Abstract
BACKGROUND: Anxiety sensitivity (AS) - the tendency to perceive benign physiological stimuli as harmful - is a risk factor for anxiety disorders. Cross-sectionally, AS has been linked to increased negative > neutral neural activity in key nodes implicated in threat detection and interoceptive - i.e., the amygdala (AMYG) and insula (INS). Examining the unique contributions of AMYG-INS blood‑oxygen-level-dependent (BOLD) response to neutral and negative stimuli to the prospective prediction of AS could increase understanding of the factors predisposing individuals to worsening AS over time. METHODS: Forty-six participants, including 33 patients with mixed internalizing disorders, underwent fMRI scans to assess insula and amygdala activation in response to neutral and negative pictures. AS was measured via self-report at baseline (Time 1) and approximately 1.5 years later (Time 2). We assessed whether BOLD to negative and/or neutral pictures at baseline predicted changes in AS over time. RESULTS: Greater insula and amygdala activation in response to neutral pictures at baseline predicted higher AS 1.5 years later, controlling for initial levels of AS and BOLD response to negative pictures. Cross-sectionally, greater insula and amygdala activation in response to negative pictures relative to neutral pictures was associated with higher Time 1 AS. CONCLUSIONS: Heightened AMYG-INS BOLD to benign stimuli precedes and may place individuals at risk for increased AS. Once established, heightened AS appears to be characterized by a neural pattern that is more often-observed in the internalizing disorders - i.e., exaggerated response to negative (> neutral) stimuli.