Letter to the editor: does ketamine exert a fast-acting antidepressant effect via inhibition of pro-inflammatory cytokines?

Letter to the Editor Does ketamine exert a fast-acting antidepressant effect via inhibition of pro-inflammatory cytokines ? We read with great interest the excellent article by Horacek and colleagues (Horacek et al. 2010), in which the authors indicated that the decrease in theta cord-ance could be a marker and a predictor of ketamine exerting a fast-acting antidepressant effect. We appreciate the work of their suggestive findings, which may be promising in explaining the underlying mechanism of ketamine exerting a fast-acting anti-depressant effect. Pro-inflammatory cytokines including IL-1 and TNF-a have been implicated in major depressive disorder (Hayley et al. 2005). Moreover, IL-1 may enhance brain serotonin transporter activity in cultured sero-tonergic cells and nerve terminals in vitro, resulting in the reduction of serotonin levels in the synaptic cleft (Zhu et al. 2010). The therapeutic effect exerted by conventional antidepressants is mainly due to an increase in the level of monoamine transmitters via inhibition of serotonin and/or norepinephrine transporters located in presynaptic membranes. Unfortunately, these drugs exhibit an antidepressant effect at least 2–4 weeks after administration. Thus, there is a compelling conclusion that the therapeutic lag is a great limitation for conventional antidepressants. Ketamine, a N-methyl-D-aspartic acid (NMDA) receptor antagonist, is often used for anaesthesia. Recent literature (Li et al. 2010) has demonstrated that keta-mine exerts a robust and fast-acting antidepressant effect within 2 h after administration. However, the mechanism underlying the rapid-onset antidepressant effect of ketamine is incompletely understood. On the other hand, ketamine has been recommended for patients with sepsis because it may inhibit the endotoxin-induced pro-inflammatory cytokines including IL-1 and TNF-a both in vitro and in vivo (Taniguchi & Yamamoto, 2005). The coincidence of the fast-acting antidepressant and anti-inflammatory effects of keta-mine suggests that one possible mechanism underlying the fast-acting antidepressant effect of ketamine can be attributed to its inhibition of pro-inflammatory cytokines. Further research is required to understand the perspective and discover the underlying mechanism. (2005). The pathogenesis of clinical depression : stressor and cytokine-induced alterations of neuroplasticity. Neuroscience 135, 659–678. (2010). Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers : implications for antidepressant effect. (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. The authors reply The influence of a subanaesthetic dose of ketamine on circulating pro-inflammatory cytokines and serotonin in brain In response to …