Anxiety and depression increase significantly during major stressors, such as the COVID-19 pandemic. Unfortunately, psychosocial stress is one of the main factors contributing to anxiety and depression. There is evidence that stress is associated with increased inflammation — increased levels of inflammatory cytokines, circulating monocytes and activation of microglia, which are found in patients with anxiety and mood disorders.
Chronic stress has long been associated with the pathogenesis of psychological disorders such as depression and anxiety. Recent studies have shown that chronic stress can cause neuroinflammation: activation of resident immune cells in the brain, microglia that produce inflammatory cytokines. Numerous studies have shown that the inflammatory cytokine, interleukin-1 (IL-1), the main regulator of the recruitment and activity of immune cells in the brain, is a key mediator of psychopathology. However, how IL-1 disrupts neural circuits, causing behavioral and emotional problems seen in psychological disorders, has not been determined.
A groundbreaking study by neuroscientists, is the first to determine the role of the neuronal receptor for IL-1 (nil-1R) in psychological disorders. The researchers demonstrate that nil-1R is at the intersection between social stress, inflammation, and anxiety in rodent stress models.
For this study, the researchers wanted to determine the extent to which IL-1 acts directly on hippocampal neurons to influence cognitive and mood changes under stress. To determine the IL-1R-mediated neuronal response, they used novel and complex IL-1R transgenic/reporter lines, in which IL-1R can be selectively removed or IL-1R restored on certain cell types, including glutamatergic neurons. They also used modified viruses to manipulate hippocampal neurons and investigate the role of IL-1R in triggering behavioral responses to stress. Their data show that social damage-induced IL-1R signaling in hippocampal neurons perpetuates inflammation and contributes to deficits in social interaction and working memory.
The research team has previously described in detail how psychosocial stress leads to activation of peripheral immunity, increased levels of circulating monocytes, and robust neuroimmunological responses in the brain. These reactions include increased levels of IL-1 and other inflammatory cytokines, activation of glial brain cells and movement of peripheral immune cells to the brain, and increased activity of specific neuronal pathways. This work makes it clear that the inflammation – related effects of stress are not only global effects, but are also associated with increased levels of IL-1 signaling in certain brain circuits.
According to the American Anxiety and Depression Association, nearly 40 million people in the United States (18%) experience an anxiety disorder. Worldwide, WHO estimates that 1 in 13 people suffer from anxiety. Anxiety disorders are the most common mental disorders worldwide, with the most common anxiety disorders being specific phobias, major depressive disorders, and social phobias.
“We are experiencing unprecedented levels of stress that will have long-term consequences for millions of people of all ages around the world. When psychosocial stress becomes chronic, its effects are not only emotionally but also physically draining and can lead to high blood pressure, heart disease, and even addictive behavior (addiction),” said Randy Blakely, Ph. D., executive director of I – BRAIN FAU.