Serotonin and Depression: Myths vs Science Explained

Depression is extraordinarily common, yet also one of the most misunderstood mental health conditions. For decades, the primary explanation for depression was that a chemical imbalance in your brain was the culprit, and that it was easily fixed with medication.

While this approach isn’t completely without merit, it’s incomplete. Investigating the serotonin and depression myth that grew from this oversimplification isn’t about undermining past or current treatments or being dismissive of your experience with depression. Instead, it’s about working to fill the gaps with a more accurate (and more empowering) approach. 

In a very real way, learning about the science of depression and serotonin is the first step toward understanding yourself and your experience. This deeper understanding can help you make more informed decisions about your treatment and feel less alone in what you’re going through.

Man sitting on couch with head resting on hand worrying about serotonin and depression

What Is Serotonin? Brain Function, Mental Health, and the Basics

Serotonin is a neurotransmitter in your body and sends signals between nerve cells. Though it’s often referred to as the “happiness chemical,” it’s responsible for regulating many different aspects of your daily experience, from your appetite to sleep patterns to memory and mood.[1]

The vast majority of serotonin isn’t produced in your brain. Instead, 90 percent of serotonin is made in your gut from tryptophan, an amino acid derived from the food you eat.[1],[1],[2]

The connection between serotonin and depression was first explored in the 1950s and 1960s, when researchers discovered that early antidepressants affected serotonin. They also noticed that those same drugs relieved depression.[2]

Naturally, it was assumed that low serotonin causes depression. However, this was an inference, not a proven fact. Just because the drugs affected serotonin and improved depression symptoms didn’t automatically mean serotonin was the cause of depression.[3],[4]

Serotonin vs Dopamine in Depression

Like serotonin, dopamine is a neurotransmitter, but it’s involved in different processes. Where serotonin is closely associated with emotional regulation and mood stability, dopamine is primarily involved in motivation, pleasure, and reward.[1],[3]

Why is this distinction important?

First, if you’ve experienced depression, you know that one of its most debilitating symptoms is the inability to feel pleasure. Since dopamine is closely tied to the reward system in your brain, this element of depression may relate better to a dopamine dysregulation than a serotonin dysregulation.[1],[3]

Second, it helps explain why some people respond well to SSRIs, and others don’t. If depression were caused by low serotonin in every person, then SSRIs and their serotonin-boosting effects would work for everyone.[2],[5]

Third, if you’ve tried SSRIs and they haven’t worked, it doesn’t mean you can’t be treated. It means your depression might respond better to a different approach, like bupropion, an antidepressant that works on dopamine rather than serotonin.[2],[4],[6] Since depression is so complex, treatment isn’t one-size-fits-all. Finding the right medication or combination of treatments may take time, but the options available have expanded significantly.

Where Did the Chemical Imbalance Theory Come From?

British psychiatrist Alec Coppen is credited with proposing a depression neurotransmitter imbalance theory in 1967. His theory (the serotonin theory of depression) was built upon the findings of his contemporaries that serotonin was largely responsible for depressive symptoms.[7],[2],[8]

However, Coppen’s hypothesis was never meant to be a complete explanation of serotonin’s relationship with depression. Instead, it was supposed to be a jumping-off point for additional research in the area.[7],[2] Over the years, the notion that depression was a direct result of a serotonin imbalance took on a life of its own. It reached a fever pitch in the 1990s when SSRIs became a popular treatment for depression.[8]

At the time, 80 percent of the general public believed a chemical imbalance caused depression. While it certainly could be one underlying cause of depression, science has never established it as fact.[8]
This gap between public perception and scientific evidence is important to understand, not to discredit treatment, but to develop a more accurate picture of what depression involves.

Serotonin Imbalance Symptoms

The serotonin and depression myth goes deeper, still. Even today, people are told their symptoms, like low mood, fatigue, and feelings of hopelessness, are directly caused by a serotonin imbalance.[6],[8]

As a result, the way depression has been explained to you might not tell the whole story. Though it can be validating to think a simple chemical imbalance causes your depression, it can also be limiting. Explaining your pain is one thing, but attributing that pain solely to neurotransmitter levels in your body can make recovery feel out of your control.[3] Recognizing that depression has multiple contributing factors can actually open up more pathways to healing.

Does Low Serotonin Cause Depression?

The million-dollar question is whether or not low serotonin causes depression. The answer is complicated.

As explained above, the serotonin and depression myth is that there’s a direct correlation between low serotonin and depression. However, this is not supported by research. In fact, recent research found no consistent evidence that people with depression have lower serotonin activity than people without depression.[8]

However, this doesn’t necessarily mean serotonin deficiency depression isn’t a real thing. It means that the interaction of the two is too complex an issue to be explained by a simple causal relationship.[7],[3]

Here’s an example: studies show that artificially lowering serotonin levels in healthy people doesn’t cause depression.[8] However, artificially lowering serotonin in people who have had depression in the past can potentially cause a relapse. The assumption is that serotonin might be involved in vulnerability to and recovery from depression rather than being a central cause of it.[3],[7]

What research does support, though, is a relationship between serotonin and anxiety disorders. For example, SSRIs are commonly and often effectively used to treat numerous anxiety issues, like post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and generalized anxiety disorder.[1],[9]

This is of note because anxiety and depression commonly co-occur: as many as 50 percent of people with major depressive disorder also meet the diagnostic criteria for an anxiety disorder.[1] If you’ve experienced both anxiety and depression and were treated with SSRIs, this explains why symptoms for both disorders might have been reduced.[3]

Brain Chemistry Myths About Depression

Two primary myths about brain chemistry and depression are worth addressing.

First, the notion that SSRIs work for depression, therefore depression must be caused by low serotonin, uses circular logic. It’s like saying ibuprofen relieves headaches, so an ibuprofen deficiency must be the cause.[3] A treatment working to relieve your symptoms doesn’t necessarily indicate what caused the problem.

Second, depression being a permanent state because it has roots in biology is another popular myth. The reality is that even if neurobiological factors are involved, your brain is incredibly adaptable. It can repair itself, regrow neurons, and rebuild neural networks.[4],[6] This capacity for change is called neuroplasticity, and it’s the foundation for why therapy, lifestyle changes, and medication can all produce real improvements with time.

Identifying these myths is important. But it’s also necessary to understand that complex hypotheses like the serotonin theory of depression aren’t debunked overnight. It isn’t a scandal. Coppen wasn’t trying to be misleading. It means that researchers are refining our understanding of complex processes over time.[6]

How Antidepressants Affect Serotonin

As touched on earlier, SSRIs prolong the action of serotonin in the synapse. Increasing levels of serotonin like this relieves depressed mood and reduces anxiety.[9] The paradox is that if low serotonin isn’t a direct cause of depression, why do SSRIs work so well for so many people?

Perhaps the best answer is this: SSRIs may not correct serotonin deficits, but instead help the brain change how it processes emotional information.[3] In other words, SSRIs might bias the brain toward more positive interpretations of the information it receives. Some research shows that this happens very early in depression treatment, even before you notice your mood improving.[3] This process could be what helps set the stage for a gradual recovery from your symptoms.

An alternative theory called the emotional relearning model suggests that antidepressants don’t simply shift how your brain processes emotional information. Instead, the idea is that antidepressants work with your brain’s natural ability to change. This is a more positive approach: it’s not patching a broken system, but helping the system adapt.[7],[3] In treatment, this often allows medication to create a window of opportunity for therapy and lifestyle changes to take hold.

Mental Health Medication Explained

While we may not fully understand the underlying processes of antidepressants, what’s certain is that they are nonetheless effective in treating depressive symptoms in most people.[6] This isn’t only with SSRIs, either; many highly effective and widely used medicines work in ways that we don’t completely understand.[5]

The value of medications like SSRIs stands independently of any theory about what causes depression in the first place. They work and work well to reduce many symptoms of anxiety and depression, and as a result, your daily functioning can be greatly improved. As noted above, for many people, medication provides the stability needed to engage more fully in therapy and make meaningful lifestyle changes.

Decisions about prescribing medications aren’t based on one or two factors. Instead, mental health professionals take your mental health history, symptoms, clinical trial evidence, and many other elements into account. It’s far more involved than saying, “Here’s a pill for your low serotonin.”[11]
 Neurotransmitters other than serotonin and dopamine are involved, too.

Noradrenaline, for example, plays a part in alertness and the stress response, which contributes to symptoms like low energy, reduced alertness, and diminished focus.[2] As another example, low levels of glutamate, which is the brain’s main excitatory neurotransmitter, are associated with the onset and progression of depression.[10]

Neurotransmitter research is much more evolved today than it was in the 1960s when the serotonin hypothesis was first devised. Researchers can now use sensors in living brains to study neurotransmitter activity, bringing the science one step closer to catching up with the complexity of depression’s root causes.[2] These advances offer the possibility of more targeted treatments in the future.

More recently, research has focused on neuroinflammation as a possible contributing factor for the development of depression. The idea is that the immune system and neurotransmitters might work together to cause depression in some people. This theory might help explain why physical ailments like chronic pain so often occur alongside depression.[2],[6]

The takeaway is encouraging: we are gaining a deeper understanding of depression, what causes it, and how to treat it. If you’ve found it difficult to find an effective treatment, or if you feel like your depression defies explanation, it’s a reason for hope.

Mission Connection: Psychiatric Treatment for Depression

The changing science of depression and serotonin’s role in it can be confusing. But it doesn’t invalidate how you feel or reduce the effectiveness of the treatments you’ve tried. If medication like SSRIs has helped you, that help is real, regardless of whether our original understanding of treatment for serotonin imbalance was complete or not.[5]

Treating depression is much broader than prescribing a single pill. You may take medication, but the most effective treatment likely also includes therapy and lifestyle support to address the many different factors contributing to your experience.[2],[6] Not everyone responds to the same treatments. That’s not an individual failure on your part; it just shows how incredibly complex depression is.

The science of depression continues to evolve, and that’s good news. The more we understand it, the better treatment options and the more personalized those treatments can be. At Mission Connection, we understand just how important individualized care is.

Our team offers compassionate, evidence-based care to help you navigate the complexities of living with depression. If you or someone you love is going through a difficult time, you don’t have to figure it out on your own. Start your recovery today by reaching out.

Woman working from home using laptop at desk smiling after support with serotonin and depression