Sleep fails to depotentiate amygdala-reactivity to negative emotional stimuli in youth with elevated symptoms of anxiety.

Sleep-related problems often precede escalating anxiety in early adolescence. Pushing beyond broad sleep-mental health associations and toward mechanistic theories of their interplay can inform etiological models of psychopathology. Recent studies suggest that sleep depotentiates neural (e.g., amygdala) reactivity during reexposure to negative emotional stimuli in adults. Persistent amygdala reactivity to negative experiences and poor sleep characterize anxiety, particularly at the transition to adolescence. We propose that sleep depotentiates amygdala reactivity in youth but fails to do so among youth with anxiety. Participants (n = 34; 18 males; age, mean [M] = 11.35, standard deviation [SD] = 2.00) recruited from the community and specialty anxiety clinics viewed valenced images (positive, negative, and neutral) across two fMRI sessions (Study, Test), separated by a 10-12-hour retention period of sleep or wake (randomized). Mixed linear models regressed basolateral amygdala (BLA) activation and BLA-medial prefrontal cortex (mPFC) functional connectivity to negative images on Time, Condition, and Anxiety Severity. There were greater reductions in BLA activations to negative target images from Study to Test in the Sleep Condition, which was blunted with higher anxiety (b = -0.065, z = -2.355, p = 0.019). No such sleep- or anxiety-related effects were observed for BLA-mPFC functional connectivity (ps > 0.05). Sleep supports depotentiation of amygdala reactivity to negative stimuli in youth, but this effect is blunted at higher levels of anxiety. Disruptions in sleep-related affective habituation may be a critical, modifiable driver of anxiety.