Gut problems such as gastric irritation early in life may change the way the brain is wired and raise the risk of depression and anxiety later on, said American researchers who found that gastric irritation in newborn rats appeared to increase expression of the stress hormone, corticotrophin-releasing factor CRF, and raise sensitivity to stress later in life.
Many current explanations for the link between gut problems and mood disorders is that the mood disorder causes the gut problem: anxiety and depression change stress hormone levels and these cause the gastric problems such as irritable bowel and functional dyspepsia.
But Dr Pankaj Pasricha of Stanford University School of Medicine in California and colleagues suggest in a paper published recently in PLoS ONE that some human psychological disorders may be the result, rather than the cause, of gastrointestinal problems such as irritable bowel syndrome.
“Gastric irritation during the first few days of life may reset the brain into a permanently depressed state,” said Pasricha, a professor and chief of gastroenterology and hepatology.
“The gut and the brain are hardwired together by the vagus nerve, which runs from the brain to the body’s internal organs,” Pasricha told the press.
He explained that the gut has its own, relatively independent nervous system and that “communication between the gut and the adult brain is elaborate and bi-directional, and changes in the gut are signaled directly to the brain”.
As it is clear that not all stomach upsets result in lifelong mood disorders, the researchers suggest it is the timing of the irritation that is important. Together with colleagues from the University of California-San Francisco and the University of Kansas, Pasricha and his team at Stanford tested these ideas using laboratory rats.
In previous work, the Stanford team had shown that inducing mild stomach irritation in newborn rats, causing temporary gut inflammation or injury, led to raised sensitivity and functional abnormalities that lasted long after the initial damage had been repaired.
This led them to wonder if this type of injury early in life might also affect the development of the central nervous system, and in turn, cause depression and anxiety.
So they induced functional dyspepsia in 10-day-old male rats and then assessed their behavior when they reached 8 to 10 weeks old. They found that compared to untreated rats, the treated rats were more likely to display depressed and anxious behaviors such as less consumption of sugared water and less activity in forced-swimming tests, and a preference for dark rather than light areas in a maze.
Also, following a stress test of a saline injection, the treated rats also had higher than normal resting levels of the stress hormones corticosterone and corticotrophin-releasing factor, or CRF.
To confirm that the difference in behavior was not due to the rats sensing gut pain, the researchers blocked their ability to feel sensation from their gut with a drug, and found it made no difference to their behavior.
In contrast, when they blocked the action of CRF, which is known to be linked to depression in humans and other animals, they found the treated rats behaved more like the untreated rats in tests.
The researchers suggested in their conclusions that “transient gastric irritation in the neonatal period can induce a long lasting increase in depression- and anxiety-like behaviors,”, and that “depression-like behavior may be mediated by the CRF1 receptor”.
Pasricha said:
“It seems that when the rats are exposed to gastric irritation at the appropriate point in time, there is signaling across the gut to the brain that permanently alters its function.”
As a next step, the researchers will be investigating what triggers such a signal and how it acts in the brain, and looking at the potential for such a discovery to lead to new treatments for depression and anxiety in humans.
Pasricha said they’d like to know whether the vagus nerve is involved and how it affects the brain.
“The vast majority of humans don’t experience any long-lasting consequences from transient infections,” he noted.
“But there may be subset of patients who are genetically predisposed to this effect by mechanisms we don’t yet understand,” he added.
The US Food and Drug Administration (FDA) has recently approved electrical stimulation of the vagus nerve as a new treatment for depression that does not respond to other treatments. The researchers hope their efforts will help to increase understanding in this type of treatment.
Stanford’s Department of Medicine funded the study.
“Transient Gastric Irritation in the Neonatal Rats Leads to Changes in Hypothalamic CRF Expression, Depression- and Anxiety-Like Behavior as Adults.”
Liansheng Liu, Qian Li, Robert Sapolsky, Min Liao, Kshama Mehta, Aditi Bhargava, and Pankaj J. Pasricha
PLoS ONE 6(5): e19498. Published online 12 May 2011.
DOI:10.1371/journal.pone.0019498
Additional source: Stanford School of Medicine.
Written by: Catharine Paddock, PhD