To quash depression, some brain cells must push through the stress

A bid to unlock the secrets of resilience in the brain prompted researchers to look for cells that overreacted in the face of stress. What they found was surprising: More overreaction in these cells, not less, seemed to make mice hardier in the face of adversity.
(Justin Renteria)

The nature of psychological resilience has, in recent years, been a subject of enormous interest to researchers, who have wondered how some people endure and even thrive under a certain amount of stress, and others crumble and fall prey to depression. The resulting research has underscored the importance of feeling socially connected and the value of psychotherapy to identify and exercise patterns of thought that protect against hopelessness and defeat.

But what does psychological resilience look like inside our brains, at the cellular level? Such knowledge might help bolster peoples’ immunity to depression and even treat people under chronic stress. And a new study published Thursday in Science magazine has made some progress in the effort to see the brain struggling with -- and ultimately triumphing over -- stress.

A group of neuroscientists at Mount Sinai’s Icahn School of Medicine in New York focused on the dopaminergic cells in the brain’s ventral tegmentum, a key node in the brain’s reward circuitry and therefore an important place to look at how social triumph and defeat play out in the brain. In mice under stress because they were either chronically isolated or rebuffed or attacked by fellow littermates, the group had observed that this group of neurons become overactive.

It would logically follow, then, that if you don’t want stressed mice (or people) to become depressed, you would want to avoid hyperactivity in that key group of neurons, right?


Actually, wrong, the researchers found. In a series of experiments, they saw that the mice who were least prone to behave in socially defeated ways when under stress were actually the ones whose dopaminergic cells in the ventral tegmental area displayed the greatest levels of hyperactivity in response to stress. And that hyperactivity was most pronounced in the neurons that extended from the tegmentum into the nearby nucleus accumbens, also a key node in the brain’s reward system.

The researchers wondered whether inducing similar hyperactivity in mice prone to depression -- effectively pushing these cells to signal even faster and harder -- might help bolster them against succumbing to passivity and defeat when under stress? Using antidepressant medication, viruses and lights that turn circuits on and off, they found that it could. By activating the chemical processes that induced the same level of hyperactivity seen in the ventral tegmenta of resilient mice, they made depression-prone mice more hardy and happy in the face of stress.

The results suggest something profound about the brain and depression: that in the healthy and psychologically resilient, stress induces its own chemical countermeasures, fostering a sort of psychological equilibrium. Someday medications might employ strategies that help promote such equilibrium to head off depression before it starts, as well as to treat it once it has set in.