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Anxiety is a ubiquitous and unavoidable experience of life. It can be adaptive but also debilitating. Anxiety involves subjective feelings (e.g., worry and a sense of threat), physiological responses (e.g., tachycardia and hypercortisolemia), and behavioral responses (e.g., avoidance and withdrawal). Anxiety and fear share many subjective and physiological characteristics, and there is much debate about how best to distinguish them. Fear, as characterized by Walter Cannon in the 1920s, is generally viewed as a reaction to danger, whereas anxiety is a feeling of fear that is out of proportion to any real threat. When anxiety is persistent and intrusive, it is referred to as generalized anxiety disorder. When it is manifested as sudden and repeated episodes of panic, it is called panic disorder.
Anxiety is often a prominent manifestation of depression, trauma-related stress disorders, and certain personality disorders, such as obsessive-compulsive disorder. According to Freudian psychology, anxiety is a signal of intrapsychic conflict, usually between an unconscious wish and a learned prohibition. Research during the past decade has elucidated the neuronal circuitry and molecular biology that underlie many of the manifestations of anxiety and the actions of anxiolytic medications.
Fear and behavior resembling anxiety are studied in animal models, which usually entail stress in the form of exposure to a potentially dangerous environment (e.g., an elevated open platform), avoidance of noxious stimuli, and learned associations between neutral stimuli and noxious stimuli. Stimuli that are perceived as potentially dangerous on the basis of prior learning (e.g., conditioned fear) are processed by pathways leading from the thalamus and sensory cortex to specific limbic structures, particularly the amygdala and hippocampus, which are critical for the initiation and mediation of learned responses to fear.1 Monkeys with lesions of the amygdala no longer display a fear of snakes; cats with such lesions show no fear of dogs. Humans with damage to the amygdala have difficulty perceiving fear on someone's face and do not learn normally to identify stimuli that signal danger. A recent functional neurologic imaging study has shown that physiologic activation of the amygdala occurs when a subject is shown fearful faces even if the subject has no conscious awareness of having seen such a face.2
Specific neurons of the...