Finding Answers for Families

2012 ANNUAL REPORT© 2013 Autism Speaks Inc.

Autism Speaks and Autism Speaks It‘s Time To Listen & Design are trademarks owned by Autism Speaks Inc. All rights reserved.

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Executive Summary

1. The Committee of Principal Investigators of the BSRC includes 24 members,

representing 21 different research programs and two multi-site networks. 2. Over 2,800 infants at risk for ASD have been enrolled thus far in BSRC projects; as

well as over 1,700 low risk siblings without a family history of ASD. This is the largest cohort of high risk families in the world.

3. There are 1900 siblings with 36-month outcomes included in the dataset 4. In 2012, 37 papers were published in peer-reviewed journals on topics directly

relevant to the mission of the BSRC. 5. In 2012, the IBIS research group published findings of brain differences in younger

siblings as early as 6 months of age. This discovery points to very early changes in brain development before some behavioral symptoms are seen.

6. BSRC research programs provided research training to 45 doctoral students and 27 post-doctoral fellows.

7. Twelve new grants were awarded to members of the BSRC in 2012 to support further research on high risk infants.

8. The BSRC biorepository was launched in 2012. It will collect biomaterials and expanded behavioral and environmental exposure information on 445 high risk families. This is the largest single collection of biomaterials from high risk siblings. Funding was provided through a partnership between Autism Speaks and the Simons Foundation.

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Baby Sibling Research Consortium (BSRC) - Mission The BSRC focuses on investigations of infants at risk for autism spectrum disorders (ASD) using a variety of methods, including behavioral and neurobiological measures. Building upon the diverse, yet integrally aligned set of investigators, the BSRC creates a framework of the individual researchers and research groups while at the same time creating a framework for collaborative research activities (with new or existing funding at each site) and data sharing through this new entity. As BSRC investigators, we have agreed to pool our data for collaborative projects. This will accelerate progress in complex scientific issues related to early detection and intervention for infants at high risk for ASD and milder disorders. These activities and research advances are critical in understanding how to reduce the age of diagnosis and improve access to early intervention services for all children.

Members of the BSRC The organization is made up of a Committee of Principal Investigators (CPI) representing major research groups participating in the BSRC. Each member of the BSRC is a PI on a funded project investigating infants/toddlers at risk for ASD.

Committee of Principal Investigators Susan Bryson, Ph.D. Dalhousie University, Halifax, Canada Alice Carter, Ph.D. University of Massachusetts, Boston Leslie Carver, Ph.D. UCSD Tony Charman, Ph.D. Institute of Psychiatry, London, representative for British

Autism Study of Infant Siblings (BASIS) Kasia Chawarska, Ph.D. Yale University Suzanne Curtin, Ph.D University of Calgary Karen Dobkins, Ph.D. UCSD Deborah Fein, Ph.D. University of Connecticut Judith Gardner, Ph.D. Institute for Basic Research Jana Iverson, Ph.D. University of Pittsburgh Scott Johnson, Ph.D. UCLA Ami Klin, Ph.D. Emory University Rebecca Landa, Ph.D. Kennedy Krieger Institute Catherine Lord, Ph.D. Weill Cornell Medical College and New York

Presbyterian Hospital Daniel Messinger, Ph.D. University of Miami Charles Nelson, Ph.D. Children‟s Hospital of Boston Sally Ozonoff, Ph.D. MIND Institute, UC Davis Joseph Piven, M.D. University of North Carolina Sally Rogers, Ph.D. MIND Institute, UC Davis Wendy Stone, Ph.D. University of Washington/Vanderbilt University Mark Strauss, Ph.D. University of Pittsburgh

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Sara Webb, Ph.D. University of Washington/Seattle Children‟s Research Institute

Nurit Yirmiya, Ph.D. Hebrew University, Jerusalem Israel Lonnie Zwaigenbaum, M.D. University of Alberta, Edmonton, Canada

Associate Members Jessica Brian, Ph.D. Holland Bloorview Hospital, Toronto Ira Cohen, Ph.D. Institute of Basic Research, NY Annette Estes, Ph.D. University of Washington Heather Cody Hazlett, Ph.D. University of North Carolina, Chapel Hill Ted Hutman, PhD University of California Los Angeles Suzanne Macari, Ph.D. Yale University Sarah Patterson, Ph.D. Children‟s Hospital of Philadelphia Frederic Shic, Ph.D. Yale University Helen Tager-Flusberg Boston University Zachary Warren, Ph.D. Vanderbilt University Gregory Young, Ph.D. University of California at Davis

Autism Speaks Project Staff Geraldine Dawson, Ph.D. Alycia Halladay, Ph.D. Andy Shih, Ph.D. Lauren Elder, Ph.D.

NIH Project Staff NICHD: Alice Kau, Ph.D.

External Advisory Committee The following individuals serve on the External Advisory Committee for the BSRC: Heidi Feldman, M.D. (Stanford University) Alan Fogel, Ph.D. (University of Utah) Nathan Fox, Ph.D. (University of Maryland) Peter Mundy Ph.D. (UC Davis/MIND Institute) – continuing member Alison Singer (Autism Science Foundation and parent) Ezra Susser, M.D. (Columbia University)

BSRC Officers: Executive Committee The BSRC Executive Committee is responsible for organizing and coordinating all functions of the BSRC. Current officers (for 2011-2012) include:

Chair Rebecca Landa Member Daniel Messinger Member Kasia Chawarska Member Sally Ozonoff

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BSRC database

The BSRC database, now in its third year of funding, grew by approximately 25% of its previous size over the last year with the addition of many thousands of new longitudinal assessments from BSRC member sites. The database now contains data from 2,838 high-risk infant siblings and 1,703 control infants, most of whom are still currently being followed prospectively by active sites. This centralized database has been integral to a number of collaborative research projects that would not otherwise have been possible at any single site alone. The database continues to feed and support a number of collaborative projects, one of which was recently published in the Journal of the American Academy of Child and Adolescent Psychiatry (Messinger, et al., 2013), documenting the significant cognitive and social developmental problems that exist in a relatively high proportion of high-risk infant siblings who are not ultimately diagnosed with ASD.

An increasing number of additional collaborative projects are currently underway that all utilize the BSRC database and analytic support, including a project led by the database PI (Gregory S. Young) involving an Item Response Theory (IRT) analysis of ADOS items across different ages, groups, and test versions; a project led by Rebecca Landa examining latent class growth trajectories of primary and secondary symptoms of autism over the first 3 years of life; a project led by Jana Iverson involving an item analysis of measures of motor development at 6 months of age that are associated with later diagnosis of ASD; a project led by Kasia Chawarska examining constellations of behavioral features at 18 months that are predictive of outcome at the age of 3 years; a project led by Lonnie Zwaigenbaum examining growth trajectories of head circumference in children who ultimately develop ASD; and at least 3 other collaborations that are in the early stages of planning and development looking at things such as ethics, resiliency, and the broader autism phenotype. Importantly, each of these projects would simply not be possible without the collaborative efforts of the BSRC members in pooling their data together into a central database.

The BSRC database is continuing to grow, with annual resubmissions of site data to increase sample sizes and keep data current with the addition of new data. A recent project funded jointly by Autism Speaks and the Simons Foundation for the collection of biological samples and clinical measures is expanding the data collection on 400 families to the databases. The new clinical data will be stored in the BSRC database, with formal collaboration between the BSRC database, AGRE database, and the National Database for Autism Research.

Internally, the BSRC database has also established a hierarchy of data cleaning and quality control procedures that involve everything from checking all values of all data points to sophisticated multivariate analytic models that test for overall data integrity. For the coming year, the database PI and staff are working to implement real-time data visualization (graphs, tables, reports) in a secure web-browser format for BSRC members to use for purposes of planning collaborative projects. These interactive data visualization tools will extend the utility of the BSRC database by making project planning and collaboration easier than ever, including interactive graphs like histograms for examining data distributions, scatterplots for examining bivariate associations, and power analyses based on user input. As this past year has shown, the BSRC database has clearly become

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an essential and uniquely useful tool for the many collaborations among the BSRC members, and promises to evolve in ways that facilitate answering new questions about autism with the rare and unique resource provided by the BSRC database.

Annual Meeting Summary In October, the BSRC met in Seattle, WA to review recent progress and identify new areas of research to study. The discussion focused on the symptoms of autism that emerge before 12 months of age, including those which can be observed by clinicians or possibly parents, and the others which reflect underlying neurobiological processes. An example of some of these signs is below:

Some of the major findings of the BSRC this year were in the area of working towards identifying attentional and biological markers before a behavioral diagnosis could be made, and linking those markers to autism-relevant signs and symptoms. The group met to discuss how these exciting discoveries could be converted into tools that heathcare providers and parents could use for better identification and detection techniques. One such finding that was discussed was the report by Rebecca Landa that the presence of head lag was an early predictor of autism diagnosis as well as social and communication delays in high risk siblings. A subset of the BSRC, led by Jana Iverson, is working to determine what kind of observations in motor function would be useful and at what ages for an early autism identification. Kasia Chawarska discussed their most recent work on deficits in regulation of attention to complex social scenes in six month old infants who later were diagnosed with ASD. Future endeavors will advance these findings into clinically relevant applications.

Eye tracking technology used to study

brain activity

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In addition to new data and findings, the meeting offered the opportunity for the consortium to work on existing projects and database analyses. For example, Kasia Chawarska reported back on a new analytic approach aimed at identifying diagnostic features for ASD and broader autism phenotype at 18 months. Daniel Messinger directed a project to understand proportion of high risk infants who have non-ASD delays. This investigation, using the BSRC shared database, led to the submission of a manuscript that appeared in print in 2013. A new project, led by Rebecca Landa, has been launched to examine how infant siblings of children with ASD develop in the first three years of life. Finally, two new interest groups were added to the growing list of productive projects. This includes the ethics of studying high risk infants and an understanding of the broader autism phenotype in families. These two join the existing interest groups to study motor behaviors, biological markers including EEG, resiliency in development of infant siblings, and trajectories in high risk infants and developmental outcomes of high risk siblings. Ongoing research projects which have developed from workgroups such as the repository are listed

at the end of the report.

Studying brain activity in a 3 month old

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Four major findings in high-risk infant research based on published research in 2012 Wolff, J.J., Gu. H., Gerig, G., Elison, J.T., Styner, M., Gouttard, S., Botteron, K.N., Dager, S.R., Dawson, G.,, Estes, A.M., Evans, A.C., Hazlett, H.C., Kostopoulos, P., McKinstry, R,C, Paterson, S.J., Schultz, R.T., Zwaigenbaum, L., & Piven, J.; IBIS Network. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. American Journal of Psychiatry,169(6), 589-600. DOI: 10.1176/appi.ajp.2011.11091447. PubMed PMID: 22362397; PubMed Central PMCID: PMC3377782.

This longitudinal diffusion tensor imaging study followed 92 infant siblings of children with ASD from 6 to 24 months of age, at which time high-risk siblings (HR) were classified according to ADOS outcomes. Developmental trajectories for 15 white matter pathways of interest were compared between HR children who did (n=28) versus did not (n=64) meet criteria for ASD at 2 years age. Trajectories were significantly different for 12 of 15 white matter pathways representing structural connectivity across multiple brain regions. Most trajectories for the HR ASD+ group were characterized by increased fractional anisotropy (FA) at 6 months followed by blunted change over time such that by 2 years age, children who were ASD+ had lower FA values than their HR ASD- counterparts. These results suggest that an atypical but highly dynamic process of brain wiring may underlay the early emergence of ASD.

Zwaigenbaum L, Bryson SE, Szatmari P, Brian J, Smith IM, Roberts W, Vaillancourt T, Roncadin C. Sex differences in children with autism spectrum disorder identified within a high-risk infant cohort. J Autism Dev Disord. 2012 Dec;42(12):2585-96.

This study examines sex differences in 3-year-olds with autism spectrum disorders (ASD) drawn from a high-risk (HR) infant sibling sample, as well as well as HR infants not diagnosed with ASD and low-risk comparison infants. Of 319 participating HR infants, 85 were diagnosed with ASD, including 57 of 176 boys (32.4 %) and 28 of 143 girls (19.6 %). Thus, relative odds of ASD in boys compared to girls was 1.65 (95% CI = 1.11-2.45), lower than the 3-4:1 sex ratio reported in most ASD samples. While there were modest sex differences on the Mullen Scales of Early Learning, Vineland Adaptive Behavioral Scales, ADOS and ADI-R at age 3 years, differences between boys and girls with ASD within the HR group mirrored sex differences in the non-ASD groups. The modest male-to-female ratio,

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combined with a relatively high cognitive level, suggests that we have identified an unanticipated number of higher-functioning girls with ASD.

Further assessment and follow-up of HR sibling cohorts may inform community-based practitioners to help ensure that both boys and girls with ASD are identified as early as possible, and also clarify how the natural history of ASD might vary between the sexes.

Landa, R.J., Gross, A.L., Stuart, E.A., & Bauman, M. (2012). Latent class analysis of early developmental trajectory in baby siblings of children with autism. Journal of Child Psychology and Psychiatry, 59, 986-996.

Recent research has shown that younger siblings of children with autism are at increased risk for social and communication delays, including autism spectrum disorders (ASD). Little is known about the developmental trajectories of infant siblings of children with ASD (siblings-A) in the first three years of life. This is the first study to employ a novel analytic strategy ("Latent Class Analysis") to elucidate the different types of developmental trajectories in siblings-A across language, cognitive, and motor domains in the first three years of life. In this prospective, longitudinal study, the researchers found four main types of development from birth to 36 months. In all four types of development, infants showed rather typical levels of functioning in all aspects of development when they were 6 months old. The first group consisted mainly of children who were primarily unaffected from symptoms. Compared to the test norms, this group exhibited accelerated rates of language and cognitive development beginning at 18 months of age. In the second group, children generally showed typical rates of development across all aspects of development. The third group of children were slow to develop language but by age 3, scored within normal limits on the language scales of the test. This group of children showed motor delays by 30 months of age. In the fourth group, children's rate of development was much slower than the expected based on the test normative sample. The researchers also found that children whose ASD was diagnosed after age 14 months were about equally distributed across developmental groups 2-4. That is, about a third showed normal development with average nonverbal outcome. About another third showed receptive language and motor day, and about a third showed widespread deficits and a decline in rate of development over time. In children with early diagnosis of ASD (by age 14 months), very few exhibited a normal rate of development. About a third showed receptive

Infant sibling at Kennedy Krieger Institute participating in a study looking at very early

markers of ASD

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language and motor delays, but most were in group four, showing declining rates of development in all domains studied. The results of this study show that children with ASD have different developmental profiles and indicate that clinicians should continue to track the development of high risk infants through at least 36 months. Even though brain development seems to be abnormal as early as 6 months (see Wolff, above), the onset of developmental delays may not become obvious until later, and the timing of onset of developmental delays is variable in this high risk group.

Elsabbagh M, Mercure E, Hudry K, Chandler S, Pasco G, Charman T, Pickles A, Baron-Cohen S, Bolton P, Johnson MH; BASIS Team. (2012) Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism. Curr Biol. Feb 21;22(4):338-42.

The British Autism Study of Infant Siblings (BASIS) was founded on a strong alliance of researchers, clinicians, families, and charities who all shared common goals: to understand how autism emerges over time, through charting the development of infants at increased risk for developing the condition, by virtue of having an older diagnosed sibling. Previous BASIS studies have found that infant siblings show subtle differences in their early development that can be observed more clearly using direct brain measurement. This project expands on these findings by following the development of over a hundred infant siblings from as young as 6-months to the age of three years when some of them received a diagnosis of autism. As early as 6-months, the researchers found a different pattern of brain response to social information, such as eyes looking towards you or away from you, in those infants who were later diagnosed with autism. In some infants, subtle differences in brain function early in life transform over time into the behavioural symptoms of autism. Not all infants who show differences in their brain function develop autism, suggesting that additional factors, possibly those that “protect” the infant will need to be understood.

Baby at Boston University/BCH study wearing the NERS cap

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Publications in 2012 This section of the report presents a summary of the papers and book chapters published in 2012 by members of the CPI on topics directly related to their research on infants/toddlers at risk for ASD. [** Indicates more than one CPI member as co-author]

BASIS Bedford, R., Elsabbagh, M., Gliga, T., Pickles, A., Senju, A., Charman, T., Johnson, M. H., & the BASIS team. (2012). Precursors to social and communication difficulties in infants at-risk for autism: Gaze following and attentional engagement. Journal of Autism and Developmental Disorders, 43, 2208-2218.

Elsabbagh, M., Mercure, E., Hudry, K., Chandler, S., Pasco, G., Charman, T., Pickles, A., Baron-Cohen, S., Bolton, P., Johnson, M. H. and the BASIS Team. (2012). Infant neural sensitivity to eye gaze predicts characteristics of autism at two years. Current Biology, 33, 338-342.

Guiraud, J. A., Tomalski, P., Kushnerenko, E., Ribeiro, H., Davies, K., Charman, T., Elsabbagh, M., Johnson, M. H., & the BASIS Team (2012). Atypical audiovisual speech integration in infants at risk for autism. PLoS One, 7, e36428. Gliga, T., Elsabbagh, M., Hudry, K., Charman, T., Johnson, M. H. and the BASIS Team. (2012). Gaze following, gaze reading, and word learning in children at-risk for autism. Child Development, 83, 926-938. Stahl, D., Pickles, A., Elsabbagh, M., Johnson, M. H., & the BASIS team. (2012). Novel machine learning methods for ERP analysis: A validation from research on infants at risk for autism. Developmental Neuropsychology, 37, 274-298. Wan, M. W., Green, J., Elsabbagh, M., Johnson, M. H., Charman, T., Plummer, F., & the BASIS Team. (2012). Parent-infant interaction in infant siblings at risk of autism: A controlled observational study. Research in Developmental Disabilities, 33, 924-932.

Susan Bryson, Dalhousie University **Kuwaik GA, Roberts W, Zwaigenbaum L, Bryson S, Smith IM, Szatmari P, Mackinnon BM, Tanel N, Brian J. (2012) Immunization uptake in younger siblings of children with autism spectrum disorder. Autism [Epub ahead of print; PubMed PMID: 23045216]. **Zwaigenbaum L, Bryson SE, Szatmari P, Brian J, Smith IM, Roberts W, Vaillancourt T, Roncadin C. (2012) Sex differences in children with autism spectrum disorder identified within a high-risk infant cohort. J Autism Dev Disord, 42(12):2585-96.

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Karen Dobkins and her students at U. California San Diego

Leslie Carver, University of California San Diego **Cornew, L. Dobkins, K., Akshoomoff, N.A., McCleery, J., & Carver, L.J. (2012). Social referencing in infants at risk for autism: Evidence for a broader autism phenotype at 18 months of age. Journal of Autism and Developmental Disorders, 42, 2611-2621. Kasia Chawarska, Yale University Macari, S., Campbell, D., Gengoux, G.W., Saulnier, C.A., Klin, A.J., Chawarska, K. (2012). Predicting developmental status from 12 to 24 months in infants at risk for Autism Spectrum Disorder: A preliminary report. Journal of Autism and Developmental Disorders, 42, 2636-2647. Chawarska, K., Macari, S., & Shic, F. (2012). Context modulates attention to social scenes in toddlers with autism. Journal of Child Psychology and Psychiatry 53(8), 903-913. Steiner, A., T. Goldsmith, Snow A., & Chawarska, K. (2012). Practitioner‟s guide to assessment of Autism Spectrum Disorders in infants and toddlers. Journal of Autism and Developmental Disorders 42(6), 1183-1196

Karen Dobkins, University of California at San Diego **Cornew, L. Dobkins, K., Akshoomoff, N.A., McCleery, J., & Carver, L.J. (2012). Social referencing in infants at risk for autism: Evidence for a broader autism phenotype at 18 months of age. Journal of Autism and Developmental Disorders, 42, 2611-2621.

The research team at Yale University

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Infant Brain Imaging Study, Joe Piven PI Wolff JJ, Gu H, Gerig G, Elison JT, Styner M, Gouttard S, Botteron KN, Dager SR, Dawson G, Estes AM, Evans AC, Hazlett HC, Kostopoulos P, McKinstry RC, Paterson SJ, Schultz RT, Zwaigenbaum L, Piven J; IBIS Network. (2012) Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. American Journal of Psychiatry, 169 (6):589-600. Hazlett HC, Gu H, McKinstry RC, Shaw DW, Botteron KN, Dager SR, Styner M, Vachet C, Gerig G, Paterson SJ, Schultz RT, Estes AM, Evans AC, Piven J; IBIS Network. (2012) Brain volume findings in 6-month-old infants at high familial risk for autism. American Journal of Psychiatry, 169(6):601-8. Kim SH, Fonov V, Dietrich C, Vachet C, Hazlett HC, Smith R, Graves MM, Piven J, Gilmore JH, Dager SR, McKinstry R, Paterson S, Evans AC, Collins LD, Gerig G, Styner M.; The IBIS network. (2012) Adaptive prior probability and spatial temporal intensity change estimation for segmentation of the one-year-old human brain. Journal of Neuroscience Methods, Note: vol. 212, no. 1, pp. 43–55, M. Datar, P. Muralidharan, A. Kumar, S. Gouttard, J. Piven, G. Gerig, R.T. Whitaker, P.T. Fletcher. (2012) Mixed-Effects Shape Models for Estimating Longitudinal Changes in Anatomy. Spatio-temporal Image Analysis for Longitudinal and Time-Series Image Data, Lecture Notes in Computer Science, Vol. 7570, Edited by Stanley Durrleman, P. Thomas Fletcher, Guido Gerig, Marc Niethammer, Springer Berlin / Heidelberg, pp. 76--87. 2012. Fishbaugh J, Prastawa M, Durrleman S, Piven J, Gerig G; IBIS Network. (2012) Analysis of longitudinal shape variability via subject specific growth modeling. Med Image Comput Comput Assist Intervention, 15(Pt 1):731-8. Vardhan, M. Prastawa, S. Gouttard, J. Piven, G. Gerig. (2012) Quantifying regional growth patterns through longitudinal analysis of distances between multimodal MR intensity distributions,” In Proceedings of IEEE ISBI 2012, pp. 1156--1159. DOI: 10.1109/ISBI.2012.6235765 M. Farzinfar, C. Dietrich, R. G. Smith, Y. Li, A. Gupta, Z. Liu, and M. Styner (2012) Entropy based DTI quality control via regional orientation distribution. Biomedical Imaging (ISBI), 2012 9th IEEE International Symposium pp. 22–25. Jana Iverson, University of Pittsburgh Sheinkopf, S.J., Iverson, J.M., Rinaldi, M.L., & Lester, B.M (2012). Atypical cry acoustics in

6-month old infants at-risk for Autism Spectrum Disorder. Autism Research, 5, 331-339.

Taffoni, F., Focaroli, V., Formica, D., Guglielmelli, E., Keller, F., & Iverson, J.M. (2012).

Sensor-based technology in the study of motor skills in infants at risk for ASD.

Proceedings of the Fourth IEEE RAS/EMBS International Conference on Biomedical

Robotics and Biomechatronics, 1879-1883.

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Scott Johnson, UCLA Hutman, T., Rozga, A., DeLaurentis, A.D., Sigman, M., & Dapretto, M., Pre-Empathic Behaviors are Associated with Language Skills, Infant Behavior & Development, 2012, 35 (3), 561-569. (NIHMSID #388649) Hutman, T., Chela, M., Gillespie-Lynch, K., & Sigman, M., Selective Visual Attention at Twelve Months: Signs of Autism in Early Social Interaction, Journal of Autism and Developmental Disabilities, 2012, 42 (4): 487-498. Navab, A., Gillespie-Lynch, K., Johnson, S.P., Sigman, M., & Hutman, T., Eye Tracking as a Measure of Responsiveness to Joint Attention in Infants at Risk for Autism, Infancy, 2012 Jul/Aug, 17 (4), 416-431. Ami Klin, Emory University

Shultz, S., Klin, A., & Jones, W. (2012). Inhibition of eye blinking reveals subjective perceptions of stimulus salience. Proceedings of the National Academy of Sciences, 108(52), 21270-5. **Macari, S. L., Campbell, D., Grace, W.G., Saulnier, C., Klin, A., & Chawarska, K. (2012). Predicting Developmental Status from 12 to 24 Months in Infants at Risk for Autism Spectrum Disorder: A Preliminary Report. Journal of Autism and Developmental Disorders, 42(12), 2636-2647.

**Steiner, A. M., Gengoux, G. W., Klin, A., & Chawarska, K. (2012). Pivotal Response Treatment for Infants At-Risk for Autism Spectrum Disorders: A Pilot Study. Journal of Autism and Developmental Disorders, 43(1), 91-102.

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Rebecca Landa, Kennedy Krieger Institute/Johns Hopkins University Bhat, A., Galloway, J.C., & Landa, R.J. (2012). Relation between early motor delay and later communication delay in infants at risk for autism. Infant Behavior & Development, 35, 838-846. Flanagan, J.E., Landa, R., Bhat, A., & Bauman, M. (2012). Head lag in infants at risk for autism: A preliminary study. American Journal of Occupational Therapy, 66, 577–585. Hess, C., & Landa, R.J. (2012). Predictive and concurrent validity of parent concern about young children at risk for autism. Journal of Autism and Developmental Disorders, 42, 575-584. Landa, R.J., Gross, A.L., Stuart, E.A., & Bauman, M. (2012). Latent class analysis of early developmental trajectory in baby siblings of children with autism. Journal of Child Psychology and Psychiatry, 59, 986-996. ***Newschaffer, C., Croen, L., Fallin, D., Hertz-Piccioto, I., Nguyen, D., Lee, N.,…Shedd-Wise, K. (2012). Infant siblings and the investigation of autism risk factors. Journal of Neurodevelopmental Disorders, 4(7), 1-16. Daniel Messinger, University of Miami Ibanez, L., Grantz, C.J., Messinger, D.S. (2012). The development of referential communication and autism symptomatology in high-risk infants. Infancy, 1–21.

Daniel Messinger‟s lab group at University of Miami

Rebecca Landa‟s research team at Kennedy Krieger

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Charles Nelson‟s infant siblings studies lab

team

Ekas, N. Haltigan, J.D., Messinger, D.S. (2012). The Dynamic Still-Face Effect: Do Infants Decrease Bidding Over Time When Parents are Not Responsive? Developmental Psychology. McDonald, N. & Messinger, D. (2012). Empathic Responding in Toddlers at Risk for an Autism Spectrum Disorder. Journal of Autism and Developmental Disorders, 42(8), 1566-1573.

Charles Nelson, Children’s Hospital of Boston Seery, A.M., Vogel-Farley, V., Tager-Flusberg, H., &

Nelson, C.A. (2012). Atypical lateralization of ERP

response to native and non-native speech in infants

at risk for autism spectrum disorder. Developmental

Cognitive Scienc, 5C:10-24.

Tierney, A.L., Gabard-Durnam, G., Vogel-Farley, V.,

Tager-Flusberg, H., & Nelson, C.A. (2012).

Developmental trajectories of resting EEG power: An

Endophenotype of Autism Spectrum Disorder. PLoS

One 7(6): e39127.

Sally Ozonoff, University of California at Davis **Newschaffer, C.J., Croen, L.A., Fallin, M.D., Hertz-Picciotto, I., Nguyen, D., Lee, N.L., Berry, C.A., Farzadegan, H., Hess, H.N., Landa, R.J., Levy, S.E., Massolo, M.L., Meyerer, S.C., Mohammed, S.M., Oliver, M., Ozonoff, S., et al. (2012). Infant siblings and the investigation of autism risk factors. Journal of Neurodevelopmental Disorders, 4(7), 1-16. PMCID: 3436647 Wendy Stone, University of Washington/Vanderbilt University Warren, Z.E., Foss-Feig, J.H., Malesa, E.E., Lee, E.B., Lounds Taylor, J., Newsom, C.R., Crittendon, J., & Stone, W.L. (2012). Neurocognitive and behavioral outcomes of younger siblings of children with autism spectrum disorder at age five. Journal of Autism and Developmental Disorders, 42, 409-418. Key, A.P.F., & Stone, W.L. (2012). Processing of novel and familiar faces in infants at average and high risk for autism. Developmental Cognitive Neuroscience, 2, 244-255. Key, A.P.F., & Stone, W.L. (2012). Same but different: Nine-month-old infants at low and high risk for autism look at the same facial features but process them using different brain mechanisms. Autism Research, 5, 253-266. PMID: 22674669.

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Mark Strauss, University of Pittsburgh Dundas, E., Gastgeb, H., & Strauss, M.S. (2012) Left visual field biases when infants process faces: A comparison of infants at high- and low- risk for autism spectrum disorders. Journal of Autism and Developmental Disabilities, 42, 2659-2668. Lonnie Zwaigenbaum, University of Alberta

**Kuwaik GA, Roberts W, Zwaigenbaum L, Bryson S, Smith IM, Szatmari P, Mackinnon BM, Tanel N, Brian J. Immunization uptake in younger siblings of children with autism spectrum disorder. Autism. 2012 Oct 8. **Zwaigenbaum L, Bryson SE, Szatmari P, Brian J, Smith IM, Roberts W, Vaillancourt T, Roncadin C. Sex differences in children with autism spectrum disorder identified within a high-risk infant cohort. J Autism Dev Disord. 2012 Dec;42(12):2585-96.

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Newly Funded Grants in 2012 BASIS Innovative Medicines Initiative (EU/EFPIA) Declan Murphy (PI) 2012-2017 “European Autism Interventions – A Multicentre Study for Developing New Medications (EU-AIMS)” Simons Foundation Mark Johnson (PI) 2012-2014 “Developing NearInfraRed Spectroscopy (NIRS) as a brain function indicator in infants at-risk for later autism” Autistica Mark Johnson (PI) 2012-2015 “Renewal of the British Autism Study of Infant Siblings” Suzanne Curtin, University of Calgary NICHD A. Vouloumanos (PI) & S. Curtin, (Co-PI) 2012-2017 "Divergent processing for conspecifics as early markers for Autism Spectrum Disorder" Kasia Chawarska, Yale University NIMH R03: K. Chawarska (PI) “Pivotal Response Treatment for Infants at Risk for ASD: A Pilot Intervention. “ Judith Gardner, IBR Autism Speaks Gardner (PI) 2012-2015 "Very Early Behavioral Indicators of ASD Risk among NICU Infants: A Prospective Study" Infant Brain Imaging Study, Joe Piven, PI NICHD J. Piven (PI) 2012-2017 “A Longitudinal MRI Study of Infants at Risk for Autism” NIMH John Pruett (PI) 2012-2017 “fcMRI in Infants at High Risk for Autism” Autism Speaks J. Piven (PI) 2012-2013 “A Longitudinal EEG Study of Infants at Risk for Autism: Network Capacity Building (Phase I)” Scott Johnson, UCLA NIH S. Bookheimer and S. Johnson, (PI) 2012-2017 Neural assays and longitudinal assessment of infants at very high risk for ASD

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Ami Klin, Emory University NIMH Klin A (PI) 2012-2017 “NIH Autism Center of Excellence: Mechanisms of Risk and Resilience in ASD: Ontogeny, Phylogeny and Gene Disruption” Rebecca Landa NIMH Landa (PI) 2012-2017 “Autism: Social and Communication Predictors in Siblings” Charles Nelson, Children’s Hospital of Boston Autism Speaks Brandon Keehn (PI) 2012-2014 “Understanding the Etiological Significance of Attentional Disengagement in Infants at Risk for Autism Spectrum Disorder “ Nurit Yirmiya The “Shalem” Foundation Yirmia, N. (PI) 2012-2015 “The risk for developmental delays among preterm born children”

Ami Klin‟s team at Emory University

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Doctoral and Postdoctoral Training on BSRC Projects

The following graduate students and post-doctoral fellows were actively involved in the research programs directed by members of the CPI that focused on high risk infants. BASIS Doctoral students Rachel Bedford - Doctoral student (IOE, London) Kate Graham - Doctoral student (Birmingham University) Sissy Stefanidou – Doctoral student (Birmingham University) Post-doctoral fellows: Anna Blasi – Postdoctoral Fellow (Birkbeck, London) Teodora Gliga – Postdoctoral Fellow (Birkbeck, London) Elena Orekhova – Postdoctoral Fellow (Birkbeck, London) Emily Jones – Postdoctoral Fellow (Birkbeck, London) Greg Pasco – Postdoctoral Fellow (IOE, London) Sarah Lloyd Fox – Postdoctoral Fellow (Birkbeck, London) Sam Wass – Postdoctoral Fellow (Birkbeck, London) Susan Bryson, Dalhousie University Lori Sacrey, postdoctoral fellow, Dept. of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta. Supported by CIHR Autism Research Training Program Fellowship Suzanne Curtin, University of Calgary Danielle Droucker Jennifer Ference, Social Sciences and Humanities Research Council of Canada; Alberta Innovates Health Solutions; Killam Fellowship; Autism Research Training (ART) Kasia Chawarska, Yale University Doctoral Students Rebecca Doggett, MA, Predoctoral Clinical Psychology Fellow Postdoctoral Fellows Daniel Campbell, PhD., Autism Speaks Postdoctoral Fellow in Statistics Judah Koller, PsyD, Postdoctoral Fellow in Clinical Psychology Sophy Kim, PhD, Postdoctoral Fellow in Clinical Psychology Nita Vaswani, MD, Developmental-Behavioral Pediatrics Fellow

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Justin Rowberry, MD, Developmental-Behavioral Pediatrics Fellow Karen Dobkins, UCSD and Leslie Carver, UCSD Katherine K.M. Stavropolous Deborah Fein, University of Connecticut Alexander Hinnebusch, supported on R01 HD039961. Judith Gardner, Institute of Basic Research, NY Yocheved Bensinger-Brody, MA PT, M. Phil. Funding Sources: Research Fellowship, Center for Developmental Neuroscience and Developmental Disabilities, Staten Island, NY; Doctoral Student Grant Award, CUNY Infant Brain Imaging Study, Joe Piven, PI Doctoral Students Philip Cali.; Doctoral student, Educational Psychology; University of Washington; clinical assessment trainee; IBIS Shanna Alvarez; Doctoral student, Educational Psychology; University of Washington; IBIS Neda Sadeghi, M.S., Doctoral Student, University of Utah, Dept. Bioengineering. Avantika Vardhan, M.S., Doctoral Student, University of Utah, Dept. Bioengineering, Breanna Winder, MS, Doctoral Student (currently completed her APA Clinical Psychology Internship), Bryn Mawr University, Dept. Psychology. Post-doctoral Fellows Jason Wolff, Ph.D, UNC Stanley Durrleman, PhD, University of Utah (mentor G. Gerig) Terisa Gabrielsen, PhD, Center for Autism Research, Children‟s Hospital of Phlladelphia Michele Villalobos, PhD, Center for Autism Research, Children‟s Hospital of Phlladelphia Neva Corrigan, PhD, University of Washington (mentor SR Dager). Mahshid Farzinfar, PhD, UNC (mentor M Styner) SunHyung Kim, PhD, UNC (mentor M Styner) Jana Iverson, University of Pittsburgh Doctoral students: Meaghan Venezia Parlade, Ph.D. (on clinical internship in 2012) Nina Leezenbaum, M.S. (Autism Science Foundation Predoctoral Fellowship) Jessie Northrup, B.A.

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Postdoctoral fellow: Eve Sauer LeBarton, Ph.D. Scott Johnson, UCLA Kristen Gillespie-Lynch Ami Klin, Emory University Doctoral Students: Jennifer Moriuchi Rebecca Burger-Caplan Post-doctoral fellows: Sarah Shultz PhD Shweta Ghai PhD [Mentor: G Ramsay PhD) Rebecca Landa, Kennedy Kreiger Institute Doctoral Student: Meredith Brinster, M.S., University of Texas at Austin, Doctoral Student in Educational Psychology Post Doctoral Fellows: Klaus Libertus, Ph.D., Funding Sources: NIMH, Autism Science Foundation Kelly Sheperd, Ph.D., Research Psychologist, Project Coordinator Funding Sources: NIH and HRSA Daniel Messinger, University of Miami Devon Gangi, Funded by R01HD057284 Whitney Mattson, Funded by R01HD057284 Charles Nelson, Children’s Hospital of Boston and Helen Tager-Flusberg, Boston University Doctoral Students Boston University

Mihaela Chita Anne Seery (funded by Autism Speaks Weatherstone) Meagan Thompson Karen Chenausky

Infant siblings team at BU

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Wendy Stone and students

Harvard University Laura Edwards (Funded by Autism Speaks Weatherstone)

Post-doctoral Fellows Brandon Keehn (Funded by Autism Speaks) April Levin (Funded by Autism Science Foundation)

Sally Ozonoff, UC Davis Doctoral Student: Meghan Miller Mark Shen Postdoctoral Fellow: AJ Schwichtenberg, PhD, NIMH K99-R00 award Wendy Stone, University of Washington Doctoral Students: Colleen Harker Sarah Edmunds Postdoctoral Fellows: Lisa Ibanez, PhD (funded by NICHD Supplement) Mark Strauss, University of Pittsburgh Holly Gastgeb, PhD Lisa Sperle, BS Katherine Hauschild, BS Sara Jane Webb, University of Washington Rachel Kincade

Nurit Yirmiya, Hebrew University

Doctoral Students:

Yaari Maya Harel Ayelet – MA student Gabsi Neta – MA student Rotzak Natalie – MA student Ruth Carmon – MA student

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Chen Ben-Yaakov – MA student Lonnie Zwaigenbaum, University of Alberta Doctoral students: Ellen Drumm, MSc Student, Ontario Institute of Special Education, University of Toronto Tamara Germani, PhD Student, Dept. of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Supported by U Alberta Entrance Scholarship Shelley Mitchell, PhD Student, Dept of Speech Language Pathology, University of Toronto Stelios Georgiades, PhD Student, Dept of Clinical Epidemiology and Biostatistics, McMaster University , Supported by CIHR Autism Research Training Program Julie Longard, PhD Student, Dept. of Psychology, Dalhousie University, Supported by CIHR Autism Research Training Program Gillian Filliter PhD Student, Dept. of Psychology, Dalhousie University, Supported by y CIHR Autism Research Training Program and Autism Speaks Dennis Weatherstone Pre-doctoral Fellowship Ainsley Boudreau, PhD Student, Dept. of Psychology, Dalhousie University, Supported by CIHR Autism Research Training Program Postdoctoral fellows: Lori Sacrey, postdoctoral fellow, Dept. of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta (note: co-supervised by Dr. Bryson, Dalhousie University) („Early Reaching Behavior in ASD‟). Supported by CIHR Autism Research Training Program Fellowship Vickie Armstrong, postdoctoral fellow, Dept of Psychology, Dalhousie University

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AS Toddler Treatment Network: Report Update

Established in 2007, the Toddler Treatment Network brought together researchers of AS funded projects which used randomized control trials of behavioral interventions prior to 26 months of age. These studies share several commonalities, including (1) they are parent-implemented, and (2) they all involve naturalistic delivery of interventions addressing the earliest autism behavioral phenotype and thus are heavily focused on communication: joint attention, imitation, gestures and language. The projects use different intervention models, most of which involve adaptations of existing preschool interventions to make them more infant-appropriate. The intervention involve techniques that can be implemented outside the clinic, allowing parents and caregivers to use these techniques in different settings, decreasing the time between parent‟s initial concern and beginning intervention, thus hopefully improving developmental outcome in the long run. Because they require less “in clinic” time, they may also be very cost effective. A summary of each of these projects can be found here: http://www.autismspeaks.org/science/research/initiatives/toddler_treatment_network.php The overarching goals of the network are to a) improve measurement tools regarding outcomes for toddlers and their families, b) define or identify the best practices for designing and implanting efficacious parent-delivered interventions, c) improve research designs and analytic approaches for early intervention studies, d) facilitate young researchers to develop productive programs of high quality treatment research and e) disseminate evidence of efficacy of early intervention with toddlers. As there are similarities in outcome measures, methods of intervention and study design, in addition to discovering project-specific effects, the group prepared to combine data across sites. In 2011 a meta analysis of TTN research was funded by Autism Speaks and is being led by members Sally Rogers and Paul Yoder. In 2012, the network expanded to invite junior and more established researchers in the field. A total of 65 researchers from over a dozen projects came together in Toronto Canada for the first Early Intervention for Autism Conference. The discussions fell into several important topics: We spent the day learning about the latest findings from this research. I see it as falling into five important areas:

1. Earlier is better. We know that earlier interventions produce greater gains for individuals with ASD. This year, we even heard about early intervention studies enrolling infants at high risk of developing autism. This research is exciting but very preliminary. We don‟t know yet whether it produces benefits or what they might be.

2. Intensity matters. It‟s also clearer than ever that the benefits of quality therapy increase with the number of hours a child is receiving. This encourages us to look for practical ways to maximize the amount of time children are actively engaged in therapy.

3. Parent participation. One potential way to increase intervention hours is for parents to continue practice at home. The latest findings support the idea that this can enhance the benefits of professionally delivered therapy. Parent-led activities also

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expand therapy opportunities into broader environments. This may be important for helping children transfer skills from one situation to the next.

4. Individualized goals. Each child with ASD will respond best to strategies tailored to his or her personal needs and skills. Some children need more emphasis on communication skills. Others need greater help with social interaction or challenging behavior.

5. Delivering evidence-based interventions to the community. Developing and studying the benefits of early interventions is not enough. We have much work ahead to move effective interventions into our communities. We must redouble our efforts to make sure these programs are available to all children with ASD. At this year‟s meeting, we discussed how Autism Speaks Move the Needle initiative is advancing this important work.

As a result of the meeting, a workgroup convened through 2012 to describe and define the term “naturalistic behavior intervention”. This is important because different types of interventions have different names and may be considered for insurance coverage differently. Of interest, these interventions have important common elements that are evidenced based and effective. Therefore, a white paper or consensus paper will help thousands of individuals who are struggling to understand the difference to the approaches and help justify insurance coverage.

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Ongoing Collaborative Projects (2012)

A: Prospective Study of Head Circumference in Infants at Risk for ASD Project Leader: Lonnie Zwaigenbaum Working group: Lonnie Zwaigenbaum, Wendy Stone, Karen Dobkins, Sally Ozonoff This was the first collaborative data project of the BSRC. Supplemental funds were provided by AS to set up the data management team and database at Vanderbilt University. Current analyses indicate atypical increased head circumference in infant siblings of children with ASD compared to low-risk infants with no family history of ASD. However, it does not appear that increased HC is associated with the likelihood of autism among infant siblings in this particular sample. An abstract was presented at IMFAR 2008. An additional funding supplement was awarded by AS to update the data to reflect current outcome status in participating high-risk and low-risk infants, finalize quality control, and conduct additional analyses. With funding in 2010 to create a BSRC database, these tasks were transferred to UC Davis (Gregory S. Young, PI) and analyses are being finalized. It is expected that a draft of a manuscript from this project will be completed and submitted for publication in 2013 B: BSRC DNA Biorepository Project Leader: Lonnie Zwaigenbaum Working Group: Lonnie Zwaigenbaum, Stephen Scherer, Sally Ozonoff, Rebecca Landa, Daniel Messinger, Wendy Stone, Karen Dobkins, Zachary Warren There has been substantial progress in identifying ASD susceptibility genes; specifically, rare de novo and inherited „copy number variants‟ (CNVs) involving neuronal synaptic genes. These rare variants appear to be highly penetrant, and collectively, account for a significant proportion of ASD cases. If genetic markers could be used to identify infants likely to develop ASD, this could revolutionize opportunities for earlier diagnosis and treatment. Thus, advances in genetic research, coupled with the availability of high-risk infant cohorts, have created the unique opportunity to test the predictive validity of genetic variants for ASD diagnoses. With new peer-reviewed grant funding from Autism Speaks and the Simons Foundation, the BSRC Biorepository was formally established in 2012. Six BSRC sites have begun recruitment of families and collection of blood samples as well as supplementary phenotype and pregnancy/birth and home environmental data. We are progressing towards a target sample of 445 at risk families by 2014. Co-principal investigator Dr. Stephen Scherer is leading the genetic analyses in this unique sample, supported by additional project funding from Autism Speaks. With rapid developments in genomic technology, we are working towards securing funding to make the leap from CNV microarray approaches to exome or whole genome sequencing in the full sample, creating exciting opportunities to examine the potential clinical utility of sequence variants to predict developmental course and outcomes in high-risk infants. The BSRC Biorepository promises to generate new genomic-based strategies for early detection of ASD, and will also provide a long-term resource for future biomarker research.

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C. The broader range of outcomes in later siblings of children with ASD Project leaders: Daniel Messinger and Gregory Young Workgroup members: Becky Landa, Jana Iverson, Mark Strauss, Lonnie Zwaigenbaum, Sally Rogers, Sally Ozonoff, Alice Carter, Wendy Stone, Susan Bryson The BSRC followed-up on the 2011 report that one in five high-risk siblings met criteria for ASD at age 3 by investigating the outcomes of the children without ASD. Study of the broader range of outcomes was published in early 2013. As a group, high-risk siblings without an ASD outcome exhibited higher mean ADOS severity scores (more symptoms) and lower verbal and non-verbal developmental quotients than low-risk controls at 3 years. A latent class analyses characterized typical outcomes of HR siblings and LR controls. HR siblings were over-represented (21% HR versus 7% LR) in latent classes characterized by elevated ADOS severity and/or low to low average developmental quotients. However, the remaining HR siblings without ASD outcomes (79%) belonged to classes in which they were not over-represented with respect to LR siblings. In sum, looking only at HR siblings without an ASD outcome, HR siblings exhibited higher mean levels of ASD severity and lower levels of developmental functioning than LR children. However, the class membership of four-fifths of the HR siblings was not significantly different from that of LR siblings. One-fifth of HR siblings belonged to classes characterized by higher ASD severity and/or lower levels of developmental functioning. This is the first empirically derived characterization of an early-emerging pattern of difficulties in a minority of 3-year-old HR siblings. It suggests the importance of developmental surveillance for all HR siblings and early intervention for a minority of these children. D. Trajectories of high risk infants Project leader: Rebecca Landa Workgroup members: Sally Ozonoff, Alice Carter, Lonnie Zwaigenbaum, Karen Dobkins, Leslie Carver, Kasia Chawarska, Joe Piven, Tony Charman, Scott Johnson, Wendy Stone, Jessica Brian, Suzanne Macari, Gregory Young, Heather Cody Hazlett, Alden Gross, Elizabeth Stuart There is heterogeneity in developmental course in the first three years of life in later-born siblings of children with autism spectrum disorders (ASD) (siblings-A). Approximately 19% of siblings-A will have an outcome of ASD (Ozonoff et al., 2011). Within the group of children with ASD outcomes, heterogeneity in developmental trajectory is expected (Landa, Holman, & Garrett-Mayer, 2007; Landa, Gross, Stuart, & Bauman, 2012). Within the group of siblings-A with non-ASD outcomes, there may also be heterogeneity in trajectory (Landa et al., 2012). There is evidence that some non-ASD siblings-A show disruption in one or more aspects of development around age 6 months, but do not later manifest an ASD (Young et al., 2009; Flanagan, Landa, Bhat, & Bauman, in press). Furthermore, there is evidence that different developmental systems (e.g., motor, language, nonverbal cognitive, social) vary in trajectory for different subgroups of siblings-A. Thus, these developmental systems may vary in timing of growth spurts, plateau, or decline in rate of growth; or in actual frequency or diversity of behaviour (Landa et al., 2007; Ozonoff et al., 2010) within and across subgroups of siblings-A, depending on outcome classification. This work group is analyzing developmental trajectories of later-born siblings of children with ASD whose data are in the BSRC database. We are examining whether there are distinct classes of development within infant siblings of children with ASD (siblings-A), from

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6 through 36 months of age, across developmental domains including motor, language, cognitive, and social functioning. This will enable us to define diversity of distinct contours of developmental trajectories in the first three years of life within siblings-A, regardless of outcome classification; stability of growth within various aspects of development from 6-36 months, and stability of ASD symptomatology from the second year of life through the third birthday; how trajectories across different developmental systems are related within different developmental classes for siblings-A, yielding information about relative timing of growth, attenuation of growth, plateau, and even diminishing skills within those classes; differences and similarities in trajectories between low risk controls and siblings-A; and whether specific child characteristics are related to specific classes developmental trajectories (e.g., gender, number of children in the family with ASD, severity of autism in the proband, age at which parent first became concerned about the child, age of onset of intervention). E. Symptom profiles of 18-month-old infants at risk for ASD: Associations with diagnostic outcome at 36 months. Project leader: Kasia Chawarska Workgroup members: Tony Charman, Sally Ozonoff, Becky Landa, Lonnie Zwaigenbaum, Charles Nelson, Jessica Brian, Gregory Young, Fred Shic, Suzanne Macari, Ted Hutman, Helen Tager-Flusberg, Daniel Campbell, The project employs a non-parametric decision-tree learning algorithm (Classification and Regression Trees, or CART) to predict 36-month clinical best estimate diagnosis using item-level data from the ADOS-G Module 1 at 18 months. This approach has recently been used by our group (Macari et al., 2012) as well as by others (Lord et al., 2011) to address issues related to classification of individuals with complex clinical presentations. Understanding the different combinations of traits at 18 months that lead to the “same” ASD diagnosis at the age of 3 will facilitate our understanding of different „pathways‟ to ASD diagnosis, aid in the development of early screening and diagnostic methods as well as lead to the identification of potentially more homogenous subgroups within the autism spectrum, resulting in advances for genetic, neuroimaging, and treatment research. We have completed our data analysis and are currently in the process of writing up the manuscript. The following sites contributed their data to the project: Harvard/BU, The Canadian Group, UCLA, MIND Institute, Kennedy Krieger Institute, and Yale.

Completed Collaborative Projects Developmental Outcomes in Later-born Siblings of Children with ASD Project Leaders: Sally Ozonoff and Nurit Yirmiya At the December 2007 meeting, several BSRC sites presented data on developmental outcomes of siblings at risk. It was agreed that this topic would be the focus of a collaborative project, as a primary project for the Consortium. During 2008, data were collected from all sites that had outcome data on at least a portion of their sample. In 2009, a database was created to merge data across sites, data were cleaned, and analyses performed. Final results were obtained in 2010 and submitted for publication. Data from

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664 infants with an older sibling with autism were included in the final analyses. 18.7% of infants developed an ASD. Infant sex and the presence of more than one older affected sibling were significant predictors of ASD outcome, with an almost three-fold increase in risk for males and an additional two-fold increase in risk if there was more than one older affected sibling. In contrast, the age of the infant at study enrollment, the sex and functioning level of the infant‟s older sibling, and other demographic factors did not predict ASD outcome. This data, pooled across 12 sites, indicates that the sibling recurrence rate of ASD is higher than suggested by previous estimates. This paper was published in Pediatrics in September 2011 and generated a great deal of media and public attention, including 523 news stories, in 17 languages, with estimates of over 12 million viewers.

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In Memory of Marian Sigman Marian Sigman died on April 30th, 2012 at the age of 70. As a post-doc at UCLA, she became interested in the discontinuity between measures of IQ in infancy and later in childhood. This inspired a career of longitudinal research, first linking the efficiency of information processing in infancy with IQ in childhood and adolescence. Later, she led several studies that examined associations between early deviations of development in autism and later outcomes in the domains of language and social behavior. She contributed to the identification of deficits in joint attention, symbolic play, and empathy in children with autism. Her work demonstrated that children with autism can achieve secure patterns of attachment. She was among the first to advocate for the importance of examining infant siblings of children with autism as a means to characterize the prodrome of autism.

She was the Co-Director of the UCLA Center for Autism Research & Treatment, Associate Editor of Child Development, Chair of the Advisory Committee of the National Childcare Study, and founding President of both the International Society for Infant Studies (ISIS) and the International Society for Autism Research (INSAR). In May 2009, she received the Lifetime Achievement Award from INSAR. She is survived by two children, four grandchildren, and countless grateful students and colleagues.

Acknowledgements We want to thank the generous families who have donated their precious time to participate in these studies. Without them, this research and these important discoveries would not be possible

BSRC research at IBR in NY is studying infants from birth