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Autism Spectrum Disorders Key Issues in Mental Health Vol. 180 Series Editors Anita Riecher-Rössler Basel Norman Sartorius Geneva Autism Spectrum Disorders Phenotypes, Mechanisms and Treatments Volume Editors Marion Leboyer Créteil Pauline Chaste Paris 5 figures, 4 in color, and 6 tables, 2015 Basel · Freiburg · Paris · London · New York · Chennai · New Delhi · Bangkok · Beijing · Shanghai · Tokyo · Kuala Lumpur · Singapore · Sydney Key Issues in Mental Health Formerly published as ‘Bibliotheca Psychiatrica’ (founded 1917) Prof. Marion Leboyer Dr. Pauline Chaste Université Paris-Est, INSERM, AP-HP Centre Hospitalier Sainte Anne Pôle de Psychiatrie des Hôpitaux Universitaires 1 rue Cabanis Henri Mondor FR–75014 Paris (France) 40 rue de Mesly FR–94010 Créteil (France) Library of Congress Cataloging-in-Publication Data Autism spectrum disorders (Leboyer) Autism spectrum disorders : phenotypes, mechanisms, and treatments / volume editors, Marion Leboyer, Pauline Chaste. p. ; cm. -- (Key issues in mental health ; vol. 180) Includes bibliographical references and index. ISBN 978-3-318-02601-6 (alk. paper) -- ISBN 978-3-318-02602-3 (e-ISBN) I. Leboyer, Marion, editor. II. Chaste, Pauline, editor. III. Title. IV. Series: Key issues in mental health ; v. 180. [DNLM: 1. Child Development Disorders, Pervasive. W1 BI429 v.180 2015 / WS 350.8.P4] RJ506.A9 618.92’85882--dc23 2014027395 Bibliographic Indices. This publication is listed in bibliographic services. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. 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Box, CH–4009 Basel (Switzerland) www.karger.com Printed in Germany on acid-free and non-aging paper (ISO 9706) by Kraft Druck, Ettlingen ISSN 1662–4874 e-ISSN 1662–4882 ISBN 978–3–318–02601–6 e-ISBN 978–3–318–02602–3 Contents 1 From Autism to Autism Spectrum Disorders Mercati, O.; Chaste, P. (Paris) 5 Autism Spectrum Disorders and Coexisting Mental Health Problems Ståhlberg, O.; Nilsson, T.; Lundström, S.; Anckarsäter, H. (Gothenburg) 20 Autism and Medical Comorbidities Schiff, M. (Pittsburgh, Pa./Paris); Asato, M.R. (Pittsburgh, Pa.) 34 The Cognitive Profile in Autism Spectrum Disorders Mandy, W.; Murin, M.; Skuse, D. (London) 46 Social Functioning in Autism Merhoum, N.; Mengarelli, F.; Mottolese, R.; Andari, E.; Sirigu, A. (Bron) 54 Sensory Processing in Autism Behrmann, M.; Minshew, N.J. (Pittsburgh, Pa.) 68 On the Neuroimaging of Autism in the Context of Human Brain Diversity Houenou, J. (Créteil/Gif sur Yvette); Chaste, P. (Paris) 80 Architecture of the Genetic Risk for Autism Chaste, P.; Devlin, B. (Pittsburgh, Pa.) 97 Molecular Pathways in Autistic Spectrum Disorders Gallagher, L. (Dublin); Shen, S. (Galway); Anney, R. (Dublin) 113 Environmental Factors and Autism Spectrum Disorder Persico, A.M. (Rome/Milan); Merelli, S. (Milan) 135 Early Signs and Early Intervention Freitag, C.M. (Frankfurt am Main) 151 Psychotropic Treatment of Autism Pallanti, S. (Florence/New York, N.Y.); Bencini, L.; Cantisani, A. (Florence); Hollander, E. (New York, N.Y.) 166 Author Index 167 Subject Index V From Autism to Autism Spectrum Disorders Oriane Mercatia, b · Pauline Chastec aHuman Genetics and Cognitive Functions, Institut Pasteur, bUniversité Paris Descartes, Paris V, and cCentreHospitalier Sainte Anne, Paris, France The diagnosis of autism is based exclusively on clinical assessment in the absence of specific biomarkers. The current reference evaluation is based on standardized tools, the most widely used being the Autism Diagnostic Interview-Revised (ADI-R) [1] and the Autism Diagnostic Observation Schedule (ADOS) [2]. The ADI-R consists of an interview of the parents, which assesses the developmental history of the patient with a focus on social interactions, social communication, and repetitive behaviors. The ADOS consists of an assessment of the patient during standardized sequences of play and interviews. These tools were primarily developed to provide a categorical diagnosis, that is to say they allow determination of the presence or absence of an autistic disorder, although the concept of autism per se has never been clearly validated and has varied widely since its first description. The oldest known cases of autism far preceded the first descriptions of this disorder by psychiatrists, which were made only 70 years ago. Indeed, as early as the 12th century, one of the disciples of Saint Francis of Assisi, Brother Juniper, was described as a man of absolute honesty and candor, unable to measure the consequences of his ac- tions. Nicknamed the ‘toy of God’, he was mocked for his excessive and absurd behavior. At the end of the 18th century, the wild child Victor of Aveyron, according to the physician Itard who provided valuable descriptions, had persistent alterations of social interactions, repetitive swinging movements, and a particular sensory percep- tion after several years of education [3]. The term autism (from the Greek autós or self) was used for the first time in the early 20th century by the Swiss psychiatrist Eugen Bleuler [4], who thus referred to the social withdrawal and loss of contact with reality observed in schizophrenic patients. In 1943, the American child psychiatrist Leo Kanner [5], founder of the first hospital department of child psychiatry, at the Johns Hopkins Hospital in Baltimore, Md., USA, proposed this term to qualify a child disorder, regardless of coexisting schizophrenia. In his article ‘Autistic disturbances of affective contact’, he described 11 children, i.e. 8 boys and 3 girls, aged 2–11 years, all with an ‘innate inability to form the usual, biologically provided affective contact with people’ and an ‘anxiously obses- sive desire for the maintenance of sameness’ [5]. Although some children in this group had been previously diagnosed with schizophrenia, Kanner [5] indicated that withdrawal differs from that described in schizophrenia in that it is present from the beginning of life, while patients with schizophrenia, children or adults, show an essentially normal development followed by changes in their behavior and progressive social withdrawal. Independently of this work, in 1944 the Austrian psychiatrist Hans Asperger [6] used the term ‘autistic psychopathy’ to describe 4 boys aged 6–11 years who showed a fundamental breakdown (...) causing significant and very typical difficulties in social integration, sometimes, however, compensated by an originality of the thinking and experience that could lead subsequently to outstanding achievements. This article by Asperger [6], written in German, remained unknown for a long time. In 1981, the British psychiatrist Lorna Wing [7] contributed to exposing these works to a larger audience. Notably, based on the descriptions of Asperger [6] and 34 other cases from the clinic she managed, she proposed a definition of Asperger’s syndrome [7]. In his 1943 paper, Kanner [5] provided detailed descriptions of his patients and their common characteristics but did not formalize diagnostic criteria. In 1956, with the American psychiatrist Leon Eisenberg, he defined 2 criteria that he considered essential: – a profound lack of affective contact – elaborate repetitive and ritualistic behavior [8]. In 1978, Michael Rutter [9], the first professor of child psychiatry in the UK and one of the first to develop child psychology, suggested 4 criteria to define autism: – impaired social development that does not match the intellectual level of the child – delayed and deviant language that does not correspond to the intellectual level of the child – a need for immuability which leads to stereotyped games, unusual preoccupations, and resistance to change – onset of the disorder before the age of 30 months. In 1979, Wing and Gould [10] defined 3 recurrent symptoms in autism with defi- cits in 3 domains: social interaction, social communication, and social imagination. This triad of symptoms was used as the basis for building diagnostic criteria in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders [10], the inter- national benchmark for the diagnosis of mental disorders. The recent evolution of diagnostic criteria for autism in this manual reflects the shifts that occurred in the understanding of autism symptoms and pathophysiology. 2 Mercati · Chaste In the DSM-IV-TR (4th edition – text revised) [11], autism was defined by the triad of Wing and Gould [10], with the third item (deficit in social imagination) being replaced by the presence of repetitive behaviors (or stereotypies) and restricted interests, seen as a result of the lack of social imagination initially mentioned. Autistic disorder was classified in the category of ‘pervasive developmental disorders’, which in- cluded 4 other disorders: – Asperger’s syndrome, which was distinguished from autism by the absence of language and cognitive delay – disintegrative disorder of childhood, characterized by a period of normal development of 2–4 years followed by the onset of autistic symptoms – Rett’s syndrome, the genetic etiology of which is known and which affects only girls – pervasive developmental disorder not otherwise specified (PDD-NOS). This diagnosis concerns patients with ‘severe and invasive alterations in social interactions or verbal and nonverbal communication, or behavior, interests and stereotyped activities’, who do not meet all the criteria for a specific PDD. The conceptualization of these disorders has changed dramatically over the past 10 years, which is reflected in the DSM-5, the new edition of the DSM manual published in May 2013 [12]. Indeed, several studies have supported 1 category and 2 dimensions of symptoms [13–17], leading to the collapse of the earlier diagnostic categories of pervasive developmental disorders into a single category of autism spectrum disorder or ASD. This term was proposed in 1988 by Doris Allen [18] and reflects the heterogeneity of the symptoms of autism. In addition, the diagnostic criteria were grouped into 2 broad areas instead of 3: – impairment of social interaction and communication (both elements were previously assessed separately and are now considered one aspect of the disease) – restricted and repetitive behaviors. It is now widely accepted that in each domain of impairment there is a gradient in the severity of symptoms which can vary considerably from one individual to anoth- er and in the same person at different ages, leading to a different clinical presentation in each individual. Thus, the following dimensional scales have been developed to as- sess autistic symptoms quantitatively: the Social Responsiveness Scale (SRS), which measures the severity of social responsiveness deficit [19]; the Children’s Communi- cation Checklist (CCC), which assesses the social dimension of communication [20]; the Repetitive Behavior Scale, which assesses repetitive behaviors [21], and the Autism Spectrum Quotient, which assesses autistic symptom severity as a whole [22]. Interestingly, this revised vision is consistent with the emerging picture of the mechanisms underlying autism spectrum disorders and should help several areas of autism research moving forward. Indeed, accepting to deal with clinical heterogeneity instead of solving it should help further the already immense progress that has been made in this domain. From Autism to Autism Spectrum Disorders 3