Is The Serotonin Theory of Depression Now Debunked?

Serotonin deficiency has dominated the science of depression over the years, with the universally acknowledged claim being that depression is caused by a chemical imbalance in the brain - specifically a lack of serotonin. This is why many individuals who are clinically diagnosed with depression are prescribed SSRI medication (selective serotonin reuptake inhibitors). However, is the link between serotonin and depression a myth? I shall discuss this within the article below.

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Is Depression Really Linked To Serotonin?

Although the serotonin theory of depression has been one of the most influential over the last 30 years or so, there is in fact very little evidence to support it and it is certainly now being challenged. UCL recently grouped all of the studies around serotonin and depression and they couldn’t find a solid link. One study they included compared individuals’ levels of serotonin in the blood and brain fluid. Strikingly, there was no difference found in people with depression and those without depression.
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It is clear that we need to look at depression in a different light, particularly as treatment is so heavily based on this seemingly incorrect theory. At Functional Medicine Associates, we have seen multiple patients with mood disorders who have been on serotonin medication for years. Although it may help for some, it’s increasingly becoming clearer that it may not be the best or most effective choice of treatment. As the UCL researchers put it:

 “In fact, drug trials show that antidepressants are barely distinguishable from a placebo when it comes to treating depression. Also, antidepressants appear to have a generalised emotion-numbing effect which may influence people’s moods.”

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Is There a Link Between Depression and Inflammation?

Inflammation is becoming more relevant in regards to one cause of depression which is likely multifactorial in nature. More and more people are likely to be depressed because they are experiencing inflammation and are displaying ‘sickness behaviour’. We all know sickness behaviour, as it can be experienced when you have a flu like virus. 

The way your immune system responds to viral infections is to ramp up its immune army to defend you.  During this process, your immune system creates an orchestrated attack where inflammation is increased and individuals commonly feel depressed, fatigued, want to socially isolate and just stay in bed. 

In other words, inflamed individuals experience side effects that are classically represented as depression symptoms. This isolation away from others is an evolutionary protective measure to the rest of the tribe. (No point getting everyone sick!)

This sickness behaviour may increasingly happen with any chronic disease that has inflammation as a dominant underlying mechanism. If you are obese you are more likely to be depressed and anxious. If you have Rheumatoid Arthritis, you are also more likely to be depressed due to the action of the immune system increasing inflammation. 

So we can see why the serotonin theory is being challenged and whilst low serotonin levels in some individuals may make them feel depressed there are likely lots of other things to consider. Hence why it's so important to do a detailed case history of your patient and to understand their health timeline. When did they last feel well? Did something happen to them that might give us a clue as to where to start?

This case study below is a classic example of how a detailed timeline can uncover the clues of how a patient became depressed. And what could be done over time to make her feel happier and healthier.
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An Example Case Study

A few years ago I had a patient whose health declined after completing her fifth marathon. She presented at my clinic with depression and chronic fatigue-like symptoms that had begun to appear shortly after becoming unwell during the latter stages of her fifth marathon. She had gone to her GP, who suggested medication which the patient did not feel inclined to take.

Long story short, with the patient being so healthy up until the marathon, it was clear that the action of running such an event was the key to understanding her current symptoms. I theorised that her gastrointestinal tract suffered significant trauma on the day and that the continued consequences of the marathon were still mediating her current condition. These sort of events are not uncommon in endurance events

In effect her gut wall became increasingly more permeable (AKA leaky gut) and this increased her immune system to react to increased numbers of molecules that were entering into the body. This creates what we call “sickness behaviour” and mirrors depression. In fact this patient was depressed because she was inflamed from her immune system consistently being on the attack from forgein invaders.

After appropriate gastrointestinal and blood testing, I put together a well-rounded plan for her, which had a key focus on diet and supplementation and lifestyle. Homemade fermented foods, such as sauerkraut and yoghurt became staples in her diet. The supplement choices used were mixed ingredients to support digestive mucosal repair and to reduce inflammation by helping to modulate the immune response. Alongside this, I encouraged the patient to interact socially as much as possible and continue with very low level exercise (this can act as an anti-inflammatory) Following this treatment plan, over several months the patient’s symptoms improved.

Digestive trauma is very common in endurance athletes but this does not mean that running a marathon will lead to depression for you. It is however a prime example of why it’s so important to look at every aspect possible, understand a patient's timeline from health to sickness, and identify root causes of a disease, to produce a better treatment. 

It’s key to look at the whole picture, as opposed to relying on one theory (low serotonin) and one protocol (SSRI medication) . If the patient had listened to her GP she would have taken SSRIs even though a lack of serotonin was not the problem. It sounds ridiculous but giving someone depression medication can actually make them more depressed.

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How Does Inflammation Influence Depressive States?

It is now well validated in the literature that people can be depressed because they are expressing sickness behaviour. Sickness behaviour is driven by your immune response to an invader and mediated by inflammation. One simple way of looking at it is when you have the flu, your immune system is using all your energy to get on top of the virus. You in turn have no energy or motivation, and can often feel very low. You also socially isolate yourself, which furthers this. As mentioned earlier, this is also an Evolutionary precaution to prevent passing it onto others.

How Can a DNA Test Help?

Everyone has inherited genetic variations that increase or decrease your susceptibility to various health conditions, such as depression. For example, due to genetic make up, some individuals are more prone to inflammation than others - myself included! Here is a screenshot of some of my DNA Mind test results:

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A DNA test can empower you by giving you a more informed picture of your predispositions and risks. The good news is, just because we see some genetic predispositions to disease it doesn't mean that these genes are going to play out and result in disease. Here at Functional Medicine Associates, we use your results to provide you with a personalised life plan to help you take control. For example, your results may indicate a predisposed risk of inflammation or methylation, and we can provide you with a detailed plan to help with this.

This is the beauty of this type of data. With your test results and informed lifestyle plan, you have a say in how your life plays out.

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How to Prevent and Reduce Inflammation

To reduce your inflammation, it is essentially quite simple, you just need to prioritise doing the basics well. You need:

• Movement on a daily basis (exercise is anti-inflammatory by nature and being sedentary is pro inflammatory)
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• Optimal levels of sleep

• A whole food diet as opposed to a processed diet - gut health is key due to the gut-brain axis. (Your gut bacteria has a huge influence on modulating your mood)
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• Be better with stress. Not to avoid it, but make room on a daily basis for a bit of sanctuary.
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• A maintained optimal weight - comorbidities can also increase inflammation such as type 2 diabetes and obesity.

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Depression Is a Multi-Faceted Problem

To conclude, like anything, with depression, we need a multi-system approach. Classically we used to think depression is purely a serotonin problem which now doesn’t seem to be the case. Instead, there are a whole host of factors that we need to consider such as lifestyle factors, environmental factors, and gene variants. It is important that people become aware of this and know that the theory of depression resulting from a “chemical imbalance” is being heavily challenged in the scientific literature. People need all this information to make informed decisions about whether or not to take antidepressants, and to help them consider other options that may be more beneficial for them. 

If you are interested in a DNA test or a personalised health plan, please feel free to get in touch with us to find out more about our services. We can help you to feel your best for the long-run.

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