The Depression-Serotonin Connection: What Really Causes Depression According To A Functional Medicine Expert

Brain problems have grown by leaps and bounds over the last few decades with no signs of slowing down. Depression, anxiety, brain fog, and dementia continue to plague our society and leave many people struggling to find lasting solutions to these health problems.

Up until now depression has been believed to be caused by low serotonin with antidepressants being the standard treatment option. But with new research coming out surrounding the connection between serotonin and depression, it is making us rethink how we approach this mental health problem.

As a functional medicine expert, I consult people on a daily basis in my telehealth functional medicine clinic about their health. Although this new research is certainly shaking up the conventional treatment approach to depression, it is finally shedding light on the mind-body connections we have seen for years in functional medicine.

What the research is saying

A review of multiple studies recently published in Molecular Psychiatry, (1) found no correlation between a chemical imbalance of serotonin and rates of depression. This discovery is so significant because it calls into question antidepressants—specifically serotonin reuptake inhibitors (SSRI)—as the go-to method for treating depression and how often they should be prescribed moving forward to correct low serotonin levels.

Ultimately, this research is a double edged sword - on one hand it puts us on the right path for treating depression but it also leaves us at square one. But thankfully, functional medicine has already found one commonality between all modern day health problems - depression included - and that’s autoimmune-inflammation in the brain. I believe that by starting here, we can treat depression at its source.

The Autoimmune-Inflammation Spectrum

Did you know that in addition to brain problems, autoimmune conditions are also on the rise? That’s an interesting coincidence if you ask me.

When looking at the brain, a whole area of research known as the “cytokine model of cognitive function” has been dedicated to looking at the effects of inflammation on the brain. In fact, this research has concluded that inflammation can actually damage your protective blood-brain barrier (BBB) (2) and lead to neurological autoimmunity - with brain fog, anxiety, and depression as a result by activating your brain’s immune microglia cells. Basically, your immune system ends up attacking your own brain tissue. 

And when you look at the research, this connection is only further solidified. One study (3) found that depression is more common among people with a diagnosed autoimmune disease due to the effects of inflammation on the central nervous system.

Another study published in Frontiers in Immunology (4) found that depression was linked to increased immune system inflammation that can affect the central nervous system and that antidepressants have been shown to decrease inflammation, and that higher levels of inflammation in a patient at baseline is often a predictor of how well depression treatments will work.

So even though our goal with antidepressants wasn’t to target inflammation - rather serotonin balance - we can see how they worked in favor and why they still ended up being a good solution for individuals with depression.

What about serotonin?

If the connection between inflammation and depression is so clear in research, how did serotonin get caught up in this?

It all goes back to the gut-brain connection. Your gut and brain have a special connection that started in the womb as they were both formed by the same fetal tissue. The same proteins that control your gut permeability also control your blood-brain barrier permeability. One of the greatest examples of the gut-brain connection is actually serotonin.

Close to 95% of this neurotransmitter is made and stored (5) in your gut, not in your brain! Therefore, it makes sense that if you are experiencing inflammation in your gut and brain, it can affect your serotonin levels for the worse.

Now that we understand through this study that inflammation plays a greater role than serotonin levels in depression, we can start to hypothesize the connection between the two. It may just be that you actually have enough serotonin but your body isn’t able to use it effectively because inflammation is blocking serotonin signaling. It will be interesting to see the studies come out in the next few years, especially regarding this possible serotonin-inflammation mechanism.

The Takeaway

In functional medicine, we know there is no “one-size-fits-all” when it comes to a person’s health. While you might have the same diagnoses as someone else, your individual triggers and solutions can look very different based on your particular biochemistry.

Everything from hormone imbalances, poor diet, chronic infections, and stress can be a trigger for chronic inflammation in the body. By looking at all pieces of a person’s health puzzle we can determine the best course of action to address depression, inflammation, and other health problems through identifying the root cause of someone’s symptoms. This is something I go into detail in my latest book, Gut Feelings.

While we are still learning more about depression, we can make connections, and take the information we do know and apply it in a way that facilitates whole-body healing—mental, physical, and emotional.

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe.