Digestive Irritation in Early Life Tied to Anxiety, Depression
Short-term digestive problems in early life may lead to later depression and anxiety, according to researchers at Stanford University School of Medicine. The results show that some gastrointestinal disorders, such as irritable bowel syndrome, may be the cause, rather than the result, of certain psychological conditions.
“A lot of research has focused on understanding how the mind can influence the body,” said lead author Pankaj Pasricha, M.D., professor and chief of gastroenterology and hepatology.
“But this study suggests that it can be the other way around. Gastric irritation during the first few days of life may reset the brain into a permanently depressed state.”
Researchers believe the effects may depend on when the irritation occurs during development as well as the genetic makeup of the affected person, since not all stomach problems lead to mental problems. In particular, it seems the viscera, or internal organs, are especially vulnerable early in development.
Pasricha, along with lead researcher Liansheng Liu, collaborated with investigators from the University of California-San Francisco and the University of Kansas on the study.
Approximately 15 to 20 percent of individuals have functional dyspepsia — a persistent or recurring pain in the upper abdomen.
Researchers like Pasricha have long observed that these people are also more likely than their peers to have anxiety or depression. Current theories hold that these stress hormones are responsible for the digestive problems.
There is another avenue to explore, however. “The gut and the brain are hardwired together by the vagus nerve, which runs from the brain to the body’s internal organs” said Pasricha.
“In addition, the gut has its own nervous system that is relatively independent. So the communication between the gut and the adult brain is elaborate and bi-directional, and changes in the gut are signaled directly to the brain.”
Since many of these patients had gastrointestinal problems in early childhood, before their psychological symptoms began, Pasricha and his colleagues wondered whether the digestive problems could instead be causing the mood disorders.
The hypothesis was bolstered by other recent studies linking depression and anxiety in humans to changes in the composition of gut bacterial populations.
To test their ideas, the scientists used a lab model of functional dyspepsia they had previously developed. Ten-day-old laboratory rats were subjected to mild stomach irritation daily for six days. It had been already proven that such treatment, which causes a temporary inflammation or injury, results in hypersensitivity and functional abnormalities when administered during the vulnerable newborn period. The problems also persist long after the initial damage has been repaired.
“We hypothesized that this treatment might also be affecting the development of central nervous system, and driving the animals to anxiety and depression,” said Pasricha.
In fact, when the rats were 8 to 10 weeks old, researchers found that those with early gastric irritation were significantly more likely than their counterparts to display depressed and anxious behaviors including a decreased consumption of sugar water, less time swimming in a pool of warm water and a preference for dark rather than light areas in a maze.
The treated rats also showed higher levels of the stress hormones corticosterone and corticotrophin after an injection of saline, and also had above normal resting levels of corticosterone and corticotrophin-releasing factor, or CRF. When the animals’ ability to perceive sensation from their gut was blocked with a drug, it did not affect their behavior, indicating that the rats were not responding to persistent pain.
In contrast, when CRF activity was inhibited (known to be associated with depression in humans and animals), the treated rats began to behave more normally in the tests.
“It seems that when the rats are exposed to gastric irritation at the appropriate point in time,” said Pasricha, “there is signaling across the gut to the brain that permanently alters its function.”
New plans are in the works to investigate exactly how that signaling is initiated and how it acts in the brain, and if it is possible to develop new ways of treating depression and anxiety in humans.
“We’d like to know whether the vagus nerve is involved, and confirm what changes may occur in the brain in response to this signal,” said Pasricha.
“The vast majority of humans don’t experience any long-lasting consequences from transient infections. But there may be a subset of patients who are genetically predisposed to this effect by mechanisms we don’t yet understand yet. Our hope is that this work will open another avenue for exploring, understanding and treating these very complex syndromes.”
In fact, electrical stimulation of the vagus nerve has recently been approved by the Food and Drug Administration for depression that is treatment-resistant; this research may help scientists better understand and optimize this new approach.
The study is published in PLoS ONE.
Pedersen, T. (2018). Digestive Irritation in Early Life Tied to Anxiety, Depression. Psych Central. Retrieved on September 28, 2020, from https://psychcentral.com/news/2011/05/17/digestive-irritation-in-early-life-tied-to-anxiety-depression/26238.html