Autism spectrum disorders (ASD) affect approximately 1 out of 150 children and adolescents in the United States, making them one of the most common neurobiological conditions. Comorbid anxiety disorders affect as many as 80% of youth with ASD, causing substantial distress and impairment over and above that caused by an ASD diagnosis alone. While cognitive-behavioral therapy (CBT) has been established as the gold standard treatment for anxiety disorders among typically developing youth, and innovative work by the investigative team supports its utility in children with ASD and comorbid anxiety, a protocol does not exist for early adolescents with ASD and comorbid anxiety disorders. In fact, there are no empirically supported treatment options for early adolescents with ASD and comorbid anxiety disorders;and existing pharmacological interventions may have some disadvantages (e.g., limited efficacy in this population, side effects, and potential drug x drug interactions). Accordingly, we are proposing to develop a CBT protocol for anxiety and comorbid ASD in early adolescence, as well as a credible comparison protocol (Relaxation Training;RT) for use in a future multisite clinical trial to test the efficacy of CBT in this population. In response to the Recovery Act Limited Competition, each site will hire and train at least three new study staff to conduct this study. Initial protocol development efforts will focus on adapting relevant treatment elements from an efficacious CBT program for younger children with ASD and comorbid anxiety to the characteristics and clinical needs of early adolescents. Developmentally appropriate, novel treatment components will then be added. An extant RT treatment protocol will also be modified for use with early adolescents with ASD. In response to the NIH Roadmap Initiative, attention will be paid to protocol adaptability with varying presentations. Measures of treatment integrity and competence will be developed along with the protocols. Thereafter, protocol and measure development will be refined through our experiences treating 18 young adolescents (ages 11-14 years) with ASD and comorbid anxiety disorder(s) as well as through clinician, patient, and expert feedback. The feasibility of implementation of both protocols will then be examined in the context of a pilot study incorporating all the features of the planned future efficacy trial comparing CBT and RT, but with a limited sample size (N = 48). At the end of the project, refined treatment manuals will be completed, integrity and competence measures will be finalized and tested for reliability and validity, and the three recruitment sites will have developed protocols promoting and assessing the consistency of treatment delivery and assessment procedures across sites, and a linked R01 grant to test the efficacy of CBT will be written. The three recruitment sites for this study are the University of California, Los Angeles (UCLA);the University of South Florida;and the University of Miami. The UCLA Neuropsychiatric (Semel) Institute's Biostatistics Core will provide data management services. Considering the rising number of youth diagnosed with ASD, and the lack of empirically supported treatment options for those young adolescents with comorbid anxiety, our proposed work toward an efficacious CBT protocol will provide a timely contribution to public health efforts. PUBLIC HEALTH RELEVANCE: Comorbid anxiety disorders affect as many as 80% of youth with autism spectrum disorders, causing substantial distress and impairment over and above the autism spectrum diagnosis alone. Cognitive behavioral therapy (CBT) is the gold standard treatment among typically developing youth with an anxiety disorder but has yet to be adapted to meet the unique needs of adolescents with ASD and comorbid anxiety. With more youth being diagnosed with ASD after the early childhood period, a treatment protocol such as that proposed could contribute to public health efforts to address the mental health needs of early adolescents with ASD.