Weighing in on Depression

July 30, 2008— -- Is ice cream an antidepressant?

Some patients with depression will eat a pint of Ben and Jerry's ice cream at night before they go to bed. They feel comforted -- at least briefly -- by the high-calorie treat. Of course, it doesn't take too many nights of this before the pounds start piling up.

New research published in the journal Nature Neuroscience this month may shed some light on the biological relationship between depression and appetite. While it does not show that Ben and Jerry's is an antidepressant, it does suggest that a brain chemical, that motivates the consumption of the ice cream, may be.

The chemical is called ghrelin, and it is naturally produced in the brain and the stomach. It was only discovered in 1999 by researchers who named it based on the Proto-Indo-European word root "ghre" for "grow," referring to its ability to stimulate growth hormone. But it turns out to be the most potent appetite stimulant known.

Researchers have known for several years that ghrelin levels rise before meals and in association with hunger. They have also known that injecting the chemical into the brains of rats causes them to eat much more and gain weight. Two years ago, investigators showed that a vaccine against ghrelin could reduce body fat and weight gain in rats.

A Weighty Issue

Weight gain is a large issue in depression and its treatment. A major source of the problem are the medications themselves.

One patient recently told me she had been depression-free, eating well, and exercising four times a week, yet she inexplicably had been gradually putting on weight in the context of continuing to take an antidepressant to prevent the return of the illness.

Most of the serotonin-selective reuptake inhibitor antidepressants -- the Prozac family -- carry less risk for weight gain than the older medications, such as the tricyclic antidepressants. However, some newer medications, such as Remeron, can also lead to waistline expansion.

But we can't blame everything on the medications. Before there were medications, there were appetite and weight changes associated with depression. Many of the earliest descriptions of depression report a loss of appetite and of weight. This accompanies a severe form of the illness referred to as "melancholic depression." But overeating and weight gain can also occur and these are characteristic of "atypical depression."

The occurrence of appetite and weight changes, both in depression and in response to antidepressants, suggests that mood and hunger might be linked by some common brain mechanism. But until now, there has not been a clear indication as to what that mechanism might be.

Comforting Results

Researchers at the University of Texas Southwestern Medical Center sought to explore the mood-food relationship to ghrelin by using mice. It is not intuitively obvious that the moods of mice would have any relationship to those in people. But there does seem to be a connection.

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.