Toxoplasmosis and Behavior

Last August I wrote an article about some extraordinary new evidence implicating Toxoplasma gondii in some psychological and psychiatric illnesses. Latent infection with Toxoplasma gondii is amongst the most prevalent of human infections and it had been generally assumed that it is asymptomatic unless there is congenital transmission or reactivation because a person has an immune system that has become depressed or compromised. That assumption is being completely re-evaluated. 

The article generated some extremely interesting correspondence and some spirited discussions.

Here is a very insightful letter from a physician:

Dear Dr. Petty,

I thought about the concept of psychological illness caused by a virus or other organism. I was wondering what would be the mode of dispersion of such a virus. Upper respiratory tract infections, skin and gastrointestinal infections spread by cough, by touch and hand to mouth respectively. How would such a brain virus or protozoal organism promote itself? Of course it could be by the above methods but it seems that there should some way that the specific disease process is connected to a behavior that helps it to spread itself. 

Then I got to thinking; diseases have learned physical ways to disseminate themselves, I wonder if a disease could change behavior to promote it's own dissemination and survival? I imagine that if that were true, people with the flu would be sociable, people with infectious diarrhea would be sociable and hungry, people with AIDS would have increased libido. I haven't yet seen any data for this. Although I've always felt that there was one disease that did alter behavior in a way that is conducive to disseminating itself, and that is rabies. The host goes from being docile, to seeing all others as the enemy. He then attacks them, bites them and thus passes on the organism. A true mind altering virus, although it's psychology works better with animals than with people. Do you think that there are other diseases that spread purely by behavior, that cause the host to seek out the next host and not just pass the disease from one to another just due to proximity?

This was my response:

What great questions!

And believe it or not, there's quite a lot of empirical research on these very topics.

There is a whole textbook on the behavioral effects of parasites edited by Janice Moore entitled  Parasites and the Behavior of Animals. Here's an interesting one: rats and mice are hard wired to avoid cats. Millions of years of programming have ensured that Tom's very presence would send Jerry packing. Cats carry Toxoplasma gondii and if mice or rats become infected with it, usually by eating cat poop, they lose their fear of felines. So now Tom can have lunch at his leisure.

I've also talked about the way in which people with creativity and schizotypal personality disorder (i.e. carriers of genetic risk) tend to be promiscuous, while people with schizophrenia have fewer children. Both groups tend to get more sexually transmitted diseases than the general population. It would be tempting to think that toxoplasmosis can be spread that way, however there's a 32-year old study in German that showed that Toxoplasma was not transmitted by intercourse. However, cytomegalovirus, a common partner to Toxoplasma may be. And both modulate dopamine activity in the regions of the brain involved in salience.

I have done a very detailed literature search encompassing papers written in all the languages that I can read, and have not been able to find any clear evidence of behavior change induced by HIV, influenza or infectious diarrhea: what interesting and important questions to research.

We do have some more data confirming the effects of Toxoplasma infections on the behavior of rats: they become less anxious and therefore do not respond to environmental threats as quickly as uninfected rodents. An antipsychotic medication (haloperidol), a mood stabilizer (valproic acid) and two chemotherapeutic agents - pyrimethamine or Dapsone – have all been shown to prevent the development of Toxoplasma-induced behavioral change.

Another recent study from the Departments of Parasitology, Microbiology and Zoology, Charles University, the Centre of Reproductive Medicine and GynCentrum, in the Czech Republic also speaks to the significance of latent Toxoplasma infections: the presence of the parasite in the blood of pregnant women increases their chance of giving birth to boys. The increased survival of male embryos in infected women may be explained by Toxoplasmosis infections modulating and suppressing the immune system.

If Toxoplasma plays a part in the development of some psychiatric illnesses, yet a high proportion of the population carries it without any problems, one obvious question is what activates it? Environmental stress might, perhaps, cause the Toxoplasma to become reactivated and play a part in the development of specific psychiatric symptoms.

This story is continuing to develop and I am going to watch it closely. If it is confirmed, it could open up some brand new avenues for helping treat and perhaps even prevent some types of psychiatric illness.

Comments

[Stuart]

Dr Petty, in thinking about your comments I thought it would be easy enough to administer the antidote for T.gondii to individuals who test positive and demonstrate psychotic behavior to see if they improve. It seems such a low tech, simple thing to do with potentially great benefit. But alas I found it is not that simple, see below:
Dear Stuart –
A fine idea, but it is complicated by the fact that there is no antidote that eradicates Toxo infection. All known drug treatments only zap the acute form (tachyzoite), not the latent encysted form (bradyzoite). The latter stage is the one linked to the putative neurological effects. Incidentally, this is also why Toxo is such a big problem in AIDS patients…our drugs can control the acute toxoplasmosis, but the parasite will convert into a cyst impervious to the drugs. Drugs must be withdrawn within 2-3 weeks due to toxic side effects, and the acute toxoplasmosis comes right back. Many labs are busy investigating this conversion of the parasite from tachyzoite to bradyzoite in hopes of subverting this clinically relevant process.

I hope this was informative. Thanks for writing…Bill

Bill Sullivan, Ph.D.
Assistant Professor of Pharmacology & Toxicology
Center For AIDS Research
Indiana University School of Medicine

[Richard Petty]

Dear Stuart,

Thank you so much for your note.

Sad to say Dr. Sullivan is totally correct. If only it were a matter of dishing out some pyrimethamine or Dapsone to humans we would all have jumped on it. It is difficult to imagine the suffering of some people with chronic mental illness and we would do almost anything ethical to help them.

But I remain optimistic. If the toxoplasmosis story really holds up, it raises all kinds of possibilities. Medicines are in development at this moment that may actually be able to hit the bradyzoites themselves. Most have been too toxic to use, but there are some like 2-hydroxy-3- (1'-propen-3-phenyl)-1,4-naphthoquinone (PHNQ6), sulfadiazine and sulphamethoxazole have been shown to help and there’s a new approach using DNA vaccination with bradyzoite antigens. I am a great believer in human ingenuity!

Kind regards,

RP

[Stuart]

"Vaccination as a control strategy against the coccidial parasites Eimeria, Toxo and Neospora" Maybe we are getting closer than you think!