What’s the first thing that comes to mind when you ponder the question – what exactly causes depression? If something along the lines of “a chemical imbalance” in the brain is what comes to mind, you’re not alone. 

For decades, the idea that depression is caused by a chemical imbalance – namely low levels of a specific brain chemical known as serotonin – has been widely accepted by doctors, mental health practitioners, and the general public alike. But can depression really be traced back to a simple alteration in serotonin levels? New research is revealing that the answer may be no – and that our approach to depression may have been largely misguided for years.

Today we’re going to dive into exactly what serotonin is, how it really impacts the brain, how new research is debunking the myth that depression is caused by low serotonin, and explore some of the underlying factors that may contribute to the real cause of depression.

Depression Defined: What Exactly Is Depression?

In simplest terms, depression is a condition that can significantly affect the way you feel, think, and act. But depression is much, much more than a passing feeling of sadness or an occasional “case of the blues”. Depression can be all-consuming – making it difficult to carry out even basic day-to-day tasks and have a disruptive impact on your relationships, your health, your ability to work, and even your ability to take care of yourself.  

There’s no “one-size-fits-all” when it comes to depression – it can feel and look a little different for everyone, but can involve feelings like:¹

• Persistent and pervasive feelings of sadness, hopelessness, or “emptiness” 
• A distinct lack of joy or pleasure
• Little interest in the things you used to enjoy
• Difficulty focusing, remembering, or making decisions
• Low or non-existent self-esteem
• Diminished energy levels and feelings of extreme fatigue
• Irregular eating patterns (eating too much or too little)
• Difficulty sleeping
• Aches and pains
• Thoughts of self-harm or suicide

So what causes these intense and lingering feelings that can leave you feeling like there’s a dark, gloomy cloud looming over your life? For decades now, depression and its troublesome symptoms have been attributed to a chemical imbalance in the brain – more specifically depression has been blamed on low levels of an important neurotransmitter known as serotonin.

What Does Serotonin Do In the Brain?

Serotonin, more formally known as 5-hydroxytryptamine or 5-HT, is a signaling chemical that your body uses to carry messages between nerve cells in your brain and throughout your body. This dynamic signaling chemical plays an important role in numerous bodily functions ranging from digestion to bone health and from sexual function to wound healing. But this little molecule is most notably associated with its distinct function in the brain in a process that goes something like this:^2,3,4,5

• The synthesis of serotonin originates with the ingestion of an essential amino acid known as tryptophan, which is processed and transformed by your body into an active form of serotonin.
• While the majority of your serotonin is actually produced by cells outside of your brain and nervous system, certain cells within your brain are able to produce and secrete this crucial compound.
• Your brain cells release serotonin into what’s known as synaptic clefts – the space between two neurons or brain cells that fire off and receive the electrical impulses that control your every thought, feeling, and action.
• Each of your neurons contains any number of serotonin receptors – microscopic structures that free-floating serotonin is able to bind to.
• Studies have found that there are at least 15 different types of serotonin receptors – all eliciting a slightly different response when serotonin molecules bind to them.
• When serotonin binds to these receptors, it triggers your neurons to fire off electrical signals – activating and modulating your brain's electrical circuitry.
• These electrical impulses stimulated by the release of serotonin influence just about every one of your behavioral and neuropsychological processes – including mood, perception, anger, memory, attention, and more. 
• After serotonin is secreted and binds to these receptors, it is then transported by a protein known as the serotonin transporter, or SERT, which terminates serotonin signaling by driving the reuptake or reabsorption of serotonin back into your neurons.  

Now let’s dive a little deeper into the theory behind how this small but mighty molecule causes depression.

Serotonin and Depression: Is Depression Caused by Low Serotonin?

It’s been widely accepted for decades that depression is the end result of chemical abnormalities or imbalances within the brain. In particular, depression has been attributed to a deficiency in serotonin concentration levels and/or a disruption in the brain's ability to absorb or utilize available serotonin. This serotonin-based hypothesis speculates that the brain is either:

• Unable to secrete adequate levels of serotonin
• Has an abnormally low number of serotonin receptors
• Has weakened or decreased ability to bind serotonin to available serotonin receptors
• And/or does not appropriately reabsorb or reuptake secreted serotonin back into the neuron

This theory of inadequate serotonin activity driving the symptoms of depression has been the basis of many treatment options and an entire class of anti-depression medications known as selective serotonin reuptake inhibitors or SSRIs which inhibit the reuptake or reabsorption of serotonin – allowing more free-floating serotonin to remain available to bind to receptor sites.

So is depression really caused by an imbalance in serotonin? The answer to that question is complicated – and might just be no. While at first glance, this theory seems to make sense, recent research has found that this widely accepted and deeply ingrained theory on the origin of depression may not be so accurate after all.

The Serotonin Theory of Depression Debunked: What the Research Says

Recent studies have found that the theory of depression being rooted in an imbalance in serotonin is lacking in evidence. These findings revealed no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. In fact, most studies found no evidence of reduced serotonin activity in people with depression compared to people without depression. And what’s more, additional studies found that reducing serotonin availability did not consistently lower mood.^6,7

More time and research are needed to truly understand the role serotonin may or may not play in depression, but these findings are monumental and will continue to have a major impact in how depression is approached moving forward.

So if depression isn’t in fact caused by low serotonin or a chemical imbalance in the brain, what really causes it then?

So, What Really Causes Depression Then?

While the question of what exactly causes depression is simple, the answer is anything straightforward. Your brain is a highly complex and dynamic system that relies on countless compounds, hormones, chemical reactions, and electrical signals to regulate how you think, feel, and function. Meaning the factors that can throw this delicate system off kilter are diverse and innumerable. 

While we certainly can’t pinpoint a singular cause that can be identified as “the” root cause of depression, some factors that can have a dramatic influence on your thoughts, feelings, and overall mood include:^7,8,9,10

• Genetics: Your genes can affect both the structure and function of your brain – both of which can influence how you feel, think, and your general mood.
• Environmental factors: Your brain is sensitive and intricately connected to every other system within your body. So things like contact with environmental toxins, nutrient deficiencies, and exposure to stressors can shift the balance in your brain. 
• Stress, thought patterns, and traumatic events: Recurrent patterns of thoughts, feelings, and focus (like feelings of chronic stress or worry), or even an event that your brain interprets as traumatic can literally rewire your brain – essentially changing the way it functions.
• Biochemistry: While studies have found that depression may not be as simple as a chemical imbalance, that doesn’t mean that imbalances in your biochemistry cannot alter the way you feel and contribute to depression. If your neurotransmitters, hormones, and other signaling molecules are out of whack, it can subsequently throw your brain off-kilter too.
• Gut Health: The health of your gut directly impacts your brain health and your mood thanks to a crucial and intricate communication channel known as the gut-brain axis. You can read more about the link between your gut health and your mood by clicking right here. 
• Inflammation: Inflammation can impact every facet of your well-being – including your brain health and your mental state. Chronic low-level inflammation can be hard to detect but can chip away at your physical and mental balance. 

The truth is, depression is complicated and likely not caused by one single underlying factor.

So, How Is Depression Treated?

If you’re struggling with depression, there’s no cookie-cutter approach to treatment. But there are certainly some things you can implement that may help. Here’s what I recommend:

• Prioritize logging adequate hours of high-quality sleep every night: Sleep deprivation can drastically alter your brain and your mood and leave you feeling downright crummy
• Support a happy healthy gut: Your gut directly impacts your mood
• Minimize your exposure to environmental toxins: These toxic compounds can trigger inflammation, mimic hormones and neurotransmitters, and disrupt your entire body's equilibrium 
• Address any factors that may be triggering low-level inflammation: Inflammation can be triggered by anything from a poor diet to a hidden infection
• Eat a healthy, well-rounded diet full of nutrient-dense foods: Your brain relies on countless nutrients to run effectively, so be sure you’re fueling it with healthy, foods full of brain-boosting nutrients
• Spend time outdoors: Soaking up natural sunlight, coming into contact with the earth's surface through a practice of grounding, and simply connecting with nature on a regular basis can do wonders for mental health
• Prioritize spending time with loved ones and making time for fun: All work and no play is a recipe for unhappiness – so be sure to make time to do things you enjoy with people you love
• Incorporate mood-boosting supplements: Supplements like my Mood Essentials contain a carefully calibrated combination of vitamins, minerals, amino acids, and other nutrients that are necessary for the synthesis of neurotransmitters, healthy nerve transmission, and healthy brain chemistry – supporting healthy brain function and naturally elevating your mood.
• Reframe stress: Chronic stress can put a major damper on your physical and mental health – which can significantly contribute to depression. Learning to mitigate unnecessary stress and rechannel unavoidable stress into more creativity and motivation can help you become “stress-proof”. Click here to learn more about how you can work on becoming stress-proof in your own life.

Again, while these steps can certainly help manage and reduce symptoms and even help address some of the root causes that may be contributing to depression, there’s no one-size-fits-all when it comes to addressing this multifaceted condition. For that reason, if you’re grappling with depression I cannot overemphasize the importance of working with both a Functional Medicine Doctor and a qualified mental health professional.

Together, these practitioners can combine their expertise to help identify the root causes that might be contributing to your symptoms and help come up with a comprehensive plan to help support you and help you heal –  mind, body, and soul. 

Are You Struggling With Depression?

If you’ve been grappling with persistent feelings of emptiness, sadness, or distress or have been navigating an official diagnosis of depression, it can feel overwhelming and isolating, to say the least. While we may not have all the answers yet when it comes to addressing depression, the good news is, the more we learn about this complex condition, the better we can combat it. 

If you’re in the trenches and feel like you’re battling a dark gloomy cloud that seems to loom over every aspect of your life, please know that you are not alone and there is hope for finding relief. If you’re ready to take the next step in beating depression, please don’t go at it alone. Seek out the guidance of experienced practitioners to guide and support you every step of the way.

If you’re looking for more practical and implementable ways you can prioritize your physical, mental, and emotional well-being to help you manage depression, I encourage you to head over and check out the hundreds of resources I have available on my blog, my YouTube channel, and in my weekly newsletter (which you can subscribe to by entering your information at the bottom of this page).

And if you need a little reminder that you’re never alone in this journey, that you do have the strength to persevere and overcome, and that there are brighter days ahead, be sure to pre-order a copy of my upcoming book Unexpected: Finding Resilience Through Functional Medicine, Science, and Faith. I wrote this book because I know what it’s like to feel defeated, hopeless, utterly frustrated, misunderstood, and most of all – alone. And I also know that if I can overcome the health challenges, life obstacles, and hard-learned lessons I’ve encountered and use them to create vibrant health and happiness – that you’re more than capable of doing the same! Sometimes all we need is a little unexpected spark of inspiration – which is what I hope with all my heart this book can provide in some way or another.

Has there ever been a time in your life when you’ve felt alone or unsure where to turn for answers?

In Unexpected: Finding Resilience through Functional Medicine, Science, and Faith, Dr. Jill Carnahan shares her story of facing life-altering illness, fighting for her health, and overcoming sickness using both science and faith so that others can learn to live their own transformative stories.

Dr. Jill’s riveting and compassionate exploration of healing through functional medicine demonstrates how to replace darkness and fear with hope and find profound healing, unconditional love, and unexpected miracles in the process.

Resources:

1. NIMH » Depression (nih.gov)
2. The serotonin theory of depression: a systematic umbrella review of the evidence | Molecular Psychiatry (nature.com)
3. The Expanded Biology of Serotonin (nih.gov)
4. Physiology, Serotonin – StatPearls – NCBI Bookshelf (nih.gov)
5. Frontiers | The Serotonin Transporter and Early Life Stress: Translational Perspectives (frontiersin.org)
6. What causes depression? – Harvard Health
7. Researchers Find No Evidence That Depression is Caused by Low Serotonin | Contemporary Clinic
8. Where in the Brain Is Depression? – PMC (nih.gov)
9. Brain structure alterations in depression: Psychoradiological evidence – PMC (nih.gov)
10. Targeting inflammation in depression: Ketamine as an anti-inflammatory antidepressant in psychiatric emergency – ScienceDirect