A whiff of madness

For a short time, the scientific community was excited about the smell of schizophrenia.

In 1960, a curious article appeared in the Archives of General Psychiatry suggesting not only that people with schizophrenia had a distinctive smell, but that the odour could be experimentally verified.

The paper by psychiatrists Kathleen Smith and Jacob Sines noted that “Many have commented upon the strange odour that pervades the back wards of mental hospitals” and went on to recount numerous anecdotes of the supposedly curious scent associated with the diagnosis.

Having worked on a fair few ‘back wards of mental hospitals’ in my time, my first reaction would be to point out that the ‘strange odour’ is more likely to be the staff than the patients but Smith and Sines were clearly committed to their observations.

They collected the sweat from 14 white male patients with schizophrenia and 14 comparable patients with ‘organic brain syndromes’ and found they could train rats to reliably distinguish the odours while a human panel of sweat sniffers seemed to be able to do the same.

Seemingly backed up by the nasal ninja skills of two different species, science attempted to determine the source of the ‘schizophrenic odour’.

Two years later researchers from Washington suggested the smell might be triggered by the bacteria Pseudomonas aeruginosa but an investigation found it was no more common in people with schizophrenia than those without the diagnosis.

But just before the end of the 60s, the original research team dropped a scientific bombshell. They claimed to have identified the schizophrenia specific scent and got their results published in glittery headline journal Science.

Using gas chromotography they identified the ‘odorous substance’ as trans-3-methyl-2-hexenoic acid, now known as TMHA.

At this point, you may be staring blankly at the screen, batting your eyelids in disinterest at the mention of a seemingly minor chemical associated with the mental illness, but to understand why it got splashed across the scientific equivalent of Vogue magazine you need to understand something about the history, hopes and dreams of psychiatry research.

For a great part of the early 20th century, psychiatry was on the hunt for what was called an ‘endogenous schizotoxin’ – a theorised internal toxin that supposedly triggered the disorder.

A great part of the early scientific interest in psychedelics drew on the same idea as psychiatrists wondered whether reality-bending drugs like LSD and mescaline were affecting the same chemicals, or, in some cases, might actually be the ‘schizotoxins’ themselves.

So a chemical uniquely identified in the sweat of people with schizophrenia was big news. Dreams of Nobel Prizes undoubtedly flashed through the minds of the investigators as they briefly allowed themselves to think about the possibility of finally cracking the ‘mystery of madness’.

As the wave of excitement hit, other scientists quickly hit the labs but just couldn’t confirm the link – the results kept coming in negative. In 1973 the original research team added their own study to the disappointment and concluded that the ‘schizophrenic odour’ was dead.

Looking back, we now know that TMHA is genuinely an important component in sweat odour. Curiously, it turns out it is largely restricted to Caucasian populations but no link to mental illness or psychiatric disorder has ever been confirmed.

The theory seems like an curious anomaly in the history of psychiatry but it occasionally makes a reappearance. In 2005 a study claimed that the odour exists but is “complex and cannot be limited to a single compound, but rather to a global variation of the body odor” but no replications or further investigations followed.

I, on the other hand, am still convinced it was the staff that were the source of the ‘strange odour’, but have yet to get research funding to confirm my pioneering theories.

Now available in Italian L’odore della schizofrenia
(thanks Giuliana!)

27 Comments

  1. Raine
    Posted September 12, 2011 at 12:04 am | Permalink

    LOL!!! I was diagnosed as a schizophrenic in 1985 in South Africa and was under “the microscope” for quite a while and most certainly enjoyed being able to laugh about the posts regarding “Mental Illness” stuff, and became quite tame in the various “cages”… however, you might like to read a letter to me from my Doc, posted in my biography at southafricanartists.com under Raine Carosin… yeah, fashions change, but, strangely enough, history also repeats itself in cycles of a set amount of years… ah, the synchronicity of it all… but, gotta keep my feet on the ground, coz it’s scary to be… well, just to BE is scary!!! LOL!!!! Thanks for taking the time to post this story…

  2. Posted September 12, 2011 at 1:48 am | Permalink

    “Serum cortisol and DHEA-S levels may be used as a biological marker for the diagnosis of schizophrenia; however, further studies with larger sample sizes are warranted to support this finding.” — Serum cortisol and dehydroepiandrosterone-sulfate levels in schizophrenic patients and their first-degree relatives. Yıldırım O, Dogan O, Semiz M, Kilicli F. Psychiatry Clin Neurosci. 2011 Sep 6. doi: 10.1111/j.1440-1819.2011.02252.x

    This would explain why rats could be trained to detect odor differences as they have been with fear etc., and explain failure to replicate with humans who cannot be trained to discriminate at such invariably changing levels of hormone metabolism — except as we have shown with a metabolite of DHEA and sex difference in women’s responses to an androstenol/androsterone mixture.

  3. Emmy
    Posted September 12, 2011 at 5:12 pm | Permalink

    I’m sure it was disappointing for “researchers” who want to treat the mentally ill like they would some poor, wretched lab animal.

    • Posted September 12, 2011 at 6:16 pm | Permalink

      I doubt that any researcher ever wanted to treat mental illness in a person the way they would treat a lab animal. The problem is the failure to recognize cause and effect relationships, especially those that include natural body odors that dictate the behavior of other animals. Rats can sniff out differences, but humans can’t? That’s utter foolishness. Clearly, the problem is that rats are easier to train for odor detection. Like them, however, we can detect genetically determined differences in the odors of our conspecifics (other people), which is more than suggestive of the likelihood that schizophrenics have a discernible genetically determined odor. I have discussed this with a few well-educated researchers who cannot get funding for research that might prove cause and effect. But most of us agree, we should not need to demonstrate the very same thing in every species to extend concepts across animal species.

      • Emmy
        Posted September 12, 2011 at 6:25 pm | Permalink

        I didn’t make my point very clear. Let me try again. Here is the original title of the article:

        “Demonstration of a Peculiar Odor in the Sweat of Schizophrenic Patients”

        To understand my point, simply replace the words “schizophrenic patients” with “black people”. Now do you understand what I mean?

    • Posted September 19, 2011 at 11:25 am | Permalink

      Please don’t classify researchers in this way- I was a researcher for many years and I have also been mentally ill. We never treated anybody in an inhumane manner, always asked permission before talking about personal information and always gave people the option of not answering or of asking us to leave. Researchers are usually hunting for some characteristic of people with a diagnosis which would enable a medicine to be developed. Then the medicine could maybe “neutralise” some chemical in the body which makes people ill/not function in the usual way. The clues are obviously very hard to find as we haven’t invented any drugs that work without side effects. However, it’s far better to have a mental illness these days than in the past when people were chained up and hosed down. Researchers HAVE found some drugs that help some people and I’m personally very grateful for modern antidepressants.

      • Emmy
        Posted September 19, 2011 at 4:58 pm | Permalink

        I’m a researcher as well (animals, not people) I think it’s clear that I did not mean all researchers. I think we have to ask ourselves if people with serious mental illness are able to consent to such an experiment. The idea that this could lead to a cure is stretching it. Is the experiment inherently unethical? No, but if I were involved I’d make sure the idea did not get out into the public eye unless it yielded important results, which it obviously did not. When you’re working with a population who are this vulnerable to public degredation I think it’s obvious you have to be more careful what you announce. It amazes me how supposedly intelligent researchers could be so clueless.

  4. Raine
    Posted September 12, 2011 at 6:23 pm | Permalink

    About the odours… well, I challenge anybody to the fact that when you are usually taken by force (against one’s own will) and put in a place full of others who have experienced the same panic, no doubt there is the sweet smell of sweat, tears and other body odours… i remember equasing my experiences at mental institutions as being very much like what the holocaust was like… I was petrified and scared and lost and all i wanted to do was to be free again… yup, there are smells, that’s for sure…

    • Posted September 12, 2011 at 7:01 pm | Permalink

      Indeed, and those smells would have correlates with levels of DHEA and cortisol, and their metabolism, as suggested. The metabolism crosses species boundaries — except that levels of DHEA-sulfate are higher in humans than any other primate.

  5. Posted September 12, 2011 at 6:35 pm | Permalink

    My first thought was “It must be something in the medicine they are taking”.

    Anyway my brother has schizophrenia but I never perceived any kind of different smell from him.

  6. Raine
    Posted September 12, 2011 at 7:34 pm | Permalink

    sorry, didn’t know, or realise, but still, logically, any peoples put into a place that they don’t want to be will or against their will, emit odours of fear… dogs can even smell fear… sorry if I’m off the point, but I’m doing a few things around the house and emails intermittently, so, and, also struggling with a headache… let me rather sign off and leave you with this thought: my experience has taught me that people will do anything to keep the money/funds/grants coming in to feed and clothe themselves, to the point of even experimenting on their own … that’s my thought on the world as a whole, and knowing a bit about being a “mental patient”…

    • Posted September 12, 2011 at 10:19 pm | Permalink

      I think that the problem is people who will do anything except familiarize themselves with the basic principles of biology. Levels of biological organization: the gene-cell-tissue-organ-organ system pathway, which is required to link sensory input to behavior, are all but ignored in favor of psychobabble that links cause and effect, but only for the relatively uneducated. Not that anyone needs this education. But, those who bill themselves as psychologists and psychiatrists should be more responsible than the lay population In this regard, I reviewed Janov’s “Biology of Love.” It markets “Primal Scream” and the “rebirthing therapy,” which led to the death of a 10 year old girl in Denver. Clearly, those who should be patients may be running the asylums. And perhaps schizophrenics and racists should be afraid of anyone who does not smell like them.

  7. Posted September 12, 2011 at 8:17 pm | Permalink

    I recall the smell of schizophrenia being mentioned in one of those Thomas Harris novels, IIRC. (Red Dragon perhaps?)I wondered then if it was true. Having had contact with a number of diagnosed schizophrenics in my time, I’ve never noticed anything unusal scent-wise, though, or at least specific to any psychiatric illness.

  8. Posted September 12, 2011 at 10:28 pm | Permalink

    Hi, first time caller..
    An interesting post. Leads me into the thriving area of metabolomics and the search for common markers for all sorts of different conditions via various biological fluids including sweat. Success? We’ll see but I assume its going to be complicated given the variables involved.
    At least one condition with a psychiatric presentation has a potential odour element to it, PKU (phenylketonuria). Indeed it was smell which lead the famous Dr Folling to conclude the presence of phenylacetate / phenylpyruvic acid and determine the onwards biochemistry. With the advent of the Gutherie test, most people diagnosed with PKU would not probably present with any odour as a result of their lifelong dietary changes.

  9. Raine
    Posted September 12, 2011 at 11:05 pm | Permalink

    …with all that’s happened to me, in and out of asylums, i’m terrified of all people, and it takes ages for me to trust… but I do like people who smell like cookies… and as for the “insane” running the lunatic asylums, well, you have a valid point there, as most people who become “helpers” are the ones who actually want to help themselves sort out a problem or two in a “profitable” way, because they know that if they don’t deal properly with themselves, they will end up in an institution or something, being a patient, and it’s like cowboys and indians – nobody wanted to be the indians, all us kids wanted to be the cowboys with our guns and shoot the indians… who wants to be a loser, and besides, the survival instinct within even a child is extremely strong… nobody wants to be the patient… ah, i’m babbling and should be getting on with my chores… :-}

    • Posted September 13, 2011 at 12:08 am | Permalink

      At least it’s not psychobabble! And I have a paper about socioaffective neuroscience to complete.

      • Raine
        Posted September 13, 2011 at 12:38 am | Permalink

        the biggest word i know that boggles the mind is supercalifragilisticsexpialidocious, and i don’t even know how to spell it… that’s all I can think of at this moment that makes sense to me… ah, if music be the food of love, play on, maestro, play on, but what buys that food…????? anyways, i’ve had such fun tonight with this subject, but it’s bedtime, so goodnight dear fellows, enjoy yourselves and strive for happiness… thanks for letting me play…

  10. Mike Roberts
    Posted September 13, 2011 at 1:28 am | Permalink

    Around 1979, I published a paper in The Journal of Orthomolecular Psychiatry, in which I proposed what I thought was a plausible mechanism for the presense of TMHA, starting with an abnormal methylation of catecholamine neurotransmitters that are implicated in schizophrenia.

    By now, the working hypothesis coming from this idea would be this:

    Catatonic schizophrenics (who were the patients with the malodorous compound) have a defect in the COMT gene, resulting in methylation of catecholamine neurotransmitters in the para-, or 4-position, instead of the meta-, or 3-position. This abnormally methylated compound has transmitter activity that the normally methylated compound does not, giving rise to the symptoms common to catatonia.

    Instead of, or in addition to, further metabolism to end-products that get excreted in the urine, the metabolite breaks down, either by chemical decarboxylation and oxidation or by the same steps, mediated by Pseudomonas in the axilla, to TMHA, which may be excreted in sweat.

    It would be interesting to pick this up again, especially since there are so many new tools available as avenues for research, that were not around in the late 1970′s.

    Thank you for writing this article.

    • Posted September 13, 2011 at 3:35 pm | Permalink

      Mike,
      I would like to see someone pick back up on this also, given what is now known about the epigenetic influences of odors on hormones; of hormones on behavior; and of odor-driven behavior on the behavior of conspecifics in non-human animals and in humans. Given the finding indicating that rats could distinguish differences in the odors of schizophrenics, and the studies that show their ability to sniff out many other disease processes, combining this with evidence from molecular biology that we have the same abilities (although we don’t use them) would lead to the rather obvious conclusion that all species are dependent on olfactory/pheromonal indications of both mental and physical fitness, or they could not determine who or what might be the best mate. Too bad there’s no funding for such studies, largely because so many people think that we are primarily visual creatures.

  11. Posted September 19, 2011 at 11:12 am | Permalink

    Interesting about the smell in old psychiatric wards. I smelled something odd in 2 different psych hospitals in 2 states of Australia in the early 1970s (as a psychology student). At one in NSW I mainly smelled it in the mixed diagnosis chronic back wards where all types of people with mental retardation, and/or organic disorders (eg. dementia from hydrocephalus), and/or traditionally classified psychoses. In South Australia I smelled it in the rather primitive chronic psychosis ward (long since closed, thank goodness), where everyone was in separate “cells” with bars on the windows- so it wasn’t a collective smell as I thought in NSW. I couldn’t relate the smell to anything, and like several people above, attributed it to a combination of natural sweat smells and medication. I think most people would have been on chlorpromazine at the time. Years later it occurred to me that the smell was like feces without the sulfurous, pungent, “cutting” effect (meaning the way that smell takes over all others around you!). There was no ammonia aspect to it either, so it can’t have been due to urinary incontinence. I know many of the people in NSW had fecal incontinence, but that made individuals smell in the usual way. This other smell was a vegetable-like, dried feces one, not strong, just persistent. When I worked in a general hospital psychiatric ward in the 1980s & 90s [swift patient turnover], there was no distinctive smell at all- nor from the staff! I thought the smell was real in both locations – not created by me as part of some “prejudice” – I’ve always been quite warm & friendly towards people with psychiatric difficulties and get on well with them. However, I’ve retained very strong “scent imagery” & think I could match the smell to something now if I ever smelled it again.
    I wonder what it’s all about?

  12. Raine
    Posted September 19, 2011 at 10:17 pm | Permalink

    Hi, I’m back… Been reading all the entries and what a lot of information: it sure is interesting, and I’m thinking about the dogs they have that can sniff out cancer, and drugs and stuff… What I’d like at this moment is a pack of wolves that could smell out the cruel and horrible “people” and rush them straight into a cell… sorry, but, working for an animal charity and hearing about yet another bludgeoning of an animal just because it peed on a couch has me inscensed… (my spelling is atrocious!) and I bet I have a different smell to me now than when I’m cool, calm and collected… i know that there are certain smells that when I smell them or remember them, or when they “suddenly” come into my nostrils, they bring memories, and I guess my smell would depend upon whether I am happy or sad or frightened by that smell… I know I can’t stand hospital smells and avoid them like the plague… so, smells can also be triggers for certain behaviour, as in lavender to calm the nerves in some people, and ether to knock one totally out… I do hope that you all carry on this discussion as it is very interesting. I was intrigued when a nursing sister at the institution I was in said that schizophrenics could be identified by something in their blood… Yeah, must get on with my stuff… Warmest wishes, Raine

  13. Laura
    Posted September 24, 2011 at 3:58 pm | Permalink

    Fantastic article w/(mostly)thoughtful responses. As a hyperaware and hypersensitive individual with mental illness (as well as an entire family of mentally ill peoples) I can affirm that not only does schizophrenia have a distinct scent, I believe and would postulate that all mental illness creates its’ own smell. My sister, who is schizo-effective and has disassociative disorder/PTSD (along with a bevy of personality disorders) has an acrid vinegary scent that I have also detected while staying as a patient in a psych ward. Depression smells overly yeasty, like too much bread in too small a space. My own anxiety kicks up something much like celery and acid. Diet, genetics, ethnic background and environment probably due contribute as well, but in my experience, there does seem to be a commonality, regardless of diet or ethnicity. The import of this does not strike one at first until you consider that if a specific chemical is released through the pores as it breaks down, then that chemical had to originally come from somewhere else. If that “somewhere else” can be found, perhaps we will see new and improved treatments for mental illness. I am one of the lucky ones in that I can monitor and take care of my own mental flaws. True, I am constantly tormented, but I deal with that with lots of exercise. But I digress. Great article, I absolutely love mindhacks.

  14. Raine
    Posted September 25, 2011 at 12:34 am | Permalink

    me love mindhacks totally – i’m sure herein lies the cure to many ailments, imaginary; hereditary; real-but-not-verified; scary and downright out of this particular world… I would love it if there is some stuff out there for discussion here under subject: SYNCRONICITY… I find it totally fascinating how I seem to go in circles so that I recognise that I’m in a particular cycle again and sometimes I am even able to recognise the “symptoms” or “signs” of the cycle to know what to do next or what NOT to do next, rather…. please keep mindhacks going and please, don’t charge us ever, coz i have NO MONEY… and I need to be able to “read” other people’s thoughts, whether they are top of the class or backseat drivers… I need so much to be able to relate to others and find similarities in thought so that I am able to deal in a better fashion with “daemons” (which I believe are just old, very old, spirits having a badhairday! LOL!)… anyways, this steers from the subject… on with the mind… :-}

  15. Raine
    Posted September 25, 2011 at 7:49 pm | Permalink

    …been pondering… it must always be kept in mind that in controlled environments, the patients have hardly much choice as to their intake of breakfast, lunch and supper, and so they consume and exhude the same protein and vegetation… like the smells from individuals who consume onions after a long abstinence from the veg/fruit, or garlic or rum… it all plays a big role. There’s also the rumour that some institutions put “drugs” directly into the foods that are consumed by the patients… well, those are my thoughts up to date on this subject… warmest wishes…

  16. Raine
    Posted October 4, 2011 at 10:37 pm | Permalink

    I found this interesting article on the web: url pasted below… It’s not making me rush off to a Doc, but it is a couple of points of view: (ps, didn’t copy the whole article, so you have to go to the url for the complete goodie…)

    “By all means, a phantom smell could mean something serious,” says the psychiatrist and nationally recognized smell and taste expert. “It absolutely needs to be evaluated. It could be a tumor – that’s on the top of your list of things to rule out – but it could also be a cyst or some infectious agent housed in the area of the brain where the smell is processed.”
    Brief episodes of phantom smells or phantosmia – smelling something that’s not there – can be triggered …”

    http://bodyodd.msnbc.msn.com/_news/2009/11/10/4380036-phantom-smells-may-be-a-sign-of-trouble

  17. Catherine
    Posted September 11, 2012 at 5:01 am | Permalink

    I have been intrigued by this subject for decades since my teenage son definitely emitted this odd pungent smell after school and work. The GP couldn’t explain it. He was subsequently diagnosed as schizophrenic and has been on drugs ever since. I wrote to Abram Hoffer who replied that it was a common “mousy” smell in the old wards, but couldn’t explain it either.
    I have always wished for more serious research into this phenomenon as it may hold some answers. But then – the drug companies wouldn’t be interested in finding such answers – could threaten their stronghold on the drug market.

  18. Posted October 27, 2012 at 2:35 am | Permalink

    My mother has suffered from fairly extreme schizophrenia all my life, she is now in her early 70′s. Her clothes have always had a very strong odour even when she was young. It is a smell that I have never smelt on anyone else and does increase in intensity when she is close to an episode. I thought that this could be down to the fact that her hygiene is not the best as is often the case with those who have a mental illness, but even now that she receives hone care nursing she has the same smell. I have also heard comments from other people that people with extreme depression give off a strange smell as well. It is something that I have always remembered about my mother from my childhood so it could just be her or there is something in the research.


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