Catherine E. Lord - US grants

[unreadable] DESCRIPTION (provided by applicant): The diagnosis of autistic spectrum disorders (ASD) has increased in uniformity and reliability in the last 10 years due to a number of factors, including the agreement between American Psychiatric Association and the World Health Organization committees to propose nearly identical categorizations and the increasingly widespread use in research of standardized diagnostic instruments. Two instruments, the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) have been adopted by most North American and British researchers, as well as translated into French, Spanish, German, Korean, Portuguese, Danish, Norwegian, Swedish and Icelandic. More recently, a screening instrument, the Social Communication Questionnaire (SCQ; formerly the ASQ), has also received attention. However, much work remains to be done to make the instruments more useful for research purposes and clinical service. The present proposal uses analyses of an existing data set of over 1100 individuals with scores on the ADIR, ADOS, intelligence tests, the Vineland Adaptive Behavior Scales, and clinical best estimate diagnoses, with replication of findings in three other large datasets from the University of Wisconsin, Autism Genetics Research Exchange and the International Molecular Genetics Autism Consortium. In addition, data will be collected from the ongoing clinic at the University of Michigan using various manipulations (e.g., testing the effect of "current" versus "ever" probes) and small, targeted samples will be collected from currently underrepresented samples (e.g., severe to profoundly retarded individuals without autism). The purpose of the analyses will be to generate severity scores (within and across domains) that are independent of chronological age and language level for each instrument, generate a "certainty of caseness" rating that takes into account contributions of different instruments across age and language level and allows combination of information across instruments, reduce the number of items and the complexity of the algorithm for each instrument, and test the usefulness of the SCQ as a screening for possible autism in a yet-to-be diagnosed population of children referred to developmental disabilities and general child psychiatry clinics. In addition, the usefulness of a simpler, two domain plus language level approach to conceptualization of the autistic spectrum will be tested.

[unreadable] DESCRIPTION (provided by applicant): This is an application for an R25, Training in Research Diagnosis of Autistic Spectrum Disorders. Autism is a disorder that is defined behaviorally and for which there is neither a clear biological marker nor etiology, although there is strong evidence of genetic contributions. Research has been constrained by the need for reliable and standard diagnostic formulations of these autistic spectrum disorders to ensure comparability of populations. The introduction of two semistructured diagnostic instruments, the Autism Diagnostic Interview-Revised (ADI-R, Lord, Rutter, & LeCouter, 1994) and the Autism Diagnostic Observation Schedule (ADOS, Lord, Rutter, DiLavore, & Risi, 2000), in the 1980's and updated in the 1990's provided this opportunity and has contributed to replicability of findings in neurobiological research since that time. A newer screening questionnaire, the Social and Communication Questionnaire (Berument et al., 1999) has the potential to offer brief screening of potential participants as well. The diagnosis of autism is made complicated by a number of factors, including heterogeneity in IQ and changes in symptoms across development. A "spectrum" of disorders from classical autism to atypical autism, Asperger's Syndrome and Pervasive Developmental Disorder, Not Otherwise Specified (PDD-NOS) that are not reliably distinguished by clinicians all can occur with twin pairs and families. Because the primary features of autism involve social and communication deficits, the contexts in which these behaviors are observed are very important. What the examiner does with the child or adult affects the subject's behavior and the examiner's judgments. Assessments that specify both which aspects of the subject's behavior are scored and what the examiner does (or asks an informant about) provide a compromise between standardized approaches and the need for clinical flexibility in dealing with a population that may range from one extreme to the other in IQ and age. The purpose of this training grant is to provide hands on training in administration and scoring of the instruments for researchers, through annual 2 1/2 day workshops for a total of 30 trainees on each of the two diagnostic instruments and the screening instrument. Follow-up workshops (designed for 30 participants) and a website, with FAQs and a bulletin board (to respond to as many as 50 inquiries a week), and training videotapes (22 in total) will provide mechanisms for maintenance of reliability and support for those learning administration and coding. The addition of training specifically to train other trainers will enable more professionals to train research groups that are requesting training for newly funded or ongoing research projects. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): In response to a request for applications (FRA-DC-05-001) for the adaptation or development of language measures that can be used in the characterization of the behavioral phenotypes of language disorders, the goal of our project is to design an instrument that quantifies the use of pragmatics, syntax and semantics in the spontaneous language of children from 2 to 10 years who are suspected of having a language disorder. We will integrate knowledge from developmental psycholinguistics, speech pathology, and psychometrics to design an instrument that moves beyond traditional measures of language ability to assess processes that underlie language acquisition and use associated with different language and developmental disorders in a user-friendly, reliable way that provides continuity of measurement from preschool age to school age children. Building on the framework of naturalistic observations used in the Autism Diagnostic Observation Schedule (ADOS), we will create an instrument with a specific focus on assessing spontaneous language use in a broader population of children with language impairments, including alternate versions in order to measure progress and versions in both English and Spanish. Three phases of development are proposed: 1) Identification of major components of language to be covered by the instrument through consultation with a group of psycholinguists and a group of community "consumers" including speech pathologists, special education teachers and parents, 2) Transcription of 100 and coding of 30 existing ADOS videotapes of stratified samples of two groups of 2 - 10 year-old children from two sites (University of Michigan and Boston University), those with a) developmental delays or language impairments other than autism, and b) those with autism spectrum disorders, to assess what aspects of language are easily observable and codable during existing contexts in the ADOS Modules 2 and 3 and 3) Pilot testing of the new instrument, including additional tasks and a range of new codes, in order to assess the feasibility and psychometric properties of the new measure. Public Health Significance: In the project, a new assessment tool to evaluate the pragmatics, syntax and semantics of children with language impairments will be designed and pilot tested. The tool will provide ways of measuring the severity of children's difficulties in language use that can be employed in studies of the relationship between various neurobiological factors. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Longitudinal Studies of Autism Spectrum Disorder: 2 to 23 As the number of preschool children identified with autism spectrum disorder (ASD) increases each year, so too is the number of children with ASD moving into adolescence and adulthood. The aims of the project are to determine predictors of adolescent and adult outcome measured in terms of adaptive skills, quality of life, positive affect, and symptoms of anxiety and depression. The project represents a shift in emphasis from attention primarily on negative outcomes, to consideration of coping strategies for individuals and families and their impact on well-being and independence. In Study 1, the natural history of behavioral, cognitive, language, and social development from ages 2 to 23 will be examined in two well-described samples of children from North Carolina and Chicago referred for possible ASD, and a group of non-spectrum developmentally delayed controls. One hundred eighty seven out of 213 original children currently remain in the Early Diagnosis study initially funded by NIMH and NICHD. These children (i.e., the EDX probands) were seen at ages 2, 3, 5 and 9. Their families have been participating in phone interviews and completing packets of questionnaires since the children were 11 years old with a focus on relationships among adaptive skills, behavior problems, pubertal development, and adolescent onset of seizures. This data collection is still ongoing (ages are now 16-20). The proposal is for families to receive two face-to-face assessments 3 years apart and semi-annual packets collected over 5 years. Study 2 will focus more specifically on psychiatric comorbidity and mood disorders in ASD, as well as the relationship between coping resources, comorbidity and quality of life. Because comorbid conditions only occur in a subset of individuals with ASD, several new cohorts of Michigan children and adolescents with a current diagnosis (CDX) between the ages of 9 and 23 will be recruited to increase sample size and power. Two hundred and ten Michigan children and adolescents will be recruited over three years and approximately 156 reassessed 3 years later. Study 2 will employ a mixed cross-sectional longitudinal design. Analyses will incorporate existing data from the EDX study, as well as newly collected data from the EDX probands and new CDX Michigan recruits. Relevance: These studies will provide important information about individual differences in developmental trajectories in ASD and allow us to more fully understand the factors that contribute to positive and negative aspects of outcome in young adults. Findings will lead to better targeted interventions for families, children, adolescents, and adults to improve independence and quality of life for individuals and families affected by ASD. PUBLIC HEALTH RELEVANCE: Longitudinal Studies of Autism Spectrum Disorder: 2 to 23 This project will examine early predictors of positive and negative outcomes in adolescents and young adults with autism spectrum disorders (ASD). Because of the rising number of children diagnosed with ASD, more research is needed to understand the factors that are related to better outcomes in adolescence and young adulthood. This project will provide information that will be useful in developing new ways to improve quality of life for individuals with ASD and their families. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): To enhance participant recruitment efforts for genetics studies and other large- scale etiological research efforts, there is a need for an instrument that can be practically and efficiently employed in research studies of autism spectrum disorders (ASD). The current proposal aims to develop a research screening instrument that is based on questions from the Autism Diagnostic Interview-Revised (ADI-R;Rutter et al., 2003), but that is substantially shorter and easier to administer. The newly developed ADI Research Screening Interview will be appropriate for use in person or on the telephone. Development of the ADI Research Screening Interview will involve two large samples of children with ASD and non-ASD diagnoses. Existing data from a total of 979 assessments of children with ASD and 257 assessments of children with non-ASD diagnoses will be used to develop the instrument. A separate group of approximately 180 participants with ASD and 240 with non-ASD diagnoses will be recruited from ongoing research studies and specialty diagnostic clinics to test the new measure. Given recent findings that children with certain non-ASD diagnoses are often misclassified by ASD screening and diagnostic measures (e.g., Towbin et al., 2005;Bishop, et al., 2007), a particular strength of this proposal is the recruitment of children with targeted non-ASD diagnoses, including intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), anxiety disorder, and an early developmental risk group. With the advent of new technologies making genetic testing more accessible and less expensive, researchers are increasingly calling for a way to rapidly screen large populations for ASD first, and then carry out more intensive phenotyping after genetic tests are analyzed. The availability of a diagnostic screening instrument with high levels of sensitivity and specificity will dramatically reduce the time and expense that is currently required to determine diagnostic status of ASD research participants. The option of administering the screening protocol by telephone will facilitate access to more diverse participant populations for whom travel may be less feasible and who are traditionally under-represented in ASD research. PUBLIC HEALTH RELEVANCE: This proposal will result in the development of a new screening instrument to identify children with autism spectrum disorders (ASD). Several investigations are currently underway in order to better understand the causes of ASD. Many of these studies require very large numbers of participants;however, current methods for identifying participants for such studies are often expensive and time-consuming and require intensive training. To address these issues, we aim to create a short parent interview that can be administered on the telephone to quickly identify potential participants for ASD research. This new instrument will facilitate research into ASD etiology by increasing the speed and effectiveness of participant recruitment efforts. In addition, such an instrument may have other practical uses clinically. In communities where the wait for an ASD evaluation is extremely long or there are no local resources for diagnostic evaluations, an efficient screening instrument that could be administered by phone might help triage children in need of further evaluation and/or be used to qualify children for certain intervention services pending a more complete diagnostic evaluation at a later time.

DESCRIPTION (provided by applicant): This application entitled "Development of a Brief Screener for Research in Autism Spectrum Disorders" addresses broad challenge area (04) Clinical Research, 04-MH-101* Autism: Addressing the challenge. The proposal aims to develop a research screening instrument based on questions from the Social Communication Questionnaire (SCQ: Rutter, Bailey, &Lord, 2003) and the Autism Diagnostic Interview- Revised (ADI-R;Rutter, LeCouteur &Lord, 2003) that can be more effectively and practically employed in research studies of autism spectrum disorders (ASD). The newly developed measure will be the ADI Research Screening Questionnaire, a brief parent-report instrument that is designed to identify ASD in children ages 2 to 18 years. Development and validation of the new measure will involve two very large groups of children from multiple sites across the U.S. Existing data from a total of 2293 assessments of children with ASD, 792 assessments of children with non-ASD diagnoses, and 600 typically developing siblings of children with ASD will form the basis of the Measure Development sample. A separate sample of 1340 participants with ASD, 510 participants with non-ASD diagnoses, and 200 typically developing siblings of children with ASD will be recruited from ongoing research studies and specialty diagnostic clinics to validate the newly developed measure. Analyses of data from these two independent samples will result in a new instrument that can be used to rapidly ascertain potential participants for ASD research. The availability of a measure that quickly and accurately differentiates children with ASD from children with other developmental disorders will be invaluable to etiological and epidemiological research efforts, as it will significantly reduce the time and expense that is currently required to designate study participants as either having or not having ASD. Development of a Brief Screener for Research in Autism Spectrum Disorders This project will result in the development of a new screening instrument that can be used for research studies of autism spectrum disorders (ASD). Because of the need to identify large numbers of participants for genetics studies and other investigations of the causes of ASD, researchers require a way to rapidly screen large numbers of children and identify those who are highly likely to have a diagnosis of ASD. This project will provide researchers with the ability to quickly select potential participants so that they can more effectively carry out their investigations into the causes of ASD.