A Decisive Blow to the Serotonin Hypothesis of Depression


From Psychology Today: “Almost as soon as it was floated in 1965 by Harvard psychiatrist Joseph Schildkraut, the serotonin hypothesis of depression—reduced and simplified by pharma marketing to the ‘chemical imbalance’ theory of depression and anxiety—has been subject to critical research and found wanting.

The poor standing of the hypothesis in the scientific literature, however, barely dented its afterlife in textbooks, across clinical and treatment settings, and on mental health apps and websites. Nor has it dispelled the continued use of the phrase as ‘shorthand’ between doctors and patients and in everyday settings, including for quite different mental states and conditions . . .

Cut to the Present-day

A major new review of the research—the first of its kind exhaustively reviewing the evidence, published today in the journal Molecular Psychiatry— . . . found ‘there is no evidence of a connection between reduced serotonin levels or activity and depression.’

The peer-reviewed umbrella review—representing one of the highest forms of evidence in scientific research—was extrapolated from meta-analyses and systematic reviews on depression and serotonin levels, receptors, and transporters involving tens of thousands of participants.

Although ‘the serotonin hypothesis of depression is still influential,’ Moncrieff and coauthors noted, citing widely adopted textbooks published as recently as 2020 and surveys indicating that ’85-90 percent of the public believes that depression is caused by low serotonin or a chemical imbalance,’ the primary research indicates there is ‘no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.’

. . . Moncrieff explained in the press release:

‘Patients should not be told that depression is caused by low serotonin or by a chemical imbalance and they should not be led to believe that antidepressants work by targeting these hypothetical and unproven abnormalities. In particular, the idea that antidepressants work in the same way as insulin for diabetes is completely misleading. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.’

Invited to extrapolate the review’s findings for Psychology Today, Moncrieff added:

‘Antidepressant use has reached epidemic proportions across the world and is still rising, especially among young people. Many people who take them suffer side effects and withdrawal problems that can be really severe and debilitating. A major driver of this situation is the false belief that depression is due to a chemical imbalance. It is high time to inform the public that this belief is not grounded in science.'”



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  1. I’m not surprised the serotonin hypothesis would have come from Harvard in 1965. My mother worked for the Harvard School of Public Health then, for Jean Mayer in nutrition research. I understand the culture.

    What she was aware of was links to the food industry — especially that part which produced grains — donating to Harvard, and the “recommendations” that warned us away from saturated fats, cholesterol, butter, red meat, eggs, etc., not really being supported by any kind of rigorous data.

    They just wanted to believe.

    Those nutrition recommendations were debunked starting in the 90’s. However, my mother told me as a kid in the 80’s all about how questionable they were. She wasn’t talking publicly about it, though, and neither were other researchers. Or former researchers. She was not on speaking terms with Jean Mayer by then.

    This may seem like a side note. However, when I went to Harvard much later, I learned about the strategic significance of the Crimea — which is now one of the reasons for the current war in Ukraine — as being tied to trade between the grains industry of Southern Russia and Ukraine, and the Middle East.

    The Middle East depends on grains from southern Russia and Ukraine, as they are a desert. Or they used to depend on that. Most such grains must be shipped through the Crimea, a tiny bottleneck, making it so whoever controls the Crimea controls all the trade between Southern Russia and the Arab world.

    This means that leveraging the Middle East (and other countries) for oil production would be made easier by getting the populations of those countries, like the Middle East, addicted to easily transportable grains. Thus, exaggerating the health benefits of grains as compared to meats, milk, butter, etc., would not have only benefitted the grains industry but would have benefitted all industries dependent on cheap oil. As the best way to encourage oil rich countries to produce high volumes of oil for cheap prices is to make them as dependent on possible on food imports from oil consuming countries.

    The Soviet Union’s mismanagement of agriculture resulted in all food exports from Russia/Ukraine to the Middle East ceasing, and the Middle East had to get its food elsewhere, and even the Soviet Union had to get much of its food from imports as well. Both the Soviet Union and the Middle East started ramping up oil production exactly as such food import dependency started happening.

    Long digression, but it suggests we have a systematic problem with how huge sectors of the economy are capable of warping scientific “opinion” and skewing in all sorts of ways, with psychiatry perhaps just the tip of the iceberg, a small part of a much larger problem worldwide.

    On top of it, actually, in an economy with lots of technology assisted mass production, it becomes necessary either to have huge welfare systems for all those not employed, as machinery makes things so efficient only a small number of people need to be employed feeding everyone. Or, alternative to welfare systems, whole areas of the economy that simply provide non-essential goods and services need to kind of sprout up, to create excuses to employ people, and to spread the wealth around.

    Something HAS to happen to put money in the hands of all those not employed producing the bare necessities of life, which is a lot of people now with technology. It either has to be welfare, or “non-essential” products and services.

    I believe there is a connection, for instance, between Europe’s super generous welfare system, compared to the USA, and the fact that they have lower rates of ADHD diagnosis and ritalin prescription, and lower rates of psychiatric drug use and cheaper healthcare systems. Indeed, welfare reform in the Clinton Era piggy backed on Harvard professor, Joseph Biederman’s bought and paid for diagnosis of “childhood bipolar disorder.”

    I think this can become a problem, as whole business sectors lobby to try to get government to “decree” THEIR goods/services to be more “essential” than the rest, and it all gets decided politically. When we were much poorer and 70 percent of the population worked only to provide us the food we need, there wasn’t much choice, what the other 30% of the economy was.

    Now, we actually DO have choice, theoretically. Oddly enough, I think technology has created a situation that enhances the power of the government so much compared to what it used to be that, although we theoretically have more choices regarding what we can do with our economy than we used to, in practice, we are less free. Wealth has created tons and tons of straitjackets.

    Because businesses and special interests lobby lobby lobby to try to make it all “not a choice.” And they are all extraordinarily wealthy compared to before. And our economy is, in some ways, more fragile because it is so complex. And so centralized. If a war in Ukraine can potentially cause mass starvation in so many other parts of the world, that portends to an enormous amount of economic centralization. Some of the countries threatened with the worst starvation due to the Ukraine war are actually parts of Africa that have very very fertile soil — but, political conditions have resulted in governments being bribed by foreign interests interested in exploiting such countries for raw materials mining, and these governments have undermined local farmers so badly as to make those countries dependent on food imports — which are only granted in return for raw materials exports. The undermining of local farmers the only tactic that can work to create threatened starvation level conditions, unless men agree to go work in dirty hazardous mines.

    However, the extreme exploitation of the third world countries, for cheap labor, creates a completely different problem for us at home. We are like the fat and sedentary middle classes of Ancient Rome, who were granted political patronage off the surplus the Roman Empire extracted from the provinces, only they lead poisoned them into passivity and complacency.

    Also, it’s almost like the machinery of the centralized economy wants the bribed middle classes who get all the “goodies” to kind of be steady recipients of largess. Except, the market for luxuries and non-essential goods is anything but steady. In order for the economy not to be at the whim or mercy of transient fads too much, authorities can only make the economy work by making certain non-essential goods “essential” in this steady way.

    Computers and internet service is a good way to create economic stability and predictability. And the healthcare system is a good way. Long long ago, I believe foot binding of women in China may have had a motive of limiting the kind of disruptive fluctuations to the economy that would happen when women had babies who took all their time, and then became more mobile and able to do various work as the babies got older. Foot binding limited their activities to stuff like textiles — and textiles can tolerate more fluctuation in the labor force than necessities like food production.

    Think about it this way. Women help produce food too, then there is a baby boom, so many women are taken out of food production even while more food needs to be produced. It’s better if such women never STARTED helping out with food production in the first place. Since the economy is somewhat flexible. If there are, initially, lots of young women helping out with food production, you need fewer men working at food production. So several young men become blacksmiths, carpenters, etc, who would have stayed in food production.

    Then there is a baby boom and tons of women drop out of producing food to have babies, who eat more. Then, and only then, does society figure out “we have too many young men working as blacksmiths and carpenters, more than we need — and how do we get them back to producing food, that is not so easy. It’s better if women had never started helping out producing food in the first place. What if we do foot binding for women, that will keep everything steady and predictable for us.”

    I feel like some sort of economic “pressure” like that was responsible for foot binding of women in China. And somehow the same economic “issue” may also favor psychiatric drugs that create permanent dependency. The need for stability. And I think maybe the exact same economic “issue” might have caused mandatory lead poisoning in Ancient Rome.

    In each case, you have products or policies that cause systematic disability and predictable dependency, all of which helps to provide a predictable “stabilizing” force to the economy. And, somehow, wealthy economies worry about such predictability more than less wealthy economies.

    I should note, I believe the economics departments of college campuses may suffer from corruption similar to that of psychiatry. Let us suppose that is so. Maybe what I am talking about, the common thread you can weave through foot binding, lead paint in Rome, and psychiatry and bad nutrition recommendations — maybe that is some sort of economic phenomenon we could figure out and publicly identify, and we can’t expect college economics departments to do it. More than the mere fact that business sectors are self interested and lobby. Because everyone lobbies — but it seems the business sectors who enjoy the best success may be those that, in some STRUCTURAL WAY, are able to provide some sort of economic predictability and stability.

    Well, universities do think long term, and they want not a big one time donation, but several small ones that go on in perpetuity. It is also true that, because most of the economy is non-essential, it is a fact that academia monopolizes part of the non-essential economy, but other parts of the non-essential economy don’t require workers with college degrees.

    Bloat or expand psychiatry, and you raise the value of a psychiatric education in academia. If less money were spent — in the whole economy — in psychiatry, where else might it be spent? How about Disney world. Well, you don’t need an advanced education in order to work at Disney World. Colleges want to maximize the need for EDUCATED WORKERS.

    The problem with that is, sometimes you end up with academia acting as charlatans. They want to find fault with EVERYONE who is not under their tutelage, or who hasn’t purchased an expensive education. You even have that in the diversity industry.

    More and more and more, it’s all about “education education education.” Always for a price. The solution to everything. And if you don’t have an education, what are you? Backwards, archaic, inferior. Even one of the latest Nobel Prize Winners, Malala, was all about “sending girls to school.” I hate sitting still for long periods of time. I hate being cooped up indoors under a schedule imposed by others. My mother hated school too.

    I think someone needs to voice the opposing view.

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  2. Where are the reparations for the patients who were lied to in their lives destroyed? My life was destroyed entirely by Psychiatry and its endless lies. Chemical imbalance, treatment resistant depression, ect, borderline personality disorder, non-compliant, lack of awareness, it was all just one lie after another and destroyed anything good I ever had in any potential I had to deal with the trauma of my childhood and live a decent life.

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    • Not sure they will get reparations. Best thing to do for someone is try the best to help them out from now on. Money not the solution to everything. Think of the focus on reparations, even while our whole society and economy has degraded so much that the things money can buy aren’t worth it. So you can’t throw more money at the problem.

      I do wonder, though, whether it might help if those charlatans in academic institutions really got the shaming and humiliation they deserve. Sometime punishment helps, and they are a class of people who don’t get enough of that.

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