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Studies That Are Changing How We Treat Depression and Serotonin

Top functional medicine pro, Dr. Will Cole recently shared his thoughts on emerging research around serotonin, depression, and SSRIs, the most commonly prescribed antidepressants on the market.

According to Cole, after decades of in-depth study, “there is no clear evidence that serotonin levels or serotonin activity is responsible for depression.” This news represents an important ups and downs in how we deal with depression, a condition that affects more than 13% of adults in the US. We asked Cole to expand on his recent statement, and he gave us this insightful piece…

There isn’t any question it: brain health problems have become an epidemic in our society. Everything from brain fog to depression is on the rise with no sign of slowing down.

While depression has long been considered a byproduct of low serotonin, new research is questioning everything we thought we knew about the origins of this mental health problem.

At my telehealth functional medicine clinic, I have spent years consulting patients around the world about their health. While this new research may come as a surprise to many, in functional medicine, it is finally revealing the greater connection we have long seen regarding the mind-body relationship.

Recent Research On Depression And Serotonin

A review of several studies recently published in Molecular Psychiatry, found no correlation between a chemical imbalance of serotonin and levels of depression. This finding is significant because it calls into question antidepressants—specifically serotonin reuptake inhibitors (SSRIs)—as the primary method of treating depression and how often they should be prescribed to correct low serotonin levels.

While this discovery is a step in the right direction, it actually takes us back to square one when it comes to finding effective treatment methods and uncovering the root causes of depression in the first place.

This is where functional medicine and bio-individuality come into play. In functional medicine we understand that there is rarely a “one size fits all” treatment for a person’s health problems. In a similar vein, people rarely have the same triggers, even if they have the same diagnosis. That said, there is one common factor among many modern brain problems, depression including: autoimmune inflammation in the brain.

Autoimmune-Inflammation Connection

As I mentioned earlier, brain problems are on the rise. Do you know what else is also on the rise? You guessed it—an autoimmune condition. In fact, nearly 50 million Americans have been diagnosed with an autoimmune disease. There are currently 100 recognized autoimmune conditions and at least 40 more disease processes that may have an autoimmune component (at least we know now!).

A new area of ​​research known as the “cytokine model of cognitive function” is dedicated to looking at how inflammation can damage the protective blood-brain barrier (BBB) ​​and possibly cause brain problems such as what is now referred to as neurological. autoimmunity.

So what does depression have to do with inflammation? Turns out, a lot. Inflammation has the potential to trigger depression, make it worse, and even be the root cause. This inflammation activates the brain’s immune microglia cells, which can trigger an inflammatory-autoimmune response. In other words, people’s immune systems may attack their brain and nervous tissue in response to inflammation that can start elsewhere, such as in the gut. A study published in Frontiers in Immunology found that depression was associated with increased inflammatory activation of the immune system which ultimately affected the central nervous system.
Interestingly enough, research has also shown that depression and anxiety are more common in patients with autoimmune diseases than chronic degenerative conditions, possibly due to the direct effects of inflammatory cytokines on the central nervous system. Furthermore, a person with one autoimmune disease has a higher chance of suffering an immune system attack on other systems, such as the brain.

This is where it gets really interesting, in the same study published in Frontiers in Immunology, they did explain that antidepressants have been shown to reduce inflammation, and that higher levels of inflammation in patients at baseline are often a predictor of how well depression treatments will work. We may not at first targeting inflammation with antidepressants, but we can see how they work in our favor once we begin to understand the mechanism.

Gut-Brain Connection

If research looks at the relationship between brain inflammation and depression, where does serotonin play a role at all?

Your gut and brain are actually formed from the same fetal tissue as you grew in your mother’s womb, and continue their special bond throughout your life through what’s known as the gut-brain axis. The same proteins that regulate intestinal permeability also determine the permeability of your blood-brain barrier. Basically, what affects one, affects the other.

One of the greatest examples of this is serotonin gut health. Surprisingly, nearly 95% of these neurotransmitters are made and stored in your gut—no your brain! No wonder the medical literature often refers to your gut as your “second brain.” Therefore, it makes sense that if you have inflammation in your gut and brain, it could affect your serotonin levels for the worse.

Because of this new study, we now understand that depression has less to do with serotonin levels in your brain than the level of inflammation you experience and what it does to your serotonin signals. More studies need to be done, but one could hypothesize that serotonin signaling could turn off due to inflammation in the brain. Your body might actually be have enough serotonin, but chronic inflammation prevents it from using it effectively.

Bringing It All Together

In functional medicine, we view each symptom as a “check engine light,” a sign that something deeper is going on beneath the surface. Depression is no different. By continuing to study the mechanisms of inflammation that can trigger health problems — and furthermore, what triggers inflammation in people — we can begin to treat the root causes of these brain health problems.

Chronic infections from fungi and biotoxins, hormonal imbalances such as thyroid problems, poor diet, stress, unresolved trauma, and more, can all be triggers of inflammation in a person’s health journey. Ultimately, it’s up to us in functional medicine to piece together all the pieces of a person’s health puzzle and form a plan of action to deal with depression and other health problems. I dive deep into this topic in my upcoming book Gut Feelingfor preorder now.

While we’re still learning more about depression, we can make connections, and take the information we know and apply it in ways that facilitate whole-body healing—mental, physical, and emotional.


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