Stress, genetics can trigger depression

It seems to be common sense that hard times are associated with developing depressive symptoms. When a personal crisis occurs, many people who had been coping pretty well become clinically depressed.

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The two classic examples are losing a relationship or losing a job. However, if a company terminates 100 employees, most of them don't develop a depressive illness. An important question is why one employee manages to cope while another develops a mood disorder.

Seven years ago, an important paper published in one of our most respected scientific journals reported that people with a genetic variant of the serotonin transporter gene were more likely to become depressed when they had experienced stressful situations.

If a person had this genetic variant and wasn't exposed to very stressful situations, they weren't any more vulnerable to depression than if they had the more protective form of the gene. It was only when they had experienced severe personal distress that their depressive symptoms occurred. People without this genetic variant were often able to tolerate quite severe stress and not develop symptoms.

There has been much discussion of this finding. Many studies were done that measured stressful experiences in a variety of different ways. About a year ago, a paper reviewed only 14 of these studies and concluded that people with this genetic variant weren't very much more vulnerable to stress. There were problems with this analysis, but it was published in a good journal and it made some doctors a bit skeptical about the finding.

This week, a new analysis of 56 studies concluded that there was a strong relationship. They demonstrated that people with the less active form of the serotonin transporter gene were more vulnerable to developing depression when they experienced severe stress.

The analysis found:

The strongest relationship was between severe stresses during childhood that then seemed to haunt the person for the rest of their life. This finding supports the view that young children are particularly vulnerable and that early abusive experiences can have a long lasting impact. The next most difficult type of stress was serious medical problems. This also makes sense as we have known for many years that some people become very depressed when faced with the prospect of having to deal with a serious medical illness.The least dangerous kind of stress was the hassles of everyday living that we're all familiar with and that sometimes get out of hand. However, even this kind of stress was associated with an increased risk of depression if a person had this genetic variant.

The bottom line is that this new analysis provides strong evidence that stress can trigger depression and that the onset of depression is far more likely in people who are genetically vulnerable to developing a mood disorder.

Does this mean that if you have the variant, you are doomed to become depressed? Absolutely not. It just means that you're more vulnerable to developing symptoms.

Does the study prove that if you don't have the variant, you won't develop a depression if you're exposed to intense stress? Again, absolutely not. It just means that the risk is lower.

Perhaps the most important point that this analysis makes is that there is a biological vulnerability to depression just like there is a biological vulnerability to diabetes, asthma, or cancer.

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