Anxiety clinical trials at UCSD

Anxiety disorders remain are among the most prevalent psychiatric conditions and are associated with negative outcomes spanning poor health to increased suicide risk. While exposure therapy is recognized as a gold standard empirically supported treatment, many individuals fail to achieve adequate response. Exposure therapy is grounded in fear extinction learning models, which suggest that anxiety diminishes when individuals repeatedly confront their fears. To improve exposure-based interventions, it is critical to enhance our understanding of underlying mechanisms of fear extinction and how to better target these mechanisms. Fear extinction requires basic neurocognitive abilities that allow individuals to learn from and adapt to experiences confronting feared situations. Emerging cross sectional and experimental data suggest that working memory is a particularly important neurocognitive process that is associated with fear learning outcomes. By enhancing working memory through experimental manipulations like cognitive training, we may improve the fear extinction learning processes essential for successful exposure therapy. Unlike other neurocognitive enhancements (e.g., medications), computer-based working memory training offers high mechanistic precision, ease of administration, and low cost. The long-term goal of this research is to develop a novel mechanistic understanding of the neurocognitive processes involved in exposure-based fear extinction learning, ultimately aiming to improve interventions for anxiety disorders. This study will test the effects of manipulating working memory prior to a massed exposure paradigm, comparing working memory training plus massed exposure (WMT+Ex) to a sham training plus massed exposure (ST+Ex) condition. Using public speaking anxiety as a clinical exemplar, we will employ a rigorous experimental trial design combined with a validated single-visit speech exposure paradigm to assess fear extinction learning outcomes through multiple measures, including behavioral, physiological, neural, and self-report. The central hypothesis is that WMT+Ex will improve markers of fear extinction learning considered to underlie clinical response in exposure therapy. Specific aims are to 1) determine the extent to which working memory training delivered prior to massed exposure improves behavioral and neural markers of fear extinction learning, and 2) evaluate the effects of working memory training delivered prior to massed exposure on fear extinction learning occurring during exposure. This study is expected to achieve two goals: first, to advance our understanding of the neurocognitive mechanisms of fear extinction through a rigorous experimental design, and second, to validate a combined working memory training and exposure paradigm. If successful in enhancing fear extinction, this approach could be further explored in therapeutic formats to assess its clinical effects.