> In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of

> In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. Research at Yale has shown that damage of these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine. There's burgeoning evidence that depression is tied to a lack of neurogenesis (creation of new brain cells), which may also be tied to serotonin levels. Some believe that the reason SSRIs take weeks to have antidepressive effects, even though serotonin levels are restored almost immediately, is that it takes a while for that to stimulate new brain cells. It's far from certain though that serotonin has anything to do with depression or neurogenesis. The atypical antidepressant tianeptine (currently unapproved in the US, but widely used in western europe) apparently reduces serotonin levels while boosting neurogenesis, the study of which is summarized well by Stanford neuroscientist Robert Sapolsky [1]: > … tianeptine prevented many of these stress-induced changes. These included the spectroscopic alterations, the inhibition of cell proliferation, and a significant increase in hippocampal volume (as compared with stress + vehicle animals). Of significance (see below), tianeptine did not prevent the stress-induced rise in cortisol levels. The restoration of hippocampal volume is important because it's been shown that low hippocampal volumes correlate with emotional abuse in adolescents [2] (also by Yale researchers). This was breathtaking for me - bad parenting literally causes brain damage. Special K and tianeptine aren't the only efforts at curing depression through neurogenesis. Neuralstem [3] is testing a drug in humans to treat major depressive disorder by restoring hippocampal volume, with a controlled study to complete early next year. That is the only new drug I'm aware of. Regardless, the serotonin model of depression, the one which produced Prozac etc. isn't the last word, and it's looking more likely that a dearth of new synapses may be the culprit in clinical depression. [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ [2] http://www.medpagetoday.com/Pediatrics/DomesticViolence/30029 http://www.medpagetoday.com/Pediatrics/DomesticViolence/3002... [3] http://www.neuralstem.com/pharmaceuticals-for-depression http://www.neuralstem.com/pharmaceuticals-for-depression