The Serotonin Hypothesis of Depression

I am all for accurate information when it comes to managing your own health. Today I want to explore some misinformation about the causes and treatment of depression.

Serotonin chemical structure


You may have heard the idea, especially if you have ever been treated for depression, that depression is caused by a lack of a particular chemical, serotonin, in the brain. And you may have heard that antidepressants help lift depression by correcting this serotonin shortage.

The problem is, it isn’t true. It has been known for quite some time that it isn’t true. I don’t mean it isn’t true that antidepressants can help treat depression – the issue is with the claim about how they work. The science is covered thoroughly in the November 2005 article from journal PLOS Medicine, Serotonin and Depression: A Disconnect between the Advertisements and the Sientific Literature:

… to propose that researchers can objectively identify a “chemical imbalance” at the molecular level is not compatible with the extant science. In fact, there is no scientifically established ideal “chemical balance” of serotonin, let alone an identifiable pathological imbalance. To equate the impressive recent achievements of neuroscience with support for the serotonin hypothesis is a mistake.

With direct proof of serotonin deficiency in any mental disorder lacking, the claimed efficacy of SSRIs is often cited as indirect support for the serotonin hypothesis. Yet, this ex juvantibus line of reasoning (i.e., reasoning “backwards” to make assumptions about disease causation based on the response of the disease to a treatment) is logically problematic—the fact that aspirin cures headaches does not prove that headaches are due to low levels of aspirin in the brain.

Our brains work in a very complex way using a combination of electrical and chemical communication. Billions of neurons communicate between each other by releasing chemicals at connection points known as synapses. Different synapses are responsive to different chemicals, so altering the balance of chemicals tends to affect different areas of the brain depending on the chemical in question.

The most common class of antidepressant medication used today, SSRIs, work in the brain by blocking a mechanism that “recycles” serotonin. The effect of this is that, in the parts of the brain that communicate using serotonin, serotonin is present for longer and in higher levels at the synapse. This increase in serotonin at the synapses occurs within hours of ingesting an SSRI – so if treatment of depression was as simple as correcting a shortage of serotonin, SSRIs should improve mood within a matter of hours. But they don’t. It is generally expected to take four to six weeks from initiation of an SSRI until noticable changes in mood occur.

This immediately tells us that something more complicated is happening than simply the increase in serotonin. The truth is, nobody actually knows exactly what happens, or why it seems to help lift depression in some patients.

If SSRIs work, though, why does it matter how?

It matters because the idea that depression is caused by a chemical imbalance implies that the cause of the problem is entirely biological and requires a biological solution. In practice, research shows that there are a variety of interventions that can significantly help alleviate depression – including exercise, social interaction and several forms of psychological therapy. The false notion that we already know what causes depression has the potential to limit further advances in understanding and treatment of the condition.

About Paul McQueen

Dr Paul McQueen is a Clinical Psychologist, holding a Doctorate in Clinical Psychology from the University of Melbourne. He has experience working in both adult and child mental health services in Queensland and Victoria. Dr McQueen is comitted to providing high quality, evidence-based interventions for a range of mental health conditions. He specialises in the treatment of Obsessive Compulsive Disorder, Borderline Personality Disorder and Depression.

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