The accepted wisdom that depression is a result of a chemical imbalance in your head has been resoundingly debunked.
So, if you suffer from depression, what do you do now? First, don’t simply stop taking your SSRIs, if that is your prescription. Talk to your doctor.
You can also take a look at depression by analyzing the symptoms, which are real. Many symptoms overlap with other illnesses. You can be proactive and make better choices in diet and lifestyle that may help.
The truth is that scientists know very little about the physiological factors and processes that contribute to depression. But some research suggests that inflammation may be a driving factor in depression. And, you can address inflammation. Scientific evidence shows clearly that inflammation plays a significant role in depression.
Understanding the mind-body connection
Conventional western medicine considers the mind and body to be two separate entities with no specific point of connection between them. Doctors tend to think of them as separate systems in the person.
This is one area in which functional medicine sees things differently. Some call the mind-body connection “embodied cognition.” This is the idea that the mind is connected to the body, and the body influences the mind. It works in reverse as well. The mind influences the overall well-being of the body. Plenty of scientific research supports this view. However, most doctors still see the mind and body as separate from each other.
Let’s look at an example.
Many people suffer from arthritis: osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, and lupus among others. Arthritis is caused by inflammation. But in many patients, joint pain is not the only symptom they suffer from. People with arthritis often experience:
- Low energy
- Prolonged periods of sadness
- Hopelessness
- Worthlessness
- Sleep disturbances
- Guilty thoughts
Doesn’t that sound like depression? And many doctors might think, “Of course they are depressed! Wouldn’t you be if you were in that much pain?”
This is the conventional western medical explanation. The body is in pain from arthritis, which can be explained by inflammation. The changes in mood and behavior are explained by the patient thinking about the implications of having arthritis. Simply put, they suggest the state of the mind reflects the physical state, not that the inflammation of the body affects changes in the mind.
But the functional medicine approach offers a more logical reason. A person suffering from arthritis is not depressed because they think about the pain and inflammation. They are depressed due to the inflammation.
To prove this innovative approach, scientists had to discover the mechanisms by which inflammatory changes in the body cause changes in the brain leading to depression.
Thanks to new research, scientists have identified a few mechanisms through which inflammation can cause depression.
Inflammation is a major driver of depression
Doctors once believed that the immune system was kept separate from the brain by the blood-brain barrier (BBB). The blood-brain barrier is a microvasculature system that regulates the movement of substances like cells and proteins between the blood and the central nervous system.
The blood-brain barrier represented the physical separation of the mind and body. After all, how could important proteins in the blood affect the brain if they couldn’t cross the blood-brain barrier?
But researchers now know that there are certain types of proteins that can cross the blood-brain barrier. One category of proteins with this ability can create powerful inflammatory effects throughout the entire body, including the brain.
These inflammatory proteins are called cytokines.
What are cytokines?
Cytokines are messenger molecules responsible for regulating cell-to-cell interactions and communications. They are powerful regulators of the immune system’s inflammatory response to disease and infection, as well as normal cellular processes.
Cytokines can be divided into two groups based on their functions:
- Pro-inflammatory
- Anti-inflammatory
A subtype of white blood cells called T lymphocytes is a major source of cytokines. T lymphocytes are an essential part of your immune system. They recognize foreign particles with their highly variable cell-surface receptors. Of the various types of T lymphocytes, T cells are known as the predominant producers of cytokines. T cells can be further divided into two groups:
- T helper (Th) type 1
- T helper (Th) type 2
Pro-inflammatory vs. anti-inflammatory cytokines
Cytokines secreted by Th1 are typically pro-inflammatory, which means they can be activated during cell injury, infection, invasion, and inflammation. Some pro-inflammatory cytokines include:
- Interferon-γ
- Tumor necrosis factor-α
- Interleukin-1β (IL-1β)
- IL-6
On the other hand, cytokines produced by Th2 are anti-inflammatory and help control the Th1 cytokine response. Major anti-inflammatory cytokines include:
- IL-4
- IL-5
- IL-10
- IL-11
- IL-13
Your immune system needs a balance of Th1 and Th2 responses to prevent excess inflammation. Inflammation can develop due to an imbalance between the responses.
In addition, pro-inflammatory cytokines overstimulate the microglia, a group of specialized cells whose primary job is to clean out damaged neurons and maintain a healthy nervous system. Overstimulated microglia cause a significant increase in the production of pro-inflammatory cytokines, such as IL-1β, as well as neurotoxic substances like reactive oxygen species. Microglia are the only type of cell in the central nervous system capable of producing quinolinic acid – a potent neurotoxin and contributor to depression. These factors can lead to worsening depression.
Tryptophan and depression
Pro-inflammatory cytokines significantly influence four important neurotransmitters: serotonin, dopamine, noradrenaline, and glutamate.
Glutamate is very important to the central nervous system. Glutamate is the main excitatory neurotransmitter in your brain, which your nerve cells need for sending signals to one another. Glutamate is also involved in learning and memory. But glutamate can also be neurotoxic at excessive levels when receptors are overstimulated.
One predominant receptor involved in depression is called N-methyl-D-aspartate (NMDA). Microglia produce the pro-inflammatory cytokine IL-1β. In turn, IL-1β increases the expression of the NMDA receptor. Much of the tryptophan supply in our bodies gets converted into quinolinic acid and kynurenic acid, both of which bind to the NMDA receptor.
Kynurenic acid and quinolinic acid act differently – kynurenic acid blocks the receptor while quinolinic acid activates it. Pro-inflammatory cytokines, through the activation of microglia, cause a higher ratio of quinolinic acid to kynurenic acid, leading to overstimulation of the NMDA receptor.
The activation of the NMDA receptor doesn’t just release glutamate. It further activates microglia, which only releases pro-inflammatory cytokines. IL-1β also produces a toxic substance called nitric oxide, resulting in more glutamate.
Typically, glial cells called astrocytes take up the excess glutamate. Astrocytes help protect neurons from toxic effects. However, astrocytes can be the target of pro-inflammatory cytokines. And people with depression usually have an imbalance of pro-inflammatory cytokines.
Some scientists believe that inflammation leads to a decrease in astrocyte density. This disrupts neuroplasticity, the brain’s ability to reorganize itself in response to injury and disease. And, once microglia are activated, they stay stimulated for several months creating a vicious inflammatory cycle.
This vicious cycle may be the reason why it can be so hard to heal from depression. However, this is still an emerging science.
Healing from depression
The conventional treatment models for depression are inadequate. And new research is debunking accepted wisdom about the role of serotonin in depression. Still, at least 50% of those who recover from their first episode of depression experience one or more additional episodes in their lifetime.
Recent research shows that ketamine, an NMDA blocker, may be an effective treatment for depression. Again, this is emerging science. But you can be proactive about reducing inflammation. Your choices in diet and lifestyle can play a significant role. Eliminate highly processed foods with refined carbohydrates and sugars, cut back on alcohol, eliminate tobacco, eat a diet rich in fruits, vegetables, and lean protein, and start moving your body. A walk in the afternoon or a trip to the gym is a great start.