“High levels of the ‘hunger hormone’ ghrelin have an antidepressant effect”, BBC News reported today. It said that a study in mice found that those whose food intake was restricted for 10 days had four times the normal levels of ghrelin, and showed fewer signs of anxiety and depression in behavioural tests.
According to the BBC, the researchers said there have been suggestions that blocking the body’s response to the hormone could be a possible weight-loss treatment. This new study however, found that it may also produce “unintended effects on mood”.
The researchers are quoted in the article as saying that although signs of depression and anxiety decrease as ghrelin levels increase, “an unfortunate side effect…is increased food intake and body weight”. The researchers now want to look at the antidepressant effect of ghrelin in conditions such as anorexia.
This study has shown a link between ghrelin and anxiety and depression-like behaviour in mice. However, much more research will be needed to determine whether this hormone plays a role in anxiety and depression in humans.
Where did the story come from?
Dr Michael Lutter and colleagues from the University of Texas Southwestern Medical Centre carried out the research. The study was funded by the US National Institutes of Health, the Foundation for Prader-Willi Research, NARSAD Young Investigator Award, and a University of Texas Southwestern Disease-Oriented Clinical Scholar award. The study was published in the peer-reviewed scientific journal Nature Neuroscience.
What kind of scientific study was this?
Chronic stress can lead to changes in eating patterns and metabolism, and eating and metabolism may in turn affect mood, but this has not been thoroughly studied. In this laboratory study in mice, the researchers looked at whether mood was affected by the hormone ghrelin. This hormone is released by the digestive system and tells the brain that the animal needs to eat.
In the first part of their experiment, the researchers split the mice into two groups: one group could eat as much as they wanted, while the other group had their food intake cut by 60% for 10 days so that their ghrelin levels would increase. The mice then took part in two standard tests to measure their depression- and anxiety-like behaviours: a maze test and a swimming test. In the maze test, the researchers looked at how long the mice spent exploring the open and closed corridors of the maze, how often they entered the different types of corridor, and how fast they went. Mice showing anxiety-like behaviour prefer closed corridors to open corridors. In the swim test, mice were placed in water and the researchers measured how long they continued to swim. Mice with depression-like behaviour will not swim as long.
The researchers then repeated this experiment in mice who had been genetically modified so that their ghrelin signalling was blocked. These mice had a missing protein, which is found on the surface of brain cells and binds to ghrelin to allow it to transmit its signal. In this second set of experiments, the researchers took two groups of mice and injected one group with ghrelin, and the other with salt water, then compared their performance on maze and swim tests.
In the third set of experiments, the researchers looked at ghrelin levels in mice that had been exposed to chronic stress by being caged with more aggressive mice. Mice which have been exposed to these conditions show depression-like behaviours, including avoidance of other mice. The researchers also exposed mice with blocked ghrelin signalling to similar conditions and examined the effects.
What were the results of the study?
The researchers found that mice with restricted food intake had ghrelin levels four times higher than mice that could eat what they wanted (normal mice). The food-restricted mice showed more anxiety- and depression-like behaviours than normal mice on the maze and swim tests. These effects on mood were not seen if food was restricted in mice whose ghrelin signalling had been blocked.
They also found that injecting mice with ghrelin reduced their anxiety- and depression-like behaviours during maze and swim tests. Mice which had been exposed to chronic stress had elevated ghrelin levels and ate more food. Chronic stress in mice whose ghrelin signalling had been blocked led to worse depression-like behaviours (avoidance of other mice), and their food intake was not altered.
What interpretations did the researchers draw from these results?
The researchers concluded that they had identified a previously unknown role for ghrelin in regulating mood. Ghrelin levels can be increased by chronic stress and can reduce anxiety and depression-like behaviours. These findings may be relevant to the psychological effects of conditions such as anorexia, where ghrelin levels are known to be altered.
What does the NHS Knowledge Service make of this study?
This study has shown a link between ghrelin, a hormone that promotes hunger, and anxiety and depression-like behaviours in mice. However, how ghrelin might cause a reduction in these behaviours in mice is not clear, and other factors will also play a role.
Much more research will be needed to look into whether this hormone plays a role in anxiety and depression in humans.
Sir Muir Gray adds...
Never mind the mice; to prevent weight gain walk an extra 3000 steps (30 mins) a day; if you want to accelerate weight loss, walk an extra 60 mins a day.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 16 June 2008
Links to the science
Nature Neurosci 2008; Jun 15 [Epub ahead of print]