NARSAD Grantee and 2010 Outstanding Achievement in Mood Disorders Research Prizewinner Carlos Zarate, M.D., and team, at the National Institute of Mental Health (NIMH) discovered a brain signal, detectable by noninvasive imaging, that may become a biomarker, or biological predictor, of which depressed patients will respond to an experimental, rapid-acting antidepressant (ketamine) as well as to identify how it works. The work is reported online in the journal Biological Psychiatry.
The signal is among the latest of several such markers, including factors detectable in blood, genetic markers, and a sleep-specific brain wave, recently uncovered by the NIMH team. They illuminate the workings of ketamine, and may hold promise for more personalized treatment. Ketamine works through a different brain chemical system than conventional antidepressants. It initially blocks a protein on brain neurons, called the NMDA receptor, to which the chemical messenger glutamate binds. However, it is not known if the drug's rapid antidepressant effects are a direct result of this blockage or of downstream effects triggered by the blockage, as suggested by animal studies.
Zarate explains: "We are investigating ketamine in multiple ways -- studying genes, gene expression, synapses, cells, circuits, and symptoms with neuroimaging, genetics, electrophysiological measures and other techniques," explained Zarate. "These studies hold hope for predicting the likelihood of response and for gaining insights into mechanisms of action."