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 Research & Giving News Article  Depression and Anxiety “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. Zigman, an assistant professor of internal medicine and psychiatry who received a 2007 NARSAD Young Investigator award. Mouse moods Previous studies had suggested that fasting prompts the gastrointestinal tract to release ghrelin, which then plays a role in sending hunger signals to the brain. Research groups, including Dr. Zigman’s, have suggested that blocking the body’s response to ghrelin signals might help control weight by reining in food intake and boosting energy use. “However, this new research suggests that if you block ghrelin signaling, you might actually increase anxiety and depression,” Dr. Zigman said. Dr. Lutter, an instructor of psychiatry and a NARSAD 2008 Young Investigator, led the study that Nature Neuroscience released online on June 15 ahead of print publication. To study ghrelin’s effects on mood, he and his colleagues limited some laboratory mice to a low-calorie diet for 10 days, while they let others eat all the food they wanted. Ghrelin levels quadrupled in the calorie-limited mice, which acted less anxious and depressed than the others in standard test situations such as a maze. Dr. Lutter and associates also tested genetically altered mice that could not respond to ghrelin. Those animals received the same low-calorie diet but did not show decreased anxiety or depression. The scientists then tested whether ghrelin would control depression in a model of chronic stress that involved exposing mice to a “bully” mouse each day for ten days. Mice subjected to this treatment tend to avoid other mice, although long-term treatment with an antidepressant drug can get them back to socializing again. Four weeks after their last encounter with an aggressor, both genetically altered and wild-type mice still had elevated levels of ghrelin. However, altered mice avoided other mice more than wild-type ones did, echoing the social withdrawal seen in human depression. They also ate less than wild-type mice. From mice to humans The results of this study may explain why some people overeat when they feel anxious or depressed. “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,” Dr. Lutter said. This makes sense from an evolutionary standpoint, Dr. Zigman noted; the anti-anxiety effects of hunger-induced ghrelin may have kept our hunter-gatherer ancestors from becoming dinner themselves by keeping them calm and collected when they ventured out to find food. If ghrelin affects mood in humans the way it does in mice, this research may help scientists understand mood disorders and anorexia nervosa, a condition with ghrelin abnormalities. Dr. Lutter said, “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.” In addition to Dr. Lutter, Dr. Zigman, and Dr. Nestler, a member of NARSAD’s Scientific Council and recipient of a Distinguished Investigator award in 1996, the research team included Dr. Ichiro Sakata, Sherri Osborne-Lawrence, Sherry Rovinsky, Jason Anderson, Saendy Jung, Dr. Shari Birnbaum, Dr. Masashi Yanagisawa, and Dr. Joel Elmquist. This story was adapted by NARSAD with permission from the University of Texas Southwestern Medical Center. |
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