Saturday, September 28, 2013

Brainwashed by a microbe?

Toxoplasma gondii (source: A.J. Cann)

It’s long been known that many organisms are parasites, i.e., they survive by living off a host. In recent years we’ve learned that some of them can improve on their life strategy by manipulating their host’s behavior. A fungus, Ophiocordyceps unilateralis, will invade an ant’s brain and direct its host to go to the right height above ground, lock itself into position … and die (Ophiocordycepsunilateralis, 2013). A tapeworm, Schistocephalus solidus, will infect a fish and cause its host to turn white and prefer the water surface, thereby making it an easy prey for a passing bird—the next stage in the worm’s life cycle (Fish diseases and parasites, 2013). A protozoan, Toxoplasma gondii, after being excreted in cat feces and then picked up by a mouse, will infiltrate the brain of its new host and neutralize the fear response to the smell of cat urine. The host thus becomes a way to get back into a cat’s gut—the only place where this protozoan can sexually reproduce (Ingram et al., 2013). 

Ants, fish, mice … The sequence is troubling. What about us? Have some microbes evolved to manipulate our brains? Perhaps, but it would be hard to prove. For one thing, we’re continually being infected by seemingly benign microbes that trigger no symptoms of infection, i.e., fever, pus formation, immune response, etc. They go about their business without our knowing they’re inside us.

For another thing, a microbe can permanently alter our mental wiring and then be removed from our body. The culprit vanishes from the scene of the crime and leaves only a few ambiguous clues. This is the conclusion of a recent study on Toxoplasma gondii. When mice were infected with a weakened strain of this protozoan, they were able to overcome the infection and clear all traces of it from their brains. Yet the behavioral change remained:

[…] our data indicate that infection with all three major North American T. gondii clonal lineages results in loss of innate, hard-wired aversion to feline predator urine in mice. […] permanent interruption of mouse innate aversion to feline urine is a general trait of T. gondii infection that occurs within the first three weeks, independent of parasite persistence and ongoing brain inflammation. (Ingram etal., 2013)

It seems that T. gondii moves around the host’s brain and alters many neurons without actually taking up residence in them, apparently by injecting specific proteins through the cell wall.

Although we’re not a natural host, T. gondii does appear to alter human behavior: 

Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two versions of Cattell’s 16PF, Cloninger’s TCI and Big Five questionnaires. Most of these differences increase with the length of time since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control study. […] Toxoplasma-infected male students are about 3 cm taller than Toxoplasma-free subjects and their faces are rated by women as more masculine and dominant. These differences may be caused by an increased concentration of testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the disease. (Flegr, 2013)

T. gondii is being studied for possible behavioral effects mainly because it has attracted so much attention. But we’re probably being manipulated by other parasites. “A large number of parasitic organisms probably exist in helminths, protozoa, fungi, bacteria, archea and viruses that may influence the phenotype of their human host even more than the Toxoplasma. These organisms are, however, still waiting for research teams to engage in a systematic study of their influence on the human host” (Flegr, 2013).

Where to look? Cherchez la femme. Sexually transmitted diseases have much to gain from altering host behavior. I would especially look at bacterial vaginosis, chlamydia, and vaginal yeast.


Fish diseases and parasites. (2013). Wikipedia

Flegr, J. (2013). Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma–human model in studying the manipulation hypothesis, The Journal of Experimental Biology, 216, 127-133. 

Ingram, W.M., L.M. Goodrich, E.A. Robey, and M.B. Eisen (2013). Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS ONE 8(9): e75246. doi:10.1371/journal.pone.0075246

Ophiocordyceps unilateralis. (2013). Wikipedia


Anonymous said...

John Ringo's latest book about The Zombie Apocalypse has behavior modifying viruses.

Beyond Anon said...

It even mentions ...

Put all that together with the pathogens we already know, like toxoplasmosis, modifying them to mess up the brain is easy.

Gottlieb said...

If the parasite leaves infected with a more attractive facial aspect, then it could mean that there was a good relationship of mutual aid. It seems that schizophrenia is 80% of heritability. It may be that some people actually have more genetic predisposition to develop the disorder. It could also be that some ants have evolved to be parasitized while others do not exhibit genetic predisposition.

Gottlieb said...

Okay, I exaggerated about the mutual aid. But I talk about the less severe cases and those that have traits moderate some of the symptoms of schizophrenia.

Sean said...

"The cat craze began with the cat shows in the late nineteenth century," [Torrey] explains. "And when I went back and looked at what we know about cats as pets, it corresponded almost perfectly to what we know about the rise of psychosis." I think Torrey is basically saying it's mainly down to cats, but there are description of schizophrenia in the Atharva Veda, and Hindus of 1400 BC didn't revere cats as far as I know

Flegr mentions some opposite effects in men and women. That might lead some to think there was a sexually transmitted manipulation going on. But there are also some opposite effects of toxo in humans from rural and urban areas according to Flegr.

In that Torrey set a lot of store on high rates of Schizophrenia in urban areas, what to make of there being opposite effects on rural and urban humans irrespective of sex?

I'm beginning to wonder if growing up in urban areas has a far more profound effect (apart from any pathogens) than has been realized. There has been some research suggesting that is the case: here.

As for sexually transmitted diseases altering human behavior; yes, where there was a lot of multi partner sexual activity such a disease could evolve. However, I have to wonder about how a disease from a sexually highly active population would adapt when it arrived in a monogamous population. I think in such an environment the putative disease would evolve an enhanced capacity for vertical transmission.

Sean said...

heaTaca123Correct link for effects of being brought up in an urban area here.

Anonymous I said...

Excellent post, Peter.

Carboxyl Hydra said...

Given that parasitism has evolved independently over and over again among plants and animals, is it possible that it exists among human beings as either memetic or genetic strategy? E.g., parasitic professions or (gulp) ethnic groups? Orwell's Animal Farm describes bureaucratic parasitism by the pigs:

Somehow it seemed as though the farm had grown richer without making the animals themselves any richer-except, of course, for the pigs and the dogs. Perhaps this was partly because there were so many pigs and so many dogs. It was not that these creatures did not work, after their fashion.
There was, as Squealer was never tired of explaining, endless work in the supervision and organisation of the farm. Much of this work was of a kind that the other animals were too ignorant to understand. For example, Squealer told them that the pigs had to expend enormous labours every day upon mysterious things called "files," "reports," "minutes," and "memoranda". These were large sheets of paper which had to be closely covered with writing, and as soon as they were so covered, they were burnt in the furnace. This was of the highest importance for the welfare of the farm, Squealer said. But still, neither pigs nor dogs produced any food by their own labour; and there were very many of them, and their appetites were always good.

ErisGuy said...

If being born that way exempt one from moral rules, does being infected carry the same exemption?

Anonymous said...

The Amygdala War: Toxoplasma gondii’s surgical strike against the amygdala

Sean said...

All kinds of things can affect the brain and the amygdala specifically, I already mentioned that living in a city affects its responsiveness, so does meditation.

Meditation can actually increase the amount of gray matter in the brain.

Peter Fros_ said...


Are there behavior-modifying viruses? T. gondii is a protozoan and the other behavior-modifying microbes seem to be fungi, worms, or other multicellular organisms.


Yes, there's always the possibility of commensalism. But a lot of parasites seem to have no problem with trashing their hosts.


Yes, cats are probably the main vector for T. gondii. A friend of ours advises against having cats if you want to have children. She says that cats carry pathogens that induce miscarriage or birth defects. I used to think she was paranoid, but now I'm not so sure.


Parasitism is a universal problem for human societies, at both the individual and group levels.


If you want to live in a society, you should be able to live by its rules. If, for whatever reason, you cannot live by those rules, you should be excluded from society. This is a point that many well-meaning people have trouble processing. Perhaps one cannot help being the sort of person one is. Nonetheless, society has a right to defend itself, and this right to collective defense includes the right to exclude.


I've seen that claim before, but there might be self-selection bias. People who meditate, and who persist on a regular basis, are not typical. I used to attend a Zen temple, and the people who kept at it for a long time seemed to have been a different group of people from the very beginning.

Anonymous said...

For a long time people figured that brain manipulation by t. gondii w/out evidence of oocysts was a silly argument. Not so after this latest research. Your observation that t. gondii is probably only one of many such parasites that can manipulate behavior w/out being noticed is spot on.

We may be the chosen final hosts for such parasites as are cats for t. gondii or the intermediary host as are rodents for those protozoa or we may be reproductive dead ends for many but still be subject to their machinations.

It seems more and more likely human male homosexuality that is the result of such manipulators, f not t. gondii, then something similar. (BTW, t.gondii is omnipresent in ovine flocks).

Sean said...

"However, genome-wide scans have revealed that genes most strongly associated with schizophrenia/bipolar risk are to be found in the mother's--not the sufferer's--major histocompatibility complex (containing the key genes for the immune system). See here and cited paper here. A recent review here. Schizophrenia strikes after puberty so sex hormones may be somehow implicated.

As I read it it's being suggested that all kinds of prenatal infections can trigger certain opposed immune responses that differ and result in a few types of brain damage, which produce just a couple of classes of syndromes. It does not seem established that differences between infection by a bug that is a manipulating brain changer (like toxoplasma) and a bug that is has not evolved for manipulation of brains are crucial in producing the specific behaviour of a paricular class of mental illness.

The best evidence for manipulation would be an epidemic of humans doing something that is contrary to their reproductive fitness, otherwise inexplicable, could spread an infection, and is specific (ie not part of a general pattern of behaviour, like schizophrenics having no concern with personal hygene). Personally, I think you have identified such a behaviour, and it exists in the real world. (not just in French farces or Catherine Millet's memoirs).

Anonymous said...

T. gondii moves around the host’s brain and alters many neurons without actually taking up residence in them, apparently by injecting specific proteins through the cell wall.

Oh, Peter. Neurons do not have a cell wall. "Plasma membrane", you surely meant.

Sean said...

Toxoplasma gondii and the blood-brain barrier involves intracellular transport, anon.

Schizophrenia is virtually unknown before puberty and the highest rates are in the early twenties, when sex hormones reach their highest levels and exert the maximum neuroexcitatory effect.

ACCORDING to G. Cochran: "Schizophrenia is more common in men than women – about 1.4 to 1." and there is a "higher rate of diagnosed schizophrenia among blacks... Afro-Caribbeans (as much as 15 times higher...)".

Men have more testosterone than women, and black Africans have higher levels of testosterone.
So, it has something to do with prenatal inflammation (that can be due to causes other than infection; see here) and sex hormones.

Matt said...

Morphometric face analyses of schizophrenics don't seem to be similar to the shape morphs for 2D:4D - -

"Both male and, particularly, female patients evidenced significant facial dysmorphology.

There was narrowing and reduction of the mid to lower face and frontonasal prominences, including reduced width and posterior displacement of the mouth, lips, and chin; increased width of the upper face, mandible, and skull base, with lateral displacement of the cheeks, eyes, and orbits; and anterior displacement of the superior margins of the orbits."

In general, if you search for 2D:4D and schiz you generally fin - "More 'feminized' 2D:4D phenotype has been demonstrated in schizophrenia versus same-sex controls."

This reflects the prenatal picture.

Serum t levels are not obviously high in identified schizophrenics, but there is some speculation present online that high serum levels can predispose to onset (and wouldn't necessarily need to be high after that).

One issue with women, men and schiz is that women much more often manifest borderline schizophrenia / borderline personality disorder, which most shares a genetic etiology with schiz out of various psychiatric disorders.

A major difference between these disorders is that the distorted thinking of BPD is layered onto the intentions, emotions and actions of other people, which may reflect and interaction of a basically similar problem with greater female tendencies towards negative emotion (neuroticism) and greater interest and affection in other people (agreeableness / sociability / interdependence).

Sean said...

G.Cochran again WHEN the normal bacterial flora of the colon are hammered by a broad-spectrum antibiotic, C. difficile often takes over ... bacteriotherapy, more commonly called a stool transplant, works like gangbusters, curing ~94% of patients."

I think a major problem for rogue bacterial vaginosis and vaginal yeast strains' sexual transmission would be the normal flora in the vaginal environment. I seem to have read somewhere that douching is likely to result in infections.

Still, it is interesting that "C. albicans traffics to and infects the brain by binding to gp96, a unique receptor that is expressed specifically on the surface of brain endothelial cells."

JayMan said...

@Peter Frost:

"I've seen that claim before, but there might be self-selection bias. People who meditate, and who persist on a regular basis, are not typical. I used to attend a Zen temple, and the people who kept at it for a long time seemed to have been a different group of people from the very beginning."

That's been my suspicion. So much health and well-being advice is tainted because it's based on worthless observational studies.

Ian said...

HIV might be a good candidate for investigation. Severe cognitive impairments are observed in sufferers, but it may be that more subtle behavioural changes predisposing towards risk-taking and hyper-promiscuity occur earlier.