Weighing in on Depression

Antidepressant medications all have predictable effects, for example, on mice in the "forced swim test." In this test, mice are forced to swim in a narrow cylinder from which they cannot escape. After a brief period of vigorous attempts to escape from the water, the mice adopt an immobile posture, essentially giving up trying to escape. Giving up is akin to being depressed, and antidepressants prolong the time of escape activity.

In the current study, mice were fed a low-calorie diet, so that their ghrelin levels rose. The result was prolonged activity on the forced swim test, suggestive of an antidepressant-like effect. Then, another group of mice was injected with ghrelin. The same effect was observed.

Another mouse model of depression is called the chronic social defeat stress procedure. It involves subjecting one mouse to a more aggressive bully mouse, and doing it over and over. The mouse that has been bullied begins to act withdrawn, somewhat like a depressed person. Treatment with antidepressants reverses this behavior.

So, the researchers examined normal mice and mice genetically engineered to be deficient in ghrelin signaling. They found that, without ghrelin signaling, mice subjected to chronic social defeat stress were even more withdrawn than they were normally, suggesting, again, that ghrelin was exerting an antidepressant-like effect.

It is an intriguing formulation. Stress gets us upset and feeling low. Ghrelin picks us back up some, and also makes us hungrier, and so we eat ice cream. And then we associate the ice cream with feeling better.

There is, no doubt, far more to the story. For example, the same researchers have also recently shown similar findings with another brain chemical called orexin. I do not have space here to describe those results, but I thought I would simply whet your appetite further. Maybe it will put you in a good mood.

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, Md. If you have questions or comments, please e-mail at moods@jhu.edu. To participate in our genetic and clinical studies, call 1-877-MOODS-JH.

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