Psychiatrists Still Promoting Low-Serotonin Theory of Depression


On Slate Star Codex, psychiatrist Scott Alexander asserts that the now widely discredited notion that depression is caused by a serotonin deficiency “was never taken seriously by mainstream psychiatry” and was never promoted by psychiatrists or pharmaceutical companies. He further suggests that no one at Mad in America has evidence that they did promote it.

Alexander’s post was a response to a recent article in iO9, exploring the rise and fall of the low-serotonin theory of depression.

On Critical Psychiatry, Duncan Double responds to Alexander’s post, noting that at the very least “there’s no doubt that many people have been taken in by the theory.” Duncan adds that many psychiatrists and pharmaceutical companies alike have confused or misled the public with chemical imbalance theories of various kinds, because the public often doesn’t realize that “the ‘chemicals in depression’ may not be much different from those that create normal feelings. It may not make much sense to view depression as a neurochemical disorder.”

For his part, Alexander argues that the notion that psychiatrists once promoted the idea of low serotonin as a cause of depression and Selective Serotonin Reuptake Inhibitors (SSRIs) as proper treatment for that deficiency is all simply a false “narrative” invented by “antipsychiatry” activists. These activists then “frame it as ‘proof’ that psychiatrists are drug company shills who were deceiving the public.” Alexander points to quotes of American Psychiatric Association officials in a post by MIA Blogger Philip Hickey, and notes that none of the quotes specifically describe a low-serotonin explanation for depression. The Hickey post cited is not actually about that topic, but about the promotion of the phrase “chemical imbalance”; nevertheless, Alexander broadly refers to Hickey and all of Mad in America as “antipsychiatry”, and he then writes, “If the antipsychiatry community had quotes of APA officials saying it’s all serotonin deficiency, don’t you think they would have used them?” Alexander argues, “The idea that depression is a drop-dead simple serotonin deficiency was never taken seriously by mainstream psychiatry.”

There seems to be a lot of evidence to the contrary still today readily available even on the web, though. For example, a 2004 Washington University in St. Louis press release, about a study published in Biological Psychiatry, states that the “brain’s serotonin receptors” are “at abnormally low levels in depressed people” and that antidepressants “work by increasing serotonin levels in the brain.” And there is prominent psychiatrist Richard Friedman writing in the New York Times in 2007 that psychiatrists were soon going to be able to conduct “a simple blood test” to determine “what biological type of depression” a person had and then treat them with the right drug. “For example,” writes Friedman, “some depressed patients who have abnormally low levels of serotonin respond to S.S.R.I.’s, which relieve depression, in part, by flooding the brain with serotonin.”

There’s also a lot of evidence that the low-serotonin theory of depression is still today being taken seriously by mainstream psychiatry and is still being promoted to the public.

A current University of Bristol public education website on depression explains that, “Low serotonin levels are believed to be the cause of many cases of mild to severe depression(.)”

A current Harvard Medical School special health report, “Understanding Depression”, explains that, “Research supports the idea that some depressed people have reduced serotonin transmission. Low levels of a serotonin byproduct have been linked to a higher risk for suicide.”

And WebMD‘s “Depression Center” states that, “There are many researchers who believe that an imbalance in serotonin levels may influence mood in a way that leads to depression. Possible problems include low brain cell production of serotonin, a lack of receptor sites able to receive the serotonin that is made… According to Princeton neuroscientist Barry Jacobs… common antidepressant medications known as SSRIs, which are designed to boost serotonin levels, help kick off the production of new brain cells, which in turn allows the depression to lift.”

And if the theory was never taken seriously and isn’t being taken seriously, no one has apparently told the National Academy of Sciences or two news media outlets with expert psychiatric editorial boards yet. Psychiatry Advisor‘s February 12, 2015 headline for a report about a Duke University study is, “Serotonin Deficiency May Up Depression Risk.” Psychiatry Advisor explains that, “(m)ice with normal serotonin levels, the control group, did not demonstrate depression symptoms a week after the social stress, while the serotonin-deficient rodents did(.)” The study, appearing in the Proceedings of the National Academy of Sciences, states that, serotonin deficiency has been “implicated in the etiology of depression” though a cause-effect relationship has not yet been “formally established.” The researchers write that their results, “provide additional insight into the serotonin deficiency hypothesis of depression.” Medical News Today headline their report on it even more strongly: “Mouse study finds that serotonin deficiency does increase depression risk.” (Medical News Today notes in passing that an earlier, somewhat similar study by a different team came to the exact opposite findings.)

MIA Bloggers Jonathan Leo and Jeffrey Lacasse explore the whole topic in a 2005 PLoS Medicine article, “Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature,” and in a 2007 article in Society titled, “The Media and the Chemical Imbalance Theory of Depression.” And in two 2012 posts on Mad in America, Leo and Lacasse argue that most serious psychiatric researchers did indeed know all along that there was no evidence that low serotonin caused depression, even as the media and public over decades became ever more convinced that it did. However, for Leo and Lacasse those facts prompt a different question than they do for Alexander; namely, Leo and Lacasse ask where the historical evidence is of prominent psychiatric association officials making concerted efforts to stop the public from believing serotonin deficiencies could cause depression. “(I)f the Psychiatry Community knew all along that the theory was not true, then why did they not clarify this issue for the general public?” write Leo and Lacasse. “Why did the professional societies not publicly set the record straight?” Leo and Lacasse then describe NPR interviews with psychiatrists who admit that they are still today telling patients “that serotonin imbalance causes depression, even though they know this isn’t the case.”

No one should believe the chemical imbalance theory (Critical Psychiatry, April 7, 2015)

Chemical Imbalance (Slate Star Codex, April 5, 2015)

The Most Popular Antidepressants Are Based On An Outdated Theory [UPDATED] (iO9, April 1, 2015)

Psychiatry DID Promote the Chemical Imbalance Theory (Mad in America, June 6, 2014)

Brain’s serotonin receptors at abnormally low levels in depressed people (Washington University in St. Louis press release, May 10, 2004)

On the Horizon, Personalized Depression Drugs (New York Times, June 19, 2007)

Depression (University of Bristol, accessed April 11, 2015)

What causes depression? (excerpt from Understanding Depression, Harvard Medical School, accessed April 11, 2015)

Depression Health Center — Serotonin: 9 Questions and Answers (WebMD, accessed April 11, 2015)

Serotonin Deficiency May Up Depression Risk (Psychiatry Advisor, February 12, 2015)

Mouse study finds that serotonin deficiency does increase depression risk (Medical News Today, February 10, 2015)

Sachs, Benjamin D., Jason R. Ni, and Marc G. Caron. “Brain 5-HT Deficiency Increases Stress Vulnerability and Impairs Antidepressant Responses Following Psychosocial Stress.” Proceedings of the National Academy of Sciences 112, no. 8 (February 24, 2015): 2557–62. doi:10.1073/pnas.1416866112. (Abstract)

Leo, Jonathan, and Jeffrey R. Lacasse. “The Media and the Chemical Imbalance Theory of Depression.” Society 45, no. 1 (November 28, 2007): 35–45. doi:10.1007/s12115-007-9047-3. (Full text)

Lacasse, Jeffrey R, and Jonathan Leo. “Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature.” PLoS Med 2, no. 12 (November 8, 2005): e392. doi:10.1371/journal.pmed.0020392. (Full text)

Psychiatry’s Grand Confession (Mad in America, January 23, 2012)

Revising the History of the Serotonin Theory of Depression? (Mad in America, January 29, 2012)

What is Serotonin and Signs of Serotonin Deficiency? (Health Ambition)


  1. Wow, these fools are really amazing. Since they can’t defend their nonsense, they deny they ever said it, even though there are tons of statements by them easily findable on the internet and in other publications.

    They have become so used to telling any lies they want and not being challenged that they think they can get away with it forever. But those days will soon be over.

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  2. “I am not one who easily loses his temper, but I confess to experiencing markedly increased limbic activity whenever I hear someone proclaim, “Psychiatrists think all mental disorders are due to a chemical imbalance!” In the past 30 years, I don’t believe I have ever heard a knowledgeable, well-trained psychiatrist make such a preposterous claim, except perhaps to mock it. On the other hand, the “chemical imbalance” trope has been tossed around a great deal by opponents of psychiatry, who mendaciously attribute the phrase to psychiatrists themselves.2 And, yes—the “chemical imbalance” image has been vigorously promoted by some pharmaceutical companies, often to the detriment of our patients’ understanding.3 In truth, the “chemical imbalance” notion was always a kind of urban legend- – never a theory seriously propounded by well-informed psychiatrists.” – Ron Pies, M.D., July 11, 2011

    See more at:

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    “If we take something to be the truth, we may cling to it so much that even if the truth comes and knocks at the door, we won’t want to let it in.” (1)
    Overspecialization has led to a silo mentality in psychiatry, impeding the cross fertilization of ideas and discoveries which can improve the lives of many. Add to this the nature of the pharmaceutical industry which profits greatly from the sale of medications and big budget advertising campaigns seemingly run on the principles espoused by Goebbels, the Nazi Propaganda Minster; it is no wonder the field of psychiatry is held in such low regard by many.
    “Many mental health programs are not staffed with physicians practiced in medical diagnosis and thus are unprepared to detect a large proportion of physical diseases in their patients…California’s state mental health programs fail to detect many diseases that could be causing or exacerbating psychiatric disorders” (2)

    In 1995 a study found that from 5–40% of psychiatric patients have medical ailments that would adequately explain their symptoms. (3) The next year, in 1996, Sydney Walker III, M.D., a psychiatrist, in his book, A Dose of Sanity, claimed studies have shown that from 41% to 75% of individuals are initially misdiagnosed, often due to overlooked treatable conditions. (4) In 2009, it was found that up to 25% of mental health patients have medical conditions that exacerbate psychiatric symptoms. (5)
    The use of the Koran Algorithm would significantly reduce the number of individuals misdiagnosed, however utilizing other research done since would also reduce the number of people diagnosed with various mental illness and steer them into appropriate treatments.

    There are 4 reasons in the medical model for brain dysfunction 1: Anatomical abnormalities or damage. 2: Lack of oxygen or glucose 3: Electrolyte imbalance 4: Neurotransmitter deregulation: the imbalance of brain chemistry. (6) (#4 has the least evidence to support it)
    Trauma can result in shrinkage of the hippocampus (7)which is adjacent to the amygdala, and can be considered the emotional center of the brain. This shrinkage affects the communication between areas of the brain and is responsible for heightened fear and anger responses.
    This means trauma would fit into category 1 – Anatomical abnormalities or damage. Several proven non-drug methodologies are available to treat trauma, including Somatic Experiencing (, Eye Movement Desensitization and Reprocessing (, and Tension & Trauma Releasing Exercises ( or the book The Revolutionary Trauma Release Process by David Berceli, Ph.D.)
    Then there is magnesium deficiency – which falls into category 3 – Electrolyte imbalance, magnesium being an electrolyte, as well as a key component in the production of serotonin. “…Magnesium is essential in regulating central nervous system excitability thus magnesium deficiency may cause aggressive behavior, depression, or suicide. Magnesium calms the brain and people do not need to become severely deficient in magnesium for the brain to become hyperactive… a marginal magnesium intake overexcites the brain’s neurons and results in less coherence – creating cacophony rather than symphony – according to electroencephalogram (EEG) measurements.” (8)
    In order to reduce costs and improve treatments for those with a mental health diagnosis, we need to move away from a system dominated by the drug industry.
    More in Liberty & Mental Health – You Can’t Have One Without the Other
    May all beings be happy and peaceful
    May all beings be safe and secure
    May all beings be healthy and prosperous
    May all beings live joyfully and with ease (9)
    1. The Heart of Understanding, © 1988 by Thich Nhat Hahn (pg. 8)
    2. A Medical Algorithm for Detecting Physical Disease in Psychiatric Patients, Hospital and Community Psychiatry Vol. 40 No. 12 Dec 1989, Pg. 1270 by Harold C. Sox, Jr., M.D., Lorrin M. Koran, M.D., Carol H. Sox, M.S. , Keith I. Marton, M.D., Fred Dugger, P.A., Teruko Smith, R. N.
    3. Allen MH, Fauman MA, Morin SF. Emergency psychiatric evaluation of “organic” mental disorders. New Dir Mental Health Serv 1995;67:45-55.
    4. A Dose of Sanity by Sydney Walker III, M.D. 1996, pg 13/ Hoffman, Robert Science News, Vol. 122, September 11, 1982; Herringm M.M., Debate over ‘false positive schizophrenics’ Medicine Tribune, September 25, 1985. Pg 3; Koranyi, Erwin K., “Undiagnosed physical illness in psychiatric patients,” American Family Physician, Vol. 41, No. 4, April 1990
    5. Christensen RC, Grace GD, Byrd JC. Refer more patients for medical evaluation. Curr Psychiatr 2009;8:73-74.
    6. Biology and Human Behavior: The Neurological Origins of Individuality, Professor Robert Sapolsky, Stanford University, The Great Courses, The Teaching Company © 1996
    7. Does Stress Damage the Brain, by J. Douglas Bremmer MD, Biologivcal Psychiatry 1999; 45:797-805; Traumatic Amnesia, Repression, and Hippocampus Injury due to Emotional Stress, Cortisosteroids and Enkephalins by R. Joseph, Ph.D. Child Psychiatry Hum Dev. 1998 Winter;29(2):169-85
    8. Transdermal Magnesium Therapy ©2007 by Mark Sircus, Ac., O.M.D pg.5
    9. Discourse On Loving-kindness (Metta Sutta) by the Buddha

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  4. This is the defence of “psychiatry knows better.” The subtext is that psychiatry is such a subtle and intelligent field that no one except a psychiatrist could possibly understand it. While other doctors study the body, only the psychiatrist KNOWS the mind.

    In truth, I think, psychiatry often attracts a type of person who feels superior to others, who likes to claim esoteric knowledge that others will never have access to because those others are inferior. Psychiatrists’ grandiose visions of themselves make such ridiculous defence plausible to them.

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  5. This is similar to how some of the psychiatrists who most vehemently attacked our early research showing that child abuse is linked to psychosis are now saying ‘what’s all the fuss? We always knew that’ and are even putting their names on trauma-psychosis studies

    But the good news is that psychiatry HAS been forced to abandon many of it’s sillier ideas. It would of course render them a bit more likeable if they would apologise for their earlier stupidity and the damage it has caused to millions, but, as a colleague said to me when I was complaining about the hypocrisy of the latest trauma-psychosis converts ….. ‘John, you’ve won and you’re still bitching!’

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    • Based upon my research, John, and a confession to me by an ethical pastor who said the “dirty little secret of the two original educated professions” was that the psychiatric industry has historically been in the business of covering up child abuse for the religions, with the psychiatric stigmatizations and drugs for decades.

      I pray to God you continue in your research into the symptoms of child abuse and (in my case) concerns of child abuse being misdiagnosed as “psychotic.” And such misdiagnoses resulting in inappropriate neuroleptic treatment.

      Especially since the neuroleptics are known to actually cause the symptoms of schizophrenia, when inappropriately given to non-psychotic patients misdiagnosed with psychotic symptoms, by doctors seemingly wanting to profit off of child abuse victims, rather than dealing with the potential legal ramifications of such a situation.

      Medical proof of my concerns that the neuroleptics actually cause the symptoms of schizophrenia from

      “neuroleptics … may result in … the anticholinergic intoxication syndrome … Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.”

      I have concern the most common cause of schizophrenia may actually be misdiagnosis of adverse childhood experiences or child abuse as “psychosis.” Then these misdiagnoses of actual crimes being claimed to a brain diseases, being treated with the neuroleptics. And then the above mentioned anticholinergic intoxication syndrome, but psychiatrically industry denied, adverse effects of the neuroleptics, being claimed to be schizophrenia instead.

      It may be likely be that the most common etiology of schizophrenia is actually misdiagnosis of the central symptoms of neuroleptic induced anticholinergic intoxication syndrome, as schizophrenia. Which means the very drugs the doctors are using to try to cure patients’ psychosis, are actually what is actually what caused the psychosis in the first place.

      That’s what happened to me, I doubt I’m the only one.

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  6. Also, I really wish this would all lead to an epic legal battle. The people vs psychiatry. In any other situation, lying so blatantly and in the face of evidence, would be seen as culpability. They know they’re doing something wrong. They know they are hurting, even killing people, and even worse, ruining children’s lives with brain damage and permanent movement disorders, for the sake of their otherwise financially worthless careers…

    The only hope for justice, is that some day a great legal power will catch on to this and decide that the millions of brain damaged victims of psychiatry deserve justice.

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  7. This shrink is out to lunch. All I have to do is google chemical imbalance, and I come up with a gazillion examples put forth by both psychiatry and pharma. Youtube is filled with archived commercial advertisements, too. The internet has killed the memory hole, and the lame attempts by psychiatry to deny that they ever put forth this garbage will fail again and again.

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  8. Thanks for your response, but I don’t think this is a very fair summary of my piece, nor does it respond to my real point.

    I contrast the claim (A) “Depression is complicated, but it seems to involve disruptions to the levels of brain chemicals in some important way” with the claim (B) “We understand depression perfectly now, it’s just a deficiency of serotonin”.

    Then I admit you have amply proven people have made (A) but that far fewer people, and less important, made (B).

    I think that the supposed counterexamples you provide only prove my point. Going through the first couple:

    >> “The brain’s serotonin receptors are at abnormally low levels in depressed people and that antidepressants work by increasing serotonin levels in the brain.”

    But when I look up the press release you are citing, the very first sentence is “Little is understood about how depression makes people feel sad, but neuroscientists do know that the brain chemical serotonin is involved.” Further, this is a study of exactly the sort you originally claim doesn’t exist – evidence for the involvement of serotonin other than the effectiveness of SSRIs.

    >> “Low serotonin levels are believed to be the cause of many cases of mild to severe depression.”

    Again, specifies “believed to be” and “many” (rather than all) cases. Again, cites the non-SSRI evidence you claim doesn’t exist. Also, the site appears to be Bristol University Chemistry Department’s “Molecule of the Month” page, which has no relation to any psychiatrist.

    >> “A current Harvard Medical School special health report, “Understanding Depression”, explains that, “Research supports the idea that some depressed people have reduced serotonin transmission. Low levels of a serotonin byproduct have been linked to a higher risk for suicide.”

    If you read this report, the very first sentence is “It’s often said that depression results from a chemical imbalance, but that figure of speech doesn’t capture how complex the disease is.” It then goes on to present various theories, including the serotonergic one, but specifies that this is one of many causes and explains exactly what research (beyond SSRI-effectiveness) supports it.

    Given that your first three examples all support my point, I’m not really sure what you’re trying to do here. I would just recommend to everyone reading this that they look at my blog post rather than getting their impression of it from how it was presented here.

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  9. Scott Alexander: Your post is extremely long and covers a lot; I do not claim in my post to be providing a complete summary of every issue and point. I also encourage people to read it themselves, which is why I posted a link to it.

    Yes, you’re right, many psychiatrists, media, pharmaceutical companies and others promoting the serotonin deficiency theory of depression have often included generalized, softening “qualifiers” and “equivocations” such as the ones you quoted, even as they have also made those very bold, unequivocal claims explicitly intended to persuade that I quoted. Taken in full context, then how are such qualifiers different than brash infomercials on television with legal disclaimers like, “not all results will be the same for all people”?

    I know of no one (certainly not me) who has ever said that there were never any studies making tenuous, feeble attempts to draw links between serotonin levels and depression in different ways — there were hundreds, I believe (I haven’t counted) as the psychiatric community and pharmaceutical industry made enormous efforts to try to prove the theory or buttress its apparent validity in the public eye. And as I note, those are still being produced today. What critics have often correctly pointed out, however, is that the main, strongest argument that psychiatrists have often used in support of the low-serotonin theory has always been that SSRIs allegedly boost serotonin levels. Of course, most of the public has never known that SSRIs have barely beaten placebos in clinical trials, so they’ve not been able to understand the true spuriousness of even that argument.

    I notice that your argument has now changed to “far fewer people” and “less important” psychiatrists made such claims, rather than none at all made such claims. Very well; apparently we would now only potentially disagree on subjective notions such as how many is “fewer” and how unimportant is “less important”, rather than disagreeing on the main issue at hand. And then Leo and Lacasse’s question becomes all the more significant: Where is the evidence that the “important” psychiatrists were vigorously trying to correct the public record and clarifying that these were only weak hypotheses with no compelling evidence to support them instead of weighty theories with ever mounting evidence to support them?

    And that brings us to the critical factual gap in your whole argument: How do you account for the fact that the vast majority of media and the public for many years believed that low serotonin could cause depression? Did they just make it up on their own, without ever consulting any “important” psychiatrists?

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    • I agree with Rob – whether these things were “claimed” by “mainstream psychiatrists” or whether they merely stood by and allowed this gigantic misimpression be spread without a word of caution or contradiction is not that important. What is most relevant is that psychiatry benefitted both financially and in terms of status from this belief, and they either actively or tacitly approved of it, depending who you talk to. Bottom line is that many if not most consumers/survivors who have directly interacted with mainstream psychiatrists have been told that a “chemical imbalance” is a causal factor in their depression (or almost any other “mental illness”).

      It is also interesting that Scott does not acknowledge the misdirection involved even in the “chemical imbalance” concept itself, which he seems to acknowledge is promoted by mainstream psychiatrists. It it really better to say, “We don’t understand this complex disease of the brain” while still assuming it IS, de facto, a disease of the brain when there is no convincing evidence that any particular disease state is involved, and while there is HUGE piles of confirmatory evidence that trauma is a robust predictor of almost any “mental illness” you can name?

      The issue is not the specifics of a “serotonin imbalance.” It is the continued insistence that somehow, with more research, we will eventually “prove” what mainstream psychiatrists really want to believe – that depression is ultimately a primarily biological “disease” that requires drug “treatment.” This premise, in my view, has long since been proven false. The “complexity” of depression as a “brain disease” is observed largely because the researchers are not bothering to take in the myriad social and psychological and even non-brain-related physiological factors that are almost always involved.

      — Steve

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  10. I was curious so I did some searching. The following quote was the closest I found to a direct statement regarding low levels of serotonin as a cause:

    “These data indicate that low serotonin levels alone cannot cause depression. However, serotonin does have a direct effect on mood, and low levels of serotonin contribute to the etiology of depression in some depressed patients. ”

    J Psychiatry Neurosci 1993 Nov; 18(5):235-44

    But in reading the 2005 PLoS Medicine article linked to in the post, it appears to support what Scott Alexander is saying at least as far as the medical community’s literature is concerned:

    “To our knowledge, there is not a single peer-reviewed article that can be accurately cited to directly support claims of serotonin deficiency in any mental disorder, while there are many articles that present counterevidence. ”

    Of course that still leaves the question on why the marketing material was not attacked by the same community. There are many who are in my face with what “science says” and who willing mock those who question it, but here it was given a pass. I can only surmise that it was a matter of convenience for both physicians and patients.

    With that said, I support learning from history and using that as a guide but not in dwelling on it to drive a point home. And this is only because I find the present to have enough issues of its own.

    The most recent meme I have experienced with several physicians and one neuropsychologist (no psychiatrists involved since I’ve never seen one) goes as follows. I tell a physician about my fatigue > they tell me that haven’t found a marker for a psychical illness > they say antidepressants > I give them a WTH look > immediate words are “antidepressants are safe”.

    Why are they saying that when it’s not in response to a question I’ve asked nor even the reason for my WTH look?

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  11. That’s supposed to be “…a marker for physical illness…” in my comment above, although I suppose it could equally apply to a psychical illness as the neuropsychologist didn’t find any evidence of that either.

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  12. Y’all just dunt geht it, doodz.

    At first, depression was caused by a lack of paddling, hot drops and laziness. (See “Great Expectations” for the psychic energizing abilities of swallowed acetone. Maybe it alters neurotransmitters as well.)

    I believe this breakthrough was followed by liver flabbiness and yet more general lassitude, initially discovered by
    JK Jerome. His story “Three Men in a Boat” is a fine example of MDD cured by taking a ludicrously bad boat voyage (_don’t_ get out of the boat, man) then returning home. Liver and neurotransmitters completely cured, all’s well with the world once more.

    “Are you a Bromide or a Sulfite?” No matter, either one cures bipolar. Combine with “Is Sex Necessary?” and you have a sure fire cure for SAD. And, the bromide is probably better at reuptaking everything the brain has to offer.

    Aspirin quickly fell by the wayside: witness “Death of a Salesman”. Linda only gave Willy two tablets when he needed a steady 8-week regimen to set his norepinephrine on fire! Score: Aspirin 0, death by suicide 1.

    In the meantime, big pharma develops an experimental TB treatment which also seems to energize some patients. They _may_ have stumbled across an actual anti-depressant! But Kenneth, what is the frequency? (In easy to follow words, why does it work?)

    60+ years later we don’t know for certain, although there are theories galore. Granted that it is for an antidepressant which is no longer in use, you’d think we’d have a very good understanding as to how it works. And just why was that approach (inhibition of diamine oxidase, if that indeed was the preferred random side-effect du jour) abandoned? MAOI inhibitors sound sorta-kinda similar, but to me that’s like saying a hemoglobin inhibitor is similar. Inhibit something! Anything! You’ll get it eventually… you’ll see… prostaglandins… adrenals… xycarbalaise…

    So then we pick on neurotransmitters. Makes sense, right? They transmit stuff, so if we adjust them something will happen. We think. Oops! If we just tweak dopamine all over nothing much will happen unless we give them 1500mg of lovely pink diphenhydramine, in which case they get to see hallucinations of limbless men in laundry cleaner bags. Not much of an antidepressant, but it sure improves your sex life!

    Alright, let’s get serious. Selectivity! Brilliant! Genius! No more bad hallucinations… Mostly.

    I challenge people to tell me, if dopamine is tied to depression, why Benadryl doesn’t do jack shit for it. If it’s serotonin, L-tryptophan.

    Anyone up for a round of psychotherapy, Carl Rogers-style? It really works, but it takes time, energy, commitment and love. No quick fixes; life is not a Jack-in-the-Box restaurant. You want to be awesome? WORK FOR IT.

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  13. Great posting. Psychiatrists have promoted the chemical imbalance falsehood for 5 decades, as have many drug companies, family physicians/GPs, some psychologists, some therapists, some aspects of the nutrition industry, and many public figures. I address this and many related issues in detail in my latest book, Foreword by Robert Whitaker, to be published 02 September 2015, “Depression Delusion Volume One: The Myth of the Brain Chemical Imbalance”. “Depression Delusion” refers to the bizarre fact that the brain chemical imbalance falsehood meets all of psychiatry’s DSM5 criteria for a delusion. Feel free to contact me at [email protected] for further information.

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  14. We are glad that Dr. Alexander has looked into how the chemical imbalance theory has been portrayed. One question that we think his blog raises is: If the pharmaceutical companies and psychiatrists have not promoted this theory then who did? It is hard to argue that it has not become imbedded in pop culture? How did this happen? The misguided media?

    One thing that we would like to point out is that for the most part the terms “chemical imbalance theory” and “serotonin theory” are pretty much interchangeable in the popular press. Over the past several decades the profession’s focus has moved from implicating norepinephrine, to dopamine, to serotonin, to a combination of all three, or two, etc.. Some in the media use the term “chemical imbalance” while others use the term “serotonin imbalance.” And even then they all fall under the “biological theories” of mental illness. Of all the transmitters, serotonin has probably gotten the most credit simply because of the commercial success of Prozac. In our papers, whatever we have said about the serotonin theory applies equally to all the other transmitters. To say that an alteration in dopamine is the cause of depression is just as problematic as saying an alterations in serotonin is the cause. We imagine that when it comes to the companies, their belief in which transmitter is the most important is strongly correlated with the mechanism of the drug they are promoting.

    But more importantly, we think the way Dr. Alexander presented the theory is subtly, but importantly, different from how the theory was originally proposed. In the original presentation, the chemical imbalance was presented as the cause of the depression, but Dr. Alexander presents it as a result of the depression. I think there are very few people who would argue that emotional stress can lead to biological changes. However, this is not what the “chemical” or “biological theories” have stated. Here is how it is worded in Up-To Date: “Mood disorders, such as depression and bipolar disorder, are caused by chemical imbalances in the brain.” As Seymour Kety, the biological psychiatrist behind the schizophrenia adoption studies, stated: “there are now substantial indications that serious mental illnesses derive from chemical rather than psychological, imbalances” (See Kety, It’s Not All in Your Head, Saturday Review, 1976). Here is the wording from Nancy Andreasen’s 1983 book Blaming the Brain. The important point here is how she stresses that altered biology is the cause:

    “1) The major psychiatric illnesses are diseases. 2) These diseases are caused principally by biological factors and most of these reside in the brain. 3) As a scientific discipline, psychiatry seeks to identify the biological factors that cause mental illness. 4) The treatment of these diseases emphasizes the use of somatic therapies.” (See page 29 in her book for a more complete discussion).

    All of her statements are up for debate, yet she lays out a simplistic set of steps that leads readers to the idea that emotional distress is caused by faulty biology, which needs to be treated with a medication. Granted, she doesn’t use the word “chemical imbalance” in the above quote but in 1983 when it came to “biological factors” the dominate theories of psychopathology were in reference to transmitters. Later on in her book she refers to the Catecholamine Hypothesis as the “cause of affective disorder.” Her statements are very much in line with the famous Zoloft ad of the miserable ovoid creature with a chemical imbalance who is miraculously cured by a medication.

    We agree that when it comes how the profession currently discusses depression that it has moved beyond transmitters and onto other theories, such as alterations in circuits. However it is important to point out that just these are also only theories. As just one example of how comments about circuits have replaced the old promises of chemical imbalances, in a 2012 blog post Thomas Insel stated: “mental disorders appear to be disorders of brain circuits…” Yet, later on in the very same blog post he states, “In truth we still do not know how to define a circuit.” If it was wrong to tell patients that their depression was caused by a chemical imbalance, then it would seem to be wrong to tell them that their depression is caused by faulty circuits. For an excellent discussion of the Biomedical Model we recommend this paper by Brett Deacon titled: “The Biomedical Model of Mental Disorder: A Critical Analysis of its validity, utility and effects on psychotherapy research.” Available at:

    We welcome any evidence from Dr. Alexander that alterations in serotonin or any other neurotransmitters are the cause of depression.

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    • The claims of psychiatrists about this discipline being based on neuroscience are laughable. We can’t figure out how a brain of C. elegans works (despite knowing all the 200 or so neurons by name and knowing their connectome) lest anything more complicated. We have a lot of interesting observations from patients and animal models but we can also have a mouse without cortex which behaves just fine and we don’t even know why would it need this kind of crucial structure at all. We have people born without large portions of their brains who have relatively normal lives and others who are in vegetative state and we can’t really explain that very well either. And these are rather huge things – trying to explain personality and mood through neurobiology is laughable quackery at this point.

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  15. Rob Wipond –

    Having reread the recently re-posted Leo and LaCasse article and Dr. Hickey’s current blogpost first, I have to say that your AP style here is very good journalistically. Straight through on track with the ideal of unbiased reporting. Scott Alexander has the problem facing many geniuses, that of mistaking the unhelpful facts as mere opinions.

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