Fig. 3

Hypothetical interactions among activated stress systems and disrupted sleep in PTSD. Note that multiple positive feedback loops result in depicted effects at any one node further driving effects at other nodes. Experimental evidence for many specific interactions depicted is provided in text. For clarity, the following mechanisms mentioned in the text are not depicted: 1) interaction between sympathetic activation and the HPA axis, 2) possible negative feedback mechanisms involving hypothalamic corticotropin releasing factor (CRF) that may explain hypocortisolemia in PTSD, and 3) direct effects of stress systems on extinction memory and habituation. The dashed line depicts an additional positive feedback mechanism whereby poor extinction memory promotes continued activation of neuroendocrine stress systems by failing to inhibit expression of conditioned fears. HPA hypothalamic-pituitary-adrenal, CRF corticotropin releasing factor, NE norepinephrine