Neuroanatomical hypothesis of panic disorder, revised

Objective: In a 1989 article, the authors provided a hypothesis for the neu roanatomical basis of panic disorder that attempted to explain why both med ication and cognitive behavioral psychotherapy are effective treatments. He re they revise that hypothesis to consider developments in the preclinical understanding of the neurobiology of fear and avoidance. Method: The author s review recent literature on the phenomenology, neurobiology, and treatmen t of panic disorder and impressive developments in documenting the neuroana tomy of conditioned fear in animals. Results: There appears to be a remarka ble similarity between the physiological and behavioral consequences of res ponse to a conditioned fear stimulus and a panic attack. In animals, these responses are mediated by a "fear network" in the brain that is centered in the amygdala and involves its interaction with the hippocampus and medial prefrontal cortex. Projections from the amygdala to hypothalamic and brains tem sites explain many of the observed signs of conditioned fear responses. It is speculated that a similar network is involved in panic disorder. A c onvergence of evidence suggests that both heritable factors and stressful l ife events, particularly in early childhood, are responsible for the onset of panic disorder. Conclusions: Medications, particularly those that influe nce the serotonin system, are hypothesized to desensitize the fear network from the level of the amygdala through its projects to the hypothalamus and the brainstem. Effective psychosocial treatments may also reduce contextua l fear and cognitive misattributions at the level of the prefrontal cortex and hippocampus. Neuroimaging studies should help clarify whether these hyp otheses are correct.