Preventing depression W
hen approaching diseases, scientists usually look for two things — ways to cure them and ways to prevent them. But with mental illnesses, we have neither. For example, SSRIs are the most popular antidepressant medications, but they only suppress symptoms. Yet pharmaceutical research has focused almost entirely on fine-tuning these drugs rather than looking for ways to prevent mental disorders from occurring in the first place. That may change, thanks in part to work done by neuroscientist (and TED Fellow) Rebecca Brachman PhD.
What if we could inoculate people against depression and trauma?
Eight years ago, Brachman stumbled upon a drug that proved to protect against the detrimental effects of acute or chronic stress — a potentially paradigm-shifting discovery that’s opening up a new field of preventative psychopharmacology. Now Brachman, who is a Jacobs Institute Runway Fellow at Cornell Tech supported by Schmidt Futures, and her colleagues are creating prophylactic compounds that could prevent mental illness from taking hold by fortifying our bodies’ natural stress resilience. If these efforts are successful, we could not only inoculate people against the negative effects of trauma but perhaps also reduce the overall incidence of depression — the leading cause of disability worldwide, according to the WHO — in the general population.
The idea to use drugs as a preventative against mental illness is a new idea in medicine.
The idea to use drugs as a preventative against mental illness is a new idea in medicine. In fact, Brachman discovered the possibility by accident when she was doing routine preliminary work to start experiments using an emerging rapidacting antidepressant. She christened this new class of drugs “alexigents” — from the Greek alexo, meaning “to protect.” Scientists don’t know for sure what causes depression, but they do know that for both depression and PTSD, the body’s capacity for resilience in the face of trauma plays a part. “Stress resilience” is
42
the ability to recover from a stressful experience, for the body to bounce back to homeostasis. Resilience can protect against developing a psychiatric disorder in the face of stress; it varies from person to person and can fluctuate over the course of one’s life.
“We haven’t known for long that stress resilience is an active biological property,” she says. “It was more thought of as an ‘absence of risk factors.’ People with a genetic predisposition or environmental exposure in childhood were considered at risk for depression. Meanwhile, people without those factors were assumed, by default, to be comparatively resilient.” Today scientists know that’s not the whole story. “The risk factors for depression and the factors that promote resilience are not all necessarily on the same spectrum,”
Brachman explains. “Instead, we now know that resilience involves a separate, active biological process — which also means we might be able to enhance it.” There’s one accepted idea that Brachman thinks needs to change — that cortisol and other stress hormones are all bad. It‘s not true, she says. “At the NIH, I did another set of experiments with my colleague, Dr. Michael Lehmann, where we showed that if you block corticosterone (the main stress hormone in mice), you lose the beneficial antidepressant effect of exercise. You need the stress hormones.” This is because stress hormones are essential and part of the body’s selfprotective response. Brachman explains that cortisol makes sugar available for extra energy and increases blood pressure. “Cortisol makes more resources — energy, oxygen, and so on — available to your body to respond appropriately to a stressor