Manama, Bahrain, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Chest Disease, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Manama, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
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Stefanyshyn V, Sheiko M, Pyantkovska N, Stetsyuk R, Pokhylko V, Fishchuk L, Rossokha Z. Combination of 15q24 Microdeletion Syndrome and Metabolic Imbalance in a Patient with Atypical Autism. J Mol Neurosci 2024; 74:1. [PMID: 38180598 DOI: 10.1007/s12031-023-02183-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 11/16/2023] [Indexed: 01/06/2024]
Abstract
Autistic spectrum disorders (ASD) in children are becoming increasingly common, reaching epidemic proportions. Among the various causes contributing to the development of ASD, the leading place belongs to both chromosomal pathologies and genetic syndromes and their consequence - metabolic imbalance or severe metabolic disorders. Depending on the degree of metabolic pathway damage, certain phenotypes of ASD are formed. A deletion of ~3.1 Mb of chromosome 15q24 was detected in the examined 2-year-old boy with a "mild phenotype" of autism without an obvious delay in mental development. A wide range of additional studies included genetic testing of folate metabolism genes and analysis of metabolites of the methylation cycle and detection of antibodies to folic acid alpha receptors. A heterozygous variant of the MTHFR gene (rs1801133), moderate hyperhomocysteinemia, hypermethylation, and an increased titer of antibodies to alpha receptors of folic acid were revealed in the patient. This clinical case indicates the need for a multifaceted clinical and laboratory examination in children with ASD to identify the metabolic phenotype and prescribe personalized treatment. A personalized treatment strategy will improve the cognitive functions, psycho-emotional state, and social adaptation of individuals with ASD in the long term."
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Affiliation(s)
| | | | | | | | | | - Liliia Fishchuk
- State Institution "Reference-Centre for Molecular Diagnostic of Public Health Ministry of Ukraine", Kyiv, Ukraine.
| | - Zoia Rossokha
- State Institution "Reference-Centre for Molecular Diagnostic of Public Health Ministry of Ukraine", Kyiv, Ukraine
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Sallam DE, Shaker YS, Mostafa GA, El-Hossiny RM, Taha SI, Ahamed MAEH. Evaluation of serum interleukin-17 A and interleukin-22 levels in pediatric patients with autism spectrum disorder: a pilot study. BMC Pediatr 2024; 24:18. [PMID: 38183030 PMCID: PMC10768424 DOI: 10.1186/s12887-023-04484-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 12/13/2023] [Indexed: 01/07/2024] Open
Abstract
BACKGROUND Many neurodevelopmental abnormalities are connected to autism spectrum disorder (ASD), which can result in inflammation and elevated cytokine levels due to immune system dysregulation. Interleukin (IL)-17 A and IL-22 have been linked to the regulation of host defense against pathogens at the barrier surface, the regeneration of injured tissue, and the integration of the neurological, endocrine, and immune systems. Several studies have investigated the possible connection between IL-17 A and ASD as well as the severity of behavioral symptoms, but few of them included IL-22. OBJECTIVES To measure serum levels of interleukin (IL)-17 A and IL-22 in children with ASD and to investigate their association with disease severity. METHODS This pilot study was performed on 24 children with ASD and 24 matched controls. Childhood Autism Rating Scale (CARS) assessed ASD severity, and serum levels of IL-17 A and IL-22 were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS In ASD patients, serum levels of IL-17 A and IL-22 showed a significant increase compared to controls (p-values < 0.001). We compared serum levels of IL-17 A and IL-22 according to the severity categories by CARS and could not find any significant differences (p-values > 0.05). Only IL-22 had a significant positive correlation with ASD severity by CARS scores. CONCLUSIONS Raised serum levels of IL-17 A and IL-22 are associated with ASD; only IL-22, not IL-17 A, is correlated with ASD severity. This finding proposes IL-22 as a possible future effective target for ASD treatment. To fully comprehend the significance of these cytokines in ASD and their possible effects on ASD diagnosis and treatment, more research on a wider scale is required.
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Affiliation(s)
- Dina E Sallam
- Department of Pediatrics, Pediatric Nephrology Unit, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt
| | | | - Gehan A Mostafa
- Department of Pediatrics, Pediatric Allergy, and Immunology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reham M El-Hossiny
- Department of Pediatrics, Pediatric Neuropsychiatric Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sara I Taha
- Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
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Önal S, Sachadyn-Król M, Kostecka M. A Review of the Nutritional Approach and the Role of Dietary Components in Children with Autism Spectrum Disorders in Light of the Latest Scientific Research. Nutrients 2023; 15:4852. [PMID: 38068711 PMCID: PMC10708497 DOI: 10.3390/nu15234852] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/15/2023] [Accepted: 11/16/2023] [Indexed: 12/18/2023] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects several areas of mental development. The onset of ASD occurs in the first few years of life, usually before the age of 3 years. Proper nutrition is important to ensure that an individual's nutrient and energy requirements are met, and it can also have a moderating effect on the progression of the disorder. A systematic database search was conducted as a narrative review to determine whether nutrition and specific diets can potentially alter gastrointestinal symptoms and neurobehavioral disorders. Databases such as Science Direct, PubMed, Scopus, Web of Science (WoS), and Google Scholar were searched to find studies published between 2000 and September 2023 on the relationship between ASD, dietary approaches, and the role of dietary components. The review may indicate that despite extensive research into dietary interventions, there is a general lack of conclusive scientific data about the effect of therapeutic diets on ASD; therefore, no definitive recommendation can be made for any specific nutritional therapy as a standard treatment for ASD. An individualized dietary approach and the dietician's role in the therapeutic team are very important elements of every therapy. Parents and caregivers should work with nutrition specialists, such as registered dietitians or healthcare providers, to design meal plans for autistic individuals, especially those who would like to implement an elimination diet.
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Affiliation(s)
- Seda Önal
- Department of Nutrition and Dietetics, Health Sciences Institute, Ankara University, 06110 Ankara, Turkey;
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Fırat University, 23200 Elazığ, Turkey
| | - Monika Sachadyn-Król
- Faculty of Food Science and Biotechnology, University of Life Sciences in Lublin, 20-950 Lublin, Poland;
| | - Małgorzata Kostecka
- Faculty of Food Science and Biotechnology, University of Life Sciences in Lublin, 20-950 Lublin, Poland;
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Maric DM, Vojvodic D, Maric DL, Velikic G, Radomir M, Sokolovac I, Stefik D, Ivkovic N, Susnjevic S, Puletic M, Dulic O, Abazovic D. Cytokine Dynamics in Autism: Analysis of BMAC Therapy Outcomes. Int J Mol Sci 2023; 24:15080. [PMID: 37894761 PMCID: PMC10606637 DOI: 10.3390/ijms242015080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/29/2023] [Accepted: 09/30/2023] [Indexed: 10/29/2023] Open
Abstract
Autism spectrum disorder (ASD) has recently been linked to neuroinflammation and an aberrant immune response within the central nervous system. The intricate relationship between immune response and ASD remains elusive, with a gap in understanding the connection between specific immune mechanisms and neural manifestations in autism. In this study, we employed a comprehensive statistical approach, fusing both overarching and granular methods to examine the concentration of 16 cytokines in the cerebrospinal fluid (CSF) across each autologous bone marrow aspirate concentrate (BMAC) intrathecal administration in 63 male and 17 female autism patients. Following a six-month period post the third administration, patients were stratified into three categories based on clinical improvement: Group 1- no/mild (28 subjects), Group 2-moderate (16 subjects), and Group 3-major improvement (15 subjects). Our integrated analysis revealed pronounced disparities in CSF cytokine patterns and clinical outcomes in autism subjects pre- and post-BMAC transplantation. Crucially, our results suggest that these cytokine profiles hold promise as predictive markers, pinpointing ASD individuals who might not exhibit notable clinical amelioration post-BMAC therapy.
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Affiliation(s)
- Dusan M. Maric
- Department for Research and Development, Clinic Orto MD-Parks Dr Dragi Hospital, 21000 Novi Sad, Serbia; (D.M.M.); (M.R.)
- Faculty of Stomatology Pancevo, University Business Academy, 26101 Pancevo, Serbia;
| | - Danilo Vojvodic
- Institute for Medical Research, Military Medical Academy, 11000 Belgrade, Serbia; (D.V.); (D.S.)
- Medical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, Serbia
| | - Dusica L. Maric
- Department of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Gordana Velikic
- Department for Research and Development, Clinic Orto MD-Parks Dr Dragi Hospital, 21000 Novi Sad, Serbia; (D.M.M.); (M.R.)
- Hajim School of Engineering, University of Rochester, Rochester, NY 14627, USA
| | - Mihajlo Radomir
- Department for Research and Development, Clinic Orto MD-Parks Dr Dragi Hospital, 21000 Novi Sad, Serbia; (D.M.M.); (M.R.)
| | | | - Debora Stefik
- Institute for Medical Research, Military Medical Academy, 11000 Belgrade, Serbia; (D.V.); (D.S.)
| | - Nemanja Ivkovic
- Department of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Sonja Susnjevic
- Department of Social Medicine and Health Statistics with Informatics, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Miljan Puletic
- Faculty of Stomatology Pancevo, University Business Academy, 26101 Pancevo, Serbia;
| | - Oliver Dulic
- Department of Surgery, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
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Metwally AM, Helmy MA, Salah El-Din EM, Saleh RM, Abdel Raouf ER, Abdallah AM, Khadr Z, Elsaied A, El-Saied MM, Bassiouni RI, Nagi DA, Shehata MA, El-Alameey IR, El-Hariri HM, Salama SI, Rabah TM, Abdel-Latif GA, El Etreby LA, Elmosalami DM, Sami SM, Eltahlawy E, Ibrahim NA, Elghareeb NA, Badawy HY, Dewdar EM, Ashaat EA. National screening for Egyptian children aged 1 year up to 12 years at high risk of Autism and its determinants: a step for determining what ASD surveillance needs. BMC Psychiatry 2023; 23:471. [PMID: 37381024 PMCID: PMC10304233 DOI: 10.1186/s12888-023-04977-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 06/20/2023] [Indexed: 06/30/2023] Open
Abstract
This study aimed to provide a national estimate of the prevalence of the high risk of autism spectrum disorder (ASD) and their determinants. A national screening survey was conducted for 41,640 Egyptian children aged 1 to 12 years in two phases. Tools used were Vineland's Adaptive Behavior Scales, Modified Checklist for Autism in Toddlers, Gilliam Autism Rating scale, and Denver II Developmental screening test. The overall prevalence of children at high risk of ASD was 3.3% (95% CI:3.1%-3.5%). Children living without mothers in homes, suffered from convulsions (AOR = 3.67; 95%CI:2.8-4.8), a history of cyanosis after birth (AOR = 1.87; 95% CI:1.35-2.59) or history of LBW babies (AOR = 1.53; 95% CI:1.23-1.89) carried higher odds of being at high risk of ASD.
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Affiliation(s)
- Ammal M. Metwally
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Mona A. Helmy
- Environmental and Occupational Medicine Department, Environmental and Climate Change Research Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Ebtissam M. Salah El-Din
- Child Health Department/ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Rehan M. Saleh
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Ehab R. Abdel Raouf
- Child With Special Needs Dept./ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Ali M. Abdallah
- Quantitative Methods Department - Aswan University, Tingar, Egypt
| | - Zeinab Khadr
- Department of Statistics, Faculty of Economics and Political Science, Cairo University, Giza, Egypt
- The Social Research Center of the American University in Cairo, Cairo, Egypt
| | - Amal Elsaied
- Child With Special Needs Dept./ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Mostafa M. El-Saied
- Child With Special Needs Dept./ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Randa I. Bassiouni
- Clinical Genetics Dept./ Human Genetics and Genome Research Institute, National Research Centre , Dokki, Cairo, 60014618 Egypt
| | - Dina A. Nagi
- Clinical Genetics Dept./ Human Genetics and Genome Research Institute, National Research Centre , Dokki, Cairo, 60014618 Egypt
| | - Manal A. Shehata
- Child Health Department/ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Inas R. El-Alameey
- Child Health Department/ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Hazem M. El-Hariri
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Somia I. Salama
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Thanaa M. Rabah
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Ghada A. Abdel-Latif
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Lobna A. El Etreby
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Dalia M. Elmosalami
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Samia M. Sami
- Child Health Department/ Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Eman Eltahlawy
- Environmental and Occupational Medicine Department, Environmental and Climate Change Research Institute, National Research Centre, Dokki, Cairo, 60014618 Egypt
| | - Nihad A. Ibrahim
- Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 60014618 Dokki Egypt
| | - Nahed A. Elghareeb
- Disability Prevention General Directorate, Ministry of Health and Population, Cairo, Egypt
| | - Hala Y. Badawy
- Disability Prevention General Directorate, Ministry of Health and Population, Cairo, Egypt
| | - Eman M. Dewdar
- Disability Prevention General Directorate, Ministry of Health and Population, Cairo, Egypt
| | - Engy A. Ashaat
- Clinical Genetics Dept./ Human Genetics and Genome Research Institute, National Research Centre , Dokki, Cairo, 60014618 Egypt
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24
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Metwally AM, Helmy MA, Salah El-Din EM, Saleh RM, Abdel Raouf ER, Abdallah AM, Khadr Z, Elsaied A, El-Saied MM, Bassiouni RI, Nagi DA, Shehata MA, El-Alameey IR, El-Hariri HM, Salama SI, Rabah TM, Abdel-Latif GA, El Etreby LA, Elmosalami DM, Sami SM, Eltahlawy E, Ibrahim NA, Elghareeb NA, Badawy HY, Dewdar EM, Ashaat EA. National screening for Egyptian children aged 1 year up to 12 years at high risk of Autism and its determinants: a step for determining what ASD surveillance needs. BMC Psychiatry 2023; 23:471. [DOI: https:/doi.org/10.1186/s12888-023-04977-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 06/20/2023] [Indexed: 10/31/2023] Open
Abstract
AbstractThis study aimed to provide a national estimate of the prevalence of the high risk of autism spectrum disorder (ASD) and their determinants. A national screening survey was conducted for 41,640 Egyptian children aged 1 to 12 years in two phases. Tools used were Vineland's Adaptive Behavior Scales, Modified Checklist for Autism in Toddlers, Gilliam Autism Rating scale, and Denver II Developmental screening test. The overall prevalence of children at high risk of ASD was 3.3% (95% CI:3.1%–3.5%). Children living without mothers in homes, suffered from convulsions (AOR = 3.67; 95%CI:2.8–4.8), a history of cyanosis after birth (AOR = 1.87; 95% CI:1.35–2.59) or history of LBW babies (AOR = 1.53; 95% CI:1.23–1.89) carried higher odds of being at high risk of ASD.
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25
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Almandil NB, Alismail MA, Alsuwat HS, AlSulaiman A, AbdulAzeez S, Borgio JF. Exome-wide analysis identify multiple variations in olfactory receptor genes ( OR12D2 and OR5V1) associated with autism spectrum disorder in Saudi females. Front Med (Lausanne) 2023; 10:1051039. [PMID: 36817779 PMCID: PMC9928728 DOI: 10.3389/fmed.2023.1051039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/13/2023] [Indexed: 02/04/2023] Open
Abstract
Background Autism Spectrum Disorder (ASD) is a multifactorial, neurodevelopmental disorder, characterized by deficits in communication, restricted and repetitive behaviors. ASD is highly heritable in Saudi Arabia; indecencies of affected individuals are increasing. Objectives To identify the most significant genes and SNPs associated with the increased risk of ASD in Saudi females to give an insight for early diagnosis. Methods Pilot case-control study mostly emphasized on the significant SNPs and haplotypes contributing to Saudi females with ASD patients (n = 22) compared to controls (n = 51) without ASD. With the use of allelic association analysis tools, 243,345 SNPs were studied systematically and classified according to their significant association. The significant SNPs and their genes were selected for further investigation for mapping of ASD candidate causal variants and functional impact. Results In females, five risk SNPs at p ≤ 2.32 × 10-05 was identified in association with autism. The most significant exonic variants at chromosome 6p22.1 with olfactory receptor genes (OR12D2 and OR5V1) clustered with high linkage disequilibrium through haplotyping analysis. Comparison between highly associated genes (56 genes) of male and female autistic patients with female autistic samples revealed that 39 genes are unique biomarkers for Saudi females with ASD. Conclusion Multiple variations in olfactory receptor genes (OR5V1 and OR12D2) and single variations on SPHK1, PLCL2, AKAP9 and LOC107984893 genes are contributing to ASD in females of Arab origin. Accumulation of these multiple predisposed coding SNPs can increase the possibility of developing ASD in Saudi females.
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Affiliation(s)
- Noor B. Almandil
- Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia,*Correspondence: Noor B Almandil,
| | - Maram Adnan Alismail
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia,College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Hind Saleh Alsuwat
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Abdulla AlSulaiman
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Sayed AbdulAzeez
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - J. Francis Borgio
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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Abuhamdah SMA, Naser AY, Al Awawdeh S. The Jordanian Population's Knowledge, Attitudes, and Willingness to Help People with Autism: A Cross-Sectional Study. J Multidiscip Healthc 2023; 16:1203-1213. [PMID: 37153359 PMCID: PMC10162093 DOI: 10.2147/jmdh.s407639] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/26/2023] [Indexed: 05/09/2023] Open
Abstract
Objective To assess the knowledge and attitudes of the general public in Jordan towards autism. In addition, we aimed to assess their awareness of various treatment options for autism, and their attentiveness and willingness to assist. Methods A cross-sectional survey was conducted in Jordan for the period between April and May 2022 using an online questionnaire developed based on a literature review. A total of 833 individuals in Amman city completed the questionnaires assessing participant demographics, knowledge of and attitude towards ADS, awareness of management options, perception, and ability to help. Using logistic regression, the odds ratios (ORs) and 95% confidence intervals (CIs) for those who are more likely to be informed about autism were determined. Results The participants' overall understanding of autism spectrum disorder was poor, with a mean score of 6.2 (SD: 3.1) out of 17, or 36.5%. The participants showed a moderately positive attitude towards autism, with an average agreement of 60.9% for government support for ADS children. The items about management options auditory integration training therapy had the highest level (50.1%). Additionally, the participants showed a moderate to high level of attention and ability to help people with autism. The majority confirmed that they see the need to implement changes in public facilities to meet the needs of autistic patients (71.8%). When compared to others, females, aged below 30, single, with family income less than 500 JD, holding a bachelor's degree, and working outside the healthcare field had a higher likelihood of knowing more about the autism spectrum condition (p ≤ 0.05). Conclusion Our research illustrates the lack of awareness and knowledge among the Jordanian population regarding autism. To fill this gap, educational awareness programs should be conducted to promote Jordanian knowledge regarding autism and find ways in which communities, organisations, and governments can support so as to allow for early diagnoses and an appropriate treatment plan and therapy for autistic children.
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Affiliation(s)
- Sawsan M A Abuhamdah
- Department of Pharmaceutical Sciences, College of Pharmacy, Al-Ain University, Abu Dhabi Campus, Abu Dhabi, United Arab Emirates
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
- Correspondence: Sawsan MA Abuhamdah, College of Pharmacy, Al Ain University, P.O. Box: 112612, Abu Dhabi, United Arab Emirates, Tel +971-26133228, Fax +971-24444304, Email
| | - Abdallah Y Naser
- Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman, Jordan
| | - Safaa Al Awawdeh
- Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia
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Ahumada D, Guzmán B, Rebolledo S, Opazo K, Marileo L, Parra-Soto S, Viscardi S. Eating Patterns in Children with Autism Spectrum Disorder. Healthcare (Basel) 2022; 10:healthcare10101829. [PMID: 36292276 PMCID: PMC9601475 DOI: 10.3390/healthcare10101829] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/13/2022] [Accepted: 09/19/2022] [Indexed: 12/04/2022] Open
Abstract
The purpose of this research was to analyze the eating patterns of preschool- and school-aged children with ASD, as provided by their families, in the La Araucanía Region of Chile. It involved a cross-sectional study with 72 families with children diagnosed with ASD aged between 2 and 12 years old. Food selectivity, appetite, body mass index (BMI) and frequency of food consumption were studied. The research determined that 97.67% present food selectivity, corresponding to alterations in the frequency of consumption of specific food groups. Moreover, 93.06%, 90.28%, 80.56% and 62.50% of children in the study do not meet the daily recommendations for fruit, fish, water and vegetable consumption, respectively. Therefore, it is important for these findings to be considered when designing and carrying out educational interventions regarding food in families with children with ASD for greater assertiveness and effectiveness in improving health.
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Affiliation(s)
- Danay Ahumada
- Carrera de Nutrición y Dietética, Departamento de Procesos Diagnóstico y Evaluación, Facultad de Ciencias de la Salud, Campus San Francisco, Universidad Católica de Temuco, Temuco 4813302, Chile
- Programa de Magister en Epidemiología Clínica, Facultad de Medicina, Universidad de la Frontera, Temuco 4813115, Chile
| | - Barbara Guzmán
- Carrera de Nutrición y Dietética, Departamento de Procesos Diagnóstico y Evaluación, Facultad de Ciencias de la Salud, Campus San Francisco, Universidad Católica de Temuco, Temuco 4813302, Chile
| | - Soledad Rebolledo
- Carrera de Nutrición y Dietética, Departamento de Procesos Diagnóstico y Evaluación, Facultad de Ciencias de la Salud, Campus San Francisco, Universidad Católica de Temuco, Temuco 4813302, Chile
| | - Karol Opazo
- Carrera de Nutrición y Dietética, Departamento de Procesos Diagnóstico y Evaluación, Facultad de Ciencias de la Salud, Campus San Francisco, Universidad Católica de Temuco, Temuco 4813302, Chile
| | - Luis Marileo
- Programa de Doctorado en Ciencias Agropecuarias, Facultad de Recursos Naturales, Universidad Católica de Temuco, Temuco 4813302, Chile
- Biotechnology of Functional Foods Laboratory, Camino Sanquilco, Padre Las Casas 4850827, Chile
| | - Solange Parra-Soto
- School of Health & Wellbeing, University of Glasgow, Glasgow G12 8RZ, UK
- School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow G12 8TA, UK
- Departamento de Nutrición y Salud Publica, Universidad del Bio-Bio, Chillan 3780000, Chile
| | - Sharon Viscardi
- Biotechnology of Functional Foods Laboratory, Camino Sanquilco, Padre Las Casas 4850827, Chile
- Laboratorio de Investigación en Salud de Precisión, Departamento de Procesos Diagnóstico y Evaluación, Facultad de Ciencias de la Salud, Campus San Francisco, Universidad Católica de Temuco, Temuco 4813302, Chile
- Núcleo de Investigación en Producción Alimentaria, Universidad Católica de Temuco, Temuco 4813302, Chile
- Correspondence:
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Maurer MH, Kohler A, Hudemann M, Jüngling J, Biskup S, Menzel M. Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy Number Variants in ADGRL3 (LPHN3) and Two Pseudogenes. Appl Clin Genet 2022; 15:125-131. [PMID: 36082049 PMCID: PMC9447451 DOI: 10.2147/tacg.s361239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 08/25/2022] [Indexed: 11/23/2022] Open
Abstract
We report the finding of two copy number variants (CNVs) in a 12-year-old boy presenting both with autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Clinical features included aggressive behavior, mood instability, suicidal statements, repetitive and restrictive behavior, sensitivity to noise, learning problems and dyslexia, though no intellectual disability was present. Using array-based comparative genomic hybridization (array-CGH), we identified two CNVs, both triplex duplications of 324 kb on 3p26.3, and 284 kb on 4q13.1, respectively. One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled receptor L3 (ADGRL3, former name: latrophilin-3, LPHN3), the other on chromosome 3p26.3 in the region of the two pseudogenes AC090043.1 and RPL23AP39. The patient described in the present study showed increased symptoms under methylphenidate treatment but responded positively to 3 mg per day of the atypical neuroleptic drug aripiprazole. To our knowledge, this is the first report of a CNV in the ADGRL3 gene and its first association with ASD in humans.
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Affiliation(s)
- Martin H Maurer
- Mariaberg Hospital for Child and Adolescent Psychiatry, Gammertingen, Germany
- Correspondence: Martin H Maurer, Mariaberg Hospital for Child and Adolescent Psychiatry, Burghaldenstraße 12, Gammertingen, 72501, Germany, Tel +49 7124 9237200, Fax +49 7124 923555, Email
| | - Anja Kohler
- Mariaberg Hospital for Child and Adolescent Psychiatry, Gammertingen, Germany
| | - Melanie Hudemann
- Mariaberg Hospital for Child and Adolescent Psychiatry, Gammertingen, Germany
| | | | - Saskia Biskup
- Zentrum für Humangenetik, Tübingen, Germany
- Center for Genomics and Transcriptomics, CeGaT GmbH, Tübingen, Germany
| | - Martin Menzel
- Mariaberg Hospital for Child and Adolescent Psychiatry, Gammertingen, Germany
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Alenezi S, Alyahya AS, AlKhalifah SM, Bakhsh HR, Alismail EH, Aldhalaan H, Alwazna T, Alzrayer N, AlSuwailem SS, Alnemary F, AlAnsari AMS, Alqulaq EI, Alyamani A, Amer YS, Albawardi IM, Albalawi WM, Alhassan MA, Algazlan MS, Alramady M, Ad-Dab’bagh Y. Saudi Expert Consensus-Based Autism Spectrum Disorder Statement: From Screening to Management. CHILDREN 2022; 9:children9091269. [PMID: 36138578 PMCID: PMC9496905 DOI: 10.3390/children9091269] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 08/04/2022] [Accepted: 08/17/2022] [Indexed: 11/25/2022]
Abstract
Background: There is a large gap between the needs of individuals diagnosed with autism spectrum disorder (ASD) and the currently available services in Saudi Arabia. Services are often difficult to access, inconsistent in quality, incomplete, unsatisfactory, and costly. As such, there is a national need for expert consensus on the appropriate standards for the assessment and management of children on the autism spectrum. Methodology: A guideline development group (GDC) was formed by professionals representing all related specialties and institutions involved in the management of individuals on the autism spectrum in Saudi Arabia. They met on a regular basis over 21 months. The guideline development process consisted of five steps starting from reviewing existing guidelines and ending with discussing and writing this manuscript. A formal voting process was utilized and recommendations were discussed until a consensus was reached. Results: There was consensus on the following: A specialized diagnostic assessment needs to be carried out by an experienced multidisciplinary team for children referred to assess for ASD. They should be assessed for medical etiology, their behavioral history carefully reviewed, and symptoms directly observed. Longitudinal assessments are encouraged to reflect the effects of symptoms on the individual’s ability to function while with their family, among peers, and in school settings. An additional formal assessment of language, cognitive, and adaptive abilities as well as sensory status is essential to complete the diagnostic process. Interventions should be individualized, developmentally appropriate, and intensive, with performance data relevant to intervention goals to evaluate and adjust interventions. Target symptoms must be identified to address and develop monitoring systems to track change. Conclusion: ASD is a complex condition with widely varying clinical manifestations, thus requiring evaluation and intervention by a range of professionals working in coordination. Behavioral and environmental interventions are the key to optimal outcomes, in conjunction with medications when indicated for specific symptoms. Parental involvement in interventions is vital to sustaining therapeutic gains.
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Affiliation(s)
- Shuliweeh Alenezi
- Department of Psychiatry, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
| | - Ahmad S. Alyahya
- Department of Psychiatry, Eradah Complex for Mental Health, Riyadh 12571, Saudi Arabia
- Correspondence:
| | - Shahad M. AlKhalifah
- Center for Autism Research, King Faisal Specialist Hospital & Research Center, Riyadh 11564, Saudi Arabia
| | - Hadeel R. Bakhsh
- Department of Rehabilitation, College of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia
| | - Eiman H. Alismail
- Center for Autism Research, King Faisal Specialist Hospital & Research Center, Riyadh 11564, Saudi Arabia
| | - Hesham Aldhalaan
- Department of Neuroscience, King Faisal Specialist Hospital & Research Center, Riyadh 11564, Saudi Arabia
| | - Talat Alwazna
- Department of Neurology, King Saud Medical City, Riyadh 12746, Saudi Arabia
| | - Nouf Alzrayer
- Department of Special Education, College of Education, King Saud University, Riyadh 11451, Saudi Arabia
| | | | | | - Ahmed M. S. AlAnsari
- Department of Psychiatry, College of Medecine and Medical Sciences, Arabian Gulf University, Manama 293, Bahrain
| | - Enas I. Alqulaq
- Prince Mohammed Bin Salman Center for Autism and Neurodevelopment, Riyadh 12426, Saudi Arabia
- Health Services of Ministry of Defense, Riyadh 12426, Saudi Arabia
| | - Amal Alyamani
- Prince Mohammed Bin Salman Center for Autism and Neurodevelopment, Riyadh 12426, Saudi Arabia
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah 23311, Saudi Arabia
| | - Yasser S. Amer
- Pediatrics Department, King Khalid University Hospital, Riyadh 12372, Saudi Arabia
- Quality Management Department, King Saud University Medical City, Riyadh 12746, Saudi Arabia
- Evidence-Based Health Care and Knowledge Translation, King Saud University, Riyadh 11451, Saudi Arabia
- Alexandria Center for Evidence-Based Clinical Practice Guidelines, Alexandria University, Alexandria 5424041, Egypt
- Adaptation Working Group, Guidelines International Network (GIN), Perth PH16 5BU, UK
| | - Ibrahim M. Albawardi
- Department of Psychiatry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam 34212, Saudi Arabia
| | | | - Mohammed A. Alhassan
- Department of Psychiatry, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
| | - Maha S. Algazlan
- Department of Psychiatry, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
| | | | - Yasser Ad-Dab’bagh
- Mental Health Department, Neuroscience Center, King Fahad Specialist Hospital-Dammam (KFSH-D), Dammam 32253, Saudi Arabia
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Otaru S, Lawrence DA. Autism: genetics, environmental stressors, maternal immune activation, and the male bias in autism. EXPLORATION OF NEUROPROTECTIVE THERAPY 2022. [DOI: 10.37349/ent.2022.00025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 05/20/2022] [Indexed: 01/05/2025]
Abstract
Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders (NDD) characterized by deficits in three domains: impairments in social interactions, language, and communication, and increased stereotyped restrictive/repetitive behaviors and interests. The exact etiology of ASD remains unknown. Genetics, gestational exposure to inflammation, and environmental stressors, which combine to affect mitochondrial dysfunction and metabolism, are implicated yet poorly understood contributors and incompletely delineated pathways toward the relative risk of ASD. Many studies have shown a clear male bias in the incidence of ASD and other NDD. In other words, being male is a significant yet poorly understood risk factor for the development of NDD. This review discusses the link between these factors by looking at the current body of evidence. Understanding the link between the multiplicity of hits—from genes to environmental stressors and possible sexual determinants, contributing to autism susceptibility is critical to developing targeted interventions to mitigate these risks.
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Affiliation(s)
- Sarah Otaru
- Department of Environmental Health Sciences, University at Albany School of Public Health, Rensselaer, New York 12144, USA
| | - David A. Lawrence
- Department of Environmental Health Sciences, University at Albany School of Public Health, Rensselaer, New York 12144, USA;Clinical and Experimental Immunology, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA
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Hollander E, Jacob S, Jou R, McNamara N, Sikich L, Tobe R, Smith J, Sanders K, Squassante L, Murtagh L, Gleissl T, Wandel C, Veenstra-VanderWeele J. Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2022; 79:760-769. [PMID: 35793101 PMCID: PMC9260643 DOI: 10.1001/jamapsychiatry.2022.1717] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Importance There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties. Objective To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD. Design, Setting, and Participants The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial. Between November 22, 2016, and September 3, 2019, individuals were screened and randomly assigned to treatment groups. The primary efficacy analysis population comprised participants taking age-adjusted balovaptan equivalent to a 10-mg adult dose and participants from the concurrently randomized placebo group. This multicenter trial took place across 41 sites in the US. Participants were aged 5 to 17 years with diagnosed ASD and an IQ of 70 or greater. Data were analyzed from April 8 to November 16, 2020. Interventions Participants were randomly assigned to daily 4-mg or 10-mg adult-equivalent balovaptan or placebo, until the 4-mg group was discontinued. Main Outcomes and Measures The primary end point was change from baseline on the Vineland-II two-domain composite (2DC; socialization and communication domains) score at week 24. Results Between November 2016 and September 2019, a total of 599 individuals were screened and 339 participants were randomly assigned to receive 4-mg balovaptan adult-equivalent dose (91 [26.8%]), 10-mg balovaptan adult-equivalent dose (126 [37.2%]), or placebo (122 [36.0%]). Primary analysis included 86 participants assigned to receive 10-mg balovaptan adult-equivalent dose and 81 assigned to receive placebo (mean [SD] age, 12.1 [3.4] years; 139 male participants [83.2%]). No statistically significant differences were observed between the balovaptan and placebo groups in change from baseline on the Vineland-II 2DC score at week 24 (difference in adjusted least-squares mean, -0.16; 90% CI, -2.56 to 2.23; P = .91). No improvements for balovaptan vs placebo were observed at week 24 for any secondary end points. Balovaptan was well tolerated with no emerging safety concerns. Similar proportions of participants reported adverse events (balovaptan, 66 of 86 [76.7%] vs placebo, 61 of 81 [75.3%]) and serious adverse events (balovaptan, 1 of 86 [1.2%] vs placebo, 4 of 81 [4.9%]). Conclusions and Relevance In this randomized clinical trial, balovaptan did not demonstrate efficacy in improvement of socialization and communication in this population with pediatric ASD. Balovaptan was well tolerated in children 5 years or older. Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD. Trial Registration ClinicalTrials.gov Identifier: NCT02901431.
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Affiliation(s)
- Eric Hollander
- Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, New York
| | - Suma Jacob
- Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis
| | - Roger Jou
- Child Study Center, Yale School of Medicine, New Haven, Connecticut
| | - Nora McNamara
- Department of Psychiatry, University Hospitals, Cleveland, Ohio
| | - Linmarie Sikich
- Department of Psychiatry and Behavioral Sciences, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Russell Tobe
- Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Janice Smith
- F. Hoffmann-La Roche Ltd, Welwyn Garden City, United Kingdom
| | - Kevin Sanders
- F. Hoffmann-La Roche Ltd, Genentech, South San Francisco, California
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Alhazmi S, Alzahrani M, Farsi R, Alharbi M, Algothmi K, Alburae N, Ganash M, Azhari S, Basingab F, Almuhammadi A, Alqosaibi A, Alkhatabi H, Elaimi A, Jan M, Aldhalaan HM, Alrafiah A, Alrofaidi A. Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder. Pharmgenomics Pers Med 2022; 15:705-720. [PMID: 35898556 PMCID: PMC9309317 DOI: 10.2147/pgpm.s366826] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/14/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD. Methods This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing. Results The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control. Conclusion CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.
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Affiliation(s)
- Safiah Alhazmi
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Maryam Alzahrani
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Reem Farsi
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mona Alharbi
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Khloud Algothmi
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Najla Alburae
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Magdah Ganash
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sheren Azhari
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Fatemah Basingab
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Asma Almuhammadi
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Amany Alqosaibi
- Department of Biology, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
| | - Heba Alkhatabi
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Aisha Elaimi
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammed Jan
- College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hesham M Aldhalaan
- Center for Autism Research at King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - Aziza Alrafiah
- Department of Medical Laboratory Science, King Abdulaziz University, Jeddah, Saudi Arabia
- Correspondence: Aziza Alrafiah, Department of Medical Laboratory Science, King Abdulaziz University, P.O Box 80200, Jeddah, 21589, Saudi Arabia, Tel +966 126401000 Ext. 23495, Fax +966 126401000 Ext. 21686, Email
| | - Aisha Alrofaidi
- Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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NMR-Based Metabolomics of Rat Hippocampus, Serum, and Urine in Two Models of Autism. Mol Neurobiol 2022; 59:5452-5475. [PMID: 35715683 DOI: 10.1007/s12035-022-02912-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 06/03/2022] [Indexed: 10/18/2022]
Abstract
Autism spectrum disorders (ASDs) are increasingly diagnosed as developmental disabilities of unclear etiology related to genetic, epigenetic, or environmental factors. The diagnosis of ASD in children is based on the recognition of typical behavioral symptoms, while no reliable biomarkers are available. Rats in whom ASD-like symptoms are due to maternal administration of the teratogenic drugs valproate or thalidomide on critical day 11 of pregnancy are widely used models in autism research. The present studies, aimed at detecting changes in the levels of hydrophilic and hydrophobic metabolites, were carried out on 1-month-old rats belonging to the abovementioned two ASD models and on a control group. Analysis of both hydrophilic and hydrophobic metabolite levels gives a broader view of possible mechanisms involved in the pathogenesis of autism. Hippocampal proton magnetic resonance (MRS) spectroscopy and ex vivo nuclear magnetic resonance (NMR) analysis of serum and urine samples were used. The results were analyzed using advanced statistical tests. Both the results of our present MRS studies of the hippocampus and of the NMR studies of body fluids in both ASD models, particularly from the THAL model, appeared to be consistent with previously published NMR results of hippocampal homogenates and data from the literature on autistic children. We detected symptoms of disturbances in neurotransmitter metabolism, energy deficit, and oxidative stress, as well as intestinal malfunction, which shed light on the pathogenesis of ASD and could be used for diagnostic purposes. These results confirm the usefulness of the noninvasive techniques used in ASD studies.
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Gaziel-Guttman M, Anaki D, Mashal N. Social Anxiety and Shame Among Young Adults with Autism Spectrum Disorder Compared to Typical Adults. J Autism Dev Disord 2022; 53:2490-2498. [PMID: 35394242 DOI: 10.1007/s10803-022-05526-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2022] [Indexed: 11/26/2022]
Abstract
Social anxiety (SA) is common among young adults with autism spectrum disorder (ASD). While shame feelings predict SA among typical adults, the relationship between shame and SA in ASD remains unclear. The current study compared the relationship between SA and shame in ASD. SA, shame, and autistic self-assessment questionnaires were administered to 33 young adults with ASD (28 M/5F) and 38 typical young adults (32 M/6F, Mage = 24 years, range = 20-28 in both groups). Results showed higher SA levels in ASD than typical adults, but lower levels of shame characteristics in the former than in the latter group. Moreover, a significant moderation model showed that some aspects of shame were related to SA only in the typical group but not in ASD.
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Affiliation(s)
- Meyrav Gaziel-Guttman
- School of Education, Bar-Ilan University, Max & Anna Webb St, 5290002, Ramat-Gan, Israel
| | - David Anaki
- Department of Psychology, Bar-Ilan University, Max & Anna Webb St, 5290002, Ramat-Gan, Israel.
| | - Nira Mashal
- School of Education, Bar-Ilan University, Max & Anna Webb St, 5290002, Ramat-Gan, Israel.
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Boccuto L, Mitz A, Abenavoli L, Sarasua SM, Bennett W, Rogers C, DuPont B, Phelan K. Phenotypic Variability in Phelan–McDermid Syndrome and Its Putative Link to Environmental Factors. Genes (Basel) 2022; 13:genes13030528. [PMID: 35328081 PMCID: PMC8950073 DOI: 10.3390/genes13030528] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 02/01/2023] Open
Abstract
Phelan–McDermid syndrome (PMS) is a multi-systemic disorder characterized by both genetic and phenotypic variability. Genetic abnormalities causing PMS span from pathogenic variants of the SHANK3 gene to chromosomal rearrangements affecting the 22q13 region and leading to the loss of up to over nine megabases. The clinical presentation of individuals with PMS includes intellectual disability, neonatal hypotonia, delayed or absent speech, developmental delay, and minor dysmorphic facial features. Several other features may present with differences in age of onset and/or severity: seizures, autism, regression, sleep disorders, gastrointestinal problems, renal disorders, dysplastic toenails, and disrupted thermoregulation. Among the causes of this phenotypic variability, the size of the 22q13 deletion has effects that may be influenced by environmental factors interacting with haploinsufficiency or hemizygous variants of certain genes. Another mechanism linking environmental factors and phenotypic variability in PMS involves the loss of one copy of genes like BRD1 or CYP2D6, located at 22q13 and involved in the regulation of genomic methylation or pharmacokinetics, which are also influenced by external agents, such as diet and drugs. Overall, several non-mutually exclusive genetic and epigenetic mechanisms interact with environmental factors and may contribute to the clinical variability observed in individuals with PMS. Characterization of such factors will help to better manage this disorder.
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Affiliation(s)
- Luigi Boccuto
- Healthcare Genetics Program, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29634, USA;
- Correspondence: ; Tel.: +1-864-6561437
| | - Andrew Mitz
- Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA;
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Graecia, 88100 Catanzaro, Italy;
| | - Sara M. Sarasua
- Healthcare Genetics Program, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29634, USA;
| | - William Bennett
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children, Indianapolis, IN 46202, USA;
| | - Curtis Rogers
- Greenwood Genetic Center, Greenwood, SC 29646, USA; (C.R.); (B.D.)
| | - Barbara DuPont
- Greenwood Genetic Center, Greenwood, SC 29646, USA; (C.R.); (B.D.)
| | - Katy Phelan
- Genetics Laboratory, Florida Cancer Specialists &Research Institute, Fort Myers, FL 33916, USA;
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Almandil NB, AlSulaiman A, Aldakeel SA, Alkuroud DN, Aljofi HE, Alzahrani S, Al-mana A, Alfuraih AA, Alabdali M, Alkhamis FA, AbdulAzeez S, Borgio JF. Integration of Transcriptome and Exome Genotyping Identifies Significant Variants with Autism Spectrum Disorder. Pharmaceuticals (Basel) 2022; 15:ph15020158. [PMID: 35215271 PMCID: PMC8880056 DOI: 10.3390/ph15020158] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/16/2022] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Autism is a complex disease with genetic predisposition factors. Real factors for treatment and early diagnosis are yet to be defined. This study integrated transcriptome and exome genotyping for identifying functional variants associated with autism spectrum disorder and their impact on gene expression to find significant variations. More than 1800 patients were screened, and 70 (47 male/23 female) with an average age of 7.56 ± 3.68 years fulfilled the DSM-5 criteria for autism. Analysis revealed 682 SNPs of 589 genes significantly (p < 0.001) associated with autism among the putative functional exonic variants (n = 243,345) studied. Olfactory receptor genes on chromosome 6 were significant after Bonferroni correction (α = 0.05/243345 = 2.05 × 10−7) with a high degree of linkage disequilibrium on 6p22.1 (p = 6.71 × 10−9). The differentially expressed gene analysis of autistic patients compared to controls in whole RNA sequencing identified significantly upregulated (foldchange ≥ 0.8 and p-value ≤ 0.05; n = 125) and downregulated (foldchange ≤ −0.8 and p-value ≤ 0.05; n = 117) genes. The integration of significantly up- and downregulated genes and genes of significant SNPs identified regulatory variants (rs6657480, rs3130780, and rs1940475) associated with the up- (ITGB3BP) and downregulation (DDR1 and MMP8) of genes in autism spectrum disorder in people of Arab ancestries. The significant variants could be a biomarker of interest for identifying early autism among Arabs and helping to characterize the genes involved in the susceptibility mechanisms for autistic subjects.
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Affiliation(s)
- Noor B. Almandil
- Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia;
| | - Abdulla AlSulaiman
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (A.A.); (M.A.); (F.A.A.)
| | - Sumayh A. Aldakeel
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.A.); (D.N.A.); (A.A.A.); (S.A.)
| | - Deem N. Alkuroud
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.A.); (D.N.A.); (A.A.A.); (S.A.)
| | - Halah Egal Aljofi
- Environmental Health Research Area, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia;
| | - Safah Alzahrani
- Department of Mental Health, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.); (A.A.-m.)
- King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
| | - Aishah Al-mana
- Department of Mental Health, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.); (A.A.-m.)
- King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
| | - Asma A. Alfuraih
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.A.); (D.N.A.); (A.A.A.); (S.A.)
| | - Majed Alabdali
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (A.A.); (M.A.); (F.A.A.)
| | - Fahd A. Alkhamis
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (A.A.); (M.A.); (F.A.A.)
| | - Sayed AbdulAzeez
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.A.); (D.N.A.); (A.A.A.); (S.A.)
| | - J. Francis Borgio
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (S.A.A.); (D.N.A.); (A.A.A.); (S.A.)
- Correspondence: ; Tel.: +966-13-3330864
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A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells 2021; 11:cells11010010. [PMID: 35011571 PMCID: PMC8750892 DOI: 10.3390/cells11010010] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 12/13/2021] [Accepted: 12/16/2021] [Indexed: 01/11/2023] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We confirmed a portion of the key variants with Sanger sequencing and provided interpretation with consideration of patients’ clinical symptoms and detailed literature review. Furthermore, we showed that identification of the genetic contributions of ASD core symptoms and comorbidities may promote a better understanding of the ASD pathophysiology, lead to early detection of associated comorbidities, and facilitate pharmacologic intervention based on pathological pathways inferred from the genetic information. We will make the bioinformatics pipeline and interpretation framework publicly available, in an easily accessible format, after validation with a larger cohort. We hope that the present proposed protocol can serve as a starting point to invite discourse and debate to further improve approaches in WGS-based genetic consultation for patients with ASD.
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Dhanjal DS, Bhardwaj S, Chopra C, Singh R, Patocka J, Plucar B, Nepovimova E, Valis M, Kuca K. Millennium Nutrient N,N-Dimethylglycine (DMG) and its Effectiveness in Autism Spectrum Disorders. Curr Med Chem 2021; 29:2632-2651. [PMID: 34823458 DOI: 10.2174/0929867328666211125091811] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 10/09/2021] [Accepted: 10/11/2021] [Indexed: 11/22/2022]
Abstract
Autism is a neurodevelopmental disorder belonging to the autism spectrum disorder (ASD). In ASDs, the individuals show substantial impairments in social communication, repetitive behaviours, and sensory behaviours deficits in the early stages of their life. Globally, the prevalence of autism is estimated to be less than 1%, especially in high-income countries. In recent decades, there has been a drastic increase in the incidence of ASD, which has put ASD into the category of epidemics. Presently, two US Food and Drug Administration-approved drugs, aripiprazole and risperidone are used to treat symptoms of agitation and irritability in autistic children. However, to date, no medication has been found to treat the core symptoms of ASD. The adverse side effects of conventional medicine and limited treatment options have led families and parents of autistic children to turn to complementary and alternative medicine (CAM) treatments, which are perceived as relatively safe compared to conventional medicine. Recently, N,N-dimethylglycine (DMG), a dietary supplement, has emerged as a useful supplement to improve the mental and physical state of children with ASD. The current review discusses ASD, the prevalence of ASD, CAM approach and efficacy of CAM treatment in children with ASD. Moreover, it highlights the chemistry, pharmacological effect, and clinical studies of DMG, highlighting its potential for improving the lifestyle of children with ASD.
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Affiliation(s)
- Daljeet Singh Dhanjal
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara. India
| | - Sonali Bhardwaj
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara. India
| | - Chirag Chopra
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara. India
| | - Reena Singh
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara. India
| | - Jiri Patocka
- Department of Radiology, Toxicology and Population Protection, Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Czech Republic
| | - Bohumir Plucar
- Reflex Therapy Laboratory, Udolni 393/18, 602 00 Brno. Czech Republic
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove. Czech Republic
| | - Martin Valis
- University Hospital Hradec Kralove, Hradec Kralove. Czech Republic
| | - Kamil Kuca
- University Hospital Hradec Kralove, Hradec Kralove. Czech Republic
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Sabbagh HJ, Al-Jabri BA, Alsulami MA, Hashem LA, Aljubour AA, Alamoudi RA. Prevalence and characteristics of autistic children attending autism centres in 2 major cities in Saudi Arabia: A cross-sectional study. Saudi Med J 2021; 42:419-427. [PMID: 33795498 PMCID: PMC8128630 DOI: 10.15537/smj.2021.42.4.20200630] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 02/22/2021] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVES To assess the prevalence and characteristics of Autism Spectrum Disorder (ASD)-affected children attending autistic centers in 2 major cities in Saudi Arabia. METHODS A cross-sectional study, including ASD centers and schools (37 centers) in Makkah and Jeddah, Saudi Arabia was conducted between January and March 2020. Data were collected from records and parents of children with ASD using a questionnaire on sociodemographic, family history, consanguinity, severity, and maternal risk factors. RESULTS All centers in Makkah and Jeddah participated, with a total of 1,023 ASD children. The prevalence of ASD was 2.618 per 1,000 children for Jeddah, 3.68 per 1,000 children for Makkah and 2.81 per 1,000 children for both Jeddah and Makkah. There was no statistically significant relationship between the severity of ASD and sociodemographic, family and maternal risk factors. However, there was statistically significant relationship between severe ASD and ASD family history (p=0.029, OR: 3.46 and 95% CI 1.14 to 10.5). CONCLUSIONS The prevalence of ASD in Makkah and Jeddah was lower than the global prevalence of ASD. Individuals with a family history of ASD were more likely to have more severe ASD.
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Affiliation(s)
- Heba J. Sabbagh
- From the Department of Pediatric Dentistry (Sabbagh, Aljubour, Alamoudi), College of Dentistry (Alsulami, Hashem) and from the Department of Pediatrics (Al-Jabri), Faculty of Medicine, Jeddah, Kingdom of Saudi Arabia.
- Address correspondence and reprint request to: Dr. Heba J. Sabbagh, Assistant Professor, Department of Pediatric Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail: ORCID ID: http://orcid.org/0000-0002-9788-0379
| | - Basma A. Al-Jabri
- From the Department of Pediatric Dentistry (Sabbagh, Aljubour, Alamoudi), College of Dentistry (Alsulami, Hashem) and from the Department of Pediatrics (Al-Jabri), Faculty of Medicine, Jeddah, Kingdom of Saudi Arabia.
| | - Malek A. Alsulami
- From the Department of Pediatric Dentistry (Sabbagh, Aljubour, Alamoudi), College of Dentistry (Alsulami, Hashem) and from the Department of Pediatrics (Al-Jabri), Faculty of Medicine, Jeddah, Kingdom of Saudi Arabia.
| | - Lutfi A. Hashem
- From the Department of Pediatric Dentistry (Sabbagh, Aljubour, Alamoudi), College of Dentistry (Alsulami, Hashem) and from the Department of Pediatrics (Al-Jabri), Faculty of Medicine, Jeddah, Kingdom of Saudi Arabia.
| | - Ala A. Aljubour
- From the Department of Pediatric Dentistry (Sabbagh, Aljubour, Alamoudi), College of Dentistry (Alsulami, Hashem) and from the Department of Pediatrics (Al-Jabri), Faculty of Medicine, Jeddah, Kingdom of Saudi Arabia.
| | - Rana A. Alamoudi
- From the Department of Pediatric Dentistry (Sabbagh, Aljubour, Alamoudi), College of Dentistry (Alsulami, Hashem) and from the Department of Pediatrics (Al-Jabri), Faculty of Medicine, Jeddah, Kingdom of Saudi Arabia.
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Saleh S, Beyyumi E, Al Kaabi A, Hertecant J, Barakat D, Al Dhaheri NS, Al-Gazali L, Al Shamsi A. Spectrum of neuro-genetic disorders in the United Arab Emirates national population. Clin Genet 2021; 100:573-600. [PMID: 34374989 DOI: 10.1111/cge.14044] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/31/2021] [Accepted: 08/06/2021] [Indexed: 11/27/2022]
Abstract
Clinical and molecular characterization of neuro-genetic disorders among UAE national patients seen in the Genetic Clinic at Tawam hospital over a period of 3 years. A retrospective chart review of all Emirati patients assessed by clinical geneticists due to neuro-genetic disorders including global developmental delay, ASD, ID, ADHD, and epilepsy in combination with abnormalities of other organ systems. Each patient had proper assessment including detailed history, three-generation family history, developmental history and detailed physical examination looking for other system involvement. Hearing test and ophthalmological examination were performed when needed. Magnetic resonance imaging (MRI) of the brain, echocardiogram, and renal ultrasound were pursued as indicated. Detailed psychological evaluation and psychometric assessment were done when indicated. The review was done for a period between January 2018 and December 2020. Genetic investigations included chromosome karyotype, FISH study, metabolic/biochemical tests, chromosome microarray, gene sequencing, targeted mutation testing, trio whole exome and trio genome sequencing. A total of 644 patients with developmental delay, ID, learning difficulty, ASD, ADHD, or NNDs, were seen in genetic clinic from January 2018 to December 2020. A total of 506 patients were included in this review, all completed the genetic evaluations during the study period. There were 398 (61.8%) males and 246 (38.2%) females, with a ratio of 1.6:1. Positive family history of NDD was documented in 132 families, while 115 families had negative history and family history was unknown/unclear in the remaining. Fifty seven (11.26% [57/506]) patients had positive microarray results. Hundred ninety seven (38.9% [197/506]) patients had positive molecular testing. Genetic disorders were found in 133 (67.5% [133/197]) and inborn errors of metabolism were found in 42 (21.3% [42/197]). Consanguinity was documented in 139 patients with positive molecular diagnoses (139/197, 70.5%). Sixty nine (35% [69/197]) patients had autosomal dominant disorders, majority were De Novo (84%). Ninety-five (48% [95/197]) patients had autosomal recessive diseases, 40 mutations involved inborn errors of metabolism and 50 mutations involved genetic disorders. Pathogenic variants causing both autosomal dominant and recessive disorders were found in 98 patients (49.7% [98/197]), likely pathogenic variants causing both autosomal dominant and recessive disorders were found in 66 patients (33.5% [66/197]). X-linked related disorders were found in 10 patients (5% [10/197]). Mitochondrial mutation was found in one patient. Novel mutations were found in 76 patients (76/197 i.e., 38.56%). Twenty two patients had variants of unknown significant. The remaining 252 studied patients (252/506 i.e., 49.8%), remained undiagnosed. This study shows that neuro-genetic disorders in the UAE are very heterogeneous at clinical and molecular levels. Using microarray, WES and WGS a diagnosis was reached in 50% of the patients while no diagnosis was reached in other half of the studied patients. It is possible that some mutations were missed by WGS and WES. However, it is also possible that many of disorders in UAE population are novel and the causative mutation is not yet discovered. More researches need to be done in this population to uncover the molecular basis of these disorders.
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Affiliation(s)
- Sirine Saleh
- Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates
| | - Ela Beyyumi
- Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates
| | - Aysha Al Kaabi
- Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates
| | - Jozef Hertecant
- Genetic Division, Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates
| | - Doaa Barakat
- Psychiatry Department, Behvioral Sciences Institute, Al Ain Hospital, Al Ain, United Arab Emirates
| | - Noura S Al Dhaheri
- Department of Pediatrics & Department of Genetics & Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Lihadh Al-Gazali
- Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Aisha Al Shamsi
- Genetic Division, Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates
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Weissberg O, Elliott E. The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders. Genes (Basel) 2021; 12:genes12081133. [PMID: 34440307 PMCID: PMC8393912 DOI: 10.3390/genes12081133] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/23/2021] [Accepted: 07/23/2021] [Indexed: 11/16/2022] Open
Abstract
Chromodomain-helicase-DNA-binding protein 8 (CHD8) has been identified as one of the genes with the strongest association with autism. The CHD8 protein is a transcriptional regulator that is expressed in nearly all cell types and has been implicated in multiple cellular processes, including cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis. Considering the central role of CHD8 in the genetics of autism, a deeper understanding of the physiological functions of CHD8 is important to understand the development of the autism phenotype and potential therapeutic targets. Different CHD8 mutant mouse models were developed to determine autism-like phenotypes and to fully understand their mechanisms. Here, we review the current knowledge on CHD8, with an emphasis on mechanistic lessons gained from animal models that have been studied.
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The Role of Applied Behavior Analysis to Improve Knowledge on Oral Hygiene Practices among Cooperative Autistic Children: A Cross-Sectional Study from Jazan, Saudi Arabia. Int J Dent 2021; 2021:9491496. [PMID: 34335774 PMCID: PMC8315859 DOI: 10.1155/2021/9491496] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/29/2021] [Accepted: 07/13/2021] [Indexed: 11/28/2022] Open
Abstract
Objective To assess the effectiveness of Applied Behavior Analysis (ABA) to improve knowledge regarding oral hygiene practices among cooperative autistic children. Materials and Methods A cross-sectional study was conducted among 15 children between the age group of 6–12 years and their parents who were randomly chosen from a special care autistic school in Jazan, Saudi Arabia. A mobile application was custom designed and programmed with videos on oral hygiene. A close-ended questionnaire comprising 14 questions for the cooperative autistic children and 21 questions for their parents was designed to assess their knowledge in relation to oral health and hygiene. After four weeks, a questionnaire-based knowledge assessment was conducted. The mean knowledge score was then calculated for children and their parents and compared using paired sample t-test. Results Poor knowledge regarding oral hygiene practices was revealed among the study participants. The estimated mean score among the children was 4.73 before the intervention, which significantly increased to 9.0. The estimated mean score for the parents was 9.3 before intervention and 14.6 after four weeks' period (P < 0.0001). Conclusion The application of ABA using avatars and delivered through videos can significantly improve knowledge regarding oral health hygiene among cooperative autistic children.
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Ebrahim MT, Alothman AA. Resilience and social support as predictors of post-traumatic growth in mothers of children with autism spectrum disorder in Saudi Arabia. RESEARCH IN DEVELOPMENTAL DISABILITIES 2021; 113:103943. [PMID: 33799234 DOI: 10.1016/j.ridd.2021.103943] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/06/2021] [Accepted: 03/17/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND There are few studies about the role of resilience and social support in post-traumatic growth (PTG) in parents of children with autism spectrum disorder (ASD). AIM This study examined the relationship between social support, resilience, and PTG and the predictive role of resilience and social support related to PTG in Saudi Arabian mothers. METHODS AND PROCEDURES A survey-based quantitative study was conducted in 88 mothers aged 18-46 years (M = 33.5; SD = 8.02) who had a child with ASD. They were sampled from nine day care centers in Riyadh and the Central-Eastern-Southern region. OUTCOMES AND RESULTS The findings showed a significant positive correlation between perceived social support, resilience, and PTG, and revealed that Resilience-competence was the only significant predictor of PTG-personal strength, appreciation of life, spiritual change new possibilities, and total PTG, while positive acceptance of change was a significant predictor of PTG-relating to others. Moreover, social support from friends and significant others were significant predictors of PTG-total. CONCLUSIONS AND IMPLICATIONS We found that, for mothers of a child with ASD in Saudi Arabia, the biggest factors predicting post-traumatic growth were a notion of personal competence and social support from friends. Intervention is suggested to lower the risk of trauma.
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Affiliation(s)
- Mona Tawakkul Ebrahim
- Department of Educational Sciences, College of Education, Majmaah University, Majmaah, 11952, Saudi Arabia.
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Chan MF, Al Balushi R, Al Falahi M, Mahadevan S, Al Saadoon M, Al-Adawi S. Child and adolescent mental health disorders in the GCC: A systematic review and meta-analysis. Int J Pediatr Adolesc Med 2021; 8:134-145. [PMID: 34350324 PMCID: PMC8319685 DOI: 10.1016/j.ijpam.2021.04.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 04/25/2021] [Indexed: 12/01/2022]
Abstract
Background The Gulf Cooperation Council (GCC), with a predominant ‘youth bulge’ among its 54 million people, has witnessed an exponential increase in research pertinent to child and adolescent mental health (CAMH). Aside from a few narrative reviews, to date, no critical appraisal examining the magnitude of CAMH has emerged from this region. Aims This study aimed to report the prevalence rates of CAMH disorders in the GCC through a systematic review of the existing literature followed by a meta-analysis. Methods A systematic review of the literature from the six GCC countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates) was conducted. The databases used included Scopus, ProQuest, Pubmed, and a final check was performed on Google Scholar to account for any remaining studies that may have still been under review. Meta analytic techniques were then used to estimate prevalence rates of each specific mental disorder, i.e. ADHD, depression, anxiety, stress, eating disorders, and tobacco use disorder. Results A total of 33 studies from the six countries were included. The pooled prevalence of ADHD as per the Vanderbilt ADHD Diagnostic Rating Scale (VADHDDRS), clinical judgments, Attention Deficit Disorders Evaluation Scale (ADDES), and the Strengths and Difficulties Questionnaire (SDQ) was found to be 13.125%, 13.38%, 26.135%, and 12.83%, respectively. The pooled prevalence of depressive symptoms solicited by the Patient Health Questionnaire (PHQ-9), Depression, Anxiety, and Stress Scale (DASS), and Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) was 44.684%, 45.09%, and 26.12%, respectively. The pooled prevalence of anxiety according to the DASS and the MINI Kid was 57.04% and 17.27%, respectively, while the pooled prevalence of stress as per the DASS was found to be 43.15%. The pooled prevalence of disordered eating solicited by the Eating Attitudes Test (EAT-26) was 31.55%. Lastly, the pooled prevalence of tobacco use disorder per the Global Youth Tobacco Survey was 19.39%. Discussion To date, this is the first systematic review and meta-analysis of its kind from the GCC. The prevalence rate of CAMH disorders appears to be in the upper range of international trends. The higher rates could be attributed to the existing studies using suboptimal methodological approaches and instruments to solicit the presence of CAMH.
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Affiliation(s)
- Moon Fai Chan
- Department of Family Medicine & Public Health, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Rola Al Balushi
- Department of Behavioral Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Maryam Al Falahi
- Department of Behavioral Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Sangeetha Mahadevan
- Department of Behavioral Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Muna Al Saadoon
- Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Samir Al-Adawi
- Department of Behavioral Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
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Mycobacterium tuberculosis-Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18094513. [PMID: 33922864 PMCID: PMC8122996 DOI: 10.3390/ijerph18094513] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 03/30/2021] [Accepted: 04/03/2021] [Indexed: 12/25/2022]
Abstract
The maternal system’s exposure to pathogens during pregnancy influences fetal brain development causing a persistent inflammation characterized by elevated pro-inflammatory cytokine levels in offspring. Mycobacterium tuberculosis (Mtb) is a global pathogen that causes tuberculosis, a pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of autism spectrum disorder (ASD), it is not known whether Mtb infection is sufficient to induce ASD associated behaviors, immune dysregulation and altered expression of synaptic regulatory genes. The current study infected pregnant Balb/c mice with Mtb H37Rv and valproic acid (VPA) individually and in combination. Plasma cytokine profiles were measured in offspring using the Bio-plex Th17 pro mouse cytokine panel. Mtb infection increased plasma interleukin (IL)-6 and IL-17A, while tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ and IL-1β were reduced when compared with saline. Mtb-induced maternal immune activation (MIA) offspring displayed increased grooming behavior. The study also revealed dysregulation in gene expression of synaptic molecules in the cerebellum. MIA rescued the VPA-induced effects on self-grooming and social interaction behaviors. Our finding therefore highlights a potential role of Mtb as a MIA agent that can potentially contribute to ASD.
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Jangjoo M, Goodman SJ, Choufani S, Trost B, Scherer SW, Kelley E, Ayub M, Nicolson R, Georgiades S, Crosbie J, Schachar R, Anagnostou E, Grunebaum E, Weksberg R. An Epigenetically Distinct Subset of Children With Autism Spectrum Disorder Resulting From Differences in Blood Cell Composition. Front Neurol 2021; 12:612817. [PMID: 33935932 PMCID: PMC8085304 DOI: 10.3389/fneur.2021.612817] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 03/15/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that often involves impaired cognition, communication difficulties and restrictive, repetitive behaviors. ASD is extremely heterogeneous both clinically and etiologically, which represents one of the greatest challenges in studying the molecular underpinnings of ASD. While hundreds of ASD-associated genes have been identified that confer varying degrees of risk, no single gene variant accounts for >1% of ASD cases. Notably, a large number of ASD-risk genes function as epigenetic regulators, indicating potential epigenetic dysregulation in ASD. As such, we compared genome-wide DNA methylation (DNAm) in the blood of children with ASD (n = 265) to samples from age- and sex-matched, neurotypical controls (n = 122) using the Illumina Infinium HumanMethylation450 arrays. Results: While DNAm patterns did not distinctly separate ASD cases from controls, our analysis identified an epigenetically unique subset of ASD cases (n = 32); these individuals exhibited significant differential methylation from both controls than the remaining ASD cases. The CpG sites at which this subset was differentially methylated mapped to known ASD risk genes that encode proteins of the nervous and immune systems. Moreover, the observed DNAm differences were attributable to altered blood cell composition, i.e., lower granulocyte proportion and granulocyte-to-lymphocyte ratio in the ASD subset, as compared to the remaining ASD cases and controls. This ASD subset did not differ from the rest of the ASD cases in the frequency or type of high-risk genomic variants. Conclusion: Within our ASD cohort, we identified a subset of individuals that exhibit differential methylation from both controls and the remaining ASD group tightly associated with shifts in immune cell type proportions. This is an important feature that should be assessed in all epigenetic studies of blood cells in ASD. This finding also builds on past reports of changes in the immune systems of children with ASD, supporting the potential role of altered immunological mechanisms in the complex pathophysiology of ASD. The discovery of significant molecular and immunological features in subgroups of individuals with ASD may allow clinicians to better stratify patients, facilitating personalized interventions and improved outcomes.
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Affiliation(s)
- Maryam Jangjoo
- Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Sarah J. Goodman
- Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Sanaa Choufani
- Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Brett Trost
- Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada
| | - Stephen W. Scherer
- Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- McLaughlin Centre, University of Toronto, Toronto, ON, Canada
| | - Elizabeth Kelley
- Department of Psychiatry, Queen's University, Kingston, ON, Canada
| | - Muhammad Ayub
- Department of Psychiatry, Queen's University, Kingston, ON, Canada
| | - Rob Nicolson
- Department of Psychiatry, University of Western Ontario, London, ON, Canada
| | - Stelios Georgiades
- Department of Psychiatry and Behavioural Neurosciences, Offord Centre for Child Studies, McMaster University, Hamilton, ON, Canada
| | - Jennifer Crosbie
- Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Russell Schachar
- Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON, Canada
| | - Evdokia Anagnostou
- Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
- Department of Pediatrics, University of Toronto, Toronto, ON, Canada
| | - Eyal Grunebaum
- Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON, Canada
- Division of Immunology and Allergy, The Hospital for Sick Children, Toronto, ON, Canada
- Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - Rosanna Weksberg
- Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON, Canada
- Department of Pediatrics, University of Toronto, Toronto, ON, Canada
- Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada
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Sha R, Chen Y, Wang Y, Luo Y, Liu Y, Ma Y, Li Y, Xu L, Xie HQ, Zhao B. Gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice: Neurobehavioral effects on female offspring. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 752:141784. [PMID: 32889265 DOI: 10.1016/j.scitotenv.2020.141784] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 06/11/2023]
Abstract
Emerging evidence suggests that perinatal dioxin exposure affects neurodevelopment and impairs multiple brain functions, including cognitive, language, learning and emotion, in the offspring. However, the impacts of gestational and lactational exposure to dioxin on behavior and related molecular events are still not fully understood. In this study, female C57BL/6J mice were orally administered three doses of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1 or 10 μg/kg body weight (bw)) during the pregnancy and lactation periods. The locomotion, exploration and anxiety-related behaviors were examined by an open field test of the young adult female offspring at postnatal day 68. We found that the maternal TCDD exposure, particularly at a low dose, increased movement ability, novelty-exploration and certain anxiety-related behaviors in the offspring. Such hyperactivity-like behaviors were accompanied by the upregulation of certain genes associated with cholinergic neurotransmission or synaptogenesis in the offspring brain. In accordance with the potential enhancement of cholinergic neurotransmission due to the gene upregulations, the enzymatic activity of acetylcholinesterase was decreased, which might lead to excess acetylcholine and consequent hyper-excitation at the synapses. Thus, we found that gestational and lactational TCDD exposure at low dose caused hyperactivity-like behaviors in young adult female offspring and speculated the enhancement of cholinergic neurotransmission and synaptogenesis as potential molecular events underlying the neurobehavioral effects.
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Affiliation(s)
- Rui Sha
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yangsheng Chen
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yijing Wang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yali Luo
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yiyun Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yongchao Ma
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yunping Li
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Li Xu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Heidi Qunhui Xie
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
| | - Bin Zhao
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
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48
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Siu MT, Goodman SJ, Yellan I, Butcher DT, Jangjoo M, Grafodatskaya D, Rajendram R, Lou Y, Zhang R, Zhao C, Nicolson R, Georgiades S, Szatmari P, Scherer SW, Roberts W, Anagnostou E, Weksberg R. DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders. J Autism Dev Disord 2021; 51:3610-3623. [PMID: 33394241 DOI: 10.1007/s10803-020-04792-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2020] [Indexed: 12/24/2022]
Abstract
Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes.
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Affiliation(s)
- Michelle T Siu
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Sarah J Goodman
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Isaac Yellan
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.,Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
| | - Darci T Butcher
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Maryam Jangjoo
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Daria Grafodatskaya
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Rageen Rajendram
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Youliang Lou
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Rujun Zhang
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Chunhua Zhao
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Rob Nicolson
- Department of Psychiatry, University of Western Ontario, London, ON, Canada
| | - Stelios Georgiades
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
| | - Peter Szatmari
- The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Stephen W Scherer
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.,Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.,The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.,McLaughlin Centre, University of Toronto, Toronto, ON, Canada
| | - Wendy Roberts
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada
| | - Evdokia Anagnostou
- Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.,Department of Pediatrics, University of Toronto, Toronto, ON, Canada
| | - Rosanna Weksberg
- Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada. .,Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. .,Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada. .,Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON, Canada.
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49
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Are Obese Patients with Autism Spectrum Disorder More Likely to Be Selenium Deficient? Research Findings on Pre- and Post-Pubertal Children. Nutrients 2020; 12:nu12113581. [PMID: 33266486 PMCID: PMC7700552 DOI: 10.3390/nu12113581] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/13/2020] [Accepted: 11/18/2020] [Indexed: 12/11/2022] Open
Abstract
Selenium is involved in many metabolic pathways that are critical for life. Information concerning the metabolic effects of selenium in autism spectrum disorder (ASD) and obesity is still conflicting and incomplete. The pre- and post-pubertal selenium profiles of patients with ASD and obesity have not yet been investigated. The goal of the study was to examine selenium content before and after puberty in euthyroid children diagnosed with ASD, compared to age-matched neurotypical controls, with respect to overweight or obesity as a co-existing pathology. Serum, toenail, and 24h urine selenium levels were determined by inductively coupled plasma mass spectrometry in 287 prepubertal children (mean age 8.09 years), divided into groups: ASD with overweight/obesity (ASD+/Ob+); ASD without overweight/obesity (ASD+/Ob-); non-ASD with overweight/obesity (ASD-/Ob+); and non-ASD without overweight/obesity (ASD-/Ob-). The assessment was repeated in 258 of the children after puberty (mean age 14.26 years).The lowest serum (p < 0.001), urine (p < 0.001) and toenail (p < 0.001) selenium levels before and after puberty were observed in ASD+/Ob+ patients, and the highest in ASD-/Ob-. There were no differences in serum/toenail selenium levels between ASD+/Ob- and ASD-/Ob+ groups. The presence of ASD was associatedwith lower serum (p < 0.001) and toenail (p < 0.001) selenium in BMI-matched groups. In neurotypical patients, post-pubertal serum selenium levels were lower (p < 0.001) than pre-pubertal levels. In the multiple linear regression analyses, selenium levels showed inverse relationships with BMI (p < 0.001) and male gender (p < 0.001), irrespective of the sample type. The serum (p = 0.002) and toenail (p < 0.001) selenium levels were inversely associated with the presence of ASD. ASD, obesity/overweight, and male gender have independent impacts on selenium levels in children. Puberty may affect selenium content in neurotypical children of both genders, but not in ASD patients.
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50
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Wang K, Li N, Xu M, Huang M, Huang F. Glyoxalase 1 Inhibitor Alleviates Autism-like Phenotype in a Prenatal Valproic Acid-Induced Mouse Model. ACS Chem Neurosci 2020; 11:3786-3792. [PMID: 33166134 DOI: 10.1021/acschemneuro.0c00482] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Autism spectrum disorder (ASD) is a severe neurological and developmental disorder that impairs a person's ability to socialize and communicate and affects behavior. The number of patients diagnosed with ASD has risen rapidly. However, the pathophysiology of ASD is poorly understood, and drugs for ASD treatment are strikingly limited. This study aims to evaluate the roles of glyoxalase 1 (GLO1)-methylglyoxal (MG)-γ-aminobutyric acid (GABA) signaling in ASD using a valproic acid (VPA)-induced animal model of autism. The GLO1 levels were analyzed by RT-qPCR and Western blot assay, and MG levels were measured with a Methylglyoxal Assay Kit. The open-field and sniff duration tests were used to assess the interest and anxiety of VPA mice. The three-chamber, marble-burying, and tail-flick tests were applied to determine the sociability, repetitive behavior, and nociceptive threshold of VPA mice. Our results demonstrated that increased GLO1 and decreased MG were observed in VPA mice. Administration of S-p-bromobenzylglutathione cyclopentyl diester (BrBzGCp2), a GLO1 inhibitor, was beneficial for alleviating anxiety, reducing repetitive behavior, and improving the impaired sociability and nociceptive threshold of VPA mice. BrBzGCp2 treatment may be developed as a promising therapeutic strategy for patients with ASD.
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Affiliation(s)
- Kui Wang
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao University, No 299 Nanjing Road, Qingdao, 266034 Shandong, China
| | - Na Li
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao University, No 299 Nanjing Road, Qingdao, 266034 Shandong, China
| | - Min Xu
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao University, No 299 Nanjing Road, Qingdao, 266034 Shandong, China
| | - Meng Huang
- Department of Laboratory Medicine, Lao-shan Disease Area, the Affiliated Hospital of Qingdao University, Qingdao, 266000 Shandong, China
| | - Fei Huang
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao University, No 299 Nanjing Road, Qingdao, 266034 Shandong, China
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