Depression is a debilitating condition suffered by 121 million people worldwide. (1) The rate of depression cases diagnosed has been increasing by approximately twenty percent each year. (2) The World Health Organization estimates that major depression will be the leading cause of disability by 2030. (3) It was once thought that clinical depression was the result of a chemical imbalance in the brain but that hypothesis has been disproven. In fact, there are many factors of depression.
Current research into the physiological factors of clinical depression has led to the theory of “cytokine-induced depression”, which is basically brain inflammation.
Cytokines are proteins secreted by cells as an immune response. There are inflammatory and anti-inflammatory cytokines. They can act on the cells that secrete them, neighboring cells, or cells in other parts of the body. Certain cytokines have been linked to pathologic pain. (4)
Cytokines Can Cause Brain Inflammation
Cytokines exist in the brain as in other parts of the body. Generally, chronic inflammation anywhere in the body can lead to illness and disease. One might even say that chronic inflammation WILL lead to illness and disease if left unaddressed.
Systemic inflammation of the brain can cause degeneration, manifesting in very distinct symptoms:
- obsessive-compulsive disorder (OCD) (5)
- brain fog
- impeded cognition and mental clarity
- memory loss
- attention deficit hyperactivity disorder (ADHD)
- suicidal ideation (6)
- bipolar disorder
- schizophrenia (7)
- lack of appetite
While inflammation is an appropriate immune system response to pathogens and injury, chronic inflammation occurs when the immune system is turned on but cannot shut off.
Microglia are immune cells in the brain; they serve to cleanse the brain of toxins, dead cells, and routine metabolic waste. Microglia are normally dormant, becoming active only when needed to fight infection or protect cells in the case of trauma. Activated microglia produce several different chemicals as part of the immune response, including cytokines. (8) Appropriate activation of microglia will return to normal function with no damage done once the danger has been resolved. Dysregulation of microglia receptors in the brain (caused by chronic inflammation) harms neuronal networks and changes microglia themselves. (9)
“The Immune-Cytokine Model of Depression (ICMD) is an entirely new concept for understanding the riddle of depression. This is the only model of depression to bridge the conceptual and diagnostic gap between physical and mental disorders. ICMD views depression to be any number of chronic physical-biological disorders that have mental-emotional symptoms. From the perspective of ICMD, depression isn’t really a disease, but rather a multifaceted sign of chronic immune system activation.” (10)
Immune Response and Inflammation
Dr. Datis Kharrazian, DHSc, DC, MNeuroSci has spent the last decade researching and teaching functional neurology, autoimmune disorders, chronic illness, and other related subjects. In his book Why Isn’t My Brain Working?, Kharrazian posits that a weakened blood-brain barrier is the pathway toward brain inflammation.
When this thin sheath of tissue that protects the brain is compromised, it leads to “leaky brain”, similar to leaky gut. If the blood-brain barrier is breached, the way opens to pathogens. With the introduction of pathogens comes the activation of microglia, which ultimately leads to brain inflammation. (11)
There are many conditions that can trigger microglia’s immune response activity in the brain, leading to inflammation, oxidative stress, neuron damage, and brain degeneration, including (12):