Greater Stress Response Network (SRN) Connectivity is Associated with Higher Worry in Men and Women Especially in Later Life

Background: Late-life anxiety is common and disabling, with pathological worry as a core feature. The Stress Response Network (SRN: amygdala, bed nucleus of the stria terminalis, paraventricular nucleus), which modulates threat and stress reactivity, and its interaction with the Executive Control Network (ECN), anchored by the dorsolateral prefrontal cortex, which supports emotional regulation via top-down cognitive control, may underlie individual differences in worry severity. We hypothesize higher SRN connectivity to be associated with greater worry severity and that this relationship may be moderated positively by older age, and female sex. Methods: We recruited older adults with varying worry. Resting-state fMRI was used to compute SRN connectivity and SRN-ECN connectivity. Regression models tested associations between connectivity and worry (PSWQ), anxiety (HARS), and rumination (RSQ), adjusting for age, sex, race, and education. Exploratory models examined age and sex moderation and associations with emotion regulation/suppression and cognitive function. Results: Among 131 participants who were ≥ 50 years old, with varying levels of worry severity, SRN connectivity was significantly associated with greater worry severity (B=23.51 (SE = 12.12), p<0.05), whereas SRN-ECN connectivity was not. SRN connectivity was lower with greater age (B=-0.003 (SE=0.001), p=0.04), yet older individuals reported greater worry than younger with comparable connectivity. Greater language domain cognitive function was associated with lower SRN connectivity but higher SRN-ECN connectivity, while greater overall cognitive function was associated with lower SRN-ECN connectivity. Women reported lower use of daily expressive suppression and higher performance across cognitive measures than men. Higher daily use of expressive suppression was not significantly associated with either connectivity measure. Discussion: SRN connectivity, rather than SRN-ECN connectivity, may serve as the primary neural correlate of worry, shaped by age and cognitive function.