#31 The Underlying Mechanisms of Depression
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This episode dives into a very important topic: the involvement of the immune system, especially chronic elevation of it, in depression. Chronically elevated inflammation is increasingly being shown by emerging research as having a relationship with depression.
What is inflammation?
Inflammation is part of the complex immunological response of our body's tissues to pathogens or damage, where they facilitate repair mechanisms. We need inflammation. Without it, we are vulnerable.
However, when inflammation is chronic, it can be damaging and goes from being adaptive to playing a role in driving the diseases that largely constitutes what we call aging.
In fact, suppression of inflammation is thought to be the most important driver of successful longevity, increasing in importance with advancing age.
Inflammation can become chronically elevated for a variety of reasons. Many of them are lifestyle related: poor diet, sedentary lifestyle, lack of sleep, and more. Also, especially important in the context of depression: systemic inflammation can also be increased by psychosocial stress, as well.
Inflammation as a hard biological endpoint for depression.
While it’s likely that there may be more going on with depression than just inflammation by itself, it could be an incredibly useful lens through which to look at promising avenues to potentially treat or prevent it, since controlling systemic inflammation shows promise as being both important for longevity and health in general.
Moreover, inflammation can be clinically monitored by well-known biomarkers for systemic inflammation, making it amenable to potentially tracking therapeutic success: the risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein.
A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
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Depression News
- Exercise improves depression through positive modulation of brain-derived neurotrophic factor (BDNF).
- Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014)
- Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010)
- Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013)
- Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021)
Hi Rhonda, I was wondering since sedentary lifestyle can cause inflammation. Can training too much cause the same issue or be worse? If so, how can you tell if you are going too hard? Sorry if it’s a silly question but some people never really learned how to pace themselves (wrestlers, me).