Neural mechanisms of memory bias in adolescent social anxiety persistence and remittance - PROJECT SUMMARY/ABSTRACT Symptoms of social anxiety rise dramatically at the transition to adolescence (ages 10-11), as peers increase in importance. Failure to remit in social anxiety by mid-adolescence (ages 12-13) predicts increased symptom severity, comorbid psychopathology, and diminished quality of life in adulthood. It is therefore critical to identify factors that contribute to remittance or persistence of social anxiety during the transition to adolescence, as such factors may serve as treatment targets. While much prior research on social anxiety persistence focuses on threat-based processes, gold standard treatments that target these processes rarely result in remission. Thus, there is an urgent need to develop a novel framework of investigation to identify new pathways to persistence and corresponding intervention targets. While prominent theories suggest that biased memory for negative social outcomes contribute to symptoms, such biases are relatively understudied in adolescent social anxiety. This omission is significant because memory is reconstructive and fundamentally malleable, making it an ideal target for treatment. Our preliminary data using behavior, fMRI, and neuromelanin-sensitive MRI (NM-MRI) to quantify dopamine function, suggests interplay between dopamine system function and medial prefrontal cortex (mPFC)- striatal connectivity promotes memory bias in adolescent social anxiety. Our overall goal is to apply this multi- systems approach to the longitudinal study of adolescent social anxiety. Doing so may help identify sorely needed biobehavioral targets for intervention during a key period of development, thereby preventing devastating lifelong problems. To achieve this, we will assess social anxiety symptoms, dopamine system function and brain- based functional connectivity associated with memory bias in 255 youth (10-11 years). Additional assessments of symptom expression obtained at 6-month intervals as they transition to mid-adolescence (12-13 years) will enable trajectory mapping. Our central hypothesis is that in the presence of high dopamine system function, youth with biased recall for negative peer feedback and enhanced mPFC-striatal connectivity will be more likely to persist in social anxiety versus those who remit. Specific aims are to (1) characterize longitudinal associations between memory bias and social anxiety during a critical developmental period; (2) determine the extent to which memory bias mediates the relation between mPFC-striatal connectivity and social anxiety symptom trajectories; and (3) test moderation of brain-memory bias relations by dopamine system function. This proposal will advance the field and provide novel treatment targets by characterizing the contribution of memory bias to adolescent social anxiety persistence and remittance and its neural mechanisms. Innovative features are a focus on understudied mechanisms (memory) in a key age (10-13 years) using multiple imaging modalities including NM- MRI. Our project is significant because it is a critical first step towards providing the right treatment (based on neural mechanisms) to the right youth (those who persist in social anxiety), at the right time (early adolescence, before social anxiety becomes intractable).
