The holidays can be a stressful time, but fortunately, new studies are bringing us closer to understanding all the underlying mechanisms of stress and anxiety, its effects on the body and brain, and new potential treatments.
Effects of Stress
It’s well known that stress has numerous negative physical and psychological effects, and new research points to even more connections.
Cancer
In a study with mouse models, researchers at the Washington University School of Medicine in St. Louis discovered that stress-induced neutrophil extracellular traps (NETs)—normally part of the immune response—can promote the spread of cancer.
By targeting NETs in stressed mice, they were able to significantly reduce the risk of metastasis, suggesting that stress management and NET-inhibiting drugs could play a role in cancer treatment and prevention.
Another study, conducted by researchers at the Sichuan University of China, identified a link between stress and colorectal cancer progression. Using mouse models of colorectal cancer, the team found that stress-related disruptions in circadian rhythms can impact the gut microbiome, reducing beneficial bacteria and increasing inflammation, contributing to cancer progression.
These findings highlight the gut microbiome’s critical role in stress-related cancer risks and suggest potential prevention strategies, such as targeting gut bacteria to mitigate the effects of stress and circadian disruption.
Anorexia
Researchers at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, have identified stress as a key factor in willful starvation, a hallmark of anorexia nervosa.
They found that female mice with high baseline anxiety actively sought a starvation-like state after repeated stress exposure, while male mice did not.
The findings suggest that high-anxiety individuals may be more likely to seek starvation as a coping mechanism to provide stress relief and reduce anxiety.
Joylessness
Stress can diminish the ability to experience joy, and new research in mice from the University of California, San Francisco reveals why.
The team found that disrupted communication between the amygdala and hippocampus makes some mice more susceptible to anhedonia, a reduced capacity for pleasure. In the study, “resilient” mice continued seeking rewards like sugar water after stress, while “susceptible” mice preferred plain water, indicating anhedonia. Resilient mice showed robust communication between the two brain regions, while susceptible mice exhibited fragmented connections.
After receiving injections of compounds designed to increase neural activity in the amygdala and hippocampus, the susceptible mice acted more like resilient mice, seeking sugar water rather than plain.
If these findings translate to humans, they could pave the way for new treatments targeting anhedonia, a common and difficult-to-treat symptom of depression and other psychiatric disorders.
Memory Overgeneralization
Stress can enhance the emotional intensity of memories but may also blur the lines between specific events. In conditions such as PTSD and generalized anxiety disorder, memory overgeneralization prevents individuals from being able to distinguish between dangerous and safe stimuli.
In a recent mouse study, a team of Canadian researchers identified the specific mechanism through which acute stress disrupts memory specificity, causing generalized memories encoded by larger groups of neurons.
The mechanism involves corticosterone levels, which are elevated by stress. This disrupts the function of inhibitory interneurons—specialized cells that typically keep memory engrams precise—resulting in the formation of generalized memory patterns.
In experiments, stressed mice exposed to two distinct sounds failed to differentiate between a stressful sound and a neutral one, reacting defensively to both, while non-stressed mice responded only to the stressful sound.
Administering metyrapone, a drug that inhibits corticosterone production, restored the ability of stressed mice to form specific memories.
Immunity
A study by researchers from the U.S., China, and Germany revealed that stress triggers a process that reduces levels of beneficial gut bacteria.
In studying mice, the team learned that stress activates a communication pathway between the brain and Brunner’s glands in the gut. These glands, located in the walls of the small intestine, are already known to produce mucus to help move material through the gut. They also play a key role in preventing inflammation and unnecessary immune responses.
When these glands were removed in mice, the resulting reduction in beneficial bacteria caused the gut walls to become leaky, allowing harmful substances to enter the bloodstream. The mice were less able to fight off bacterial infections and also experienced increased inflammation and heightened immune activity.
The findings highlight the connection between the brain and gut and suggest that stress-induced gut dysfunction could contribute to inflammatory diseases.
Potential New Ways to Alleviate Stress
Fortunately, research with mice has uncovered several new approaches to reducing stress and anxiety.
Activating Delta Opioid Receptors
Delta opioid receptors (DOPs) are found in areas of the brain associated with emotional regulation. Research suggests that DOP agonists, like KNT-127, offer anxiety-reducing effects with minimal side effects.
To test this, a team of researchers from Tokyo University of Science conducted experiments on mice, focusing on the neural pathway between the prelimbic cortex (PL) and the basolateral amygdala (BLA), which has been implicated in anxiety and depression.
Using an optogenetic mouse model, they activated the PL-BLA circuit and used the elevated-plus maze test to assess the anxiety-like behavior of the mice.
Mice with PL-BLA activation showed more signs of anxiety. When treated with KNT-127, the mice showed fewer anxiety behaviors, suggesting that KNT-127 reduces anxiety by targeting the PL-BLA pathway.
Turning off the Anxiety “Switch”
Researchers from the University of Aberdeen have discovered a DNA “switch” that turns on key genes in parts of the brain that influence anxiety in mice.
Deleting this switch, known as BE5.1, an enhancer that controls the BDNF gene, using CRISPR genome editing technology led to increased anxiety levels, particularly in female mice.
The researchers hope their findings could eventually lead to new drug targets for anxiety disorders. The study emphasizes the need to explore the non-coding genome further to better understand the mechanisms of mental health and other diseases.
Taking a Toad Toxin
The Colorado River toad, native to Arizona and Mexico, produces a hallucinogenic toxin called 5-MeO-DMT, which has gained attention for its potential antidepressant and anti-anxiety benefits.
Researchers from Mount Sinai Hospital and Columbia University recently used this toxin to create a new compound, 4-F,5-MeO-PyrT, which retains its therapeutic effects while avoiding hallucinogenic properties. This modification targets serotonin receptors (5-HT1A) that reduce depression and anxiety without inducing psychedelic experiences.
Testing the compound on stressed mice, the researchers observed behavioral improvements, such as increased social interaction and consumption of sugar water, indicating reduced anxiety and depression. The findings add to growing interest in psychedelics for medical use, suggesting a potential pathway for creating safer antidepressants in the future.
Listening to Music
A recent study conducted at Minzu University of China found that listening to music can prevent anxiety- and depression-like behaviors in mice exposed to chronic mild unpredictable stress.
The experiment involved four groups of mice: one subjected to stress, another exposed to music, a third experiencing both stress and music, and a control group. The mice exposed to both stress and music displayed behavior similar to the unstressed control group, while those subjected only to stress exhibited elevated anxiety- and depression-like behaviors.
Biochemical analyses revealed that music reduced oxidative stress, inflammation, and neuronal death in the brain, while promoting new neuron growth and maintaining hormonal balance in the stressed mice.
The researchers concluded that music protects against stress-induced disruptions by preventing oxidative damage, reducing inflammation, and regulating the hypothalamus-pituitary-adrenal axis to maintain brain homeostasis.
