A Multisite Neurobehavioral Assessment of FASD Sarah Mattson, PI CIFASD Mid-Year Progress Meeting Clinical Meeting January 5-7, 2010 Joint day presentations (all CIFASD PIs, the Science Advisory Board and NIAAA): 10 minute PPT presentations. Only the main PI/representative per project will present. We are looking for you to update the entire CIFASD staff on your progress, much as you would present to a scientific meeting. What have you discovered that is of benefit to the FASD community as a whole (researchers, policy makers, caregivers, individuals affected by FASD). How can your project interact or collaborate with other projects, maybe across the basic and clinical divides? Clinical only day presentations (clinical PIs, the SAB, and NIAAA): 10 PPT slide max. Focus talk on current numbers, methodologies, why goals haven't been met, plans to meet future goals, and troubleshooting ideas (if applicable). Subcontract/Site PIs/representatives can present, and probably should if they can help address the above issues. In any event they should be available to answer questions specific to their site. During this day we want to find out not only what great things you have found out, but what is hampering your work. What are the questions you want to pose, but don't have the available data to answer those questions. This is a day to try and hammer out where you are going, and what the clinical projects, the cores, and NIAAA can do to help.

Overall Progress to Date: Neurobehavioral Testing SA started data collection in June Re-post

Progress to Date: All Measures Site NB I NB II Goal (II) Dysm* 3-D DNA MRI SDSU 118 108 150 163 110 82 38 UCLA -- 48 75-95 46 45 Emory 61 100-150 50 34 UNM 31 280 5 Plains 83 36 240 UCT 113 67 33 Total 314 350 1085-1155 432 268 162 112 Goals don’t reflect the 10% budget cut in all years. UCT dysmorphology is different than reported b/c of duplicates. SDSU scheduled: MRI: 3 NP: 7 *Dysmorphology includes Phase I data for some sites

Data in Central Repository: Neurobehavior Site Children Tested Records in CR SDSU 108 107 UCLA 48 Emory 61 34 UNM 31 1 Plains 36 4 UCT 67 62 Total 350 256 correct

Data in Central Repository: Demographics Site Children Tested Dem-Static Dem-Dynamic SDSU 108 184* 97 UCLA 48 33 Emory 61 43 42 UNM 31 1 Plains 36 4 UCT 67 Total 350 207 123 *Includes Phase I data for SDSU

ARRA Supplements U01 AA014834-05S1 (7/10/2009-5/31/2011) $27,296 was granted to support undergraduate students in summer research experiences at SDSU 3 students were support (1 FT, 2 PT) for summer of 2009 1 poster is being presented at INS in February and 2 will be submitted to RSA 2 students will be sought for summer of 2010

ARRA Supplements U01 AA014834-05S2 (7/15/2009-6/30/2011) $200,000 (DC) was granted to support supplemental activities SDSU: $100,000 to retain or add personnel for recruitment, data collection, and data entry. 33% of funds have been spent, exclusively on personnel. UNM: $100,000 to retain site managers at 4 remote sites. These individuals will be responsible for recruitment, and facilitation of clinic logistics, tribal liaison, and other logistical support for the UNM CIFASD team. 99% of funds available for invoicing.

Site Specific Progress: San Diego Progress: Data Collection Completed Phase I testing. Final sample size is 118, including 20 ADHD subjects Tested, scored, and uploaded data from 108 Phase II subjects (144% of 12/31goal) Uploaded demographics data for 97 of 107 subjects Collected 3-D photos (147%), DNA, brain imaging (95%) data Coordinated dysmorphology examinations Progress: Administrative Continued material distribution, training, and reliability for all sites Held 3rd training meeting in San Diego (March, 2009) Held monthly conference calls of all PIs and site staff Collaborated with Informatics to finalize neurobehavioral and demographics data bases Created group assignment flow-chart in collaboration with other sites Progress: Analytic Completed “profile” project, paper submitted Analyzing dysmorphology/neuropsych data Rescoring and analyzing data from SCT Low IQ group

Site Specific Progress: San Diego Issues Recruitment in IQ group is behind that of other groups Dynamic demographics data for Phase I subjects is behind Phase II subjects For data analysis, missing data impeding larger analysis of Phase I data Plans Increase recruitment of low IQ subjects Assemble and enter dynamic demographics data for Phase I subjects Continued analysis of Phase I data dysmorphology/neuropsych data questionnaire data Plan 4th training meeting for 2010, hopefully in conjunction with NM hiring

Site-Specific Progress: UCLA UCLA progress for collection of data on affected children was above target, while collection of data on unaffected and ADHD populations was insufficient (overall 113% of 12/31 goal) Over a total of four days, we were able to collect dysmorphology, 3-D, and DNA data on a total of 38 affected and unaffected children We have successfully uploaded all of our neurobehavioral data and useable imaging data to the Central Repository (48 subjects uploaded), and are close to uploading the remainder of our demographic data (33 subjects uploaded). ADHD group

Site-Specific Progress: UCLA Issues ADHD recruitment is significantly behind schedule due to low interest of potential ADHD contacts, and the lack of a more effective ADHD site-specific recruitment strategy. The uploading of Neurobehavioral data to the Central Repository was slow, due in most part to difficulties in exporting repository compatible data from scoring software. Recruitment slowed during the last half of the year due to staff loss, and the compatibility of subject/ staff member availability.

Site-Specific Progress: UCLA Plans We have developed a recruitment contacts workbook targeting the ADHD population, and are planning to enhance existing relationships and create new relationships with potential recruitment contacts. We have also obtained IRB approval for ADHD-specific recruitment flyers. We are planning on developing more efficient and streamlined strategies for the scoring and uploading of neurobehavioral and demographic data to the Central Repository. We will be hiring a new Staff Research Associate within the next few months who will be trained on the CIFASD cognitive battery. This will allow us more flexibility in scheduling, and will allow us to increase our recruitment rates for all target populations.

Site-Specific Progress: Emory Data Collection-Neuropsychology After a slow start in Year 1, resulting from Institutional issues, the project has rapidly increased recruitment and testing. Currently, with 61 cases tested of the 62.5 requested, we are at 98%. A number of assessments are scheduled for the first months of 2010. More than 200 potential participants have been recruited and prescreened for alcohol exposure and ADHD status before testing, based on the “participant classification scheme” which we worked out with San Diego this year. Data Collection-Dysmorphology and 3-D Imaging Carried out a 2nd Clinic for these protocols in August 2009 raising the number of completed cases to 50 (80%)

Site-Specific Progress: Emory Data Processing Identified and resolved a number of transmission problems with data entry forms Staffing Recruited and trained a Neuropsychology tester to replace the graduate student and the Post Doctoral Fellow leaving in 2009 Received supplemental funding from CIFASD Core to support additional staff time Genetics study initiated With the cooperation of IU, completed that IRB process for the Genetics Study and received approval for this protocol to begin in August 2009.

Site-Specific Progress: Emory Issues The project is underfunded for the scope of work. This has stressed the system in a number of ways and required the reallocation of resources from other projects. This became more difficult with the addition of the Genetics project which is not funded. Project Coordinator position. We recently lost Julie Carroll from this role because we could not provide her with salary support. Subject Classification was inexact. This issue was resolved by working with San Diego and other collaborators to develop a classification mechanism.

Site-Specific Progress: Emory Issues Data uploading to the Indiana database has been slower than testing. Specific issues: Checking and preparing data for upload is time intensive and requires professional expertise. As noted above, we do not have adequate professional time allocated. We had adopted the strategy of waiting until a file was complete to upload to avoid confusion and overwriting of data. Currently, two specific sources of file incompleteness are (1) Teacher forms, whose format is inconsistent with High School structures in Georgia and (2) CANTAB computer malfunction which we have not been able to resolve despite repeated efforts. Many uploading problems, many related to the nature of the operating systems (i.e., Windows vs MAC; XP vs Windows 2003, 2007), were encountered. This required much non-reimbursed time from Julie Kable to figure out.

Site-Specific Progress: Emory Plans Subject Recruitment. We will continue to draw exposed individuals from the Clinic Data base. In addition, we will once again recruit controls through town “fairs” and by working with parents groups serving children with ADHD and other disabling conditions. Further Dysmorphology/3-D imaging “Clinics”. When convenient for Dr. Jones, we will schedule another Clinic probably in the Spring. The 3-D camera will be brought from Indiana for this Clinic which will allow us to hold it at Marcus Center rather than at the Emory Genetics Clinic which will allow for more flexible scheduling. We anticipate seeing approximately 30 children at this time. Data Uploading. Dr. Kable continues to work with SDSU, and Indiana U to resolve the uploading and software issues that have slowed the progress in this area. Recently, most of these seem to have been resolved. We continue to work on the CANTAB computer issues and, when these are resolved, will re-schedule those who have had to omit this part of the protocol.

Site-Specific Progress: Emory Plans Staffing. The project requires coordination and more testing time. Each evaluation requires a day of testing and a day of “checking” and data entry plus supervision by Dr. Kable. We are current funded for a .5 FTE tester which would provide for only a single assessment to be done weekly. We would like to be able to at least double that. Plans include: Moving Elles Taddeo to .25FTE to replace Ms. Carroll to oversee coordination. Dr. Coles will assume responsibility for the IRB activities. Training a Post Doctoral Fellow on the protocol. When she is reliable, she will be able to supplement data collection and checking at no cost until August 2010.

Site-Specific Progress: UNM/Plains One clinic was held in South Dakota where 8 FAS/FASD children were tested. A minimum of three more have been approved by tribal administrators and are set for February and March. All stimulus money has been allocated and most spent and will provide for at least four major clinics. UNM progress is inadequate for affected children especially. Staffing

Site-Specific Progress: UNM/Plains Issues Both testing and uploading are behind schedule in both sites due to staff loss, logistics, and funding to other complimentary grants. The pipeline in New Mexico is temporarily clogged, but we will address this aggressively when the new staff positions are filled, and when our dysmorphologists are in town for case conference in January. Many uploading problems, most specific to our site, were encountered when Wendy undertook this task full time for a number of weeks. Staffing

Site-Specific Progress: UNM/Plains Plans We are hiring two master's level testing personnel to replace the neuropsychologist who departed in August. They will be supervised by Wendy Kalberg and trained by SDSU before beginning a flurry of testing. The uploading, software, and scoring issues have been tackled by our site staff working in very close collaboration with personnel from UCSD, SDSU, and Indiana U, and once they are solved, all uploading will be completed very rapidly. It has been a very challenging year, but our plans will allow for substantial and rapid progress towards meeting the goals with modest resources.

Site-Specific Progress: UCT Hired neuropsychologist (Tania Badenhorst) who attended training meeting in San Diego; hired team of psychometrists, supervised by Ms. Badenhorst Translated test materials Initiated testing in June, tested 67 subjects (56% of 12/31 goal) between June and December Uploaded data from 62 subjects into CR Collected MRI data on 33 subjects, delivered data for 28 subjects Obtained permission of Wellington schools to access participants

Site-Specific Progress: UCT Issues Despite active testing, data collection is still behind site goals Caregiver and educator interview data collection is time consuming, lags behind neurobehavioral testing. Dynamic demographic data separate from retrospective questionnaires. Phase 1: data entry incomplete; questionnaire data incomplete SA children perform worse on the neurobehavioral battery – implications for multi-site analysis

Site-Specific Progress: UCT Plans Continued data collection at accelerated rate to meet 2010 site goal Continue increased Phase II Questionnaire data collection rate, including separately administered dynamic questionnaire. Complete data entry and uploading: Phase I; Phase II demographic Preliminary analysis of neurobehavioral and demographic data

Publications 2008 Aragón, A.S., Kalberg, W.O., Buckley, D., Barela-Scott, L.M., Tabachnick, B.G., and May, P. A. (2008). Neuropsychological study of FASD in a sample of American Indian children: processing simple versus complex information. Alcoholism: Clinical and Experimental Research, 32 (12), 2136-2148. Aragón, A.S., Coriale, G., Fiorentino, D., Kalberg, W.O., Buckley, D., Gossage, J.P., Ceccanti, M., Mitchell, E.R., and May, P.A. (2008). Neuropsychological characteristics of Italian children with fetal alcohol spectrum disorders. Alcoholism: Clinical and Experimental Research, 32 (11): 1909-1919. 2009 Spadoni, A.D., Bazinet, A.D., Fryer, S.L., Tapert, S.F., Mattson, S.N., and Riley, E.P. (2009). BOLD response during spatial working memory in youth with heavy prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research, 33 (12): 2067-2076 O’Hare, E.D., Lu, L.H., Houston, S.M., Bookheimer, S.Y., Mattson, S.N., O’Connor, M.J, and Sowell, E.R. (2009). Altered frontal-parietal functioning during verbal working memory in children with heavy prenatal alcohol exposure. Human Brain Mapping, 30 (10): 3200-3208. Norman, A.L., Crocker, N., Mattson, S.N., and Riley, E.P. (2009). Neuroimaging and fetal alcohol spectrum disorders. Developmental Disabilities Research Reviews, 15 (3): 209- 217.

Publications 2010 (In Press) Mattson, S.N., Foroud, T., Sowell, E.R., Jones, K.L., Coles, C.D., Fagerlund, Å., Autti-Rämö, I., May, P.A., Adnams, C.M., Konovalova, V., Wetherill, L., Arenson, A.D., Barnett, W.K., Riley, E.P., and the CIFASD. (In Press 2010). Collaborative initiative on fetal alcohol spectrum disorders: Methodology of clinical projects. Alcohol, in press. Arenson, A.D., Bakhireva, L., Chambers, C.D., Deximo, C., Foroud, T., Jacobson, J.L., Jacobson, S.W., Jones, K.L., Mattson, S.N., May, P.A., Moore, E., Ogle, K., Riley, E.P., Robinson, L.K., Rogers, J., Streissguth, A.P., Tavares, M., Urbanski, J., Yezerets, Y., Surya, R., Stewart, C.A., and Barnett, W.K. (In Press 2010). Implementation of a shared data repository and common data dictionary for fetal alcohol spectrum disorders research. Alcohol, in press. Klingenberg, C.P., Wetherill, L., Rogers, J., Moore, E., Ward, R., Autti-Rämö, I., Fagerlund, Å., Jacobson, S.W., Robinson, L.K., Hoyme, H.E., Mattson, S.N., Li, T.K., Riley, E.P., Foroud, T., and the CIFASD Consortium (In Press 2010). Prenatal alcohol exposure alters the patterns of facial asymmetry. Alcohol, in press.

2009 Manuscripts Submitted and in Preparation Mattson, S.N., Roesch, S.C., Fagerlund, Å., Autti-Rämö, I., Jones, K.L., May, P.A., Adnams, C.M., Konovalova, V., Riley, E.P., and the CIFASD. (Submitted 2009). Towards a neurobehavioral profile of fetal alcohol spectrum disorders. Status: being revised after review. Fagerlund, Å., Korkman, M., Autti- Rämö, I, Mattson, S.N., and Hoyme, H.E. (Submitted 2009). Risk and protective factors for mental and behavioral well-being in fetal alcohol spectrum disorders. Status: being revised and submitted to a different journal. In Preparation Kang, N., Vaurio, L., Riley, E.P., and Mattson, S.N. Objective measurement of activity levels in children with heavy prenatal alcohol exposure. Status: manuscript in final stages of preparation, should be submitted in early 2010. Mattson, S.N., Riley, E.P., Autti-Rämö, I., May, P.A., Konovalova, V., Jones, K.L., Roesch, S.C., and the CIFASD. Spatial learning and navigation deficits in an international sample of children with heavy prenatal alcohol exposure. Status: manuscript requires revision for resubmission.

2009 Posters and Presentations Fagerlund, Å., Korkman, M., Autti-Rämö, I., Mattson, S.N., Hoyme, H.E. (2009). Risk and Protective Factors for Mental and Behavioral Well-Being in Fetal Alcohol Spectrum Disorders. Presented at the International Neuropsychological Society meeting, Helsinki, Finland, July 2009. Journal of the International Neuropsychological Society, 15, Supplement S1, 85. Mattson, S.N., Riley, E.P., Autti-Rämö, I, Fagerlund, Å., and the CIFASD (2009). Discriminating nondysmorphic children with prenatal alcohol exposure from nonexposed controls. Presented at the Research Society on Alcoholism meeting, San Diego, June 2009. Alcoholism: Clinical and Experimental Research, 33, Supplement S1, 37A. Moore, E.S., Ward, R.E., Rogers, J.L., Mattson, S.N., Autti-Rämö, I, Fagerlund, Å., Foroud, T., and the CIFASD (2009). Identification of prenatal alcohol exposure using combined 3D facial imaging and neurobehavioral data. Presented at the Research Society on Alcoholism meeting, San Diego, June 2009. Alcoholism: Clinical and Experimental Research, 33, Supplement S1, 39A. Wetherill, L., Klingenberg, C.P., Rogers, J., Moore, E., Ward, R., Autti-Rämö, I, Fagerlund, Å., Jacobson, S.W., Mattson, S.N., Li, T.K., Riley, E.P., Foroud, T., and the CIFASD (2009). Fetal alcohol syndrome is associated with directional asymmetry. Presented at the Research Society on Alcoholism meeting, San Diego, June 2009. Alcoholism: Clinical and Experimental Research, 33, Supplement S1, 130A. Wetherill, L., Klingenberg, C.P., Rogers, J., Moore, E., Ward, R., Autti-Rämö, I, Fagerlund, Å., Jacobson, S.W., Mattson, S.N., Li, T.K., Riley, E.P., Foroud, T., and the CIFASD (2009). Identifying fetal alcohol syndrome using facial shape analysis. Presented at the Research Society on Alcoholism meeting, San Diego, June 2009. Alcoholism: Clinical and Experimental Research, 33, Supplement S1, 130A. Wetherill, L., Klingenberg, C.P., Rogers, J., Moore, E., Ward, R., Autti-Rämö, I, Fagerlund, Å., Jacobson, S.W., Li, T.K., Riley, E.P., Mattson, S.N., Foroud, T., and the CIFASD (2009). Covariation of facial shape and neurocognitive variables in fetal alcohol syndrome individuals vs controls. Presented at the Research Society on Alcoholism meeting, San Diego, June 2009. Alcoholism: Clinical and Experimental Research, 33, Supplement S1, 131A.

Results: Exposed vs. Control Observed Group Predicted Class 1 Class 2 FAS 69 88.5% of Class 73.4% of Group 25 27.8% of Class 26.6% of Group Control 9 11.55 of Class 12.25 of Group 65 72.2% of Class 87.8% of Group This shows the distribution of subjects in the exposed and control groups in the two classes resulting from the latent profile analysis. The exposed subjects were more likely to be in Class 1 and the non-exposed subjects were more likely to be in Class 2.