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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. [DOI: 10.5492/wjccm.v14.i2.99975] [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: 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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Wang Y, Li Z, Ye Y, Li Y, Wei R, Gan K, Qian Y, Xu L, Kong Y, Guan L, Fang H, Jiao G, Ke X. HD-tDCS effects on social impairment in autism spectrum disorder with sensory processing abnormalities: a randomized controlled trial. Sci Rep 2025; 15:9772. [PMID: 40118999 PMCID: PMC11928555 DOI: 10.1038/s41598-025-93631-z] [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: 10/10/2024] [Accepted: 03/07/2025] [Indexed: 03/24/2025] Open
Abstract
This study examined the effects of high-definition transcranial direct current stimulation (HD-tDCS) on social impairment in children with autism spectrum disorder (ASD), focusing on those with and without sensory processing abnormalities. A randomized double-blind sham-controlled trial involved 72 children with ASD, divided into three groups based on sensory integration status. A post-hoc analysis of 51 children aged 4-8 years who received true HD-tDCS was conducted, categorizing them into hypo-tactile, hyper-tactile, and typical tactile sensitivity groups. Therapeutic efficacy was compared across these groups. (1) The randomized cntrolled Trial: The typical sensory integration group showed significant improvements in social awareness (t = 5.032, p < 0.000) and autistic mannerisms (t = 3.085, p = 0.004) compared to the sensory integration dysfunction group. (2)The result of the post-hoc analysis: The hypo-tactile and typical tactile sensitivity groups exhibited notable improvements in social awareness, cognition, communication, autistic mannerisms, and total SRS scores. In contrast, the hyper-tactile group only had a significant reduction in social communication (t = 2.385, p = 0.022) post-intervention. HD-tDCS effectively improved social impairment symptoms in children with ASD, particularly those with typical sensory integration and either typical or hypo-tactile responsiveness.
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Affiliation(s)
- Yonglu Wang
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Zhijia Li
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
- Wuxi Mental Health Center, Nanjing Medical University, Wuxi, 214151, Jiangsu, China
| | - Yupei Ye
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yun Li
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Ran Wei
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
- Department of Child Health Care, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215000, Jiangsu, China
| | - Kaiyan Gan
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yuxin Qian
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Lingxi Xu
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yue Kong
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Luyang Guan
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Hui Fang
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Gongkai Jiao
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Xiaoyan Ke
- Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Wu SR, Nowakowski TJ. Exploring human brain development and disease using assembloids. Neuron 2025:S0896-6273(25)00128-X. [PMID: 40107269 DOI: 10.1016/j.neuron.2025.02.010] [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: 05/08/2024] [Revised: 01/10/2025] [Accepted: 02/12/2025] [Indexed: 03/22/2025]
Abstract
How the human brain develops and what goes awry in neurological disorders represent two long-lasting questions in neuroscience. Owing to the limited access to primary human brain tissue, insights into these questions have been largely gained through animal models. However, there are fundamental differences between developing mouse and human brain, and neural organoids derived from human pluripotent stem cells (hPSCs) have recently emerged as a robust experimental system that mimics self-organizing and multicellular features of early human brain development. Controlled integration of multiple organoids into assembloids has begun to unravel principles of cell-cell interactions. Moreover, patient-derived or genetically engineered hPSCs provide opportunities to investigate phenotypic correlates of neurodevelopmental disorders and to develop therapeutic hypotheses. Here, we outline the advances in technologies that facilitate studies by using assembloids and summarize their applications in brain development and disease modeling. Lastly, we discuss the major roadblocks of the current system and potential solutions.
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Affiliation(s)
- Sih-Rong Wu
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - Tomasz J Nowakowski
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
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Goldschlager J, Cintron C, Hall R, Shields T, Tolbert GL, Woldebirhan R, Agarwal K, Joseph PV. Taste processing in autism spectrum disorder: A translational scoping review. Neurosci Biobehav Rev 2025; 170:106031. [PMID: 39894423 DOI: 10.1016/j.neubiorev.2025.106031] [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: 11/22/2024] [Revised: 01/21/2025] [Accepted: 01/26/2025] [Indexed: 02/04/2025]
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent challenges in social communication and restricted/repetitive behaviors, including sensory atypicalities. Taste processing is critical for assessing the sensory and hedonic properties of food; however, it remains understudied in ASD, which may limit our understanding of the disorder's links to selective eating and nutritional deficits. This scoping review on autistic gustatory functioning followed a predefined protocol. We conducted searches across four databases and identified 37 studies involving human participants, categorized into three methodologies: questionnaires, neuroimaging, and psychophysical tests. Additionally, eight studies on ASD animal models were included to offer cross-species insights. Questionnaire data generally indicate that individuals with ASD exhibit differences in taste reactivity compared to those without ASD. Neuroimaging studies suggest potential involvement of specific brain regions, including hippocampal volume and anterior superior temporal sulcus (aSTS) connectivity in atypical taste processing. Psychophysical assessments and animal studies further reveal variability in basic taste preferences, with individuals with ASD showing particular aversion to bitterness and showing either no difference or a decreased preference for sweetness compared to typically developing peers. This review also highlights research gaps regarding specific qualitative tastes such as saltiness, sourness, and umami in ASD, limiting a comprehensive understanding of ASD's chemosensory profile and emphasizing the need for further research in these areas.
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Affiliation(s)
- Jess Goldschlager
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Coralys Cintron
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Rosangele Hall
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Tracy Shields
- National Institutes of Health Library, Office of Research Services, Office of the Director, National Institutes of Health, Bethesda, MD, USA
| | - Genesis Lucia Tolbert
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA; Molecular Pathology Unit, Center for Alzheimer's and Related Dementias, National Institute of Aging, National Institutes of Health, Bethesda, MD, USA
| | - Rama Woldebirhan
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Khushbu Agarwal
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
| | - Paule Valery Joseph
- Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism & National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
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Salabura C, Sourty A, Bat-Pitault F, Regnery K, Mayen S, Colson S. [Pain assessment for children and adolescents with autism spectrum disorders (ASD): A systematic review]. L'ENCEPHALE 2025; 51:87-94. [PMID: 38971646 DOI: 10.1016/j.encep.2024.04.007] [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: 04/03/2024] [Accepted: 04/16/2024] [Indexed: 07/08/2024]
Abstract
OBJECTIVE Pain in children and adolescents with autism spectrum disorders remains underdiagnosed due to their inherent communication difficulties. The goal of this review is to identify the most suitable methods for assessing pain in this population and for evaluating the specific perceptions of, or behavioural reactions to, pain whilst considering disorder severity and specifiers (with or without accompanying intellectual impairment, with or without accompanying language impairment). METHOD A systematic review and analysis of the international literature was conducted. RESULTS Fourteen studies were selected. No difference was found in pain-related behaviours based on the age or gender of children or adolescents with autism. Three studies showed pain-related behaviours in autism spectrum disorders to be similar to control groups. Other studies showed specific behavioural responses in autism spectrum disorders with a longer physiological and behavioural recovery time associated with an episode of acute pain in this population. Similarly, the three studies that focused on sensory perceptions of pain all showed differences in the autism spectrum disorders population compared to control groups. In hospital or daily life contexts, studies essentially showed idiosyncratic expressions, hypervigilance, motor agitation, negative emotional reactions, or vocalizations. Regarding the association of autism severity with hyposensitivity to pain, the results remain unclear even when language disorders or intellectual disabilities are also present (in conjunction with autism). The Non-Communicative Children Pain Checklist and its translation into French and Italian showed good internal validity and was used by almost half of the studies in hetero-assessment, mostly by parents. Studies recommend the inclusion of parents in the assessment in order to optimise the evaluation process. Similarly, analysis of parent/child/caregiver interviews from the studies highlights the importance of personalizing pain assessment of children and adolescents, taking into account subject-specific characteristics, pathology, and context. CONCLUSION An integrative and personalized approach to pain assessment appears to be the most appropriate for enhancing the understanding and detection of pain in individuals with autism spectrum disorders. This approach aligns well with a care setting where a nominated professional with a good expertise in autism is responsible for pain assessment. Given the complexity of identifying pain in individuals with autism, further qualitative studies, in conjunction with new pain exploration technologies, are considered necessary as well as a more extensive categorization of the population studies.
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Affiliation(s)
- Christelle Salabura
- Centre médico-psychologique infanto-juvénile, centre hospitalier Sainte-Marie, 07000 Privas, France; Groupement hospitalier les Portes de Provence, 26200 Montélimar, France.
| | - Arnaud Sourty
- Centre ressource autisme du centre hospitalier le Vinatier, 69678 Bron, France; Service de neurologie du Centre hospitalier universitaire Lyon-Sud, 69495 Oullins-Pierre-Bénite, France; Centre hospitalier Saint-Jean-de-Dieu, 69008 Lyon, France.
| | - Flora Bat-Pitault
- Assistance publique-hôpitaux de Marseille, 13009 Marseille, France; Équipe CANO-P, institut de neurosciences de la Timone, Aix-Marseille université, 13385 Marseille, France
| | - Kirsty Regnery
- Centre médico-psychologique infanto-juvénile, centre hospitalier Sainte-Marie, 07000 Privas, France; Centre ressources autisme, 26000 Valence, France
| | - Sandrine Mayen
- Faculté des sciences médicales et paramédicales, Aix-Marseille université, 13385 Marseille, France; EA3279-CEReSs, centre hospitalier d'Aix-en-Provence, 13100 Aix-en-Provence, France
| | - Sébastien Colson
- Faculté des sciences médicales et paramédicales, Aix-Marseille université, 13385 Marseille, France; EA3279-CEReSs, centre hospitalier d'Aix-en-Provence, 13100 Aix-en-Provence, France
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Camerino C. The Dynamicity of the Oxytocin Receptor in the Brain May Trigger Sensory Deficits in Autism Spectrum Disorder. Curr Issues Mol Biol 2025; 47:61. [PMID: 39852176 PMCID: PMC11763978 DOI: 10.3390/cimb47010061] [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: 11/06/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/26/2025] Open
Abstract
Sensory processing abnormalities have been noted since the first clinical description of autism in 1940. However, it was not until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 that sensory challenges were considered as symptoms of autism spectrum disorder (ASD). Multisensory processing is of paramount importance in building a perceptual and cognitive representation of reality. For this reason, deficits in multisensory integration may be a characteristic of ASD. The neurohormone oxytocin (Oxt) is involved in the etiology of ASD, and there are several ongoing clinical trials regarding Oxt administration in ASD patients. Recent studies indicate that Oxt triggers muscle contraction modulating thermogenesis, while abnormal thermoregulation results in sensory deficits, as in ASD. Activation of the Oxt system through exposure to cold stress regulates the expression of oxytocin receptor (Oxtr) in the brain and circulating Oxt, and if this mechanism is pathologically disrupted, it can lead to sensory processing abnormalities since Oxt acts as a master gene that regulates thermogenesis. This review will describe the sensory deficits characteristic of ASD together with the recent theories regarding how the modulation of Oxt/Oxtr in the brain influences sensory processing in ASD.
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Affiliation(s)
- Claudia Camerino
- Department of Precision and Regenerative Medicine, School of Medicine, University of Bari Aldo Moro, P.za G. Cesare 11, 70100 Bari, Italy;
- Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
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Vacher CM, Tsompanidis A, Firestein MR, Penn AA. Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution. J Neuroendocrinol 2025:e13489. [PMID: 39789736 DOI: 10.1111/jne.13489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 12/06/2024] [Accepted: 12/20/2024] [Indexed: 01/12/2025]
Abstract
The placenta is a fetal endocrine organ that secretes many neuroactive factors, including steroids, that play critical roles in brain development. The study of the placenta-brain axis and the links between placental function and brain development represents an emerging research area dubbed "neuroplacentology." The placenta drives many circulating fetal steroids to very high levels during gestation. Recent studies have highlighted the critical role of placental steroids in shaping specific brain structures and behaviors. This review uses a cross-species framework to discuss the genomic factors, in-utero environmental changes, and placental conditions that alter placental steroidogenesis, leading to changes in early developmental trajectories relevant for psychiatric conditions such as autism, in a sex-linked manner.
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Affiliation(s)
- Claire-Marie Vacher
- Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
| | | | - Morgan R Firestein
- Department of Psychiatry, Columbia University Irving Medical Center, New York, New York, USA
| | - Anna A Penn
- Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
- New York Presbyterian Morgan Stanley Children's Hospital, New York, New York, USA
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Zoccante L, Di Gennaro G, Rigotti E, Ciceri ML, Sbarbati A, Zaffanello M. Neurodevelopmental Disorders and Connective Tissue-Related Symptoms: An Exploratory Case-Control Study in Children. CHILDREN (BASEL, SWITZERLAND) 2024; 12:33. [PMID: 39857864 PMCID: PMC11763821 DOI: 10.3390/children12010033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/23/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025]
Abstract
Background/Objectives: Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are neurodevelopmental disorders (NDDs) with overlapping symptoms, suggesting a partially shared genetic origin. This study investigates the prevalence of connective tissue-related conditions in individuals with ASD, ADHD, or TS. Methods: A questionnaire was administered to families of 120 individuals with ASD, ADHD, or TS, collecting sociodemographic data and examining 10 types of disorders affecting various organs and systems. Statistical analyses were performed using STATA 16.0, with the significance level set at 5%. Results: Among the 120 patients, 48 had ASD, 36 had ADHD, and 36 had TS. Flat feet were significantly more common in individuals with ASD (52.1%; OR 7.20; p < 0.001), ADHD (52.8%; OR 6.73; p = 0.001), and TS (38.9%; OR 3.70; p = 0.034) compared to controls (13.6%). Hypersensitivity was more frequent in individuals with ASD (56.3%; OR 5.90; p = 0.001), ADHD (50.0%; OR 4.11; p = 0.011), and TS (58.3%; OR 5.35; p = 0.003) compared to controls (18.2%). Myopia and ptosis were more common in ADHD (30.6%). There was a possible trend towards orthodontic device use in TS (OR 3.20; p = 0.076). Flat feet and hypersensitivity were also common in fathers (31.0% and 36.4%, respectively), mothers (31.0% and 15.2%), and patients (43.8% and 55%). Conclusions: The findings of this study highlight the significant associations between ASD, ADHD, and TS and specific physical symptoms, such as flat feet, sensory hypersensitivity, and other connective tissue-related manifestations. The familial prevalence of these symptoms suggests a potential genetic underpinning, further supporting the hypothesis of shared aetiological pathways. These insights underscore the need for interdisciplinary research to explore the mechanisms linking neurodevelopmental and connective tissue disorders, aiming to improve diagnosis and management strategies.
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Affiliation(s)
| | - Gianfranco Di Gennaro
- Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy;
| | - Erika Rigotti
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37126 Verona, Italy;
| | - Marco Luigi Ciceri
- Childhood, Adolescence, Families and Family Health Centers, Via Salvo d’Acquisto 7, 37122 Verona, Italy;
| | - Andrea Sbarbati
- Department of Neurosciences, School of Medicine, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, 37124 Verona, Italy;
| | - Marco Zaffanello
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37126 Verona, Italy;
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Gonzalez-Herrero B, Happé F, Nicholson TR, Morgante F, Pagonabarraga J, Deeley Q, Edwards MJ. Functional Neurological Disorder and Autism Spectrum Disorder: A Complex and Potentially Significant Relationship. Brain Behav 2024; 14:e70168. [PMID: 39705515 DOI: 10.1002/brb3.70168] [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: 08/31/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 12/22/2024] Open
Abstract
INTRODUCTION Functional neurological disorder (FND) and autism spectrum disorder (ASD) are two complex neuropsychiatric conditions that have been historically classified within psychiatric domains, resulting in a lack of extensive research, insufficient clinical recognition, and persistent societal stigma. In recent years, there has been an increasing recognition among professionals and affected individuals of their possible overlap. This review explores the potential clinical and mechanistic overlap between FND and ASD, with particular attention to shared symptoms across sensory, motor, and psychiatric domains. METHODS We conducted a narrative analysis utilizing the PubMed, CINAHL, MEDLINE, and ScienceDirect databases from inception to June 2024. The search employed specific MeSH terms related to ASD and FND. Given the limited data availability, we included all relevant articles that explored the potential connections between FND and ASD, focusing on established findings and theoretical hypotheses areas. RESULTS Scientific evidence indicates that FND and ASD may co-occur more frequently than previously acknowledged and with notable overlaps in their clinical presentations and pathophysiology. Theoretical models that have been applied to FND and ASD, such as the Bayesian brain theory and the tripartite model of autism, may provide valuable insights into the intersection of these conditions. Although much of the current evidence remains speculative, it underscores the need for hypothesis-driven research to investigate these potential connections further. CONCLUSION ASD and FND are heterogeneous conditions that appear to co-occur in a subset of individuals, with overlapping symptomatology and possibly shared underlying mechanisms. This hypothesis-generating review emphasizes the need for further research to better understand these links, ultimately aiming to improve clinical recognition and develop targeted interventions that enhance the quality of life for affected individuals.
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Affiliation(s)
- Belen Gonzalez-Herrero
- Departamento de Medicina, Universidad Autónoma de Barcelona (UAB), Bellaterra, Spain
- Neurosciences and Cell Biology Institute, Neuromodulation and Motor Control Section, St George's University of London, London, UK
- Queen's Hospital, Barking, Havering and Redbridge University Hospitals, Romford, UK
| | - Francesca Happé
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Timothy R Nicholson
- Neuropsychiatry Research & Education Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Francesca Morgante
- Neurosciences and Cell Biology Institute, Neuromodulation and Motor Control Section, St George's University of London, London, UK
| | - Javier Pagonabarraga
- Departamento de Medicina, Universidad Autónoma de Barcelona (UAB), Bellaterra, Spain
- Instituto de Investigación Biomédica de Sant Pau, Barcelona, Spain
- Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Quinton Deeley
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- National Autism Unit, South London and Maudsley NHS Foundation Trust, London, UK
| | - Mark J Edwards
- Department of Clinical and Basic Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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Kariminezhad S, Zomorrodi R, Zrenner C, Blumberger DM, Ameis SH, Lin HY, Lai MC, Rajji TK, Lunsky Y, Sanches M, Desarkar P. Assessing plasticity in the primary sensory cortex and its relation with atypical tactile reactivity in autism: A TMS-EEG protocol. PLoS One 2024; 19:e0305013. [PMID: 39591434 PMCID: PMC11594394 DOI: 10.1371/journal.pone.0305013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 10/25/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Atypical sensory reactivity is a cardinal presentation in autism. Within the tactile domain, atypical tactile reactivity (TR) is common, it emerges early, persists into adulthood, and impedes social interaction and daily functioning. Hence, atypical TR is a key target for biological intervention to improve outcomes. Brain mechanisms informing biological interventions for atypical TR remains elusive. We previously reported hyper-plasticity in the motor cortex in autistic adults and found that repetitive transcranial magnetic stimulation (rTMS), designed to strengthen inhibitory processes in the brain, reduced hyper-plasticity. Whether the primary sensory cortex (S1) is characterized by hyper-plasticity, which may underlie atypical TR in autism is unknown. OBJECTIVES We aim to test whether hyper-plasticity in the S1 underlies atypical TR in autism, and investigate if a single session of rTMS can safely reduce hyper-plasticity in S1 in autistic adults. METHOD Plasticity will be assessed in the left S1 with integrated paired associative stimulation and electroencephalography (PAS-EEG) paradigm in 32 autistic adults and 32 age-, sex-, and intelligence quotient-matched controls. Autistic participants will be further randomized (double-blind, 1:1) to receive a single-session of either sham or active 20 Hz bilateral rTMS over the S1 and the plasticity will be re-assessed over the left S1 on the same day. CONCLUSIONS Atypical TR has been identified as one of the top clinical research priorities that can influence outcome in autistic population. The study findings can be highly valuable to further elucidate the mechanism underlying atypical TR, which in turn can help with developing a mechanism-driven intervention.
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Affiliation(s)
- Shohreh Kariminezhad
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Reza Zomorrodi
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Christoph Zrenner
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Daniel M. Blumberger
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Stephanie H. Ameis
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Hsiang-Yuan Lin
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Meng-Chuan Lai
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Tarek K. Rajji
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Yona Lunsky
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Marcos Sanches
- Biostatistical Core, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Pushpal Desarkar
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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11
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Abouzed M, Gabr A, Elag KA, Soliman M, Elsaadouni N, Elzahab NA, Barakat M, Elsherbiny A. The prevalence, correlates, and clinical implications of hoarding behaviors in high-functioning autism. Sci Rep 2024; 14:28471. [PMID: 39557866 PMCID: PMC11574268 DOI: 10.1038/s41598-024-75371-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 10/04/2024] [Indexed: 11/20/2024] Open
Abstract
This study aimed to investigate the relationships between hoarding behaviors, autism characteristics, and demographic factors in adults diagnosed with high-functioning ASD (Autism Spectrum Disorder). A total of 112 adults, aged 18-35, with high-functioning ASD completed self-reported assessments on hoarding (Savings Inventory-Revised; SI-R) and autism traits (Autism-Spectrum Quotient; AQ). Additionally, demographic data was gathered. Correlation and regression analyses were performed. The findings revealed positive correlations between hoarding and overall autism traits. Autism quotient scores accounted for 24% of the variance in hoarding inventory scores. Higher AQ scores were associated with increased SI-R scores. Specific AQ subscales were linked to particular SI-R subscales. Gender, age, education level, and employment status were connected to assessment scores. A multiple regression analysis revealed that demographic variables accounted for 19% of the variance in hoarding severity. Gender was found to moderate the impact of age on hoarding behaviors. Significant associations were identified between hoarding tendencies and autism traits in adults with ASD. Demographic variables also played a role in symptom presentation. These findings shed light on the relationship between autism characteristics and hoarding behaviors, as well as how external factors influence them. Further research is necessary to enhance understanding and guide interventions for hoarding in ASD populations.
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Affiliation(s)
- Mohamed Abouzed
- Psychiatry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
| | - Amjad Gabr
- Psychiatry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Khaled A Elag
- Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud Soliman
- Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nisrin Elsaadouni
- Psychiatry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nasr Abou Elzahab
- Psychiatry Department, Damietta Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mostafa Barakat
- Psychiatry Department, Assuit Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Ashraf Elsherbiny
- Psychiatry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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12
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Fan L, Li Q, Shi Y, Li X, Liu Y, Chen J, Sun Y, Chen A, Yang Y, Zhang X, Wang J, Wu L. Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder. BMC Med 2024; 22:504. [PMID: 39497100 PMCID: PMC11533282 DOI: 10.1186/s12916-024-03722-3] [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: 06/28/2024] [Accepted: 10/22/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. METHODS The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. RESULTS Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. CONCLUSIONS S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.
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Affiliation(s)
- Lili Fan
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Qi Li
- School of Nursing, Xuzhou Medical University, Xuzhou, 221004, China
| | - Yaxin Shi
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Xiang Li
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Yutong Liu
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Jiaqi Chen
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Yaqi Sun
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Anjie Chen
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Yuan Yang
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Xirui Zhang
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Jia Wang
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China
| | - Lijie Wu
- Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China.
- Department of Developmental Behavioral Pediatrics, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 150023, China.
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13
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Tamilson B, Poole N, Agrawal N. The co-occurrence of functional neurological disorder and autism spectrum disorder: a systematic literature review and meta-analysis. Cogn Neuropsychiatry 2024; 29:358-385. [PMID: 39888594 DOI: 10.1080/13546805.2025.2452259] [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: 06/10/2024] [Accepted: 01/03/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND Recent studies reveal increasing interest in the link between Autism Spectrum Disorder (ASD) and Functional Neurological Disorder (FND), prompting a systematic review and meta-analysis of their co-occurrence. METHOD The review covered a comprehensive literature search across multiple databases up to November 2024, focusing on peer-reviewed studies of ASD and FND co-occurrence. Twenty-four studies qualified for inclusion. RESULTS The study included 11,324 participants, predominantly female (73.4%). It estimated the proportion of ASD in FND populations to be 0.10 (95% CI: 0.07-0.15), with significant heterogeneity (I² = 97%, p < 0.01). Subgroup analysis showed variation among different age groups and diagnoses. The proportion of ASD was 0.09 in adults and 0.10 in children with FND, 0.15 in adults and 0.19 in children with Functional Tic-Like Behaviours (FTLB), and 0.07 in children with Functional Seizures (FS). CONCLUSION Many studies have reported the co-occurrence of ASD in FND, suggesting a higher-than-expected rate of 10%. Emerging themes exploring the overlapping determinants of FND and ASD, are discussed. However, the significance of this correlation and the overlapping determinants that might explain it, require further research due to the heterogeneity in methodologies, settings, conditions studied and findings. The presence of publication bias warrants cautious interpretation of the results.
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Affiliation(s)
- Bruce Tamilson
- Liaison Psychiatry Service, South West London & St George's Mental Health NHS Trust, Kingston Hospital, London, UK
- Neuropsychiatry Service, South West London & St George's Mental Health NHS Trust, St George's hospital, London, UK
- Atkinson Morley Regional Neurosciences Centre, St George's University hospital, London, UK
- Division of Psychiatry, St George's University of London, London, UK
| | - Norman Poole
- Lishman Unit (Brain injury and Functional neurology), South London and Maudsley NHS Foundation trust, Bethlem Royal hospital, Beckenham, UK
- Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK
| | - Niruj Agrawal
- Neuropsychiatry Service, South West London & St George's Mental Health NHS Trust, St George's hospital, London, UK
- Atkinson Morley Regional Neurosciences Centre, St George's University hospital, London, UK
- Division of Psychiatry, St George's University of London, London, UK
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14
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Obuchi C, Kawase T, Sasame Y, Yamamoto Y, Sasaki K, Iwasaki J, Okamoto H, Kaga K. Traits of Developmental Disorders in Adults With Listening Difficulties Without Diagnosis of Autism Spectrum Disorder And/or Attention-Deficit/Hyperactivity Disorder. J Clin Med 2024; 13:6281. [PMID: 39458230 PMCID: PMC11508553 DOI: 10.3390/jcm13206281] [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: 09/27/2024] [Revised: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Some individuals have a normal audiogram but have listening difficulties (LiD). As many studies have investigated the relationship between listening and developmental disorders, the traits of developmental disorders might explain the symptoms of LiD. In this study, we examined the traits of developmental disorders of adults with LiD to help clarify the cause of LiD symptoms. Methods: In total, 60 adults with LiD and 57 adults without LiD were included. Participants completed a questionnaire for the autism spectrum quotient (AQ) test, the Adult Attention-Deficit Hyperactivity Disorder Self-Rating Scale (A-ADHD), the Adolescent/Adult Sensory Profile (SP), and the severity of subjective LiD in daily life. Results: Before analysis, we excluded participants with LiD who were already diagnosed or met the criteria for autism spectrum disorder (ASD) or ADHD, and the results of the remaining 30 participants (50.0%) with LiD were analyzed. Adults with LiD showed higher scores than those without LiD in the AQ. Attention switching in the AQ and attention ability in the A-ADHD scale were correlated with the severity of LiD symptoms in everyday life. The AQ scores were also significantly correlated with subscales of the SP. Conclusions: Adults with LiD showed greater autistic traits than those without LiD; therefore, LiD symptoms are possibly related to autistic symptoms. Furthermore, adults with LiD might have attention disorder traits of both ASD and ADHD and sensory processing problems. These findings suggest that the attention problems in adults with LiD noted in previous studies might be related to these traits of developmental disorders.
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Affiliation(s)
- Chie Obuchi
- Institute of Human Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
| | | | - Yuka Sasame
- Department of Speech and Hearing Sciences, International University of Health and Welfare, Chiba 286-8686, Japan; (Y.S.); (Y.Y.); (K.S.); (J.I.)
| | - Yayoi Yamamoto
- Department of Speech and Hearing Sciences, International University of Health and Welfare, Chiba 286-8686, Japan; (Y.S.); (Y.Y.); (K.S.); (J.I.)
| | - Kaori Sasaki
- Department of Speech and Hearing Sciences, International University of Health and Welfare, Chiba 286-8686, Japan; (Y.S.); (Y.Y.); (K.S.); (J.I.)
| | - Junya Iwasaki
- Department of Speech and Hearing Sciences, International University of Health and Welfare, Chiba 286-8686, Japan; (Y.S.); (Y.Y.); (K.S.); (J.I.)
| | - Hidehiko Okamoto
- Department of Physiology, International University of Health and Welfare, Chiba 286-8686, Japan;
| | - Kimitaka Kaga
- National Hospital Organization Tokyo Medical Center, National Institute of Sensory Organs, Tokyo 152-8902, Japan;
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15
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Zahedi E, Sadr SS, Sanaeierad A, Hosseini M, Roghani M. Acetyl-l-carnitine alleviates valproate-induced autism-like behaviors through attenuation of hippocampal mitochondrial dysregulation. Neuroscience 2024; 558:92-104. [PMID: 39168175 DOI: 10.1016/j.neuroscience.2024.08.022] [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: 08/07/2023] [Revised: 08/11/2024] [Accepted: 08/17/2024] [Indexed: 08/23/2024]
Abstract
This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21-49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. Hippocampal analysis of oxidative factors (reactive oxygen species and malondialdehyde) and antioxidants (superoxide dismutase, catalase, and glutathione) revealed a burden of oxidative stress in VPA rats. Additionally, mitochondrial biogenesis and MMP were elevated, while the number of parvalbumin interneurons decreased. These changes were accompanied by autism-like behaviors observed in the three-chamber maze, marble burring test, and Y-maze, as well as a learning deficit in the Barnes maze. In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.
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Affiliation(s)
- Elham Zahedi
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Shahabeddin Sadr
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Ashkan Sanaeierad
- Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Marjan Hosseini
- Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Mehrdad Roghani
- Neurophysiology Research Center, Shahed University, Tehran, Iran.
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16
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Yuxi R, Shuqi J, Cong L, Shufan L, Yueyu L. A systematic review of the effect of sandplay therapy on social communication deficits in children with autism spectrum disorder. Front Pediatr 2024; 12:1454710. [PMID: 39463730 PMCID: PMC11502332 DOI: 10.3389/fped.2024.1454710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/06/2024] [Indexed: 10/29/2024] Open
Abstract
Objective To explore the efficacy of sandplay therapy in intervening social communication deficits in children with autism spectrum disorders (ASD), and whether this efficacy is influenced by the age of the children and the dosage of sandplay therapy intervention. Methods Following the PICOS principle, randomized controlled trials (RCTs) related to sandplay therapy for social communication deficits in ASD children were retrieved from seven databases: PubMed, WOS, The Cochrane Library, Embase, CNKI, Wanfang, and VIP, from the inception of each database to November 10, 2023. Two experimenters independently conducted study screening and excluded studies with concomitant diseases, incomplete data, unextractable data, and non-randomized controlled trials. The PEDro scale was used for methodological quality assessment, and the GRADEprofiler method was employed to evaluate the quality of evidence. Stata17 software was used for meta-analysis, subgroup analysis, sensitivity analysis, and publication bias testing. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as the effect statistics. Results A total of 12 RCTs (791 cases) were included. Sandplay therapy had a positive impact on the social communication deficits of ASD children [SMD = -1.42, 95%CI (-1.79, -1.04), P < 0.001]. Subgroup analysis revealed that sandplay therapy administered during the early school age (449 cases, SMD = -1.44, P < 0.05), for a duration of 22-28 weeks (208 cases, SMD = 1.69, P < 0.05), and with a frequency of once per week (218 cases, SMD = -1.67, P < 0.05) was most effective in improving on social communication deficits of ASD children. Discussion The quality of evidence in this study was rated as high, with good methodological quality, including 12 studies with better quality and no detection of bias risk. The study had high heterogeneity, which was attributed to the measurement tools and intervention duration through subgroup analysis, with no inconsistency found. Additionally, no downgrade factors related to imprecision, publication bias, or indirectness were identified. In conclusion, sandplay therapy is an effective measure to improve social communication deficits in children with ASD, and current evidence recommends early intervention using an individual sandplay therapy or integrated sandplay therapy intervention program once a week for 22-28 weeks, which can serve as evidence-based clinical guidance. Systematic Review Registration www.crd.york.ac.uk, identifier (CRD420234821750).
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Affiliation(s)
| | | | | | | | - Long Yueyu
- School of Physical Education, Shanghai University of Sport, Shanghai, China
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17
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Lee S, Jung WB, Moon H, Im GH, Noh YW, Shin W, Kim YG, Yi JH, Hong SJ, Jung Y, Ahn S, Kim SG, Kim E. Anterior cingulate cortex-related functional hyperconnectivity underlies sensory hypersensitivity in Grin2b-mutant mice. Mol Psychiatry 2024; 29:3195-3207. [PMID: 38704508 PMCID: PMC11449790 DOI: 10.1038/s41380-024-02572-y] [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: 07/10/2023] [Revised: 04/17/2024] [Accepted: 04/18/2024] [Indexed: 05/06/2024]
Abstract
Sensory abnormalities are observed in ~90% of individuals with autism spectrum disorders (ASD), but the underlying mechanisms are poorly understood. GluN2B, an NMDA receptor subunit that regulates long-term depression and circuit refinement during brain development, has been strongly implicated in ASD, but whether GRIN2B mutations lead to sensory abnormalities remains unclear. Here, we report that Grin2b-mutant mice show behavioral sensory hypersensitivity and brain hyperconnectivity associated with the anterior cingulate cortex (ACC). Grin2b-mutant mice with a patient-derived C456Y mutation (Grin2bC456Y/+) show sensory hypersensitivity to mechanical, thermal, and electrical stimuli through supraspinal mechanisms. c-fos and functional magnetic resonance imaging indicate that the ACC is hyperactive and hyperconnected with other brain regions under baseline and stimulation conditions. ACC pyramidal neurons show increased excitatory synaptic transmission. Chemogenetic inhibition of ACC pyramidal neurons normalizes ACC hyperconnectivity and sensory hypersensitivity. These results suggest that GluN2B critically regulates ASD-related cortical connectivity and sensory brain functions.
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Affiliation(s)
- Soowon Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea
- Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Korea
| | - Won Beom Jung
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea
- Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute (KBRI), Daegu, 41062, Korea
| | - Heera Moon
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea
| | - Geun Ho Im
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea
| | - Young Woo Noh
- Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea
| | - Wangyong Shin
- Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea
| | - Yong Gyu Kim
- Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea
| | - Jee Hyun Yi
- Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea
| | - Seok Jun Hong
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Korea
| | - Yongwhan Jung
- Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Korea
| | - Sunjoo Ahn
- Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Korea
| | - Seong-Gi Kim
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea.
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Korea.
- Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Korea.
| | - Eunjoon Kim
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
- Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea.
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18
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King R, Buxton H, Tyndall I. Aphantasia and autism: An investigation of mental imagery vividness. Conscious Cogn 2024; 125:103749. [PMID: 39243493 DOI: 10.1016/j.concog.2024.103749] [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: 04/30/2024] [Revised: 08/27/2024] [Accepted: 08/29/2024] [Indexed: 09/09/2024]
Abstract
OBJECTIVE The present study investigated whether autistic adults report different levels of mental imagery vividness than non-autistic adults, and, moreover, if autism is associated with aphantasia which is defined as a condition of reduced or absent voluntary imagery. DESIGN AND METHODS Clinically diagnosed and self-identifying autistic participants were compared with non-autistic participants in their mental imagery vividness (vision, sound, smell, taste, touch, bodily sensation and emotional feeling) and autistic traits using an online survey (N = 121). RESULTS The autistic group scored significantly lower than the non-autistic group on imagery vividness (d = -0.44), in addition to having a higher proportion of participants scoring at cut-off for aphantasia. Moreover, a similar difference was observed for the emotional feel (η2 = 0.11). CONCLUSION The vividness of visual and emotional mental imagery was on average lower for autistic individuals, with a higher proportion presenting at cut-off to be considered an aphantasic.
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Affiliation(s)
- Rachel King
- Department of Psychology, University of Chichester, UK
| | - Harry Buxton
- Department of Psychology, University of Chichester, UK
| | - Ian Tyndall
- Department of Psychology, University of Chichester, UK.
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19
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Sivapalan S, Sivayokan B, Raveenthiran K, Sivayokan S. Sensory Issues and Their Impact Among Autistic Children: A Cross-Sectional Study in Northern Sri Lanka. Cureus 2024; 16:e72130. [PMID: 39575000 PMCID: PMC11580710 DOI: 10.7759/cureus.72130] [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] [Accepted: 10/21/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND Sensory processing issues are among the key diagnostic criteria for autism spectrum disorder (ASD). As altered sensory processing causes autistic children to react differently to sensory experiences and has a profound impact on their development, affecting their learning ability, social interaction, and ability to adapt to a new environment, there is a need to recognize and address these issues in children diagnosed with ASD during assessments and interventions. This study aimed to identify the patterns of sensory issues and their impact, and selected correlates among autistic children attending a center for neurodevelopmental disorders in northern Sri Lanka. METHODS This institution-based, descriptive, cross-sectional study was conducted at a center for neurodevelopmental disorders in Jaffna among 100 children diagnosed with ASD. The sociodemographic details of the child, and scores of the Childhood Autism Rating Scale second edition (CARS™ 2), Sensory Profile™ 2, and a locally developed Behavioral Checklist were extracted from the records available at the center. Data were analyzed using R statistical computing software (R Foundation for Statistical Computing, Vienna, Austria) using general linear models. RESULTS All the children in this study had at least one sensory issue, with 50% having visual processing issues. The severity of ASD increased as auditory processing issues increased. Behavioral issues, in general, increased significantly with increasing auditory and visual processing issues. Repetitive behaviors significantly increased with increasing auditory processing issues, while problems with self-regulation increased significantly with increasing visual and movement processing issues. Conduct-related issues were found to increase significantly with increasing movement and visual processing issues, and attentional response issues were found to increase significantly with increasing auditory, visual, and touch processing issues. CONCLUSION The high prevalence of sensory issues in autistic children and its impact on the severity of ASD and behavioral issues are reiterated in this study. These results emphasize the importance of including interventions targeting sensory issues with the routine therapy for ASD.
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Affiliation(s)
| | - Bhavana Sivayokan
- Department of Psychological Sciences, Kansas State University, Manhattan, USA
| | - Kounthini Raveenthiran
- Mathavam - Center for Neurodevelopmental Disorders, Regional Directorate of Health Services, Jaffna, LKA
| | - Sambasivamoorthy Sivayokan
- Mental Health Unit, Teaching Hospital Jaffna, Jaffna, LKA
- Department of Psychiatry, University of Jaffna, Jaffna, LKA
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20
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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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21
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Falcão M, Monteiro P, Jacinto L. Tactile sensory processing deficits in genetic mouse models of autism spectrum disorder. J Neurochem 2024; 168:2105-2123. [PMID: 38837765 DOI: 10.1111/jnc.16135] [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: 04/21/2024] [Revised: 05/04/2024] [Accepted: 05/07/2024] [Indexed: 06/07/2024]
Abstract
Altered sensory processing is a common feature in autism spectrum disorder (ASD), as recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Although altered responses to tactile stimuli are observed in over 60% of individuals with ASD, the neurobiological basis of this phenomenon is poorly understood. ASD has a strong genetic component and genetic mouse models can provide valuable insights into the mechanisms underlying tactile abnormalities in ASD. This review critically addresses recent findings regarding tactile processing deficits found in mouse models of ASD, with a focus on behavioral, anatomical, and functional alterations. Particular attention was given to cellular and circuit-level functional alterations, both in the peripheral and central nervous systems, with the objective of highlighting possible convergence mechanisms across models. By elucidating the impact of mutations in ASD candidate genes on somatosensory circuits and correlating them with behavioral phenotypes, this review significantly advances our understanding of tactile deficits in ASD. Such insights not only broaden our comprehension but also pave the way for future therapeutic interventions.
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Affiliation(s)
- Margarida Falcão
- Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
| | - Patricia Monteiro
- Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
| | - Luis Jacinto
- Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
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22
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Erdogan MA, Nesil P, Altuntas I, Sirin C, Uyanikgil Y, Erbas O. Amelioration of propionic acid-induced autism spectrum disorder in rats through dapagliflozin: The role of IGF-1/IGFBP-3 and the Nrf2 antioxidant pathway. Neuroscience 2024; 554:16-25. [PMID: 39004410 DOI: 10.1016/j.neuroscience.2024.07.013] [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: 03/16/2024] [Revised: 07/07/2024] [Accepted: 07/09/2024] [Indexed: 07/16/2024]
Abstract
The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder.
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Affiliation(s)
- Mumin Alper Erdogan
- Department of Physiology, Izmir Katip Celebi University, Faculty of Medicine, Izmir, Turkey.
| | - Pemra Nesil
- Istanbul University, Faculty of Medicine, Istanbul, Turkey
| | | | - Cansın Sirin
- Department of Histology and Embryology, Ege University, Faculty of Medicine, Izmir, Turkey
| | - Yigit Uyanikgil
- Department of Histology and Embryology, Ege University, Faculty of Medicine, Izmir, Turkey
| | - Oytun Erbas
- Demiroglu Bilim University, Department of Physiology, İstanbul, Turkey
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23
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Moppert S, Mercado E. Contributions of dysfunctional plasticity mechanisms to the development of atypical perceptual processing. Dev Psychobiol 2024; 66:e22504. [PMID: 38837411 DOI: 10.1002/dev.22504] [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: 07/29/2023] [Revised: 03/04/2024] [Accepted: 05/11/2024] [Indexed: 06/07/2024]
Abstract
Experimental studies of sensory plasticity during development in birds and mammals have highlighted the importance of sensory experiences for the construction and refinement of functional neural circuits. We discuss how dysregulation of experience-dependent brain plasticity can lead to abnormal perceptual representations that may contribute to heterogeneous deficits symptomatic of several neurodevelopmental disorders. We focus on alterations of somatosensory processing and the dynamic reorganization of cortical synaptic networks that occurs during early perceptual development. We also discuss the idea that the heterogeneity of strengths and weaknesses observed in children with neurodevelopmental disorders may be a direct consequence of altered plasticity mechanisms during early development. Treating the heterogeneity of perceptual developmental trajectories as a phenomenon worthy of study rather than as an experimental confound that should be overcome may be key to developing interventions that better account for the complex developmental trajectories experienced by modern humans.
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Affiliation(s)
- Stacy Moppert
- Department of Psychology, University at Buffalo, The State University of New York, Buffalo, New York, USA
| | - Eduardo Mercado
- Department of Psychology, University at Buffalo, The State University of New York, Buffalo, New York, USA
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24
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Soumier A, Lio G, Demily C. Current and future applications of light-sheet imaging for identifying molecular and developmental processes in autism spectrum disorders. Mol Psychiatry 2024; 29:2274-2284. [PMID: 38443634 DOI: 10.1038/s41380-024-02487-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 02/09/2024] [Accepted: 02/13/2024] [Indexed: 03/07/2024]
Abstract
Autism spectrum disorder (ASD) is identified by a set of neurodevelopmental divergences that typically affect the social communication domain. ASD is also characterized by heterogeneous cognitive impairments and is associated with cooccurring physical and medical conditions. As behaviors emerge as the brain matures, it is particularly essential to identify any gaps in neurodevelopmental trajectories during early perinatal life. Here, we introduce the potential of light-sheet imaging for studying developmental biology and cross-scale interactions among genetic, cellular, molecular and macroscale levels of circuitry and connectivity. We first report the core principles of light-sheet imaging and the recent progress in studying brain development in preclinical animal models and human organoids. We also present studies using light-sheet imaging to understand the development and function of other organs, such as the skin and gastrointestinal tract. We also provide information on the potential of light-sheet imaging in preclinical drug development. Finally, we speculate on the translational benefits of light-sheet imaging for studying individual brain-body interactions in advancing ASD research and creating personalized interventions.
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Affiliation(s)
- Amelie Soumier
- Le Vinatier Hospital Center, 95 boulevard Pinel, 69675, Bron cedex, France.
- iMIND, Center of Excellence for Autism, 95 boulevard Pinel, 69675, Bron cedex, France.
- Institute of Cognitive Science Marc Jeannerod, CNRS, UMR 5229, 67 boulevard Pinel, 69675, Bron cedex, France.
- University Claude Bernard Lyon 1, 43 boulevard du 11 Novembre 1918, 69622, Villeurbanne cedex, France.
| | - Guillaume Lio
- Le Vinatier Hospital Center, 95 boulevard Pinel, 69675, Bron cedex, France
- iMIND, Center of Excellence for Autism, 95 boulevard Pinel, 69675, Bron cedex, France
- Institute of Cognitive Science Marc Jeannerod, CNRS, UMR 5229, 67 boulevard Pinel, 69675, Bron cedex, France
| | - Caroline Demily
- Le Vinatier Hospital Center, 95 boulevard Pinel, 69675, Bron cedex, France
- iMIND, Center of Excellence for Autism, 95 boulevard Pinel, 69675, Bron cedex, France
- Institute of Cognitive Science Marc Jeannerod, CNRS, UMR 5229, 67 boulevard Pinel, 69675, Bron cedex, France
- University Claude Bernard Lyon 1, 43 boulevard du 11 Novembre 1918, 69622, Villeurbanne cedex, France
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25
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Basile GA, Tatti E, Bertino S, Milardi D, Genovese G, Bruno A, Muscatello MRA, Ciurleo R, Cerasa A, Quartarone A, Cacciola A. Neuroanatomical correlates of peripersonal space: bridging the gap between perception, action, emotion and social cognition. Brain Struct Funct 2024; 229:1047-1072. [PMID: 38683211 PMCID: PMC11147881 DOI: 10.1007/s00429-024-02781-9] [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: 12/28/2023] [Accepted: 02/22/2024] [Indexed: 05/01/2024]
Abstract
Peripersonal space (PPS) is a construct referring to the portion of space immediately surrounding our bodies, where most of the interactions between the subject and the environment, including other individuals, take place. Decades of animal and human neuroscience research have revealed that the brain holds a separate representation of this region of space: this distinct spatial representation has evolved to ensure proper relevance to stimuli that are close to the body and prompt an appropriate behavioral response. The neural underpinnings of such construct have been thoroughly investigated by different generations of studies involving anatomical and electrophysiological investigations in animal models, and, recently, neuroimaging experiments in human subjects. Here, we provide a comprehensive anatomical overview of the anatomical circuitry underlying PPS representation in the human brain. Gathering evidence from multiple areas of research, we identified cortical and subcortical regions that are involved in specific aspects of PPS encoding.We show how these regions are part of segregated, yet integrated functional networks within the brain, which are in turn involved in higher-order integration of information. This wide-scale circuitry accounts for the relevance of PPS encoding in multiple brain functions, including not only motor planning and visuospatial attention but also emotional and social cognitive aspects. A complete characterization of these circuits may clarify the derangements of PPS representation observed in different neurological and neuropsychiatric diseases.
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Affiliation(s)
- Gianpaolo Antonio Basile
- Brain Mapping Lab, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.
| | - Elisa Tatti
- Department of Molecular, Cellular & Biomedical Sciences, CUNY, School of Medicine, New York, NY, 10031, USA
| | - Salvatore Bertino
- Brain Mapping Lab, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Demetrio Milardi
- Brain Mapping Lab, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy
| | | | - Antonio Bruno
- Psychiatry Unit, University Hospital "G. Martino", Messina, Italy
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy
| | - Maria Rosaria Anna Muscatello
- Psychiatry Unit, University Hospital "G. Martino", Messina, Italy
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy
| | | | - Antonio Cerasa
- S. Anna Institute, Crotone, Italy
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy, Messina, Italy
- Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, Rende, Italy
| | | | - Alberto Cacciola
- Brain Mapping Lab, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.
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26
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Mattioni L, Barbieri A, Grigoli A, Balasco L, Bozzi Y, Provenzano G. Alterations of Perineuronal Net Expression and Abnormal Social Behavior and Whisker-dependent Texture Discrimination in Mice Lacking the Autism Candidate Gene Engrailed 2. Neuroscience 2024; 546:63-74. [PMID: 38537894 DOI: 10.1016/j.neuroscience.2024.03.023] [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: 08/04/2023] [Revised: 02/27/2024] [Accepted: 03/19/2024] [Indexed: 04/06/2024]
Abstract
GABAergic interneurons and perineuronal nets (PNNs) are important regulators of plasticity throughout life and their dysfunction has been implicated in the pathogenesis of several neuropsychiatric conditions, including autism spectrum disorders (ASD). PNNs are condensed portions of the extracellular matrix (ECM) that are crucial for neural development and proper formation of synaptic connections. We previously showed a reduced expression of GABAergic interneuron markers in the hippocampus and somatosensory cortex of adult mice lacking the Engrailed2 gene (En2-/- mice), a mouse model of ASD. Since alterations in PNNs have been proposed as a possible pathogenic mechanism in ASD, we hypothesized that the PNN dysfunction may contribute to the neural and behavioral abnormalities of En2-/- mice. Here, we show an increase in the PNN fluorescence intensity, evaluated by Wisteria floribunda agglutinin, in brain regions involved in social behavior and somatosensory processing. In addition, we found that En2-/- mice exhibit altered texture discrimination through whiskers and display a marked decrease in the preference for social novelty. Our results raise the possibility that altered expression of PNNs, together with defects of GABAergic interneurons, might contribute to the pathogenesis of social and sensory behavioral abnormalities.
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Affiliation(s)
- Lorenzo Mattioni
- Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, Italy.
| | - Anna Barbieri
- Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, Italy
| | - Andrea Grigoli
- Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, Italy
| | - Luigi Balasco
- CIMeC - Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, Trento, Italy
| | - Yuri Bozzi
- CIMeC - Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, Trento, Italy; CNR Neuroscience Institute, via Moruzzi 1, 56124 Pisa, Italy
| | - Giovanni Provenzano
- Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, Italy.
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27
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Goswami M, Bhatara S, Bhatara M, Singh SR. Parental perspectives on oral health-related quality of life in children and adolescents with autism spectrum disorder: A systematic review. SPECIAL CARE IN DENTISTRY 2024; 44:700-718. [PMID: 38156791 DOI: 10.1111/scd.12951] [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: 07/26/2023] [Revised: 10/20/2023] [Accepted: 12/08/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Children with autism spectrum disorder (ASD) face unique challenges related to oral health, which can negatively impact their day-to-day lives, significantly compromising their overall quality of life. Primary caregivers of children with ASD have a critical role in delivering and seeking oral health care. Hence, it is vital to study their perspective towards their children's oral health and its impact on their quality of life. AIM To explore the parental perception of oral health-related quality of life in children with autism. METHODS A systematic electronic and manual search was conducted in Medline (via PubMed), Embase, Google Scholar, Scopus, and LILACS of articles published from January 2003 to May 2023 using appropriate MeSH terms, keywords, and other terms. A four-phase study selection process was followed according to PRISMA guidelines, and data extraction and synthesis were performed using an extraction form. The selected studies were critically appraised using the QATSDD and Crombie's assessment tool. The inter-reviewer agreement was assessed using the kappa with a linear weighting coefficient. RESULTS Out of the 885 results, 15 studies were included in the review after the two selection phases, and the study characteristics were summarized in tabular form. Study quality varied considerably, and out of a total possible QATSDD score of 42, scores for the individual studies ranged from 14 to 40. The risk of bias for the seven criteria was found to be low. CONCLUSION The parental perception of the OHRQoL in children with ASD is poor, and the most significant perceived impact is on the child's functional and social well-being aspects. Parental-Caregiver Perception Questionnaire was the most commonly used. The most frequent symptoms include bad breath, food lodgment, mouth breathing and night grinding. The familial impact and influence on the OHRQoL of siblings were also studied.
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Affiliation(s)
- Mousumi Goswami
- Department of Paediatric and Preventive Dentistry, ITS Dental College, Hospital and Research Centre, Greater Noida, Uttar Pradesh, India
| | - Supriya Bhatara
- Department of Paediatric and Preventive Dentistry, ITS Dental College, Hospital and Research Centre, Greater Noida, Uttar Pradesh, India
| | - Mohit Bhatara
- College of Liberal Arts (Department of Psychology), Wenzhou-Kean University, Wenzhou, Zhejiang, China
| | - Shrey Raj Singh
- Department of Ophthalmology, ICare Eye Hospital and Post Graduate Institute, Noida, Uttar Pradesh, India
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28
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Yoo LJH, Stefanovic N, Watchorn RE. Atopic dermatitis and autism: tactile hypersensitivity impeding topical therapy use. Br J Dermatol 2024; 190:759-760. [PMID: 38174351 DOI: 10.1093/bjd/ljae005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/24/2023] [Accepted: 12/27/2024] [Indexed: 01/05/2024]
Abstract
This carer perspective article offers a unique insight into the lived experience of atopic dermatitis management in the setting of codiagnosed autism spectrum disorder (ASD). It delves into the profound effects of sensory reactivity in the setting of ASD, which poised a unique therapeutic challenge to management of this inflammatory skin disease. This article highlights the importance of an individualized approach and early initiation of systemic treatment when managing individuals with neuropsychiatric comorbidities.
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29
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Deng W, Yi P, Xiong Y, Ying J, Lin Y, Dong Y, Wei G, Wang X, Hua F. Gut Metabolites Acting on the Gut-Brain Axis: Regulating the Functional State of Microglia. Aging Dis 2024; 15:480-502. [PMID: 37548933 PMCID: PMC10917527 DOI: 10.14336/ad.2023.0727] [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: 05/25/2023] [Accepted: 07/27/2023] [Indexed: 08/08/2023] Open
Abstract
The gut-brain axis is a communication channel that mediates a complex interplay of intestinal flora with the neural, endocrine, and immune systems, linking gut and brain functions. Gut metabolites, a group of small molecules produced or consumed by biochemical processes in the gut, are involved in central nervous system regulation via the highly interconnected gut-brain axis affecting microglia indirectly by influencing the structure of the gut-brain axis or directly affecting microglia function and activity. Accordingly, pathological changes in the central nervous system are connected with changes in intestinal metabolite levels as well as altered microglia function and activity, which may contribute to the pathological process of each neuroinflammatory condition. Here, we discuss the mechanisms by which gut metabolites, for instance, the bile acids, short-chain fatty acids, and tryptophan metabolites, regulate the structure of each component of the gut-brain axis, and explore the important roles of gut metabolites in the central nervous system from the perspective of microglia. At the same time, we highlight the roles of gut metabolites affecting microglia in the pathogenesis of neurodegenerative diseases and neurodevelopmental disorders. Understanding the relationship between microglia, gut microbiota, neuroinflammation, and neurodevelopmental disorders will help us identify new strategies for treating neuropsychiatric disorders.
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Affiliation(s)
- Wenze Deng
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Pengcheng Yi
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Yanhong Xiong
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Jun Ying
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Yue Lin
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Yao Dong
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Gen Wei
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
| | - Xifeng Wang
- Department of Anesthesiology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
| | - Fuzhou Hua
- Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi, China.
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30
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Fabio RA, Orsino C, Lecciso F, Levante A, Suriano R. Atypical sensory processing in adolescents with Attention Deficit Hyperactivity Disorder: A comparative study. RESEARCH IN DEVELOPMENTAL DISABILITIES 2024; 146:104674. [PMID: 38306842 DOI: 10.1016/j.ridd.2024.104674] [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: 06/25/2023] [Revised: 12/01/2023] [Accepted: 01/15/2024] [Indexed: 02/04/2024]
Abstract
Atypical sensory processing is common in Attention Deficit Hyperactivity Disorder (ADHD). Despite growing evidence that ADHD symptoms persist into adolescence, the sensory processing of individuals with ADHD in this age group is limited. The aim of this study was to assess differences in self-reported sensory experiences between adolescents with and without ADHD. One hundred thirty-eight Italian adolescents aged between 14 and 18 years (M=16.20; SD= ± 1.90) participated in the study. Sixty-nine participants with ADHD were matched by gender, age, and IQ to 69 typically developing individuals. The sensory processing of all participants was assessed using the Adolescent Sensory Profile (ASP) on the components: low registration, sensation seeking, sensory sensitivity, and sensation avoiding. Moreover, the modalities of ASP were measured: movement, vision, touch, activity level, hearing, and taste/smell. Results show that the ADHD group consistently displayed higher scores across all four components of the sensory profile compared to the control group. The subjects with ADHD also reported higher scores than the control group in all the modalities of ASP. These results confirming the presence of atypical sensory processing in adolescents with ADHD were discussed considering the Cumulative and Emergent Automatic Deficit model (CEAD).
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Affiliation(s)
- Rosa Angela Fabio
- Department of Economics, University of Messina, 98100 Messina, Italy
| | - Caterina Orsino
- Department of Cognitive, Psychological and Pedagogical Sciences and Cultural Studies, University of Messina, 98100 Messina, Italy
| | - Flavia Lecciso
- Department of Human and Social Sciences, University of Salento, Lecce, Italy
| | - Annalisa Levante
- Department of Human and Social Sciences, University of Salento, Lecce, Italy
| | - Rossella Suriano
- Department of Cognitive, Psychological and Pedagogical Sciences and Cultural Studies, University of Messina, 98100 Messina, Italy.
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31
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Ruan H, Eungpinichpong W, Wu H, Aonsri C. Effects of Parent-Delivered Traditional Thai Massage on Gait and Heart Rate Variability in Children with Autism: A Randomized Controlled Trial. JOURNAL OF INTEGRATIVE AND COMPLEMENTARY MEDICINE 2024; 30:269-278. [PMID: 37713302 PMCID: PMC10954606 DOI: 10.1089/jicm.2023.0338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2023]
Abstract
Aim: To examine the effects of parent-delivered traditional Thai massage (TTM) intervention on heart rate variability (HRV) and gait in children with autism. Methods: This was a two-armed, randomized controlled trial conducted at the Haikou Special Education School in Haikou Province, China, between October 2021 and March 2022. A total of 48 children with autism, aged between 7 and 12 years, were selected from the school and randomly divided into either the parent-delivered TTM group or the control group (no intervention) in a 1:1 ratio. In addition to their regular daily school routines, the TTM group received 16 TTM interventions (twice a week), with each session lasting ∼50 min. HRV and gait parameters were measured at baseline, completion of the 8-week intervention, and 2 months follow-up. Results: The results of this study showed that the TTM intervention had a notable positive effect on HRV, with a significant reduction in low-frequency value (p = 0.001), and increased high-frequency value (p = 0.001), compared with the controls, and the advantages persisted during the follow-up period. However, only the stride length in the TTM group was significantly longer than that in the control group at the post-test (p = 0.039) and follow-up test (p = 0.043), while none of the other parameters of gait comparison showed statistical significance. Conclusions: Parent-delivered Thai massage increased HRV levels and stride length in comparison to the control group, and some effects of the intervention were maintained over the follow-up period. Clinical Trials Registry Identifier ChiCTR2100051355; September 21, 2021.
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Affiliation(s)
- Hui Ruan
- Graduate School, Khon Kaen University, Khon Kaen, Thailand
- Physical Education, Hainan Normal University, Haikou, China
| | - Wichai Eungpinichpong
- BNOJHP Research Center, PT Division of Physical Therapy, Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
| | - Hua Wu
- Physical Education, Hainan Normal University, Haikou, China
- BNOJHP Research Center, PT Division of Physical Therapy, Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
| | - Chanada Aonsri
- Department of Special Education, Khon Kaen University Demonstration School, Khon Kaen University, Khon Kaen, Thailand
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Camerino C. The Pivotal Role of Oxytocin's Mechanism of Thermoregulation in Prader-Willi Syndrome, Schaaf-Yang Syndrome, and Autism Spectrum Disorder. Int J Mol Sci 2024; 25:2066. [PMID: 38396741 PMCID: PMC10888953 DOI: 10.3390/ijms25042066] [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: 12/05/2023] [Revised: 02/01/2024] [Accepted: 02/03/2024] [Indexed: 02/25/2024] Open
Abstract
Oxytocin (Oxt) regulates thermogenesis, and altered thermoregulation results in Prader-Willi syndrome (PWS), Schaaf-Yang syndrome (SYS), and Autism spectrum disorder (ASD). PWS is a genetic disorder caused by the deletion of the paternal allele of 15q11-q13, the maternal uniparental disomy of chromosome 15, or defects in the imprinting center of chromosome 15. PWS is characterized by hyperphagia, obesity, low skeletal muscle tone, and autism spectrum disorder (ASD). Oxt also increases muscle tonicity and decreases proteolysis while PWS infants are hypotonic and require assisted feeding in early infancy. This evidence inspired us to merge the results of almost 20 years of studies and formulate a new hypothesis according to which the disruption of Oxt's mechanism of thermoregulation manifests in PWS, SYS, and ASD through thermosensory abnormalities and skeletal muscle tone. This review will integrate the current literature with new updates on PWS, SYS, and ASD and the recent discoveries on Oxt's regulation of thermogenesis to advance the knowledge on these diseases.
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Affiliation(s)
- Claudia Camerino
- Department of Precision and Regenerative Medicine, School of Medicine, University of Bari Aldo Moro, P.za G. Cesare 11, 70100 Bari, Italy;
- Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
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Cummings KK, Jung J, Zbozinek TD, Wilhelm FH, Dapretto M, Craske MG, Bookheimer SY, Green SA. Shared and distinct biological mechanisms for anxiety and sensory over-responsivity in youth with autism versus anxiety disorders. J Neurosci Res 2024; 102:e25250. [PMID: 37840458 PMCID: PMC10843792 DOI: 10.1002/jnr.25250] [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: 11/21/2022] [Revised: 09/10/2023] [Accepted: 09/15/2023] [Indexed: 10/17/2023]
Abstract
Sensory over-responsivity (SOR) is a prevalent cross-diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co-occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ-matched youth aged 8-18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants' SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over-responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over-reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.
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Affiliation(s)
- Kaitlin K. Cummings
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jiwon Jung
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA
| | - Tomislav D. Zbozinek
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA
- Division of the Humanities and Social Sciences, California Institute of Technology, Pasadena, California, USA
| | - Frank H. Wilhelm
- Division of Clinical Psychology and Psychopathology, Department of Psychology, University of Salzburg, Salzburg, Austria
| | - Mirella Dapretto
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA
| | - Michelle G. Craske
- Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA
| | - Susan Y. Bookheimer
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA
| | - Shulamite A. Green
- Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA
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34
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Hudac CM, Webb SJ. EEG Biomarkers for Autism: Rational, Support, and the Qualification Process. ADVANCES IN NEUROBIOLOGY 2024; 40:545-576. [PMID: 39562457 DOI: 10.1007/978-3-031-69491-2_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
In this chapter, we highlight the advantages, progress, and pending challenges of developing electroencephalography (EEG) and event-related potential (ERP) biomarkers for use in autism spectrum disorder (ASD). We describe reasons why global efforts towards precision treatment in ASD are utilizing EEG indices to quantify biological mechanisms. We overview common sensory processing and attention biomarkers and provide translational examples examining the genetic etiology of autism across animal models and human subgroups. We describe human-specific social biomarkers related to face perception, a complex social cognitive process that may prove informative of autistic social behaviors. Lastly, we discuss outstanding considerations for quantifying EEG biomarkers, the challenges associated with rigor and reproducibility, contexts of future use, and propose opportunities for combinatory multidimensional biomarkers.
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Affiliation(s)
- Caitlin M Hudac
- Department of Psychology, University of South Carolina, Columbia, SC, USA.
- Carolina Autism and Neurodevelopmental Research Center, University of South Carolina, Columbia, SC, USA.
| | - Sara Jane Webb
- Center on Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, USA.
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
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Kyselicová K, Dukonyová D, Belica I, Ballová DS, Jankovičová V, Ostatníková D. Fingerprint patterns in relation to an altered neurodevelopment in patients with autism spectrum disorder. Dev Psychobiol 2023; 65:e22432. [PMID: 38010306 DOI: 10.1002/dev.22432] [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: 02/20/2023] [Revised: 09/28/2023] [Accepted: 09/29/2023] [Indexed: 11/29/2023]
Abstract
Dermatoglyphic patterns are permanently established and matured before the 24th week of gestation. Their frequencies and localization might be a good indicator of developmental instability in individuals with an altered neurodevelopment and show potential as biomarkers of autism spectrum disorder (ASD). In this study, fingerprint pattern counts and fluctuating asymmetry in the distribution of patterns are compared between 67 boys diagnosed with ASD (aged 5.11 ± 2.51 years) and 83 control boys (aged 8.58 ± 3.14 years). Boys with ASD had a higher rate of discordance in their fingerprint patterns (p = .0026), showing more often bilateral differences in the occurrence of certain patterns. A chi-square test revealed that the difference in pattern frequencies between boys with ASD and the control group is the most significant in frequencies of whorls, tented arches, and ulnar loops. Boys with ASD have significantly fewer ulnar loops, significantly more whorls, and tented arches in the right hand. The achieved results are in favor of the suggestion that prenatal influences, which play a role in the development of bilateral differences in fingerprint patterns up to the 24th week of gestation, may be a potential cause of an altered neurodevelopment in ASD individuals.
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Affiliation(s)
- Klaudia Kyselicová
- Academic Research Center for Autism, Institute of Physiology, Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia
| | - Dóra Dukonyová
- Academic Research Center for Autism, Institute of Physiology, Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia
| | - Ivan Belica
- Academic Research Center for Autism, Institute of Physiology, Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia
| | - Dominika Sónak Ballová
- Faculty of Civil Engineering, Slovak University of Technology in Bratislava, Bratislava, Slovakia
| | - Viktória Jankovičová
- Faculty of Natural Sciences, Comenius University Bratislava, Bratislava, Slovakia
| | - Daniela Ostatníková
- Academic Research Center for Autism, Institute of Physiology, Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia
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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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37
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Li M, Eltabbal M, Tran HD, Kuhn B. Scn2a insufficiency alters spontaneous neuronal Ca 2+ activity in somatosensory cortex during wakefulness. iScience 2023; 26:108138. [PMID: 37876801 PMCID: PMC10590963 DOI: 10.1016/j.isci.2023.108138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 07/22/2023] [Accepted: 10/02/2023] [Indexed: 10/26/2023] Open
Abstract
SCN2A protein-truncating variants (PTV) can result in neurological disorders such as autism spectrum disorder and intellectual disability, but they are less likely to cause epilepsy in comparison to missense variants. While in vitro studies showed PTV reduce action potential firing, consequences at in vivo network level remain elusive. Here, we generated a mouse model of Scn2a insufficiency using antisense oligonucleotides (Scn2a ASO mice), which recapitulated key clinical feature of SCN2A PTV disorders. Simultaneous two-photon Ca2+ imaging and electrocorticography (ECoG) in awake mice showed that spontaneous Ca2+ transients in somatosensory cortical neurons, as well as their pairwise co-activities were generally decreased in Scn2a ASO mice during spontaneous awake state and induced seizure state. The reduction of neuronal activities and paired co-activity are mechanisms associated with motor, social and cognitive deficits observed in our mouse model of severe Scn2a insufficiency, indicating these are likely mechanisms driving SCN2A PTV pathology.
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Affiliation(s)
- Melody Li
- Optical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan
| | - Mohamed Eltabbal
- Optical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan
| | - Hoang-Dai Tran
- Optical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan
| | - Bernd Kuhn
- Optical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan
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38
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Ciancone-Chama AG, Bonaldo V, Biasini E, Bozzi Y, Balasco L. Gene Expression Profiling in Trigeminal Ganglia from Cntnap2 -/- and Shank3b -/- Mouse Models of Autism Spectrum Disorder. Neuroscience 2023; 531:75-85. [PMID: 37699442 DOI: 10.1016/j.neuroscience.2023.08.028] [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: 01/19/2023] [Revised: 08/19/2023] [Accepted: 08/22/2023] [Indexed: 09/14/2023]
Abstract
Sensory difficulties represent a crucial issue in the life of autistic individuals. The diagnostic and statistical manual of mental disorders describes both hyper- and hypo-responsiveness to sensory stimulation as a criterion for the diagnosis autism spectrum disorders (ASD). Among the sensory domain affected in ASD, altered responses to tactile stimulation represent the most commonly reported sensory deficits. Although tactile abnormalities have been reported in monogenic cohorts of patients and genetic mouse models of ASD, the underlying mechanisms are still unknown. Traditionally, autism research has focused on the central nervous system as the target to infer the neurobiological bases of such tactile abnormalities. Nonetheless, the peripheral nervous system represents the initial site of processing of sensory information and a potential site of dysfunction in the sensory cascade. Here we investigated the gene expression deregulation in the trigeminal ganglion (which directly receives tactile information from whiskers) in two genetic models of syndromic autism (Shank3b and Cntnap2 mutant mice) at both adult and juvenile ages. We found several neuronal and non-neuronal markers involved in inhibitory, excitatory, neuroinflammatory and sensory neurotransmission to be differentially regulated within the trigeminal ganglia of both adult and juvenile Shank3b and Cntnap2 mutant mice. These results may help in disentangling the multifaced complexity of sensory abnormalities in autism and open avenues for the development of peripherally targeted treatments for tactile sensory deficits exhibited in ASD.
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Affiliation(s)
- Alessandra G Ciancone-Chama
- Center for Mind/Brain Sciences - CIMeC, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, TN, Italy
| | - Valerio Bonaldo
- Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Via Sommarive 9, 38123 Povo, TN, Italy
| | - Emiliano Biasini
- Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Via Sommarive 9, 38123 Povo, TN, Italy
| | - Yuri Bozzi
- Center for Mind/Brain Sciences - CIMeC, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, TN, Italy; CNR Neuroscience Institute, via Moruzzi 1, 56124 Pisa, Italy.
| | - Luigi Balasco
- Center for Mind/Brain Sciences - CIMeC, University of Trento, Piazza della Manifattura 1, 38068 Rovereto, TN, Italy.
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Binder MS, Bordey A. Semi-natural housing rescues social behavior and reduces repetitive exploratory behavior of BTBR autistic-like mice. Sci Rep 2023; 13:16260. [PMID: 37758896 PMCID: PMC10533821 DOI: 10.1038/s41598-023-43558-0] [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: 03/29/2023] [Accepted: 09/26/2023] [Indexed: 09/29/2023] Open
Abstract
Environmental enrichment confers numerous benefits when implemented in murine models and can reduce behavioral symptomatology in models of disease, such as autism spectrum disorder (ASD). However, previous work did not examine the impact of early-life environmental enrichment on each core feature of ASD. We thus implemented a social and physical enrichment at birth, modeling a semi-natural housing, and examined its impact on communicative, social, sensory, and repetitive behaviors using BTBR (autistic-like) and C57BL/6 J (B6, wildtype) mice, comparing them to standard housing conditions. We found that environmental enrichment alleviated the social deficit of juvenile BTBR mice and reduced their repetitive exploratory behavior but did not affect their rough versus smooth texture preference nor the number of maternal isolation-induced pup calls. Environmental enrichment only affected the call characteristics of B6 mice. One interpretation of these data is that early-life environmental enrichment has significant therapeutic potential to treat selective core features of ASD. Another interpretation is that reducing environmental complexity causes selective behavioral deficits in ASD-prone mice suggesting that current standard housing may be suboptimal. Overall, our data illustrate the extent to which the environment influences behavior and highlights the importance of considering housing conditions when designing experiments and interpreting behavioral results.
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Affiliation(s)
- Matthew S Binder
- Departments of Neurosurgery, and Cellular & Molecular Physiology, Wu Tsai Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA
| | - Angelique Bordey
- Departments of Neurosurgery, and Cellular & Molecular Physiology, Wu Tsai Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
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Li X, Hao S, Zou S, Tu X, Kong W, Jiang T, Chen JG. Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism. Mol Autism 2023; 14:34. [PMID: 37691105 PMCID: PMC10494400 DOI: 10.1186/s13229-023-00567-0] [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: 04/12/2023] [Accepted: 09/05/2023] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. METHODS We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice's behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. RESULTS Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. LIMITATIONS It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. CONCLUSIONS Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors.
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Affiliation(s)
- Xue Li
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, Zhejiang, People's Republic of China
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China
| | - Shishuai Hao
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, Zhejiang, People's Republic of China
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China
| | - Shimin Zou
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, Zhejiang, People's Republic of China
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China
| | - Xiaomeng Tu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, Zhejiang, People's Republic of China
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China
| | - Weixi Kong
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, Zhejiang, People's Republic of China
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China
| | - Tian Jiang
- Research Center for Translational Medicine, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, People's Republic of China
| | - Jie-Guang Chen
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, Zhejiang, People's Republic of China.
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
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Monday HR, Wang HC, Feldman DE. Circuit-level theories for sensory dysfunction in autism: convergence across mouse models. Front Neurol 2023; 14:1254297. [PMID: 37745660 PMCID: PMC10513044 DOI: 10.3389/fneur.2023.1254297] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 08/14/2023] [Indexed: 09/26/2023] Open
Abstract
Individuals with autism spectrum disorder (ASD) exhibit a diverse range of behavioral features and genetic backgrounds, but whether different genetic forms of autism involve convergent pathophysiology of brain function is unknown. Here, we analyze evidence for convergent deficits in neural circuit function across multiple transgenic mouse models of ASD. We focus on sensory areas of neocortex, where circuit differences may underlie atypical sensory processing, a central feature of autism. Many distinct circuit-level theories for ASD have been proposed, including increased excitation-inhibition (E-I) ratio and hyperexcitability, hypofunction of parvalbumin (PV) interneuron circuits, impaired homeostatic plasticity, degraded sensory coding, and others. We review these theories and assess the degree of convergence across ASD mouse models for each. Behaviorally, our analysis reveals that innate sensory detection behavior is heightened and sensory discrimination behavior is impaired across many ASD models. Neurophysiologically, PV hypofunction and increased E-I ratio are prevalent but only rarely generate hyperexcitability and excess spiking. Instead, sensory tuning and other aspects of neural coding are commonly degraded and may explain impaired discrimination behavior. Two distinct phenotypic clusters with opposing neural circuit signatures are evident across mouse models. Such clustering could suggest physiological subtypes of autism, which may facilitate the development of tailored therapeutic approaches.
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Affiliation(s)
- Hannah R. Monday
- Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States
| | | | - Daniel E. Feldman
- Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States
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Riquelme I, Hatem SM, Sabater-Gárriz Á, Montoya P. A multidimensional investigation of the relationship between skin-mediated somatosensory signals, emotion regulation and behavior problems in autistic children. Front Neurosci 2023; 17:1227173. [PMID: 37662109 PMCID: PMC10470890 DOI: 10.3389/fnins.2023.1227173] [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: 05/22/2023] [Accepted: 07/25/2023] [Indexed: 09/05/2023] Open
Abstract
Introduction Autistic children may have abnormal sensory perception, emotion dysregulation and behavior problems. The aim of this cross-sectional study was to explore the relationship between skin-mediated somatosensory signals and emotion/behavior difficulties in autistic children and adolescents, in comparison typically developing peers (TDP). Methods Thirty-eight autistic children and adolescents and 34 TDP completed a multidimensional assessment consisting of the measurement of somatosensory thresholds of touch, pain and temperature, a task on emotion knowledge and parent-reported questionnaires on sensory reactivity, emotion regulation and behavior. Results Autistic children had higher pain sensitivity, less sensory reactive behaviors and more behavior problems than their TDP. In contrast to TDP, several somatosensory thresholds of autistic children correlated with emotion regulation and behavior problems. Discussion Sensory dysfunction may affect the development of emotional processing and behavior in autistic children and adolescents. This knowledge can lay the foundation for future studies on co-occurring alterations in corresponding neural networks and for the implementation of early interventions, including sensory rehabilitation therapy, for promoting regulated behaviors in autistic children and adolescents.
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Affiliation(s)
- Inmaculada Riquelme
- Research Institute on Health Sciences (IUNICS-IdISBa), University of the Balearic Islands, Palma de Mallorca, Spain
- Department of Nursing and Physiotherapy, University of the Balearic Islands, Palma de Mallorca, Spain
| | - Samar M. Hatem
- Faculty of Medicine, STIMULUS Research Group (reSearch and TeachIng neuroModULation Uz bruSsel), Vrije Universiteit Brussel, Brussels, Belgium
- Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium
| | - Álvaro Sabater-Gárriz
- Research Institute on Health Sciences (IUNICS-IdISBa), University of the Balearic Islands, Palma de Mallorca, Spain
- Department of Nursing and Physiotherapy, University of the Balearic Islands, Palma de Mallorca, Spain
- Balearic ASPACE Foundation, Marratxí, Spain
| | - Pedro Montoya
- Research Institute on Health Sciences (IUNICS-IdISBa), University of the Balearic Islands, Palma de Mallorca, Spain
- Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo, Brazil
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Binder MS, Bordey A. The Novel Somatosensory Nose-Poke Adapted Paradigm (SNAP) Is an Effective Tool to Assess Differences in Tactile Sensory Preferences in Autistic-Like Mice. eNeuro 2023; 10:ENEURO.0478-22.2023. [PMID: 37596047 PMCID: PMC10470849 DOI: 10.1523/eneuro.0478-22.2023] [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: 11/22/2022] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/20/2023] Open
Abstract
One of the most prevalent deficits in autism spectrum disorder (ASD) are sensitivities to sensory stimuli. Despite the prevalence of sensory deficits in autism, there are few paradigms capable of easily assessing sensory behaviors in ASD-like mouse models. We addressed this need by creating the Somatosensory Nose-poke Adapted Paradigm (SNAP), which consists of an elevated platform with 6 holes in the center, half of which are lined with sandpaper and half are smooth, requiring mice to use their whiskers to sense the texture. The SNAP paradigm assesses tactile sensory preferences as well as stereotypy, anxiety, and locomotion. We used two wild-type (neurotypical) mouse strains, C57BL/6J (C57) inbred and CD-1 outbred mice, and two ASD mouse models, BTBR (a model of idiopathic ASD) and Cntnap2 -/- mice (a model of syndromic ASD). We found that both ASD models produced more nose pokes into the rough condition than the smooth condition, suggesting an increased preference for complex tactile stimulation when compared with the neurotypical groups, wherein no differences were observed. Furthermore, we found increased stereotypy and time spent in the center, suggestive of decreased anxiety, only for BTBR mice compared with the other mouse strains. Overall, SNAP is an easy to implement task to assess the degree of preference for complex tactile stimulation in ASD mouse models that can be further modified to exclude possible confounding effects of novelty or anxiety on the sensory preferences.
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Affiliation(s)
- Matthew S Binder
- Departments of Neurosurgery and Cellular and Molecular Physiology, Wu Tsai Institute, Yale School of Medicine, New Haven, CT 06520-8082
| | - Angelique Bordey
- Departments of Neurosurgery and Cellular and Molecular Physiology, Wu Tsai Institute, Yale School of Medicine, New Haven, CT 06520-8082
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Cardon G, Bradley M. Uncertainty, Sensory Processing, and Stress in Autistic Children During the COVID-19 Pandemic. RESEARCH IN AUTISM SPECTRUM DISORDERS 2023; 106:102202. [PMID: 37484881 PMCID: PMC10361392 DOI: 10.1016/j.rasd.2023.102202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
BACKGROUND COVID-19 increased uncertainty for most and was especially disruptive to autistic people and their families, due in part to tendencies toward intolerance for uncertainty across this population. As such, COVID presented a natural experiment of uncertainty and its correlates in autism. Previous reports have shown associations between intolerance of uncertainty, sensory difficulty, and stress. AIMS We investigated changes in sensory difficulties and stress associated with COVID-related increases in uncertainty. METHODS AND PROCEDURES Primary caregivers of 47 autistic children (ages 6-15) completed online surveys containing questions about demographics, experiences, and supports received during the pandemic. Additionally, caregivers filled out measures of intolerance of uncertainty and sensory processing for both pre- and during-COVID conditions. OUTCOMES AND RESULTS Eighty nine percent of children had significant sensory difficulties before the pandemic. This group showed significant increases in sensory difficulties and intolerance of uncertainty during the pandemic. These changes were significantly correlated with each other, suggesting that as uncertainty increased so did sensory difficulties. Disruption to routine was also significantly correlated with sensory differences and child, household, and parent stress. CONCLUSIONS AND IMPLICATIONS Our findings add to fundamental understanding of the relationship between uncertainty, sensory processing, and stress by leveraging a natural experiment in increased uncertainty. These results have the potential to contribute to improved supports for autistic individuals in clinical, educational, home, and other settings.
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Affiliation(s)
- Garrett Cardon
- Department of Communication Disorders, Brigham Young University, Provo, UT
| | - Mollie Bradley
- Department of Communication Disorders, Brigham Young University, Provo, UT
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Isakoglou C, Haak KV, Wolfers T, Floris DL, Llera A, Oldehinkel M, Forde NJ, Oakley BFM, Tillmann J, Holt RJ, Moessnang C, Loth E, Bourgeron T, Baron-Cohen S, Charman T, Banaschewski T, Murphy DGM, Buitelaar JK, Marquand AF, Beckmann CF. Fine-grained topographic organization within somatosensory cortex during resting-state and emotional face-matching task and its association with ASD traits. Transl Psychiatry 2023; 13:270. [PMID: 37500630 PMCID: PMC10374902 DOI: 10.1038/s41398-023-02559-3] [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] [Revised: 03/26/2023] [Accepted: 07/04/2023] [Indexed: 07/29/2023] Open
Abstract
Sensory atypicalities are particularly common in autism spectrum disorders (ASD). Nevertheless, our knowledge about the divergent functioning of the underlying somatosensory region and its association with ASD phenotype features is limited. We applied a data-driven approach to map the fine-grained variations in functional connectivity of the primary somatosensory cortex (S1) to the rest of the brain in 240 autistic and 164 neurotypical individuals from the EU-AIMS LEAP dataset, aged between 7 and 30. We estimated the S1 connection topography ('connectopy') at rest and during the emotional face-matching (Hariri) task, an established measure of emotion reactivity, and accessed its association with a set of clinical and behavioral variables. We first demonstrated that the S1 connectopy is organized along a dorsoventral axis, mapping onto the S1 somatotopic organization. We then found that its spatial characteristics were linked to the individuals' adaptive functioning skills, as measured by the Vineland Adaptive Behavior Scales, across the whole sample. Higher functional differentiation characterized the S1 connectopies of individuals with higher daily life adaptive skills. Notably, we detected significant differences between rest and the Hariri task in the S1 connectopies, as well as their projection maps onto the rest of the brain suggesting a task-modulating effect on S1 due to emotion processing. All in all, variation of adaptive skills appears to be reflected in the brain's mesoscale neural circuitry, as shown by the S1 connectivity profile, which is also differentially modulated during rest and emotional processing.
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Affiliation(s)
- Christina Isakoglou
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands.
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands.
| | - Koen V Haak
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
| | - Thomas Wolfers
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department of Psychology, University of Oslo, Oslo, Norway
| | - Dorothea L Floris
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
- Methods of Plasticity Research, Department of Psychology, University of Zurich, Zurich, Switzerland
| | - Alberto Llera
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
| | - Marianne Oldehinkel
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
| | - Natalie J Forde
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
| | - Bethany F M Oakley
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Julian Tillmann
- Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland
| | - Rosemary J Holt
- Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
| | - Carolin Moessnang
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Department of Applied Psychology, SRH University, Heidelberg, Germany
| | - Eva Loth
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Thomas Bourgeron
- Human Genetics and Cognitive Functions, Institut Pasteur, Université de Paris, Paris, France
| | - Simon Baron-Cohen
- Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
| | - Tony Charman
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Tobias Banaschewski
- Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Declan G M Murphy
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Jan K Buitelaar
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, Netherlands
| | - Andre F Marquand
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
| | - Christian F Beckmann
- Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, Netherlands
- Department for Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
- Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom
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Zeisel A, Thiel T, Gaigg SB, Roessner V, Ring M. Validation of the German Glasgow Sensory Questionnaire and replication of sensory processing differences in students with higher and lower Autism-Spectrum Quotient. BMC Psychiatry 2023; 23:426. [PMID: 37316778 DOI: 10.1186/s12888-023-04903-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 05/24/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND The Glasgow Sensory Questionnaire (GSQ) gives insight into sensory processing differences (hypo- and hyper-sensitivity across modalities), which is a clinically defining characteristic of autism spectrum disorder (ASD). Because there is no validated German version of this instrument, this study aimed at validating the German GSQ. Further, a replication of the GSQ's sensory processing differences was intended. METHODS University students of Technische Universität or Universitätsklinikum in Dresden, Germany, were recruited via email distribution or the university homepage and 297 German-speaking students completed the online survey, comprising the German GSQ, Autism-Spectrum Quotient (AQ) and Symptom-Checklist (SCL-90). For validation of the German GSQ, confirmatory factor analyses followed by exploratory factor analyses were applied. RESULTS The German GSQ has moderate to low validity, good to acceptable reliability, and a different internal structure from the original GSQ. Replicating the sensory processing differences in students with higher and lower AQ was not successful. CONCLUSIONS Results indicate that the GSQ, developed especially for individuals with ASD, is less informative for the general population if there are not enough individuals with higher AQ scores in the sample.
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Affiliation(s)
- Annalena Zeisel
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany
| | - Tobias Thiel
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany
| | - Sebastian B Gaigg
- Autism Research Group, Department of Psychology, City, University of London, London, UK
| | - Veit Roessner
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany
| | - Melanie Ring
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany.
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Rasmussen RN, Asiminas A, Carlsen EMM, Kjaerby C, Smith NA. Astrocytes: integrators of arousal state and sensory context. Trends Neurosci 2023; 46:418-425. [PMID: 37003933 PMCID: PMC10192111 DOI: 10.1016/j.tins.2023.03.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/24/2023] [Accepted: 03/05/2023] [Indexed: 04/01/2023]
Abstract
The integration of external information with the internal state of the body is central to the survival of virtually every multicellular organism. However, a complete picture of the mechanisms that govern this process is lacking. In this opinion article, we synthesize evidence demonstrating that astrocytes sense the momentary arousal state - through neuromodulator release - as well as the sensory inputs - through local synaptic activity - and respond to them with changes in calcium (Ca2+) signaling. We hypothesize that astrocytes integrate sensory signals with the internal state and that this process is necessary to secure optimal behavior. Finally, we argue that dysfunctional astrocytic Ca2+ signaling could be an underlying factor in disorders characterized by disrupted sensory processing.
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Affiliation(s)
- Rune Nguyen Rasmussen
- Center for Translational Neuromedicine, University of Copenhagen, 2200 Copenhagen, Denmark.
| | - Antonis Asiminas
- Center for Translational Neuromedicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | | | - Celia Kjaerby
- Center for Translational Neuromedicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Nathan Anthony Smith
- Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA.
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Olivier P, Gressens P, Barthelemy C. Neurodevelopmental disorders: research and interventions beyond classifications. J Neural Transm (Vienna) 2023; 130:181-184. [PMID: 36757475 DOI: 10.1007/s00702-023-02596-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 01/27/2023] [Indexed: 02/10/2023]
Affiliation(s)
- Paul Olivier
- Autism and NDD Scientific Interest Group (GIS Autisme et TND), Paris, France.
| | - Pierre Gressens
- Autism and NDD Scientific Interest Group (GIS Autisme et TND), Paris, France
- Université Paris Cité, NeuroDiderot, Inserm, Paris, France
| | - Catherine Barthelemy
- Autism and NDD Scientific Interest Group (GIS Autisme et TND), Paris, France
- Faculty of Medicine, University of Tours, Tours, France
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Wang CF, Yang JW, Zhuang ZH, Hsing HW, Luhmann HJ, Chou SJ. Activity-dependent feedback regulation of thalamocortical axon development by Lhx2 in cortical layer 4 neurons. Cereb Cortex 2023; 33:1693-1707. [PMID: 35512682 DOI: 10.1093/cercor/bhac166] [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: 01/12/2022] [Revised: 04/04/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Establishing neuronal circuits requires interactions between pre- and postsynaptic neurons. While presynaptic neurons were shown to play instructive roles for the postsynaptic neurons, how postsynaptic neurons provide feedback to regulate the presynaptic neuronal development remains elusive. To elucidate the mechanisms for circuit formation, we study the development of barrel cortex (the primary sensory cortex, S1), whose development is instructed by presynaptic thalamocortical axons (TCAs). In the first postnatal weeks, TCA terminals arborize in layer (L) 4 to fill in the barrel center, but it is unclear how TCA development is regulated. Here, we reported that the deletion of Lhx2 specifically in the cortical neurons in the conditional knockout (cKO) leads to TCA arborization defects, which is accompanied with deficits in sensory-evoked and spontaneous cortical activities and impaired lesion-induced plasticity following early whisker follicle ablation. Reintroducing Lhx2 back in L4 neurons in cKO ameliorated TCA arborization and plasticity defects. By manipulating L4 neuronal activity, we further demonstrated that Lhx2 induces TCA arborization via an activity-dependent mechanism. Additionally, we identified the extracellular signaling protein Sema7a as an activity-dependent downstream target of Lhx2 in regulating TCA branching. Thus, we discovered a bottom-up feedback mechanism for the L4 neurons to regulate TCA development.
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Affiliation(s)
- Chia-Fang Wang
- Neuroscience Program of Academia Sinica (NPAS), Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - Jenq-Wei Yang
- Institute of Physiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Zi-Hui Zhuang
- Neuroscience Program of Academia Sinica (NPAS), Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - Hsiang-Wei Hsing
- Neuroscience Program of Academia Sinica (NPAS), Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - Heiko J Luhmann
- Institute of Physiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Shen-Ju Chou
- Neuroscience Program of Academia Sinica (NPAS), Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
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Mavragani A, Eungpinichpong W, Wu H, Aonsri C. Physiological and Psychological Effects of Parent-Delivered Traditional Thai Massage in Children With Autism: Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2023; 12:e41839. [PMID: 36753320 PMCID: PMC9947755 DOI: 10.2196/41839] [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: 08/11/2022] [Revised: 12/09/2022] [Accepted: 12/29/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Although many autistic children receive massage as a complementary therapy, it is not included in evidence-based practice for autism because evidence of its efficacy is lacking. Further, prior studies have failed to identify objective indicators of core symptoms or elucidate their mechanisms. OBJECTIVE We developed a parent-delivered traditional Thai massage (TTM) intervention for children with autism, aiming to experimentally determine whether children with autism truly experience positive effects from parent-delivered TTM and determine possible mechanisms of the observed effects. METHODS A 2-armed, parallel randomized controlled trial was conducted between February 2022 and June 2022. Forty-eight children with autism (aged 7-12 years) were recruited from the Hainan Special Education School and randomly assigned to either a parental TTM or control group at a ratio of 1:1 based on random numbers generated with Online Research Randomizer. The generated sequences were concealed in an opaque envelope. Individuals in the parental TTM group received 16 parent-delivered TTM sessions over 8 weeks at the school's health room after school, and the control group maintained a normal daily routine. Outcomes were assessed on admission, after 8 weeks, and at a 2-month follow-up and included the effect of massage treatment on autism symptoms, measured with the Autism Treatment Evaluation Checklist score (evaluated by parents and a blinded teacher), physiological parameters (ie, heart rate variability and gait), and the Parenting Stress Index, Fourth Edition-Short Form. RESULTS We finished all data collection on June 20, 2022. Data analysis will be started, and we expect to publish results in 2023. CONCLUSIONS This study will provide further evidence for massage treatment of autism and provide support for family-based care. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2100051355; https://tinyurl.com/3dwjxsw5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/41839.
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Affiliation(s)
| | - Wichai Eungpinichpong
- Research Center in Back, Neck, Other Joint Pain and Human Performance, Division of Physical Therapy, Khon Kaen University, Khon Kaen, Thailand
| | - Hua Wu
- School of Physical Education, Hainan Normal University, Haikou, China
| | - Chanada Aonsri
- Department of Special Education, Khon Kaen University Demonstration School, Khon Kaen University, Khon Kaen, Thailand
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