A massive new study suggests depression isn’t a serotonin imbalance after all

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

Despite its popularity as a treatment for mood disorders, a lot of the mechanisms behind antidepressant medications are a complete black box. We can only guess how they work in treating bad moods.

Even more shocking, these guesses may be completely wrong, raising the question of whether depression is actually caused by a significant decrease in serotonin at all.

A new comprehensive review of previous meta-studies and systematic analyzes of the relationship of depression to serotonin levels has reached the conclusion that there is insufficient evidence to support an association between the two variables.

This does not necessarily mean that serotonin-based therapies do not act on some other mechanism that we do not yet understand. No one should consider giving up their medication without consulting Droars; BSince so many people are dependent on these medications, it is important to know what is actually going on.

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

“But I think we can safely say that after a great deal of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly due to low levels of serotonin or decreased activity.”

The origins of the speculation that mood disorders arise from chemical imbalances in the brain, can be traced back to the mid-20th century, when it was suggested that a monoamine neurotransmitter called noradrenaline was out of control in people with depression.

Serotonin – that other famous monoamine – has also been viewed with suspicion, leading to what has become the monoamine hypothesis.

With selective serotonin reuptake inhibitors (SSRIs) entering the market in the 1980s, the notion that depression was a relatively straightforward deficit of a kind of happy, nervous juice was primed for fame.

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

“Prescriptions for antidepressants have risen dramatically since the 1990s, with one in six adults in England and 2% of teenagers now being prescribed an antidepressant in a given year.”

It is not hard to see why the hypothesis is wholeheartedly accepted as fact. It’s a minor problem with a simple fix, it can be sold for profit.

Regardless of the marketing and commercial rewards, one in five people with depression personally appears to feel relief in their symptoms while on antidepressants.

The idea is now ingrained in the public psyche, about 80% of the general public accept that depression is a chemical imbalance.

If you’re among those hearing all this for the first time, the hypothesis has been on practically shaky ground since its launch in the 1990s, with study after study failing to support the idea.

Recognizing that there might be enough studies to keep the hypothesis alive, Moncrieff and her team searched prominent research archives such as PubMed and PsycINFO using terms relevant to meta-analysis investigations of depression and serotonin, excluding those associated with conditions associated with other conditions such as bipolar disorder.

Independent reviewers assessed the quality of studies using widely accepted search criteria, before providing a final account of the level of certainty for each study.

Only 17 studies made this reduction, which included a genetic association study, another comprehensive review, and dozens of systematic reviews and meta-analyses.

Overall, the evidence supporting a role for serotonin in depression has been 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 have large studies compared the genes for serotonin and its supporting proteins.

Studies that looked directly at neurotransmitter receptor and transporter behavior were slightly more supportive of a role for serotonin, but they tended to be inconsistent in their results, leaving open interpretations open.

Looking closely at individuals who have taken antidepressants successfully, it appears that they may have lower levels of serotonin. On the other hand, this may be expected over time as the body compensates for changes in biochemistry.

What is our position on that?

Studies like this are a good reminder that differences in body function can rarely be reduced to simple impotence. Depression is a complex condition, potentially arising from a variety of contributing factors (only some of which we have a lot of control over as individuals).

“Our view is that patients should not be told that depression is caused by low serotonin or a chemical imbalance, nor should they be led to believe that antidepressants work by targeting these unproven defects,” Moncrieff says.

Criticisms of the review, however, indicate that many of the included studies did not use direct measures of serotonin activity in the brain, something we were only recently able to do technologically. Therefore, more research is needed to determine how much of the placebo is and how much is due to some strange tangles in neurochemistry.

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

This research was published in Molecular Psychiatry.

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