The neurobiology of anxiety disorders

Improvements in the techniques for assessing the neurochemistry and neuroanatomy of patients with anxiety disorders during the past few decades have led to the development of a clearer picture of the biologic conditions associated with normal and abnormal anxiety states. The current data available from studies of pathologic anxiety have suggested that the pathophysiology of the anxiety disorders is quite complex and that none of the anxiety disorders emerge from a single pathologic state. Instead, the growing biochemical data base has supported the idea that pathologic anxiety states are associated with disruptions of multiple neurotransmitter systems. Similarly, brain imaging studies have implicated the involvement of multiple brain structures in the pathophysiology of the anxiety disorders. This growing information base has allowed the recent development of several integrated neuroanatomic models of normal and abnormal anxiety states that serve to guide future research by providing testable hypotheses. The goals of this article are to review the available data from neurochemical and neuroanatomic studies of patients with anxiety disorders, to present several of the models regarding the pathophysiology and neuroanatomy of anxiety disorders, and to consider the implications of these models for future research in this area. We consider here only data pertaining to panic disorder, social phobia, generalized anxiety disorder, and simple/specific phobia. Two other anxiety disorders that also have an extensive base of biologic research, post-traumatic stress disorder and obsessive-compulsive disorder, are not considered here as they have been well-reviewed recently.(6, 59, 123) In the first section, we summarize the data available on adrenergic (Table 1), serotonin (Table 2), dopamine, and gamma-aminobutyric acid (GABA) function as well as chemoreceptor sensitivity (Table 3) in these anxiety disorders. The biologic systems we have chosen to review are those that have some clear connection to anatomic structures implicated in the pathophysiology of anxiety. Studies of anxiety patients, which have examined the function of other biologic systems such as cholecystokinin and adenosine, are not considered here but are reviewed elsewhere.(8, 126) As it would be difficult to include all the biochemical data available, we primarily focus on studies that used biochemical challenges that have yielded some of the dearest findings. In the second section, we summarize the data available from neuroimaging studies of these disorders (Table 4). In the third section, we present several of the current neuroanatomic hypotheses of anxiety disorders that have arisen from these data. Finally, we consider some of the hypothetical implications of these models and suggest some directions for future research.