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[Anxiety disorder].

We reviewed recent advances in biological studies of anxiety disorders. The most important achievement was the discovery of the neural circuits of fear in the 1990s by using an animal model in which conditioned fear was induced. In the 2000s, this discovery led to further elucidation of neurotransmitters involved in fear and the precise neuronal mechanism of fear conditioning, thereby improving the understanding of neuroimaging findings of patients with anxiety disorders. The amygdala is a central region that is associated with the generation of fear, and its inactivation diminishes fear. In humans, amygdala activation has been consistently reported in anxiety disorders, indicating that hyperactivation of the amygdala is involved in the pathogenesis of anxiety disorders. Serotonin plays a key role in the treatment of anxiety disorders, and selective serotonin reuptake inhibitors (SSRIs) are currently regarded the first-line drugs used as anxiolytics. From animal studies, the mechanism underlying the anxiolytic effect of SSRIs is hypothesized as follows: SSRIs inhibit the neuronal activities of the amygdala, and this inhibition decreases the level of fear and anxiety. Animal studies of fear conditioning have proposed new treatment strategies for anxiety disorders: D-cycloserine, propranolol, and reactivation-extinction procedure. Among them, D-cycloserine, which is used as an adjunct to psychotherapy to facilitate extinction of fear, has been investigated in several randomized controlled trials, and its efficacies for several anxiety disorders have been established.

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