Infants at risk for autism a European perspective

Authors: Sven Bölte Peter B Marschik Terje FalckYtter Tony Charman Herbert Roeyers Mayada Elsabbagh

Publish Date: 2013/01/10

Volume: 22, Issue: 6, Pages: 341-348

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Abstract

Currently autism cannot be reliably diagnosed before the age of 2 years which is why longitudinal studies of highrisk populations provide the potential to generate unique knowledge about the development of autism during infancy and toddlerhood prior to symptom onset Early autism research is an evolving field in child psychiatric science Key objectives are fine mapping of neurodevelopmental trajectories and identifying biomarkers to improve risk assessment diagnosis and treatment ESSEA Enhancing the Scientific Study of Early Autism is a COST European Cooperation in Science and Technology Action striving to create a European collaboration to enhance the progress of the discovery and treatment of the earliest signs of autism and to establish European practice guidelines on early identification and intervention by bringing together European expertise from cognitive neuroscience and clinical sciences The objective of this article is to clarify the state of current European research on atrisk autism research and to support the understanding of different contexts in which the research is being conducted We present ESSEA survey data on ongoing European highrisk ASD studies as well as perceived challenges and opportunities in this field of research We conclude that although highrisk autism research in Europe faces several challenges the existence of several key factors eg new and/or largescale autism grants availability of new technologies and involvement of experienced research groups lead us to expect substantial scientific and clinical developments in Europe in this field during the next few yearsAutism spectrum disorders ASD are neurodevelopmental disorders defined by impairments across the areas of reciprocal social interaction verbal and nonverbal communication alongside a preference for repetitive stereotyped activities patterns of behaviors and interests 3 Most of the traditional clinical and basic science literature on ASD focused on the phenomenon at the age between 4 and 5 years Indeed until some 10 years ago it was fairly uncommon for children to get diagnosed with autism before the age of 3 or 4 years Even in today’s clinical practice in many cases especially for milder variants of ASD late ASD diagnoses frequently occur This is despite the fact that both major diagnostic systems DSMIVTR ICD10 in their editions published in the early to mid90s defined an early onset of symptoms 36 months of age as essential for classical autism In addition the concept of ASD in general implies pervasive developmental delay and/or deviance in a multitude of basic functions such as play motor development attention adaptive behavior particularly social reciprocity and verbal as well as nonverbal communication being apparent from early childhood onwards Also most parents are concerned about their children’s behavior from early on In a study by Chawarska et al 5 the average age of first parental concerns was 14 months On the other hand there is a substantial minority of autistic individuals who develop typically or apparently typically at first up to 24 months of age but later show a loss of skills and developmental regression 15 Furthermore the symptom severity in ASD is variable as are sociocommunicative speechlanguage and intellectual skills and children with ASD might present with striking coexisting problems unspecific to ASD eg irritability hyperactivity sleep and feeding problems or may appear typically developing to the nonexperienced or untrained observer Hence early ASD detection in infants remains challengingIn recent years a growing interest in infant development and early detection of ASD has emerged mostly driven by the insight that early identification is a prerequisite for early intervention which itself may improve longterm outcomes for individuals with ASD 6 Several methodologies have helped to study early detection and examine early development in ASD Screening instruments for early signs of ASD such as the CHecklist for Autism in Toddlers CHAT Early Screening for Autistic Traits ESAT the ModifiedCHAT and the Infant Toddler Checklist ITC have demonstrated the possibility to prospectively identify ASD at 18 months or even earlier for reviews see 1 4 in lowrisk and highrisk populations Common early signs are primarily delays and deficits in response to name and joint attention and limited or perseverative early play Nevertheless many of these signs are neither specific for nor universal to ASD with low positive predictive values and a risk for overreferral particularly in case of one stage screening Another method to study early development in ASD is retrospective analyses of home videos collected prior to diagnosis Palomo Belinchón and Ozonoff 19 summarized eight such studies from the first 2 years of life of children who were later diagnosed with ASD Consistent early signs in the first year of life were reduced response to name as well as reduced frequency of looking at faces During the second year of life pointing to request and to show as well as showing/giving objects were the most prominent atypical featuresTo focus on the early development and early detection of autism an alternative and increasingly applied approach is the longitudinal study of infant siblings of children with ASD Infant siblings are at increased risk ~20  of developing ASD compared to 1  of the general population with the risk being higher for males than for females and higher for those from multiplex 1 sibling then simplex families 18 By monitoring developmental trajectories in highrisk siblings more precise information about the first appearance of autistic behaviors has evolved for reviews see 20 25 27 A note of caution is that it is a matter of debate whether ASD aetiologies are comparable between simplex and multiplex families with ASD 14 so there may be limits on the extent to which findings from highrisk infant sibling studies generalize to the simplex population Highrisk studies consistently reported that while infants later diagnosed with ASD exhibit signs of the condition at 12 months eg lack of eye contact reciprocal smiling and social engagement no such behavioral differences have been reliably detected at 6 months 17 Nevertheless the search for behavioral and biological markers with sufficient sensitivity and specificity to be of clinical feasibility and validity using a multitude of techniques eg questionnaires behavioral observation eye tracking magnetic resonance imaging MRI event related potentials ERPs in highrisk autism populations is an ongoing quest Most recent evidence from eye tracking studies including those from ESSEA laboratories Enhancing the Scientific Study of Early Autism suggests that subtle joint attention difficulties at 13 months might be related to ASD or other altered neurodevelopmental outcomes 2 and that children with poor social and communicative skills differ from typically developed concerning eye gaze patterns leading to successful word learning 12 On the other hand in a recent US study decreased eye contact in highrisk siblings at 6 months was not related at all to ASD outcome at 24 months 16 26 Parentinfant interaction observations in 6 to 10monthold infants found less liveliness in the atrisk sample and more directedness as well as lower sensitive responsiveness of their parents compared to lowrisk controls 21 Interestingly two independent studies 22 23 suggest that some of the earliest risk markers may lie within the motor domain With respect to electrophysiological evidence Elsabbagh et al 8 using ERPs found that response to dynamic eye gaze shifts during the first year 6–10 months of age was associated with ASD diagnosed at 36 months Other neuroimaging work from the US infant brain imaging study IBIS network using diffusion tensor imaging found aberrant white matter fiber tract at 6 months and subsequent tract trajectories to be associated with and ASD diagnosis at 24 months 24Generally enhanced collaboration and networking are crucial in moving forward with challenging scientific questions in early autism research There is a need for sharing protocols and data between labs to advance practice and influence policy makers While consortia like the IBIS and Baby Sib Research Consortium BSRC are ongoing in North America until recently a comparable and competitive coherent Europewide network has not yet been established ESSEA for details please see http//wwwcostesseacom/ is a COST European Cooperation in Science and Technology action striving to establish an interdisciplinary scientific network to advance the pace of discovery about the earliest signs of autism to combine techniques from cognitive neuroscience with those from the clinical sciences and to generate European practice guidelines on early identification and intervention ESSEA is funded under the EU’s Seventh Framework Programme for Research FP7 via the European Science Foundation 2011–2014 It is a network of over 60 scientists from 22 European countries and various scientific disciplines COST is a means for European researchers to jointly develop new ideas and initiatives across scientific disciplines through transEuropean networking of nationally funded research activities COST provides financial support only for joint activities such as conferences shortterm scientific exchanges training schools and publications ESSEA intends to develop European capacity in early autism research The lack of a forum to enhance the scientific synergies between these strands of basic and applied research has previously hindered progress Increased and earlier recognition has impacted across Europe in terms of demand for diagnostic services and interventions Current health care systems across Europe are very variable in terms of their expertise and capacity to support families with young children with autism often leading to marginalization Although the primary focus of ESSEA is research it offers the potential to help build capacity for health systems and clinical care eg raise awareness spread expertise provide research to practice solutions and propose evidencebased clinical guidelinesThe goal of this article is to review European research capacities in the field of atrisk for ASD research and to support the understanding of differences in European research contexts The findings might be valuable to overcome research impediments and to highlight how using specific strengths of the European collaborative sites might be used to this effect as well as to raise awareness and influence public policy toward greater engagement in ASD issues in Europe For this purpose two surveys were sent to members of ESSEA actively involved in highrisk research and/or in the development of novel methods for early autism research WG1 and WG2 members first one on ongoing full scale pilot as well as planned highrisk studies in Europe among ESSEA sites and second another on perceived challenges and opportunities for autism research in general and highrisk research in particular among those European research sitesFor the survey of ESSEA members’ ongoing or planned highrisk autism studies and applied technologies ESSEA member principal investigators completed an open item format investigator questionnaire It inquired about ongoing or planned research projects methodologies technologies collaborative attitudes priorities collaborators interests funding and relevant publications in early autism research For researchers currently or soon to start conducting research with populations at risk for autism investigators involved in collaborative projects to complete the survey jointly the survey required information on the status principal investigators project title current sample size project’s total sample size key words for focus of study type of risk sample methodologies and technologies employed and project start

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