| dc.description.abstract | With a lifetime prevalence of over 16% and spread over all social classes, major depressive disorder (MDD) is one of the leading causes for psychosocial disability. Although there is no established mechanism for depression most drugs used in pharmacotherapy focus on the monoamine-deficiency hypothesis and inhibit the reuptake or metabolism of serotonin or norepinephrine in order to raise their plasma-levels. With over 20% of patients being resistant to treatment, and very low remission and high relapse rates, new strategies and methods for this treatment-resistant form of depression are warranted. In recent years the use of N-methyl-D-aspartate (NMDA) antagonists, and in particular the well known dissociative drug ketamine, in the treatment of clinical depression has come under increasing interest. This administration is less rigorous than more invasive treatments like deep brain stimulation. Recently the mechanism of action of this acute response, at sub-psychotomimetic doses, has been linked to eukaryotic elongation factor 2 (eEF2) kinase inhibition and desupression of brain-derived neurotrophic factor (BDNF) translation. This supports other research implying synaptic plasticity as an important factor in treating MDD. Chronic administration of ketamine is however linked to impairments of verbal fluency, cognitive processing speed, and verbal learning and its other cognitive effects are associated with potential abuse. In this report we will outline the molecular mechanisms involved in NMDA antagonism, the effects on other neurotransmitter-systems and glutamate signaling and how these relate to the positive effects on MDD. The major transduction pathways will be outlined and potential related targets highlighted. | |
