Fig. 5.

Heuristic neurobiological framework for the sleep disturbance and anxiety disorder relationship. Abnormal activation in wake, NREMS, and/or anxiety regions may generate sleep disturbance in anxiety-related disorders and promote a bidirectional sleep-disturbance-anxiety relationship. a Sleep disturbance emerges from hyperactivation in intrinsic wake circuitry. For example, here, excess arousal in NE-generating LC (green with orange halo) results in inhibition of VLPO/Intermediate Nucleus (IN) (blue) and hyperactivation of cerebral cortex. b Sleep disturbance emerges from dysfuncton in central (NREM) sleep-promoting region. For example, here failure of VLPO GABA signaling (blue, with orange “X”) disinhibits arousal centers (green). c Sleep disturbance emerges from hyperactivation of fear/threat/anxiety regions. For example, here amygdala hyperactivation (red, with orange halo) sends excitatory inputs to LC, which then inhibits VLPO-mediated sleep promotion and sends excitatory inputs to cerebral cortex, resulting in cortical hyperarousal, as in a. A common node in these examples is LC and NE signaling, but aberrant activity in other wake, NREMS, REMS, and anxiety regions may produce analogous effects