A Vaccine for Depression?

One sunny day this fall, I caught a glimpse of the new psychiatry. At a mental hospital near Yale University, a depressed patient was being injected with ketamine. For 40 minutes, the drug flowed into her arm, bound for cells in her brain. If it acts as expected, ketamine will become the first drug to quickly stop suicidal drive, with the potential to save many lives. Other studies of ketamine are evaluating its effect as a vaccination against depression and post-traumatic stress. Between them, the goal is nothing less than to redefine our understanding of mental illness itself.

Depression is the most common mental illness in the United States, affecting 30 percent of Americans at some point in their lives. But despite half a century of research, ubiquitous advertising, and blockbuster sales, antidepressant drugs just don’t work very well. They treat depression as if it were caused by a chemical imbalance: Pump in more of one key ingredient, or sop up another, and you will have fixed the problem.

But the correspondence between these chemicals (like serotonin) and depression is relatively weak. An emerging competitive theory, inspired in part by ketamine’s effectiveness, has it that psychiatric disease is less about chemical imbalance than structural changes in the brain—and that a main cause of these changes is psychological stress. “I really do think stress is to mental illness as cigarettes are to heart disease,” says Gerard Sanacora, the psychiatry professor running the ketamine trial at Yale.

The theory describes stress grinding down individual neurons gradually, as storms do roof shingles. This, in turn, changes the nature of their connections to one another and the structure of the brain. Ketamine, along with some similar molecules, acts to strengthen the neuron against that damage, affecting not just the chemistry of the brain but also its structure.

Mental hospitals don’t usually see patients until they break: a brain shaped by vulnerable genes, wrecked by the stress of loss or trauma. This isn’t how it works with other sicknesses: heart disease, cancer, AIDS. Detected early, these conditions can often be managed. Crises averted.

If Sanacora and like-minded researchers are right, we may be on the cusp of a sea change that allows for a similar approach to mental health. The new approaches may prevent mental illness before it hits, by delivering a vaccination for the mind.

he need for progress could hardly be more urgent: Of all illnesses, neuropsychiatric diseases are estimated to put the heaviest burden on society. Nearly half of Americans are affected by some sort of mental disorder at some point