Neuroanatomical circuits modulating fear and anxiety behaviors

Our understanding of the neurobiology of anxiety disorders, although not complete, has advanced significantly with the development and application of genetic, neuroimaging and neurochemical approaches.

The neuroanatomical basis of anxiety disorders is reviewed with particular focus on the amygdala and the temporal and prefrontal cortex. The functional anatomical correlates of anxiety disorders such as panic disorder, specific phobias and post-traumatic stress disorder are also discussed.

Functional neuroimaging studies in patients with anxiety disorders have shown neurophysiological abnormalities during symptom provocation tests, implicating the limbic, paralimbic and sensory association regions. The involvement of neurotransmitters such as serotonin and norepinephrine in depressive disorders is well established. Antidepressants that affect these neurotransmitter systems have also been shown to be useful in the treatment and management of patients with anxiety disorders. The role of serotonin and norepinephrine in the pathophysiology of anxiety disorders is reviewed. In addition, the involvement of the stress hormone corticotropin-releasing hormone, the peptide cholecystokinin and the amino acid transmitter gamma-amino butyric acid in anxiety disorders is reviewed.

The inconsistency in the results of biologic investigations of anxiety disorders highlights the importance of addressing the neurobiologic heterogeneity inherent within criteria-based, psychiatric diagnoses. Understanding of this heterogeneity will be facilitated by the continued development and application of genetic, neuroimaging and neurochemical approaches that can refine anxiety disorder phenotypes and elucidate the genotypes associated with these disorders. Application of these experimental approaches will also facilitate research aimed at clarifying the mechanisms of anti-anxiety therapies.