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<p> A seminal book forcing a much-needed change in the way in which we think about autism. Impressively well-researched and well-argued. A 'must-read' for all autism researchers. <p>--Prof. Jill Boucher, City University, London, UK <p> <p> <p> For too long, clinicians and researchers have treated autism as a distinct syndrome. Waterhouse challenges this view with a scholarly review of evidence. Yes, there are children with pervasive developmental difficulties, but no, they are not a homogenous group - either in terms of symptoms, or underlying causes. <p>--Prof. Dorothy Bishop, University of Oxford, UK

<p> A seminal book forcing a much-needed change in the way in which we think about autism. Impressively well-researched and well-argued. A 'must-read' for all autism researchers. <p>--Prof. Jill Boucher, City University, London, UK <p> <p> <p> For too long, clinicians and researchers have treated autism as a distinct syndrome. Waterhouse challenges this view with a scholarly review of evidence. Yes, there are children with pervasive developmental difficulties, but no, they are not a homogenous group - either in terms of symptoms, or underlying causes. <p>--Prof. Dorothy Bishop, University of Oxford, UK <p> <p> <p> Waterhouse squarely tackles the elephant in the room in autism research; the complex heterogeneity seen at all levels of analysis. She provides a compelling and scholarly rationale for accepting this heterogeneity and exploring it as the only way to gain a deeper insight into the disorder. The argument is sustained, learned and comprehensive. We shall all be dealing with this challenge for decades. <p>Peter Szatmari, McMaster University, Canada

A seminal book forcing a much-needed change in the way in which we think about autism. Impressively well-researched and well-argued. A 'must-read' for all autism researchers. --Prof. Jill Boucher, City University, London, UK This book by Lynn Waterhouse will ruffle some feathers, with its bold conclusion that there is clear detriment to maintaining the diagnostic category of autism spectrum disorder. However, the evidence she presents is compelling. In every domain she investigates - symptoms, neurobiology, etiology, correlates - she finds that there is considerable heterogeneity in autism. As well as striking differences among children with an ASD diagnosis, there is also a lack of specificity in symptoms and causes. For instance, genetic variants and environmental risks that are associated with increased risk of autism are also associated with other neurodevelopmental disorders. Waterhouse is not denying that there are children with severe developmental difficulties involving social interaction, communication and stereotyped behaviours. Rather, she is questioning whether their needs are best served by grouping them all together under a single umbrella label. Her view is that research efforts directed at finding a unifying theory of autism are misguided, and that we should be focusing on symptoms rather than an abstract diagnostic category that can obfuscate rather than clarify our understanding. --Prof. Dorothy Bishop, University of Oxford, UK Waterhouse squarely tackles the elephant in the room in autism research; the complex heterogeneity seen at all levels of analysis. She provides a compelling and scholarly rationale for accepting this heterogeneity and exploring it as the only way to gain a deeper insight into the disorder. The argument is sustained, learned and comprehensive. We shall all be dealing with this challenge for decades. Peter Szatmari, McMaster University, Canada Rethinking Autism is a book that needed to be written, and Waterhouse has written it extremely well. The central claim of the book that researchers must move beyond the construct of the ICD or DSM diagnosis of autism is very well supported, and, in my view, nearly irrefutable. The book makes clear that understanding the varied risk factors for autism symptoms and the variable pathogenesis of autism symptoms is crucial with respect to treatment implications and outcome. Some researchers have reported that a minority of boys with the fragile X premutation have autism spectrum disorder (as is illustrated by a clinical description of twins in the book). However, it is important to note that studies making a premutation-autism link have been affected by sampling bias, and the actual risk for intellectual or behavioral disability in this population, though yet to be definitively established, is probably quite low. Further, though the book correctly notes that the vast majority of individuals with the fragile X premutation have normal intellectual abilities and no autism symptoms, the book's statements on p. 53 and 193 errantly identify excess FMR1 messenger RNA found in association with the fragile X permutation as a cause for autism symptoms. While there is significant evidence that the lack of FMR1 protein is linked to autism symptoms and intellectual disability in the fragile X syndrome, there is little evidence that excess FMR1 messenger RNA in fragile X premutation causes autism symptoms or intellectual disability. What may be possible in some humans with the premutation, as Qin et al. (2011) reported for mice with the premutation, is that lower levels of FMRP protein may contribute to increased risk for autism symptoms. Allan L. Reiss, M.D., Robbins Professor and Director, Center for Interdisciplinary Brain Sciences Research Vice Chair, Department of Psychiatry and Behavioral Sciences Professor of Radiology and of Pediatrics Stanford University School of Medicine Dr. Waterhouse's note on Fragile X permutation brain effects: Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in the world. As is discussed in the book, a small but significant subset of individuals diagnosed with autism are found to have Fragile X syndrome. Moreover, as is outlined in the beginning of Chapter 2, in rare cases individuals with autism symptoms have been found to have a related genetic disorder, the Fragile X premutation. Fragile X premutation and Fragile X syndrome both result from too many repeats of three linked amino acids in a neighboring region of the Fragile X mental retardation 1 (FMR1) gene. In Fragile X syndrome, there are 200 or more repeats. By contrast, in the Fragile X premutation syndrome there are only 55-200 repeats. There is also a gray area of 41-54 repeats that has been associated with physical and mental problems. Intellectual disability and social impairment in Fragile X syndrome and Fragile X premutation have been tied to lower levels of the Fragile X mental retardation protein (FMRP) in the brain. However, not all those with Fragile X premutation have severely reduced FMR1 protein in their brains, and many have abnormally high levels of the FMR1 RNA. RNA is required for genes to produce proteins, but abnormally high levels of RNA have been found to have toxic brain effects in those with repeat mutations in a variety of genetic diseases. The toxicity of excessive FMR1 RNA in the brain has been linked to tremors, problems in walking, and cognitive decline in individuals with Fragile X premutation who develop Fragile X-associated tremor/ataxia syndrome (FXTAS) in adulthood. However, Tassone and Hagerman (2012) have noted that evidence of RNA toxicity can be found in early brain development, and they concluded that excessive FMR1 RNA is a likely cause of brain disruption in children who have Fragile X premutation.

A seminal book forcing a much-needed change in the way in which we think about autism. Impressively well-researched and well-argued. A 'must-read' for all autism researchers. --Prof. Jill Boucher, City University, London, UK This book by Lynn Waterhouse will ruffle some feathers, with its bold conclusion that there is clear detriment to maintaining the diagnostic category of autism spectrum disorder. However, the evidence she presents is compelling. In every domain she investigates - symptoms, neurobiology, etiology, correlates - she finds that there is considerable heterogeneity in autism. As well as striking differences among children with an ASD diagnosis, there is also a lack of specificity in symptoms and causes. For instance, genetic variants and environmental risks that are associated with increased risk of autism are also associated with other neurodevelopmental disorders. Waterhouse is not denying that there are children with severe developmental difficulties involving social interaction, communication and stereotyped behaviours. Rather, she is questioning whether their needs are best served by grouping them all together under a single umbrella label. Her view is that research efforts directed at finding a unifying theory of autism are misguided, and that we should be focusing on symptoms rather than an abstract diagnostic category that can obfuscate rather than clarify our understanding. --Prof. Dorothy Bishop, University of Oxford, UK The book is an argument, not an opinion piece or political manifesto. It presents a pile of research findings, and makes a case for what they tell us.I'm grateful for Lynn Waterhouse's book and fervently hope it will help knock autism research out of a rut (not to mention help improve everyday thinking about autism). Rethinking Autism moves the conversation forward and I hope it will change our thinking for the better. --Intellectualizing blog, December 17, 2013

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Dr. Lynn Waterhouse was the Director of Child Behavior Study at The College of New Jersey for 31 years, and is currently a Professor in Global Graduate Programs at the College. NIMH, NICHD, and private funding agencies supported her autism research. She worked with Dr. Lorna Wing on the APA DSM-III-R diagnostic criteria for autism.

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