Imagine a class full of college students who are about to start their final exam. Some are fairly relaxed…others are nervous but still able to focus…and some are so stressed that they’re unable to perform effectively. What causes these differences has been unclear…until now.

It makes sense that differences in the amount of the stress hormone cortisol a person releases in response to a stressful experience can determine how distressed that person actually feels. But here’s the surprise: Too little cortisol may be just as bad as too much, according to a recent study published in The Journal of Neuroscience.

Background: Most stress research in humans has involved inducing a short period of stress and classifying participants as either responders or nonresponders, based on the level of the cortisol in their saliva. In these studies, the average feelings of stress felt by participants in both groups have typically been similar.

Study details: Researchers modified existing lab procedures and induced stress for more than one hour in 79 healthy women. These women were given the Maastricht Acute Stress Test, a test aimed at activating the human stress system by combining physical stress (cold-induced pain) with the stress of being evaluated while doing mental arithmetic tasks.

Surprising: The participants who released either very high or very low amounts of cortisol over time reported feeling more stressed than those who released a moderate amount of cortisol. The high and low responders also had less gray matter in the hippocampus—a brain structure with a large number of cortisol receptors that regulate the stress response—than the moderate responders.

Related result: Another recent study found that individuals with a history of major depression showed reduced cortisol release and higher self-reported feelings of stress. According to Dr. Diego Pizzagalli, director of the Center for Depression, Anxiety and Stress at McLean Hospital/Harvard Medical School and a coauthor of both studies, “This type of data will help us identify individuals at risk for first onset and recurrence of depression.”

Bottom line: Experiencing stress and feeling stressed are not the same. Although the link should be investigated further, feelings of stress may be associated with the amount of cortisol you release in response to a stressor or with the amount of gray matter in your hippocampus. These factors are not within your control, but understanding which people are more susceptible to feeling stress or depression—and why—is a step in the right direction toward providing more effective strategies for coping with stress as well as better treatment for those with depression.

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