Explained: New study that suggests depression is not caused by serotonin imbalance in brain

The study [https://www.nature.com/articles/s41380-022-01661-0#Sec5] — ‘The serotonin theory of depression: a systematic umbrella review of the evidence’, by Joanna Moncrieff et al. — was published online on July 20 in the open access journal Nature Molecular Psychiatry.

What is the serotonin theory of depression?

“The idea that depression is the result of abnormalities in brain chemicals, particularly serotonin (5-hydroxytryptamine or 5-HT), has been influential for decades, and provides an important justification for the use of antidepressants,” the authors write in the paper.

Depression was first linked to lowered serotonin levels in the 1960s, they write, and the theory gained wide acceptance in the 1990s with the advent of Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants, which temporarily increase the availability of serotonin in the brain.

Despite some recent criticism, the serotonin theory of depression remains influential, with the “principal English language textbooks still giving it qualified support, leading researchers endorsing it, and much empirical research based on it”, the authors write.

Based on the belief that there is something wrong with the brain that requires an antidepressant to correct, these drugs are now prescribed to one in six of the adult population in England, the authors write. The idea is endorsed by official institutions like the American Psychiatric Association, which says “differences in certain chemicals in the brain may contribute to symptoms of depression”.

And what exactly is serotonin?

It is a kind of neurotransmitter, a chemical that helps transmit messages or signals from one nerve cell to another for communicating. Serotonin helps regulate mood, sleep, appetite, and other major aspects of daily functioning.

What is the conclusion of the new research?

Over the years, several studies have questioned the serotonin theory. The new study conducted an “umbrella review”, collating existing overviews of the principal areas of relevant research on serotonin and depression. The intention was to establish “whether the current evidence supports a role for serotonin in the aetiology of depression, and specifically whether depression is associated with indications of lowered serotonin concentrations or activity”.

The conclusion of the study: “The serotonin theory of depression has been one of the most influential and extensively researched biological theories of the origins of depression. Our study shows that this view is not supported by scientific evidence. It also calls into question the basis for the use of antidepressants.”

People who were taking or had previously taken antidepressants showed evidence that these drugs may actually lower the concentration or activity of serotonin, the study showed. “Although viewing depression as a biological disorder may seem like it would reduce stigma, in fact, research has shown the opposite, and also that people who believe their own depression is due to a chemical imbalance are more pessimistic about their chances of recovery,” the authors have written.

According to the researchers, there are other explanations for the effect that antidepressants have on a person. Drug trials show they are “barely distinguishable from a placebo (dummy pill) when it comes to treating depression,” and antidepressants appear to have more of a generalised emotion-numbing effect on people’s moods.

So what causes depression, then?

There is no simple answer for this yet. Stressful life events have been mentioned as a factor that exerts a strong effect on people’s risk of developing depression. One of the authors of the study, Mark A Horowitz, said in a tweet: “Poverty, insecure work, sexism, racism, interpersonal conflict, etc. all clearly associate with depression. The vast sums of money spent on looking for the chemical equation of low mood might be missing the forest for the trees.”

Several experts have said that the findings of the study should not lead anyone to immediately stop taking prescribed antidepressants. This ‘study of studies’ does make some important points, such as depression being a result of multiple factors, but more research is needed to confirm some of its big claims.

The authors have concluded that it “is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe”, and that this study is “critical” for making informed decisions about whether or not to take antidepressants.

Given that the claims in the study challenge popular belief, they will likely generate further discussion and studies before a decisive conclusion can be reached about the effectiveness of medicines for treating mental health disorders.