The Big Serotonin Myth – What Really Causes Depression?

In recent weeks, chaos has settled in the scientific sphere of Twitter. A new study has brought to the fore a debate that has long taken place behind the scenes – and doubts have been cast over a scientific theory that has been widely accepted by the public for decades.

The belief that depression is caused by a chemical imbalance in the brain may have just been debunked. The result of the study’s findings is a flurry of controversy and misleading claims about antidepressants, where the media draw their own conclusions about the effectiveness of SSRIs and the future of treating depression.

The Serotonin Myth

A new umbrella examPosted in Molecular psychiatry in July says there is “no compelling evidence” that depression is caused by low levels of serotonin.

The study analyzed seventeen existing meta-analyses and systematic reviews, pooling data from hundreds of thousands of participants. The researchers concluded that there is no support for the chemical imbalance theory of depression, which has been widely accepted by the public for decades.

The results have sparked considerable debate in the scientific community about the function of antidepressants, namely selective serotonin reuptake inhibitors (SSRIs), whose main function is to correct insufficient levels of serotonin.

Here, the chemicals in question are neurotransmitters. They act as chemical messengers in the brain, carrying signals across the space between two nerve cells. Serotonin is the neurotransmitter involved in regulating our mood, development, perception, cognition, memory and more; for this reason, it is often called our “happiness hormone”.

SSRIs prevent serotonin from being reintroduced into nerve cells, making it more widely available in the brain. According University College London (UCL), there is no other accepted pharmacological mechanism by which antidepressants affect symptoms of depression.

The study authors found no difference in blood and brain serotonin levels between people diagnosed with depression and healthy participants. Likewise, they concluded that artificially lowering serotonin does not produce depression in healthy volunteers. There was also no evidence of variation in the serotonin transporter gene between people with depression and healthy controls.

“It’s always difficult to prove a negative” said Joanna Moncrieff, professor of psychiatry at UCL and lead author of the paper, “but I think we can safely say that after a large amount of research carried out over several decades, there is no convincing evidence that depression is caused by abnormalities in serotonin, particularly by lower levels or reduced activity of serotonin.

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 serotonin abnormalities.

The article has since left many wondering how SSRIs actually work in the brain, and whether these findings indicate there is a better pharmacological option.

What the experts say

The authors of the article point out that the chemical imbalance theory is still widely accepted by the public, citing surveys that suggest that 85% to 90% of people believe that depression is caused by low serotonin levels. Despite this, it appears their findings came as no shock to many experts in the field, with most agreeing that the review does not change the current scientific understanding of depression.

“No mental health professional would currently endorse the idea that a complex heterogeneous condition like depression stems from a deficiency in a single neurotransmitter,” Explain Phil Cowen, professor of psychopharmacology at the University of Oxford. According to Professor David Curtis, Honorary Professor at UCL’s Institute of Genetics, the chemical imbalance theory is “outdated” and it complaints “It’s certainly not news that depression is not caused by low levels of serotonin.”

Some researchers, however, have opinions on the merit of the study itself. “Although general reviews can provide interesting insight into an area of ​​research, they are ultimately bound by the design and quality of the original studies on which they are based, and therefore do not allow us to draw new conclusions” , said Dr Livia de Picker, postdoctoral researcher at the University of Antwerp.

Professor David Nutt, director of the Center for Neuropsychopharmacology at Imperial College London, also adds that the review analyzes exclusively “indirect measures of serotonergic function or, even worse, simply indicators of serotonergic activity”, so “to reject the serotonergic hypothesis of depression at this stage is premature”.

However, what the article – or, more accurately, the media response to it – highlights is the gap between the understanding of depression by experts and the public. This is made abundantly clear by the many misleading claims made about antidepressants as a result of these findings.

SSRI skepticism

An important thing to address is the Molecular psychiatry The article didn’t specifically look at the effects of antidepressants, but some mainstream media are now fueling the public that this new evidence is poking holes in their effectiveness.

Like the title of Daily mail reads, “Study Casts Doubt on Widespread Use of Powerful Drugs Designed to Treat Chemical Imbalance in the Brain.” In the same way, The Guardian writes that “scientists have questioned the widespread use of antidepressants” in light of the study results. Not only is this an exaggeration, but these claims are likely to raise unnecessary doubts among one in eight British adults currently taking antidepressants.

The reality is that scientists still don’t know exactly how antidepressants work, but an abundance of clinical data shows that they do for many patients. The study in question does not change what researchers already know about these drugs. For starters, if the depression was purely the result of a chemical imbalance, antidepressants would work immediately – but, as all SSRI users know, it takes about 2-3 weeks to start feeling their effects.

In a tweet thread, neuroscientist and Honorary Research Associate at Cardiff Psychology School, Dr Dean Burnett, uses the analogy that the antiquated chemical imbalance theory is comparable to the claim that headaches are caused by “not enough paracetamol”. . The lack of paracetamol is not the cause of pain, but taking the drug still induces a positive effect.

As Burnett explains, the exact mechanisms of SSRIs are not fully understood, but “a lot of evidence suggests [serotonin] is a big part of mood regulation, “and increasing its availability in the brain” should make the brain more capable to change your mood.

Accordingly, a large part of the more recent research in SSRIs suggests that they influence neuroplasticity, a fundamental process that underlies learning and memory through the brain’s ability to alter its structure and function. It is generally thought that this increased brain plasticity makes the depressed individual more prone to undergo changes in emotional and social processing.

What causes depression and how is it treated?

Depression doesn’t have a single cause; After recent theories suggest that mood disorders are the result of many dysfunctional brain circuits and neurotransmitter systems. There is also evidence suggest that early stress triggers neurobiological changes that influence a person’s development, making them more vulnerable to depression.

However, why the serotonin depression theory was the one the public and medical professionals clung to is likely because it reduces these complex emotions to a simple biological mechanism – “something tangible and without reproach”, as Dean Burnett suggests.

Professor Joanna Moncrieff suggests that oversimplifying the science behind depression has caused more confusion than clarity. “[Patients] should not be led to believe that antidepressants work by targeting these hypothetical, unproven abnormalities,” she said. said. “Giving people this kind of misinformation prevents them from making an informed decision about whether or not to take antidepressants.”

So while SSRIs have immeasurable value in psychiatry – they have and will continue to save lives – antidepressants reflect a medical model that is not necessarily how mental health issues should be treated, and goes beyond- beyond this unique approach. to psychiatry should be a priority.

According to Professor Carhart-Harris, former head of the Imperial Center for Psychedelic Research, in a 2018 Global Psychiatry paper.

More recent interventions – psychedelic assisted psychotherapyfor example – are also taking this hybrid approach and so far the results have been extremely promising. Psychedelics have also been shown to influence the serotonin neurotransmitter system, which, according to Carhart-Harris, “opens the door to heightened sensitivity to context, an ideal prerequisite for effective change.”

The widespread use of antidepressants has long been a point of contention. With plenty of nasty side effects and potentially serious withdrawal symptoms, SSRIs are definitely not the perfect pill they were once marketed for. But whatever your position, experts at the Royal College of Psychiatrists urge SSRI users not to stop taking their antidepressants in light of this new research, and they encourage anyone with concerns about their medication to contact their GP.

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