Neurobiology of anxiety disorders and implications for treatment.
The neurobiology of the anxiety disorders, which include panic disorder, post-traumatic stress disorder (PTSD), and specific phobias, among others, has been clarified by advances in the field of classical or Pavlovian conditioning, and in our understanding of basic mechanisms of memory and learning. Fear conditioning occurs when a neutral conditioned stimulus (such as a tone) is paired with an aversive, or unconditioned stimulus (such as a footshock), and then in the absence of the unconditioned stimulus, causes a conditioned fear response. Preclinical studies have shown that the amygdala plays a key role in fear circuitry, and that abnormalities in amygdala pathways can affect the acquisition and expression of fear conditioning. Drugs such as glutamate N-methyl-D-aspartate (NMDA) antagonists, and blockers of voltage-gated calcium channels, in the amygdala, may block these effects. There is also preliminary evidence for the use of centrally acting beta-adrenergic antagonists, like propranolol, to inhibit consolidation of traumatic memories in PTSD. Finally, fear extinction, which entails new learning of fear inhibition, is central to the mechanism of effective anti-anxiety treatments. Several pharmacological manipulations, such as D-cycloserine, a partial NMDA agonist, have been found to facilitate extinction. Combining these medication approaches with psychotherapies that promote extinction, such as cognitive behavioral therapy (CBT), may offer patients with anxiety disorders a rapid and robust treatment with good durability of effect.
Garakani
Amir
A
Mount Sinai School of Medicine, New York, NY, USA.
Mathew
Sanjay J
SJ
Charney
Dennis S
DS
D000679:Amygdala / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001008:Anxiety Disorders / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D015928:Cognitive Behavioral Therapy; D003213:Conditioning, Psychological / Q000502:physiology*; D005108:Extinction, Psychological; D005239:Fear / Q000502:physiology / Q000523:psychology; D006801:Humans; D008568:Memory / Q000502:physiology; D016584:Panic Disorder / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate