UC Berkeley

Recent evidence suggests there is an intimate and causal relationship between sleep and anxiety. Despite such progress, several unknowns remain. For example which factors predispose some individuals to be vulnerable to the anxiogenic impact of sleep loss while others appear to be resilient have yet to be identified. Furthermore, whether trait-anxiety, in turn, predicts the sensitivity of individuals to amplified emotional brain reactivity associated with a lack of sleep is similarly unknown. Moreover, little is currently known about the embodied interplay between peripheral and central nervous system mechanisms leading to such abnormalities of affective processing caused by sleep deprivation. Characterizing these mechanisms is necessary not only to gain a deeper understanding of the pathophysiological pathways underlying the condition of anxiety, but also for developing effective treatments for the amelioration of anxiety as well as guiding public health policy aimed at anxiety disorder prevention. Targeting these unanswered questions, this thesis combines functional and structural MRI techniques, together with high-density EEG recordings, to test the overarching hypothesis that sleep deprivation leads to dysregulation of the extended-limbic system contributing to, and interacting with, the state of anxiety. Three specific predictions emerged from this overarching hypothesis and were tested in separate experiments. First, experiment 1 confirms the hypothesis that structural brain morphology in a network of limbic brain regions predicts vulnerability to the anxiogenic impact of sleep deprivation, and that sex moderates this interaction. Second, experiment 2 provides evidence supporting the hypothesis that trait anxiety determines the degree to which sleep deprivation amplifies limbic brain reactivity during the anticipation of potentially aversive emotional experiences. Finally, results from experiment 3 affirms the prediction that, beyond central limbic brain changes, sleep deprivation additionally dysregulates peripheral, autonomic cardiac signaling in response to affective stimuli as well as decouples the normally inter-related association between central brain and peripheral nervous systems. Collectively, these results help characterize a framework in which sleep deprivation contributes to anxiety symptomology through impairments in affective processing by both the central (limbic) and peripheral (autonomic) nervous system functioning. Moreover, these data suggest that the co-morbid features of sleep disruption and altered limbic as well as autonomic function commonly reported across anxiety disorders may be causally related. Considering the continued decreases in sleep time across society and the high prevalence of anxiety disorders, these findings have significant therapeutic, clinical and public health ramifications.