Does Stressed Equal Depressed?

Feeling down? Your genes may have a lot to do with how you handle stress.


May 8, 2007 — -- Psychiatrists in the past tended to emphasize the distinction between depressions triggered by stressors and those that spring unbidden out of a disordered brain.

But there is likely a continuum with some depressions following the onslaught of massive stressors, others occurring in the midst of placid lives, and still others somewhere in between.

Stress presumably interacts with genetic vulnerability, mediated by the stress hormone system.

One easy way to think about this is to think about an individual's resilience to stress as a dam that holds back water.

The height of the dam represents an individual's genetic resistance to stress. The higher the dam, the better that an individual can adapt to stressful situations.

Stress can be thought of as the water added by rainstorms. The stress hormone system is the drainage system that may be more or less efficient at siphoning off water as the need arises.

Just as rain is good for filling a dry reservoir, arousal can have positive psychological effects. Research has even shown that performance increases as arousal increases -- up to a certain point, at least.

Think about a student who might nod off in class during a mid-semester lecture, but writes a long and clever essay at semester's end when a course grade is on the line.

But as arousal increases further, it becomes stressful, as it creates a mismatch between demands and ability to meet those demands, which leads to decreasing performance.

If the same student has four papers and four final exams to prepare for, and his parents want to talk and e-mail extensively with him about their impending separation, he might become anxious and overwhelmed, and produce rushed, sloppy work.

There is extensive literature examining the relationship of stressors to depression.

One early study found that in the six months preceding a depression, people tended to have increased arguments with their spouse, marital separation, new jobs, changes in work conditions, serious personal illnesses, serious illness or death of family members, or family members leaving home.

While some of these could have been the result of depression, others, such as the death of a family member, are almost certainly independent of it.

Later studies have generally confirmed a relationship between stressors and depression, though the relationship is not a simple one. For example, one research group found that severe stressors often preceded depression in women; however, only about one out of five women experiencing such a stressor went on to develop depression.

And there is evidence that genetic factors and stressors interact in causing depression. A study of several thousand female twins found that the four stressors that most strongly predicted depression were death of a close relative, assault, serious marital problems, and divorce or breakup.

In people at lowest genetic risk, the likelihood of depression was low for those who had not experienced a severe stressor, and medium for those who did.

In people at highest genetic risk, the probability was low in the one group and high in the other. The high risk represents the interactive risk of depression in those with both genetic vulnerability and exposure to high stress.

Other researchers have found a specific genetic vulnerability caused by having two copies of a variant of the serotonin transporter gene that appears to increase the risk of depression through an interaction with stressors.

Cortisol, the key stress hormone, is ultimately controlled by the brain. It, in turn, influences genes in the brain. Brain control over cortisol is exerted in part by neurotransmitters -- the chemical messengers in the brain -- including serotonin. The relationship between elevated cortisol and depression was first shown in the 1950s.

But there is a chicken and egg question that arises here. Does the stress hormone abnormality cause depression, or is it the result of depression?

One way to disentangle this is to study relatives of people with depression rather than patients themselves.

A study in the April issue of the American Journal of Psychiatry looked at people who have never been depressed, but who have a relative with depression, and compared them to those without such a family history.

Cortisol levels were found to be higher in those who have depression in their families, suggesting there is a vulnerability present even in those who have never been ill.

If genetics play a role in this vulnerability, which genes are the key players? One that has been implicated may influence the recurrence of depression and the speed of response to antidepressant medications. We are studying this gene in our own laboratory at Johns Hopkins to see if it plays a role in bipolar disorder.

In the meantime, what can we do to reduce stress in patients?

First of all, effective treatment of depression reduces stress. There is a corresponding decrease in cortisol levels following treatment in most patients. We can accomplish this with our existing antidepressants, and there are also new drugs being tested for depression focused directly on blocking the stress hormones.

Additionally, most of the psychotherapy we do, the talk therapy, has a stress reduction element to it.

More specific techniques aimed at stress include education about stress as an imbalance between the level of demands and the coping skills available to handle them; instruction in progressive muscle relaxation and meditation; training in assertiveness, problem solving and time management; and strengthening social supports.

Dr. James Potash is an associate professor of psychiatry and co-director of the Mood Disorders Program at the Johns Hopkins School of Medicine in Baltimore. If you have questions or comments, please e-mail at To participate in our studies, call 1-877-MOODS-JH.