New research at UT Southwestern Medical Center has found that high levels of ghrelin, a “hunger hormone”, may have an antidepressant effect. The study may explain why some people overeat when they are stressed or depressed.
An empty stomach releases ghrelin into the bloodstream, where it then moves to the brain triggering feelings of hunger. Researchers believe treatment with either ghrelin, or a drug intended to cancel its effects, may be able to help both people who eat too much and those who are eating too little, such as cancer patients.
While levels of ghrelin are known to increase when a person doesn’t eat, the study suggests the hormone may also protect against symptoms of stress-induced anxiety and depression.
The researchers said that although blocking the body’s response to ghrelin has been suggested as a potential weight loss method, it may also have unintended consequences on mood.
“Our findings in mice suggest that chronic stress causes ghrelin levels to go up and that behaviors associated with depression and anxiety decrease when ghrelin levels rise. An unfortunate side effect, however, is increased food intake and body weight,” said Dr. Jeffrey Zigman, assistant professor of internal medicine and psychiatry at UT Southwestern and the study’s senior author.
“Our findings support the idea that these hunger hormones don’t do just one thing; rather, they coordinate an entire behavioral response to stress and probably affect mood, stress and energy levels,” said Dr. Michael Lutter, a UT Southwestern instructor of psychiatry and the study’s lead author.
It is long been known that fasting causes ghrelin to be produced in the gastrointestinal tract. The hormone then plays a key role in sending hunger signals to the brain. Scientists have suggested that blocking the body’s ghrelin response might help control weight by decreasing food consumption and increasing energy expenditure.
“However, this new research suggests that if you block ghrelin signaling, you might actually increase anxiety and depression, which would be bad,” Dr. Zigman said.
To determine ghrelin’s effect on mood, Dr. Zigman and his team restricted food intake of laboratory mice for 10 days, causing their ghrelin levels to quadruple. When compared to the control mice that were allowed free access to food, the calorie-restricted mice displayed lower levels of depression and anxiety when subjected to mazes and other standard behavior tests.
Interestingly, the researchers found that mice genetically engineered to be unable to respond to ghrelin did not experience the antidepressant-like or anti-anxiety-like effects when fed a restricted-calorie diet.
To examine whether ghrelin could regulate depressive symptoms caused by chronic stress, the researchers subjected mice to daily sessions of social stress using a standard stress induction technique exposing normal mice to very aggressive “bully” mice. Such animals have been good models for studying depression in humans.
The researchers stressed both wild-type mice and altered mice unable to respond to ghrelin. The results showed that after experiencing stress, both groups of mice had substantially elevated levels of ghrelin that persisted at least four weeks after their last encounter. However, the altered mice displayed significantly greater social avoidance than their wild-type counterparts, indicating a worsening of depression-like symptoms. They also consumed less food than the wild-type mice.
The findings were consistent when viewed from an evolutionary standpoint, said Dr. Zigman.
“Until modern times, the one common human experience was securing enough food to prevent starvation. Our ancestors needed to be as calm and collected as possible when it was time to venture out in search of food, or risk becoming dinner themselves,” he said.
The anti-anxiety effects of hunger-induced ghrelin may have provided a survival advantage, he said.
Dr. Lutter said the findings could be important in understanding conditions such as anorexia nervosa.
“We’re very interested to see whether ghrelin treatment could help people with anorexia nervosa, with the idea being that in a certain population, calorie restriction and weight loss could have an antidepressant effect and could be reinforcing for this illness,” Dr. Lutter said.
Scientists hope future research can determine which area in the brain ghrelin may be acting upon to cause these antidepressant-like effects.
The research was supported by the U.S. National Institutes of Health, the Foundation for Prader-Willi Research, the National Alliance for Research on Schizophrenia and Depression and the Disease-Oriented Clinical Scholars Program at UT Southwestern.
The study appeared in today’s online edition of the journal Nature Neuroscience, and will be published in a future print edition. An abstract of the report can be viewed here.
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