Dr. Guang Chen

时间： 2014-09-23 13:00 - 15:00

地点： 哲学楼103

The seminar will start with a brief introduction of clinical depression, suicidality, individual and societal impacts of these two devastating clinical conditions, current chemical treatments for these two conditions, and direct targets of the known anti-depression and anti-suicidality agents. Then, the seminar will outline current understanding on the neurobiology of depression from studies in genetics, early life experience, clinical brain imaging, postmortem brains of the patients, neuropsychopharmacology, and animal models. Translation models of depression for the causality research and development of novel anti-depression agents and biomarkers will also be introduced. Main portion of the seminar will be on ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDA) receptor antagonist.

Ketamine is classified as a dissociative anesthetic agent for anesthesia and pain control, and also used as an experimental tool in the mechanistic research on neuropsychiatric disorders. It is a known substance of abuse in ethnicities including Chinese. In 2000, a group of physician-scientists of the Yale University published a brief report on the anti-depression effect of ketamine. This groundbreaking finding is soon being replicated in patients with treatment resistant depression and treatment resistant bipolar depression at the National Institute of Mental Health, Maryland, USA. The clinical studies demonstrate that a single intravenous (iv) infusion with subanesthetic dose of Ketamine rapidly (within hours) produces robust and long-lasting (for days) effects on depression and suicidality. The anti-depression and anti-suicidality effects of ketamine are unlikely causally linked to its psychedelic and dissociative actions. Animal studies show that ketamine is effective in a variety of depression models which are irresponsive or only responsive to chronic treatments with antidepressants. Preclinical studies also show that ketamine rapidly restore synaptic function through synaptogenesis and increases in synaptic insertion of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These synaptic effects are like due to a pulse stimulation of molecularly diverging and functionally converging intracellular signaling pathways including ERK, AKT, GSK-3 and mTor through brain-derived neurotrophic factor (BDNF). The effects of ketamine on intracellular signaling pathways are also known to be induced by chronic treatments with antidepressants and mood stabilizers such as lithium. These data illustrate plausible novel mechanisms beyond monoamine systems to be utilized in developing new rapid-acting antidepressants.

2014-09-23

2014-09-23