Anxiety is a normal emotional and neurophysiological reaction to a perceived threat, and serves the purpose of preparing one to “freeze, take flight, or fight.” Such a reaction is obviously an appropriate and even adaptive survival mechanism in the presence of actual threats, allowing one both to escape the current threat and to avoid future ones through conditioned fear learning. When the reaction occurs in the absence of a realistic threat, however—whether because the threat itself is unlikely or because harm from the perceived threat is unlikely—then it serves no useful purpose and instead can significantly disrupt one's ability to function, thus constituting an anxiety disorder.

There are several anxiety disorders, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-TR, each with distinct characteristics, criteria, and symptoms, but all sharing the common core symptoms of excessive fear and worry. The neurobiological circuits underlying these core symptoms may thus be involved in all anxiety disorders, with the different phenotypes reflecting not unique circuitry but rather divergent malfunctioning within those circuits.

This chapter covers the neurobiology of normal fear and worry and how genetic and environmental factors may interact to affect these circuits and increase risk for psychiatric illnesses such as posttraumatic stress disorders (PTSD), which is the focus of this book.

Although acute activation of the autonomic nervous system is important for survival in response to real threats, chronic activation as part of an anxiety disorder can lead to increased risk of cardiovascular issues such as atherosclerosis, cardiac ischemia, hypertension, myocardial infarction (MI), or even sudden death.

The role of the HPA axis in anxiety disorders is discussed in more detail in Figure 1.6 as well as in Figures 2.6 and 2.7.

In situations of chronic stress, excessive glucocorticoid release may eventually lead to hippocampal atrophy, thus preventing it from inhibiting the HPA axis (E). This could contribute to chronic activation of the HPA axis (F) and increase risk for an anxiety disorder.

Upon acute exposure to a fearful situation, the lateral amygdala integrates input from several brain regions, including sensory cortex and thalamus, which provide information about stimuli associated with the fearful situation; the hippocampus, which provides memories of related fearful or traumatic experiences; and the ventromedial prefrontal cortex (VMPFC), which may provide mitigating input to suppress a fear response (A).