Updated 20th July, 2022: a new study from UCL published today has looked extensively into research about the impact that serotonin has on our brains and found no clear link.
Lead author Professor Joanna Moncrieff, a Professor of Psychiatry at UCL and a consultant psychiatrist at North East London NHS Foundation Trust (NELFT), said in a statement: “It is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.
Original story published 22nd March, 2022
There are many things we take as fact in the world of health. We assume that the benefits of drinking two litres of water a day, that measuring health through BMI and that calorie counting is the key to weight loss are common knowledge for a reason – because they are scientifically sound and provable. But when you dig a little deeper into all these things, as I have had occasion to while writing for Refinery29, you sometimes find that this common knowledge is built on a mixture of myth, marketing and scientific hypotheses. The reality of how our bodies function and what we can understand about them is far more complicated than numbers, formulas or pithy ideas.
Despite knowing this, I continue to be surprised by things that I have always assumed to be true, that turn out not to be. Most recently, a psychiatrist caught me off guard when he told me that depression is probably not the result of a chemical imbalance or a lack of serotonin in the brain, as many of think. It's much more complicated than that.
The idea that depression has a primary biological cause is not new. (Buckle up for a potted history). The hypothesis linking serotonin to depression was put forward in the 1960s by a scientist called Joseph Schildkraut, as Dr Mark Horowitz, a clinical research fellow in psychiatry at University College London (UCL), tells R29. Back then, scientists found that drugs that increased the amount of serotonin in the brain seemed to improve people's mood and, from this, concluded that maybe a lack of serotonin is the cause of depression. "We now realise that’s like concluding that headaches are caused by a paracetamol deficiency or social anxiety is caused by an alcohol deficiency."
Schildkraut's serotonin idea was knocking about for 20 years or so with no clear proof, or practical application. Meanwhile benzodiazepines like Miltown, Librium and Valium were becoming household names in the UK and the US. These mild tranquillisers were prescribed for managing stress, anxiety, and other problems. But by the 80s benzos had reached a crossroads. "In the late 1980s, there was this huge crisis about benzodiazepines," explains Dr Joanna Moncrieff, a professor of critical and social psychiatry at UCL. "They had been really widely prescribed and it became clear that people were having difficulty getting off them, and that they'd been dished out to people for a range of 'problems'."
Joanna theorises that the pharmaceutical industry was looking to draw people’s attention away from anxiety (the ailment that tranquilisers were prescribed to treat) and towards depression as a way to market the newly arrived selective serotonin reuptake inhibitors (SSRIs), a form of antidepressant that are thought to work by increasing serotonin levels in the brain.
"I don't have evidence for this but I believe that the pharmaceutical industry invented the chemical imbalance idea in order to draw a line under the benzodiazepine problem," says Joanna. "So the chemical imbalance, particularly the serotonin story, worked to convince people that they were taking something that would cure an underlying problem that was specific and targeted like other medical treatments."
In the meantime there has been 60 years’ worth of research into serotonin levels in people with depression. "People have looked in the blood of depressed people versus non-depressed people, in their urine, in the brains of people that have died who were depressed or not depressed, in the cerebrospinal fluid around people's brains – in every possible place," Mark says. When looking for low levels of serotonin, some studies found serotonin was a bit increased in people with depression, while others found that serotonin was decreased and others found no difference at all. "Overall the finding is there's no difference between patients with or without depression. And so the hypothesis of a chemical imbalance or low serotonin is dismissed in academic circles."
However that message doesn't seem to have reached the rest of us. "If you go and ask patients what causes depression," Mark says, "something like 85 to 90% of patients will say a chemical imbalance or low serotonin."
In essence, there does not appear to be conclusive evidence yet that a lack of serotonin is a cause for depression. We do know that SSRIs can markedly improve the lives of those with depression by increasing serotonin levels. But, if it was just about increasing serotonin levels, the drugs wouldn't take weeks or months to work. As yet, we don't know why SSRIs work. Which is far more complicated and less memorable than 'low serotonin = depression'.
And yet we're talking about serotonin more than ever. Searches for 'serotonin' have been trending upwards globally on Google since 2014, memes about serotonin are everywhere on Instagram and on Twitter people talk about their fandoms giving them a serotonin boost while others make TikToks about their chemical imbalances being with them 'for life'.
It's such embedded folk knowledge that I only learned that this theory was so contentious when speaking to Mark for another article about antidepressants and why they can stop being so effective over time. He mentioned it in passing and I was so surprised that I had to double back. When we speak again he tells me that my reaction isn’t uncommon. He’s mentioned the same thing to several journalists who’ve also had that experience of not realising it is somewhat mythic. In fact, when lecturing during his PhD Mark still believed it himself, at one point searching for sources to support the claim, coming up empty. "It was so deeply ingrained in my mind that I assumed it must be right."
Given this lack of conclusive proof, how did it end up becoming common knowledge?
To no one's surprise, it could be thanks to pharmaceutical companies. As Mark says: "In the 1980s when they were promoting the then new antidepressants like Prozac (fluoxetine), drug companies grabbed this hypothesis and they amplified it. They told doctors and patients that it is low serotonin or chemical imbalances causing depression, and we have these drugs that fixes it." He adds that "this hypothesis that had been put together 20 years earlier, magnificently fit [pharmaceutical companies’] marketing aims." They were able to draw a clear and direct line between depression, biology and their medication, framing it in the same way you would any other bodily deficiency.
The messaging about a clear cause and effect was not subtle, either. “There are ads from the time given to doctors in medical magazines and even ones on the TV aimed at patients in America saying depression is caused by an imbalance in chemicals and our drug (in one case, Zoloft) will right this chemical imbalance," Mark explains. "It became injected into the popular description of depression and anxiety and essentially, there's been no major push to re-educate the public that this is not the case."
Understanding this isn’t just a gotcha at big corporations or a fun tidbit to share at dinner parties. Unpicking our ideas about depression being solely linked to a lack of serotonin or chemical imbalance begins to give us space to better understand the hows and whys of depression, incentivises individuals to treat it better and helps us to question exactly what SSRIs are doing to the brain. Because the truth is we still don't know everything about how they work.
"SSRIs have some effect on the serotonin system," Joanna explains, "but they may well affect other systems as well. What the evidence tells us is that they slightly alter your depression scores on a depression scale if it's compared to placebo, but actually, the alteration on the depression scores compared to placebo is very small, probably not clinically relevant."
If SSRIs are not correcting an underlying imbalance, are they creating an imbalance? "If a depressed person is essentially like a regular person, with prolonged bad mood, giving them a drug that will increase serotonin in their brain creates an abnormal imbalance of their neuro chemistry," says Joanna.
This is not meant to sound frightening. We may not know why they work but for many people, this writer included, they do work. I take a high dose of fluoxetine to circuit-break the obsessive compulsive disorder I developed three years ago and which wouldn’t shift, no matter how much therapy and meditation I did.
But questioning the over-simplified biological narrative enables us to explore the sociocultural and psychological factors that impact our mental wellbeing and therefore look for additional forms of treatment that are not just pharmacological. As Mark puts it: "Psychiatrists are doctors and they're very used to using this biomedical model of diagnosis and treatment. But once you start opening up into more complex issues, you're talking about therapy or changes to people's lives, which is a whole different kettle of fish."
This gives us as patients more agency too. The assumption that there is a chemical problem with your brain can affect your self-image, leading you to internalise this idea that you are permanently defective or broken. It can disincentivise you from pursuing additional forms of treatment or daily self-care. While solving the problem of access to these other solutions is far from over, arming ourselves with better understanding on the drugs we are taking can pave the way for a push for better, more holistic treatment.