Threat- and reward-related brain circuitry, perceived stress, and anxiety in adolescents during the COVID-19 pandemic: a longitudinal investigation.

The Coronavirus disease (COVID-19) pandemic led to heightened anxiety in adolescents. The basolateral amygdala (BLA) and the nucleus accumbens (NAcc) are implicated in response to stress and may contribute to anxiety. The role of threat- and reward-related circuitry in adolescent anxiety during the COVID-19 pandemic, however, is not clear. Ninety-nine adolescents underwent resting-state fMRI ∼1 year before the pandemic. Following shelter-in-place orders, adolescents reported their perceived stress and, 1 month later, their anxiety. Generalized multivariate analyses identified BLA and NAcc seed-based whole-brain functional connectivity maps with perceived stress. In the resulting significant clusters, we examined the association between seed-based connectivityand subsequent anxiety. Perceived stress was associated with bilateral BLA and NAcc connectivity across distributed clusters that included prefrontal, limbic, temporal, and cerebellar regions. Several NAcc connectivity clusters located in ventromedial prefrontal, parahippocampal, and temporal cortices were positively associated with anxiety; NAcc connectivity with the inferior frontal gyrus was negatively associated. BLA connectivity was not associated with anxiety. These results underscore the integrative role of the NAcc in responding to acute stressors and its relation to anxiety in adolescents. Elucidating the involvement of subcortical-cortical circuitry in adolescents' capacity to respond adaptively to environmental challenges can inform treatment for anxiety-related disorders.