Author: Megan Thielking / Source: STAT
s ketamine makes waves in the field of mental health, there’s a mystery around the drug that continues to elude scientists: how, exactly, it works in the brains of people with depression.
ANow, scientists have uncovered a process that might contribute to ketamine’s antidepressant effect.
In new research in mice published Thursday in Science, researchers report that ketamine appears to spark the growth of neural connections that had been diminished by chronic stress. They also discovered that the survival of those new connections — known as synapses — seems to be critical to maintaining some of ketamine’s effects.“To the extent that what we’re modeling in the brains of mice captures something that’s happening in the brains of depressed people, this could be a promising future avenue for research,” said Dr. Conor Liston, neuroscientist and psychiatrist in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine and an author of the new study.
But experts caution that there are still significant unknowns about how ketamine works in the brain — and at this point, it’s not possible to confirm whether the new observations in mice are also happening in humans.
“It’s interesting, it’s fascinating, but it cannot explain the whole story. It’s one additional piece of a very complex puzzle,” said Dr. Cristina Cusin, who leads a ketamine treatment program at Massachusetts General Hospital and who wasn’t involved in the research.
Ketamine — a longtime anesthetic — is known to work on certain receptors in the brain known as NMDA receptors, which are involved in learning and memory. Research over the last two decades has suggested it can ease symptoms of depression, but scientists don’t understand the biology behind that effect, why the response to ketamine varies so much from one patient to the next, or why the drug’s effects wear off over time. With esketamine, a ketamine-derived nasal spray approved by the FDA last month for treatment-resistant depression, patients have to take eight doses over their first month of treatment before being moved to a maintenance dose.
In the new research, neuroscientists at Weill Cornell looked specifically at circuitry in the medial prefrontal cortex, an area of the brain thought to be involved in depression. Research has suggested that chronic stress can affect the number of synapses, or the connection between two neurons in the brain. Liston and his colleagues wanted to see if ketamine might have reversed those effects. So they looked at what are known as dendritic spines, tiny projections that shoot off branches of neurons known as dendrites. Most dendritic spines contain functional synapses, so scientists consider them a sign of a connection between two neurons.
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