Biological psychiatry
-
Biological psychiatry · Jun 2013
ReviewRapid-acting glutamatergic antidepressants: the path to ketamine and beyond.
Traditional antidepressants require many weeks to reveal their therapeutic effects. However, the widely replicated observation that a single subanesthetic dose of the N-methyl-D-aspartate glutamate receptor antagonist ketamine produced meaningful clinical improvement within hours, suggested that rapid-acting antidepressants might be possible. The ketamine studies stimulated a new generation of basic antidepressant research that identified new neural signaling mechanisms in antidepressant response and provided a conceptual framework linking a group of novel antidepressant mechanisms. This article presents the path that led to the testing of ketamine, considers its promise as an antidepressant, and reviews novel treatment mechanisms that are emerging from this line of research.
-
Biological psychiatry · Jun 2013
Clinical TrialNeural correlates of rapid antidepressant response to ketamine in treatment-resistant unipolar depression: a preliminary positron emission tomography study.
Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. ⋯ Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.
-
Biological psychiatry · Jun 2013
Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation.
Fearful experiences can produce long-lasting and debilitating memories. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations. In human subjects, as well as rats, posttraining stimulation of the vagus nerve enhances memory consolidation. Subjects with posttraumatic stress disorder show impaired extinction of conditioned fear. The objective of this study was to determine whether vagus nerve stimulation (VNS) can enhance the consolidation of extinction of conditioned fear. ⋯ Extinction paired with VNS is more rapid than extinction paired with sham stimulation. As it is currently approved by the Federal Food and Drug Administration for depression and seizure prevention, VNS is a readily available and promising adjunct to exposure therapy for the treatment of severe anxiety disorders.