The American journal of psychiatry
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Randomized Controlled Trial Multicenter Study Comparative Study
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. ⋯ Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
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Poor threat-safety discrimination reflects prefrontal cortex dysfunction in adult anxiety disorders. While adolescent anxiety disorders are impairing and predict high risk for adult anxiety disorders, the neural correlates of threat-safety discrimination have not been investigated in this population. The authors compared prefrontal cortex function in anxious and healthy adolescents and adults following conditioning and extinction, processes requiring threat-safety learning. ⋯ Two regions of the prefrontal cortex are involved in anxiety disorders. Reduced subgenual anterior cingulate cortex engagement is a shared feature in adult and adolescent anxiety disorders, but ventromedial prefrontal cortex dysfunction is age-specific. The unique U-shaped pattern of activation in the ventromedial prefrontal cortex in many anxious adolescents may reflect heightened sensitivity to threat and safety conditions. How variations in the pattern relate to later risk for adult illness remains to be determined.
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The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. ⋯ Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value.