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Serotonin Levels in Depression: Here’s What You Really Need to Know

Updated: Feb 9, 2023

✎ Written by: Dubravka Rebic ✓ Fact-checked by: Dr. Nathan Brown, Ph.D.

This year, people all around the world were astounded to hear about a recent discovery regarding the cause of depression. Headline after headline highlighted the findings of a scientific review that changed what 280 million people who suffer from depression worldwide believed to be true.

But why did this new discovery cause such a commotion?

Since the 1960s, we have been led to believe that depression is caused by biochemical imbalances in the brain, in particular by lower levels or reduced activity of serotonin (a neurotransmitter that plays a key role in regulating digestion, mood, sleep, and other bodily functions).

Based on this belief, doctors all around the world have been prescribing a type of antidepressant called a serotonin reuptake inhibitor (SSRI) in order to help their patients alleviate depression symptoms by increasing serotonin levels. As a result, millions of people started taking medication because they thought they had a chemical imbalance in their brain that required an antidepressant to put it right.

However, up until this point, there has been no comprehensive review of the research on the link between serotonin and depression. Not until this newly published umbrella review, which showed that we have no convincing evidence that depression is caused by lower levels or reduced activity of serotonin after all, and called into question what antidepressants actually do.

Antidepressants Work, But Scientists Are Not Sure How

Even though the study findings are groundbreaking, they don't negate the effectiveness of antidepressants for many people. In fact, the study tried to answer the question: "Do individuals with depression have lower levels of serotonin?" And, as the authors suggested, the answer is no, but the question about the role and efficacy of antidepressants wasn't addressed in the paper.

The major key findings from the review are:

  • There's no difference in the serotonin levels and their breakdown products in the blood or brain fluids between people with depression and those without.

  • Based on studies involving thousands of patients, there is no association between the gene for the serotonin transporter and depression. Similarly, no gene-stress interaction effects were found.

So, if there's no connection between low serotonin and depression, how do antidepressants work exactly?

One recent article argues that antidepressants typically take up to two weeks to impact the neurotransmitter system and to show clinical effects. By contrast, they may exert early effects by affecting neuroplasticity – altering how the brain functions over time – which translates into later clinically noticeable changes.

​Neuroplasticity is the capability of the brain to alter its structure or function in response to exposure to new stimuli or environments. The study mentioned above showed that SSRIs might foster neuroplasticity or cause stress to have less harmful effects on the brain.

But SSRIs are not the only way through which neuroplasticity can be improved.

What You Can Do To Promote Neuroplasticity

With depression, there may be issues with the quality, number, and type of neural connections, which are connections between nerve cells in the brain.

These connections are important because they allow us to learn and adapt. Neuroplasticity allows neurons and the connections they form with each other to compensate for injury and adjust their activities in response to learning or changes in the environment.

Thanks to neuroplasticity, you may change dysfunctional patterns of thinking and behavior, boost your adaptability skills, as well as develop new mindsets and abilities.

And there are many ways you can achieve this. For instance, you may positively affect neuroplasticity through medication but also through lifestyle factors like exercise, learning new things, and specific dietary modifications.

Furthermore, brain training technologies such as neurofeedback can promote neuroplasticity and train your brain to regulate your brainwaves to achieve the desired brainwave state and alleviate symptoms of depression.

How? When doing neurofeedback training with Myndlift, for example, you would play a video game or watch a video while EEG technology measures your brainwave activity. Every time your brain reaches its optimal brainwave state, you receive positive feedback, and that feedback not only earns you points but it gives you insight into your brain function—when it's in its optimal state and when it isn't.

Eventually, after consistent training, your brain learns to regulate itself and reach its optimal brainwave state without that immediate reward. As a result, you may feel more relaxed or notice an improvement in your mood.

Future Prospects in Depression Research

While the newly published review did not question the efficacy of antidepressants, the authors encouraged further research. Consequently, this paper might turn the spotlight on investigating the role of individual characteristics as well as biological and environmental influences that may act as risk or protective factors in the context of depression.

It may also shift the focus towards research on how these factors are involved in the efficacy of specific treatment approaches or a combination thereof. Furthermore, it can lead us to exciting questions about how connections in the brain function or dysfunction in depression, potentially providing further insights into the biological mechanisms of the disorder

One of the researchers, professor Moncrieff, said, "Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not."

But even though scientists don't fully understand what antidepressants are doing to the brain, if you are taking medication, it's crucial that you don't stop doing so without speaking to your doctor first.

The link between low serotonin and depression might be weak, but that doesn't mean that certain treatments are not effective. Hopefully, in the not-too-distant future, more research will be done to explain the reasons behind their efficacy.

Multiple Myndlift users report monthly changes in their behavior and lifestyle. Get matched with a Myndlift Provider by finding one in your area or enrolling in our Total Remote program.


About the author:

To help create awareness and positive change in the mental health space, Dubravka Rebic puts a lot of time and energy into researching and writing. From poring over scientific studies to reading entire books in order to write a single content piece, she puts in the hard work to ensure her content is of the highest quality and provides maximum value.

About the reviewer:

Dr. Brown is a clinical psychologist with over 35 years of experience using biofeedback and neurofeedback techniques. His clients include people dealing with depression, anxiety, ADHD, PTSD, and other stress-related conditions. He also helps those who seek to simply "raise their game" in their personal lives as well as their careers.


Reference list:

Coppen A. The biochemistry of affective disorders. Br J Psychiatry. 1967 Nov;113(504):1237-64. doi: 10.1192/bjp.113.504.1237. PMID: 4169954.

Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry (2022).

Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017 May;4(5):409-418. doi: 10.1016/S2215-0366(17)30015-9. Epub 2017 Jan 31. PMID: 28153641; PMCID: PMC5410405.

Whitehead JC, Neeman R, Doniger GM

Preliminary Real-World Evidence Supporting the Efficacy of a Remote Neurofeedback System in Improving Mental Health: Retrospective Single-Group Pretest-Posttest Study, JMIR Form Res 2022;6(7):e35636, doi: 10.2196/35636PMID: 35802411


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