Chapter 5.5 Stress hormones and anxiety disorders

Conceptually stress and anxiety are tightly linked and animal studies find activation of the hypothalamic-pituitary-adrenal (HPA) axis in anxiogenic situations. However, disruption of the HPA axis in anxiety disorders is less robust than studies with major depression. In contrast, activation of the central noradrenergic system is a robust finding in anxiety disorders. Neuroanatomical and neurophysiological studies suggest that activation of these two stress systems are linked in other species. This chapter reviews the HPA axis and sympathetic nervous system (SNS) and their function in anxiety disorders particularly panic disorder and post-traumatic stress disorder (PTSD). The picture of activation of the central noradrenergic systems without clear evidence of HPA axis pathology in anxiety disorders has led some to conclude that anxiety patients may be hypoactive in regards to the HPA axis. While this may be true, an alternative is that the prolonged activation of the HPA axis as observed in major depression is beyond what is expected under "chronic stress," and thus the problem may be in our comparison group and expecting the HPA axis in anxiety disorders to look like that in depression. Studies of individuals under chronic stress do not by and large demonstrate an over-active HPA axis leading us to conclude that patients with anxiety disorders have a fundamentally normal HPA axis that is capable of responding and is regulated properly by inhibitory circuits of the brain.