Huge New Study Suggests Depression Isn’t Serotonin Imbalance After All

For millions of people around the world, salvation after long periods of dark thoughts and oppressive feelings comes in pill form, with each dose doing its part to ensure that the balance of a humble neurotransmitter called serotonin remains relatively under control. control.

Despite their popularity as a treatment for mood disorders, most of the mechanisms behind pharmaceutical antidepressants are a complete black box. We can only guess how they work in treating depressed moods.

More shockingly, these assumptions could be completely wrong, calling into question whether depression is in fact caused by a significant drop in serotonin.

A new general review of past meta-studies and systematic reviews of the relationship between depression and serotonin levels has come to the conclusion that there is simply not enough evidence to support a link between the two variables. .

This doesn’t necessarily mean that serotonin treatments don’t work on some other mechanism that we don’t yet understand. And no one should consider going off their medication without consulting their doctor.actors. BBut since so many people are dependent on these drugs, it’s important to understand what’s really going on.

“It’s always difficult to prove a negative result,” says lead author Joanna Moncrieff, a psychiatrist from University College London.

“But I think we can safely say that after a large amount of research conducted over several decades, there is no convincing evidence that depression is caused by abnormalities in serotonin, particularly lower levels. or reduced serotonin activity.”

The origins of speculation that mood disorders result from a chemical imbalance in the brain go back further, to the mid-20th century, when a monoamine neurotransmitter called norepinephrine was proposed to go haywire in people with depression. .

Serotonin – that other famous monoamine – was also viewed with suspicion, leading to what became known as the monoamine hypothesis.

With the arrival on the market of selective serotonin reuptake inhibitor (SSRI) antidepressants in the 1980s, the idea that depression is a relatively simple deficit of a kind of neurological happiness juice began to gain traction. popularity.

“The popularity of the ‘chemical imbalance’ theory of depression has coincided with a huge increase in the use of antidepressants,” says Moncrieff.

“Antidepressant prescriptions have increased dramatically since the 1990s, with one in six adults in England and two per cent of teenagers now being prescribed an antidepressant in any given year.”

It is not difficult to see why the hypothesis is so warmly accepted as fact. It’s a simple problem with a simple solution, which can be sold for a profit.

Marketing and sales accolades aside, about one in five people with depression seem to actually experience relief from their symptoms when they take antidepressants.

The idea is now so ingrained in our public psyche that some 80% of the general public accepts that depression is a chemical imbalance.

If you’re one of those hearing all of this for the first time, the hypothesis has been virtually unstable since it took off in the 1990s, with study after study failing to support the idea.

Realizing that there might be enough studies to keep the hypothesis alive, Moncrieff and his team searched leading research archives such as PubMed and PsycINFO using terms relevant to meta-investigations. -analysis on depression and serotonin, excluding those associated with conditions related to other conditions such as bipolar. .

Independent reviewers assessed the quality of the studies using widely accepted research standards, before providing a final calculation of the level of certainty for each study.

Only 17 studies were retained, including a genetic association study, another general review and a dozen systematic reviews and meta-analyses.

Overall, the evidence supporting the role of serotonin in depression was weak at best. Comparisons between levels of serotonin (and its breakdown products in the blood) in people with and without depression found no difference. Nor huge studies comparing the genetics of serotonin and its supporting proteins.

Studies that directly examined the behavior of receptors for the neurotransmitter and its transporter were somewhat more supportive of the role of serotonin, but tended to be inconsistent in their conclusions, leaving confounding explanations open.

Looking closely at people who are successfully taking antidepressants, it looks like they might have lower serotonin levels. On the other hand, this might be expected over time as the body compensates for the biochemical changes.

So where are we?

Studies like these remind us that differences in our body’s functions can rarely be reduced to a simple deficit. Depression is a complex condition, potentially resulting from a variety of contributing factors (of which only some of them, as individuals, have much control).

“Our view is that patients should not be told that depression is caused by low serotonin or a chemical imbalance, and that they should not be led to believe that antidepressants work by targeting these abnormalities. unproven,” says Moncrieff.

Critics of the review point out, however, that many of the included studies did not use direct measures of serotonin activity in the brain, something we are only recently technologically able to do. So more research is needed to determine how much is a placebo and how much is due to some other weird tangle of neurochemistry.

It also means we need to have honest conversations about how blind we are to the nature of chronic depression and the lingering question marks about the true costs and benefits of antidepressants.

This research was published in Molecular Psychiatry.

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