Research Project
10357320
PROJECT SUMMARY Cognitive-Behavioral Therapy (CBT) is the most well-established treatment for anxiety disorders, yet up to one- half of peri-pubertal youth show insufficient response, leaving these youth at high risk for continued anxiety, depression, substance use, and suicide. This proposed Diversity Supplement aims to supplement parent grant data on negative overgeneralization with data collected from clinical services CBT, offered to participating youth, to (a) examine negative overgeneralization as a predictor of CBT outcomes and (b) support the research training and career development of the candidate, Carlos Yeguez. Negative overgeneralization is a phenotype of anxiety that refers to the tendency to generalize aversive responses from one context (house fire) to other contexts (camp-fire) that share features. In our conceptual model, participants who exhibit high negative overgeneralization present a broad, diffuse target that hinders CBT outcomes. Specifically, in these participants information learned in the context of exposure to one anxiety-provoking stimulus will not readily transfer to distally-related stimuli, requiring more intensive and longer exposure to achieve optimal outcomes. Peri-puberty provides the optimal window for preliminarily testing aspects of our conceptual model because gradients of negative overgeneralization become more pronounced during this developmental window. In accordance with the NIMH strategic plan, we examine negative overgeneralization as a multi-modality derived phenotype associated with CBT outcome using neuroimaging, behavior task, and self-report data from the parent grant. Further, we characterize the phenotype of negative overgeneralization using a declarative memory paradigm. Declarative memory paradigms are sensitive to neurodevelopmental differences in youth with anxiety disorders and enhance ecological validity because they approximate complex experiences of life and use of exposures in CBT. Further, our paradigm allows us to measure neurocomputational processes underlying negative overgeneralization based on theory and data from our team documenting its relationship with anxiety severity in peri-pubertal youth. In this proposed supplement, we will recruit a subset of N=50 peri- pubertal youths ages 10-13 years with anxiety disorders drawn from the parent grant. After completing the parent grant protocol, participants will then complete CBT for anxiety disorders offered through our team?s clinic and supplemental data collection on anxiety outcomes and self-report measures of negative overgeneralization. In Aim 1 we examine a behavioral measure of negative overgeneralization as a predictor of CBT outcome. In Aim 2 we examine a neural measure of negative overgeneralization as a predictor of CBT outcome. In Aim 3 we examine whether self-reported negative overgeneralization is associated with behavioral and neural measures of negative overgeneralization at baseline, and whether our behavioral, neural, and self- report indices of negative overgeneralization at baseline predict self-reported negative overgeneralization across treatment by examining changes in weekly self-reported negative overgeneralization.
