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Time to retire the meme that depression is caused by low levels of serotonin

We tend to cling to medical ideas long after they’re out of date.

Prozac is an antidepressant designed to boost serotonin levels.
REUTERS/Darren Staples
Prozac is an antidepressant designed to boost serotonin levels.

We tend to cling to medical ideas long after they’re out of date. One of those still-circulating-but-scientifically-expired ideas is that depression is caused by low levels of the neurotransmitter serotonin.

For the past two decades or so, we’ve been told that if we just give our serotonin levels a boost — either pharmacologically (with a serotonin antidepressant) or naturally (with, say, exercise or sun lamps) — we’ll re-balance our brain chemicals and start feeling better.

Only, as National Public Radio science reporter Alix Spiegel noted in a Morning Edition broadcast on Monday, “for many scientists who research depression, this explanation is no longer satisfying.”

Taking an antidepressant or exercising or sitting under a full-spectrum bank of lights may improve your mood, but not because you’ve replenished your stores of serotonin.

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“Chemical imbalance is sort of last-century thinking. It’s much more complicated than that,” Dr. Joseph Coyle, a professor of neuroscience at Harvard Medical School and editor of the journal Archives of General Psychiatry, told Siegel. “It’s really an outmoded way of thinking.”

Coyle believes serotonin plays a role in depression, but not, he said, because the levels get depleted.

Other scientists are even more aggressive in downplaying serotonin’s role in depression.

“I don’t think there’s any convincing body of data that anybody has ever found that depression is associated to a significant extent with a loss of serotonin,” Alan Frazer, an antidepressant researcher and chairman of the pharmacology department at the University of Texas Health Science Center at San Antonio, told Siegel.

Began with Parkinsons disease
In her broadcast, Siegel describes how “the story of low serotonin came to dominate our understanding of what causes depression.” The idea began, she says, in the mid-1960s, when scientists discovered that another brain disorder, Parkinson’s disease, was caused by a deficiency of the neurotransmitter dopamine. Could depression also be caused by some kind of chemical deficiency, the scientists wondered.

When the antidepressant Prozac — which works on a single neurotransmitter, serotonin — burst on the market in 1987, some researchers believed they had found that chemical.

But science has not supported that view. Siegel cites one such study (of many):

In the 1990s, [Dr. Pedro Delgado, now chair of the University of Texas psychiatry department] carried out a study that showed that if you take a normal person and deplete them of serotonin, they will not become depressed. He says he feels this demonstrates that low serotonin doesn’t cause depression.

Delgado has been even more outspoken than that on the issue. In an article published in the Journal of Clinical Psychiatry way back in 2000, Delgado wrote these somewhat scathing remarks: “Some have argued that depression may be due to a deficiency of [norepinephrine] or [serotonin] because the enhancement of noradrenergic or serotonergic neurotransmission improves the symptoms of depression. However, this is akin to saying that because a rash on one’s arm improves with the use of a steroid cream, the rash must be due to a steroid deficiency.”

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As Siegel reports, there is an upside to the myth that low serotonin levels cause depression: If people think their depression is triggered by a chemical imbalance — and that it can be corrected by taking a drug — they may be more likely to seek care, an action that by itself can reduce stress and, thus, improve mood.

“Still, there’s no question that the story also has downsides,” Siegel adds. “Describing the problem exclusively in biological terms has convinced many people to take antidepressants when other therapies — like talk therapy — can work just as well.”

Although Siegel doesn’t mention it in her report, prolonging the public myth that low serotonin levels cause depression has a huge upside for the pharmaceutical industry. Here’s why, as explained by the authors of a 2005 article in the open-access journal PLoS Medicine on the “disconnect” between advertisements promoting serotonin antidepressants and the scientific literature:

The impact of the widespread promotion of the serotonin hypothesis should not be underestimated. Antidepressant advertisements are ubiquitous in American media, and there is emerging evidence that these advertisements have the potential to confound the doctor-patient relationship. … These advertisements present a seductive concept, and the fact that patients are now presenting with a self-described “chemical imbalance” shows that  [direct-to-consumer advertising] is having its intended effect: the medical marketplace is being shaped in a way that is advantageous to the pharmaceutical companies. …

Patients who are convinced they are suffering from a neurotransmitter defect are likely to request a prescription for antidepressants, and may be skeptical of physicians who suggest other interventions, such as cognitive-behavioral therapy, evidence-based or not.

We need to stop framing depression as a chemical imbalance, argues Siegel (who acknowledges in her broadcast that she was prescribed Prozac for depression when she was a teenager). The biology of depression is much more complicated, she says “and, in a way, not all that reassuring. Researchers don’t really know what causes depression. They’re making progress but they don’t know. That’s the real story.”

“It’s not exactly a blockbuster,” she adds.

You can read and/or listen to Siegel’s broadcast on the NPR website.