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The authors grant unrestricted publishing and distribution rights to the publisher. The electronic versions of the chapters are published under Creative Commons Attribution-NonCommercial 4.0 International (<a href="https://creativecommons.org/licenses/by-nc/4.0/" target="_blank" rel="noopener">CC BY-NC 4.0</a>). Users are allowed to share and adapt the chapters for any non-commercial purposes as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source. The books in their entirety are subject to copyright by the publisher. The reproduction, modification, republication and display of the books in their entirety, in any form, by anyone, for commercial purposes are strictly prohibited without the written consent of the publisher.</p> Front Matter https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-front-matter AUTISM SPECTRUM DISORDERS Andreas M. Grabrucker, PhD (Editor) Copyright (c) 2021 Exon Publications https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 10.36255/exonpublications.autismspectrumdisorders.2021.frontmatter Foreword https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-foreword <p>More individuals are diagnosed with an autism spectrum disorder (ASD) today than ever before. The term ASD encompasses conditions previously referred to as autistic disorder, Asperger’s syndrome, or perversive developmental disorder not otherwise specified. The severity of ASD varies from mild to severe, and individuals with ASD differ significantly in the features they present. However, the core symptoms that include social, communication, and behavioral challenges are generally present. Despite significant research efforts, the exact causes remain poorly understood for many cases of ASD, and a combination of genetic and non-genetic factors seems likely. However, ASD occurs independently of race, ethnicity, or social background. Research in the field of ASD aims at answering several main questions: How can we diagnose ASD? What are the clinical features of ASD and their underlying pathomechanisms? What are the causative factors of ASD? How can we treat and prevent ASD? This book presents the current state of the art answers to all these questions. With contributions from clinicians, and translational and basic researchers in the field of ASD, this book provides a brief but comprehensive overview of ASD, including causes, pathology, diagnosis, and treatment. <a href="https://exonpublications.com/index.php/exon/article/view/409/749">CONTINUE READING.....</a></p> Tobias M. Böckers Copyright (c) 2021 Tobias M. Böckers https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 vii vii 10.36255/exonpublications.autismspectrumdisorders.2021.foreword Preface https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-preface <p>Autism spectrum disorders (ASD) are developmental disorders. While intellectual and sometimes physical disabilities can be features of ASD, first and foremost, having a developmental disorder simply means that individuals with ASD develop differently. These differences are mainly present in social interaction, communication, and sensory processing and become visible through a wide variety of behavioral responses that differ from individuals without ASD. However, the term “spectrum” implies that individuals with ASD are affected to varying degrees. They can also display a range of features and possible comorbidities associated with ASD. Dr. Leo Kanner published the first formal description of the behavioral differences in 1943. He described 11 children, mostly boys, and depicted the essential features of autism, all of which are still present in current diagnostic tools. At the same time, Hans Asperger, an Austrian pediatrician, was working with children displaying similar but milder features. Initially termed “autism” or “Asperger’s syndrome” after Hans Asperger, the name autism spectrum disorder was adopted in 2013.Although the defining features of ASD remain essentially the same since their clinical description in 1943, we still do not fully know what causes ASD. However, researchers have gained extensive insights into possible pathomechanisms (genetic and non-genetic) even at the molecular level of cells. <a href="https://exonpublications.com/index.php/exon/article/view/408/748">CONTINUE READING.....</a></p> Andreas M. Grabrucker, PhD Copyright (c) 2021 Andreas M. Grabrucker, PhD https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 ix x 10.36255/exonpublications.autismspectrumdisorders.2021.preface Contributors https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-contributors <p><strong>AKIRA IMAMURA, MD, PHD</strong><br>Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan</p> <p><strong>ANDREAS M. GRABRUCKER, PHD</strong><br>Department of Biological Sciences, University of Limerick, Limerick, Ireland</p> <p><strong>ANN KATRIN SAUER, MSC</strong><br>Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland</p> <p><strong>BRAM SIZOO, PHD</strong><br>Dimence Institute of Mental Health, Deventer, The Netherlands</p> <p><strong>CHIARA ALESSIA DE BENEDICTIS, MSC</strong><br>Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland</p> <p><strong>CRISTIANO STORNI, PHD</strong><br>Department of Computer Science and Information System, University of Limerick, Ireland</p> <p><strong>ELLA LOBREGT-VAN BUUREN, MSC</strong><br>Dimence Institute of Mental Health, Deventer, The Netherlands</p> <p><strong>GISELLE C. WONG, MSC</strong><br>School of Biological Sciences, University of Auckland, Auckland, New Zealand</p> <p><strong>HIROKI OZAWA, MD, PHD</strong><br>Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan</p> <p><strong>JANELLE E. STANTON, MSC</strong><br>Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland</p> <p><strong>JOHANNA M. MONTGOMERY, PHD</strong><br>Department of Physiology, University of Auckland, Auckland, New Zealand</p> <p><strong>MARJOLIJN HOEKERT, PHD</strong><br>Mental Health Service Organization GGZ Noord-Holland-Noord, Heiloo, The Netherlands</p> <p><strong>MICHAEL W. TAYLOR, PHD</strong><br>Centre for Brain Research, University of Auckland, Auckland, New Zealand</p> <p><strong>NAOKI YAMAMOTO, MD</strong><br>Department of Neuropsychiatry, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan</p> <p><strong>RONAN LORDAN, PHD</strong><br>Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</p> <p><strong>RYOICHIRO IWANAGA, PHD</strong><br>School of Health Science, Faculty of Medicine, Nagasaki University, Nagasaki, Japan</p> <p><strong>RYOSUKE MATSUZAKA, MD, PHD</strong><br>Department of Neuropsychiatry, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan</p> <p><strong>SADAO OTSUKA, PHD</strong><br>Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan</p> <p><strong>SAKSHI HANS, MSC</strong><br>Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland</p> <p><strong>SAYAKA KAWAKAMI, PHD</strong><br>National Institute of Occupational Safety and Health Japan, Nagao, Tama-Ku, Kawasaki, Japan</p> <p><strong>SHINJI KANEGAE MD, PHD</strong><br>Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan</p> <p><strong>YA WEN, PHD</strong><br>Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA</p> <p><strong>YOSHIRO MORIMOTO, MD, PHD</strong><br>Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan</p> <p><strong>YUAN YAO, PHD</strong><br>Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan</p> List of Contributors Copyright (c) 2021 Chris Morais https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 xi xii 10.36255/exonpublications.autismspectrumdisorders.2021.contributors Autism Spectrum Disorders: Etiology and Pathology https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-etiology-pathology <p><strong>ABSTRACT</strong></p> <p>Autism spectrum disorders (ASD) are a group of neurodevelopmental diseases. The cause of ASD is unknown, but several genetic and non-genetic risk factors have been characterized that, alone or in combination, are implicated in the development of ASD. Currently, no diagnostic biomarkers are available, and the diagnosis of ASD is based on typical features that include repetitive behaviors, and impaired social communication and interaction. Several pathomechanisms such as alterations in brain development and function, and synaptic defects have been proposed to contribute to these behaviors. In addition, processes outside the central nervous system may contribute to, or modify, the clinical phenotype and severity. This chapter summarizes the clinical features of ASD, highlights the important genetic and non-genetic risk factors for ASD, and introduces the current knowledge around the pathological processes within and outside the brain.</p> Ann Katrin Sauer, MSC Janelle Stanton, MSC Sakshi Hans, MSC Andreas Grabrucker, PHD Copyright (c) 2021 Ann Katrin Sauer, Janelle Stanton, Sakshi Hans, Andreas Grabrucker https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 1 15 10.36255/exonpublications.autismspectrumdisorders.2021.etiology Autism Spectrum Disorders: Diagnosis and Treatment https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-diagnosis-treatment <p><strong>ABSTRACT</strong></p> <p>The diagnostic criteria and treatment approaches of autism spectrum disorders (ASD) have changed greatly over the years. Currently, diagnosis is conducted mainly by observational screening tools that measure a child’s social and cognitive abilities. The two main tools used in the diagnosis of ASD are DSM-5 and M-CHAT, which examine persistent deficits in interaction and social communication, and analyze responses to “yes/no” items that cover different developmental domains to formulate a diagnosis. Treatment depends on severity and comorbidities, which can include behavioral training, pharmacological use, and dietary supplement. Behavior-oriented treatments include a series of programs that aim to re-condition target behaviors, and develop vocational, social, cognitive, and living skills. However, to date, no single or combination treatments have been able to reverse ASD completely. This chapter provides an overview of the current diagnostic and treatment strategies of ASD.</p> Ronan Lordan, PHD Cristiano Storni, PHD Chiara Alessia De Benedictis, MSC Copyright (c) 2021 Ronan Lordan, Cristiano Storni, Chiara Alessia De Benedictis https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 17 32 10.36255/exonpublications.autismspectrumdisorders.2021.diagnosis Autism, Adverse Events, and Trauma https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-trauma <p><strong>ABSTRACT</strong></p> <p>Clinical and scientific data show a higher risk of adverse events and trauma in people with an autism spectrum disorder (ASD). These experiences are, however, often undiagnosed and untreated in autism. Diagnosing trauma- and autism-related symptoms is complicated due to the overlap between these two. Several pitfalls and points of attention can be mentioned. This chapter highlights the importance of recognizing trauma-related symptoms at an early phase and start of trauma treatment. It also provides an overview of the current knowledge about the feasibility and effectiveness of treatment of trauma-related symptoms in people with ASD. Simultaneous training of self- and emotion regulation skills, taking into account autistic features, is recommended.</p> Ella Lobregt-van Buuren, MSC Marjolijn Hoekert, PHD Bram Sizoo, PHD Copyright (c) 2021 Ella Lobregt-van Buuren, Marjolijn Hoekert, Bram Sizoo https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 33 42 10.36255/exonpublications.autismspectrumdisorders.2021.trauma Multisensory Processing in Autism Spectrum Disorders https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-multisensory-processing <p><strong>ABSTRACT</strong>&nbsp;</p> <p>Regarding the atypical characteristics of cognition and information processing in individuals with autism spectrum disorder (ASD), recent focus has been centered around fundamental processing, such as multisensory integration (MSI). Experimental studies have reported atypical MSI, especially audio-visual integration, in both children and adults with ASD using social (e.g., faces and voices) and nonsocial stimuli (e.g., flashes and beeps). Furthermore, there has been a gradual increase in the understanding of the behavioral (e.g., higher temporal resolution) and neural mechanisms (e.g., impaired phase alignment of neuro-oscillations) underlying atypical MSI in ASD. Previous studies have proposed that prominent deficits in social cognition and interactions (i.e., higher-order functions) are influenced and/or induced by atypicalities in MSI (i.e., lower-order function). Thus, interventions targeting MSI may promote social cognition, likely resulting in better outcomes in adulthood in individuals with ASD. This chapter describes current knowledge regarding multisensory processing in ASD and future perspectives on relevant research and practices. We highlight the value of focusing on MSI for understanding the clinical characteristics of ASD and possible interventions targeting MSI for this population.</p> <p>&nbsp;</p> Sayaka Kawakami, PHD Sadao Otsuka, PHD Copyright (c) 2021 Sayaka Kawakami, Sadao Otsuka https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 43 54 10.36255/exonpublications.autismspectrumdisorders.2021.multisensoryprocessing Atypical Sensory Characteristics in Autism Spectrum Disorders https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-atypical-sensory-characteristics <p><strong>ABSTRACT</strong>&nbsp;</p> <p>Autism spectrum disorders (ASD) are characterized by atypical cognitive, social, emotional, and perceptual functioning. An increasing body of evidence suggests that patients with ASD exhibit atypical perceptual and information processing in the auditory, visual, and tactile domains. However, the detailed characteristics of this atypical sensory functioning have not been fully elucidated. This chapter provides a comprehensive review of recent research into sensory processing in individuals with ASD, using a range of neuropsychological and neurophysiological techniques. Electroencephalography studies have reported atypical electrophysiological findings during sensory processing of visual, auditory, and tactile stimulation in individuals with ASD. In addition, functional magnetic resonance imaging studies have begun to elucidate the neural areas underlying these characteristic differences in sensory functioning. Several approaches, including environmental design, and support for parents and teachers to understand and respond to atypical sensory characteristics associated with ASD have been developed. Increasing understanding of the neurobiological processes underlying sensory problems in patients with ASD will aid the development of new treatment approaches.</p> Yoshiro Morimoto, MD, PHD Akira Imamura, MD, PHD Naoki Yamamoto, MD Shinji Kanegae, MD, PHD Hiroki Ozawa, MD, PHD Ryoichiro Iwanaga, PHD Copyright (c) 2021 Yoshiro Morimoto https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 55 66 10.36255/exonpublications.autismspectrumdisorders.2021.atypicalsensorycharacteristics Genetic Overlap Among Autism Spectrum Disorders and Other Neuropsychiatric Disorders https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-genetic-overlap <p><strong>ABSTRACT</strong></p> <p>Neuropsychiatric disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, and major depressive disorder tend to be classified as distinct entities. However, increasing evidence suggests that there are overlaps among these disorders in terms of their genetic risk factors. For example, chromosomal microdeletions and duplications in 16p11.2 have been reported in individuals with ASD as well as those with schizophrenia and intellectual disability, and common copy number variations have been reported in ASD, schizophrenia, and ADHD. Genome-wide association studies have also revealed common risk variants among ASD, ADHD, bipolar disorder, depression, and schizophrenia. Moreover, next-generation sequencing techniques have revealed overlap in&nbsp;<em>de novo</em>&nbsp;mutations among ASD, schizophrenia, and intellectual disability. Together, these results indicate that there are shared genetic risks across a range of different disorders. The findings from these studies converge on postsynaptic proteins, such as L-type calcium channels and proteins involved in N-methyl-D-aspartate signaling and indicate that synaptic mechanisms may underlie many different neuropsychiatric disorders, including ASD. Future studies are likely to reveal further shared mechanisms and contribute to the development of therapies for these disorders.</p> Yoshiro Morimoto, MD, PHD Naoki Yamamoto, MD Shinji Kanegae, MD, PHD Ryosuke Matsuzaka, MD, PHD Hiroki Ozawa, MD, PHD Akira Imamura, MD, PHD Copyright (c) 2021 Yoshiro Morimoto https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 67 78 10.36255/exonpublications.autismspectrumdisorders.2021.geneticoverlap Autism Spectrum Disorders: The Mitochondria Connection https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-mitochondria <p><strong>ABSTRACT</strong>&nbsp;</p> <p>Autism spectrum disorders (ASD) are considered neurodevelopmental disorders characterized by restricted patterns of behavior and difficulties with communication and social interaction. Cumulative evidence suggests ASD have a wide range of co-occurring multisystemic conditions beyond the primary diagnosis. However, the etiology of ASD still eludes us. Finding a key cellular process responsible for the cognitive features, specific behaviors, and abnormalities in multiple systems presents major challenges to researchers. Mitochondria are multifaceted organelles involved in many cellular functions. The relationship between mitochondria and ASD has been studied for many years. Mitochondria may play a crucial role in ASD pathophysiology. By reviewing the connections between mitochondria and ASD from genes, pathways, biological activities, and clinical manifestations, we hope to provide clues for future studies that elucidate the biological basis of ASD symptoms and behaviors.</p> Ya Wen, PHD Yuan Yao, PHD Copyright (c) 2021 Ya Wen https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 79 93 10.36255/exonpublications.autismspectrumdisorders.2021.mitochondria The Gut-Microbiota-Brain Axis in Autism Spectrum Disorder https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-gut-microbiota-brain-axis <p><strong>ABSTRACT</strong>&nbsp;</p> <p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions/behaviors and increased stereotypical repetitive behavior. Gastrointestinal disorders, ranging from severe constipation to diarrhea, are particularly prevalent for people on the autism spectrum, which may relate to an underlying dysbiosis (breakdown or imbalance) in the gut microbial community. Many studies have also identified changes in the gut microbiome in ASD compared to neurotypical cohorts in animal models and human populations. Microbial probiotics to help revert these gut microbial changes have been tested in animal models of ASD. Some have shown reversal of ASD behaviors and modulating the integrity of the gastrointestinal epithelial barrier. The gut-microbiota-brain axis has been described as a multidirectional communication channel between the three systems: the gut, gut microbes, and the brain, but whether these gastrointestinal microbes play a role in the context of ASD and whether they can be harnessed as a target for gastrointestinal therapies in humans is yet to be determined.</p> Giselle C. Wong, MSC Johanna M. Montgomery, PHD Michael W. Taylor, PHD Copyright (c) 2021 Giselle Wong, Johanna Montgomery, Mike Taylor https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 95 113 10.36255/exonpublications.autismspectrumdisorders.2021.gutmicrobiota Index https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-index Index Copyright (c) 2021 Exon Publications https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 115 117 10.36255/exonpublications.autismspectrumdisorders.2021.index About the Editor https://exonpublications.com/index.php/exon/article/view/autism-spectrum-disorders-editor <p><img src="https://exonpublications.com/public/site/images/cmorais/editor-photo-150.jpg" alt="Andreas M. Grabrucker, PhD" width="150" height="169"></p> <p>Andreas M. Grabrucker, PhD, is a tenured Associate Professor at the University of Limerick, Ireland, and a member of the Bernal Institute, where he acts as the Lead for the Bio Materials Research Cluster. Dr. Grabrucker is also a member of the Health Research Institute of the University of Limerick. Dr. Grabrucker received his MSc in Biology from the Technical University of Munich, Germany, and his PhD in Molecular Medicine from Ulm University, Germany. He continued his research in the United States at Stanford University, Stanford School of Medicine. From 2011 to 2016, he was a tenure-track Assistant Professor and Executive Director of the Neurocenter of Ulm University. In 2019, he was awarded a guest professorship at the University of Modena and Reggio Emilia, Italy. His primary research focus is translational neuroscience in autism spectrum disorders. He has generated model systems to understand neurobiological processes of brain development and function and explores the use of nanotechnology for targeted drug delivery into the brain. He has published over 60 peer-reviewed articles and 13 book chapters. He is the author of the book “Eco-Neurobiology and how the environment shapes our brain”, and the first textbook detailing the role of “Biometals in Autism Spectrum Disorders.”</p> Andreas M. Grabrucker, PhD (Editor) Copyright (c) 2021 Chris Morais https://creativecommons.org/licenses/by-nc/4.0 2021-08-20 2021-08-20 10.36255/exonpublications.autismspectrumdisorders.2021.editor