CORE E: Abstract Despite an enormous increase in the basic science understanding of many IDDs, progress in the application of this basic knowledge in the clinic has been limited. The reasons for this gap in ?translation? are many, but most agree that advances in defining, dissecting, and understanding the multiple dimensions of IDD phenotypes have lagged, with a few exceptions. A few examples are illustrative. Social functioning, an obvious and foundational element of adaptive ability and quality of life, is a natural target for intervention efforts across all IDDs, yet the field lacks suitable measurement tools that are well suited for application in clinical trials, and few measures have been rigorously compared to real world functioning for their precision and validity. Social measures often applied for diagnosis (Vineland Socialization or Communication subscales, ADOS, Social Responsiveness Scale-2, Aberrant Behavior Checklist-Social Withdrawal subscale [ABC-SW]) are either insensitive to change (too few items and limited range of scoring), too broad, too burdensome for repeated short-term use, too narrow, and/or vulnerable to expectancy bias. Even though the ABC-SW subscale has received a partial endorsement as a possible endpoint for capturing treatment effects on social behavior in Autism Spectrum Disorder (ASD)(and a separate modification likewise proposed for Fragile X Syndrome [FXS] trials), a review of its performance finds it vulnerable to placebo effects. Moreover, on closer inspection, the majority of the subscale's items are restricted to social interest alone, not capturing the many other possible social dimensions of interest. An objective of our Core is to continue our existing efforts to creatively increase study impact by developing and applying novel measurement approaches. An example was the substudy of McCracken and Kasari embedded in the NIMH Research Units on Pediatric Pharmacology (RUPP) Autism Network's Methylphenidate for the Treatment of Hyperactivity in Pervasive Developmental Disorder randomized clinical trial (RUPP Autism Network, 2005). Using an abbreviated (<10- minute scripted interaction repeated weekly) modification of the Early Social Communication Scales (ESCS), we documented the first example in the literature to our knowledge of a positive drug effect on core deficits of joint attention and emotion regulation in ASD.

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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHD1)
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University of California Los Angeles
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