June 25, 2010

Another Diagnosis Of Schizophrenia, This Time With Cats

Bastet_2.jpg
my boyfriend hates my cat but he loves my         

Part 1 here.

The patient's family asks, "what causes schizophrenia?"  And you give them the speech: "there are probably many causes: genetics, some say an in utero infection, or in the old days they said it was the schizophrenogenic mother."  And then chuckle like you possess any knowledge that allows you such dismissive confidence.  I'm not saying it's true, I'm saying you have no idea if it's true.

The problem is that those aren't all potential causes of schizophrenia, they are causes of different kinds of schizophrenia, none of which you are making any attempt to distinguish.


II.

Toxoplasmosis is an organism that lives part of it's life relatively benignly in the intestine of a cat, gets pooped out, and then taken up by rats where it lodges in the brain, not benignly.  That's the cycle, back and forth.  It also can be taken up by humans, especially little fetuses.

Going from cat to rat is easy.  But how is it supposed to get back to cat?  Rats run away from cats, not towards them.  Indeed, this is innate: even rats that have never seen a cat in hundreds of generations still freak out when confronted with cat odor.

There's been plenty of research observing that schizophrenics are more likely to have been exposed to toxoplasmosis in utero than normals.  So what?  So this.

Researchers took 60 rats, and infected 30 with brain munching toxoplasmosis (verified at the end by autopsy) and the other 30 with terrible, evil saline.  And then they gave them a choice of scented cages to explore.  The scents were either: their own, water, rabbit, or cat.

Comparing infected to non-infected rats, there was only one difference in their preference for cage exploration:


fatal feline attraction preference.png



i.e. the infected rats are insane.

Note that the toxoplasmosis didn't make them more exploratory in general, only dispatched them to their likely doom.  (No, it didn't interfere with their sense of smell.)

Taking the most active infected vs. non-infected mice, and watching them over multiple explorations, not only do they not avoid the cat cage, but they develop a preference for it over other cages:


fatal feline preference.jpg




One might say that toxoplasmosis is a chronic, worsening condition characterized by poor judgment...

The rats don't simply defy danger; they specifically want to die by cat.  Rats can also get killed by minks, but minks don't hunt them.  A similar study gave rats a choice of mink maze and cat maze, the infected rats chose cat-- they chose their specific predator.

It's a truly odd coincidence that while the cat is the mortal enemy of the rat,  the cat is the natural home of toxoplasmosis.  One might even be tempted to say that somehow the toxoplasmosis willed the rat to go against its nature.  "That's dangerous talk around here, lefty, better mind your tongue."   Apologies.

But the other way to look at it is

Studies investigating the neurological basis of anxiety, which often use the reaction of potential prey to cat stimuli as a model, have found that blocking the normally anxiogenic N-methyl-D-aspartic acid receptors in the amygdala, and/or provision of serotonin (5-HT) antagonists, causes rats to approach cat odors "fearlessly," in much the same way that T. gondii-infected rats do.
So the rats become less anxious, more daring?  Odd coincidence: the toxoplasmosis infection rate in 1974 was 22% for the Brits, 84% for the French.  Maybe it makes humans chase pussy as well? 

Lafferty, in 2006, found rates of 45% in the French and 6.6% in the Brits.  How have people changed since the 1970s?  Maybe the reason "there are no real men" is because all the antibiotics have "sterilized" them.


toxo vs masculinity.PNG

III.

Let's assume that these studies show causation and not simply staggeringly awful correlations.  The semantic problem posed here is that you could choose to label the toxoplasmosis as either "schizophrenogenic" or "anxiolytic."  Both are equally valid, by which I mean completely meaningless.  The only thing you know for sure is that it was caused by the toxoplasmosis. 

Toxoplamosis is not a cause of schizophrenia, it is a cause of toxoplasmosis infection.  The schizophrenia part never existed.

IV.

If all this wasn't troubling enough, there's this:

Following a similar model as above, a group of infected rats were also given the treatment for toxoplasmosis (pyrimethamine and Dapsone).  Predictably, this cured the rat and stopped their crazy cat seeking behavior.

However, so did Depakote and Haldol, sometimes even better:

odds ratio cat cage.png
Look at this as the chance of being in the cat cage. a) is all behaviors, and b) teases them out.  You can see that untreated rats like cat cages, treated rats don't. 

What happened?  There's the obvious behavioral explanation (Haldol treated the psychosis); though Haldol does also block toxoplasmosis growth and infection.

Which means if you gave Haldol to a "schizophrenic," and saw "improvement," you would not really know if it was blocking D2 receptors or killing parasites.

And what would you have assumed had the Depakote worked?

V.

No one says syphilis is a cause of schizophrenia, but the same people would say toxoplasmosis is.  I hope you see there is no difference.

---

http://twitter.com/thelastpsych








Comments

i.e. the infected cats are ... (Below threshold)

June 25, 2010 12:26 PM | Posted by aaron: | Reply

i.e. the infected cats are insane.
???

cats or rats??

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Fascinating stuff, and beau... (Below threshold)

June 25, 2010 12:36 PM | Posted by DJMoore: | Reply

Fascinating stuff, and beautifully illustrates the problem of trying to interpret feelings from behavior.

===

My apologies, I don't usually bother to suggest correction of minor typos (I am controlling my Editors' Disease with exercise, meditation, avoidance of caffeine, and forced exposure to YouTube comments), except in cases where they radically change the meaning of what was written, as here:

In the sentence immediately following your first chart, "i.e. the infected cats are insane", I think you meant that the infected R-for-romeo Rats are insane.

Similarly here: "somehow the toxoplasmosis willed the cat to go against its nature."

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Causation is really complic... (Below threshold)

June 25, 2010 1:24 PM | Posted by Catalin: | Reply

Causation is really complicated. The subject you're circling is related more to the definition of therapeutic value(s). Causation is a very indirect route to go; was it intentional? Depends on how old you are.

Or: you are maybe implying that there may be no grounds for establishing something called psychiatry. Correct, but the real point is not if it works because it happens to work or if it works because it has to work. The question is are we kidding ourselves when we say it works? The way you answer that however, has more to do with what one has to lose professionally than to what one actually thinks.

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Your conception of psychiat... (Below threshold)

June 25, 2010 3:50 PM | Posted by Aaron Davies: | Reply

Your conception of psychiatry reminds me a bit of dermatology--while there are plenty of fully understood and treatable skin conditions, there are also a lot of things where you'll just get told "dermatitis" and given a cortisone scrip.

Perhaps a first step would be to stick "idiopathic" in front of all psychiatric conditions. (Well, except for those where "iatrogenic" is more appropriate....)

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So a giant chart with a per... (Below threshold)

June 25, 2010 3:52 PM | Posted by Shannon: | Reply

So a giant chart with a per-person viral and bacterial inventory from various sources (spinal fluid, gut, skin, etc.) and corresponding behavioral traits might tease out the differences between "[oblique idiopathic disorders or unexplainable mental defect]" and treatable or at lest understandable conditions which can be dealt with rationally, increasing the effectiveness of treatment and our understanding of how medications actually work???

You realize there is a movement comprised of people who are all for evaluating human "disease" in a way that acknowledges that what we know about how medicines and diseases work might not be right, and everyone thinks they're crazy. I bet you they don't even watch TV.

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Correct me if I'm wrong, bu... (Below threshold)

June 25, 2010 5:00 PM | Posted by RC: | Reply

Correct me if I'm wrong, but schizophrenics are typically oblivious to danger or they are paranoid, perceiving danger when it does not really exist. Correct?

The rats that were infected didn't become oblivious to danger, nor did they become paranoid. THEY ACTIVELY SOUGHT DANGER!! This could be the definition of insanity, or it could be (again, I'm not an expert) the risk-taking behavior of an adrenaline junkie with ADHD.

As a person with ADHD, I know all too well the allure of skydiving, driving fast, and sordid drunken affairs. I'm quite aware that they are dangerous, BUT THAT'S WHAT MAKES IT FUN!

I'm sure Depakote and Haldol would help fix this by making me numb to any and all forms of pleasure, but right now Ritalin is my drug of choice for that purpose. I'd be interested to know how the risk-taking behavior of these mice would change when treated with psychostimulants.

Perhaps toxoplasmosis and not organophosphates are to blame for the rising number of kids diagnosed with ADHD. Or, more likely, perhaps rats are not the best subjects to model human behavior.

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Sorry RC, but what was your... (Below threshold)

June 25, 2010 11:16 PM | Posted, in reply to RC's comment, by Anonymous: | Reply

Sorry RC, but what was your point again?

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Re-read my last paragraph S... (Below threshold)

June 26, 2010 3:47 AM | Posted, in reply to Anonymous's comment, by RC: | Reply

Re-read my last paragraph SLOWLY, preferably having taken the psychostimulant of your choice.

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Speaking of rats (and corn ... (Below threshold)

June 26, 2010 10:10 AM | Posted by Whatever: | Reply

Speaking of rats (and corn flakes)

http://www.westonaprice.org/modern-foods/567-dirty-secrets-of-the-food-processing-industry.html

ouch

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Excellent post as usual... (Below threshold)

June 26, 2010 5:07 PM | Posted by Vince: | Reply

Excellent post as usual

It's a very interesting topic; impressive how fine-grained some of the behavioral modification can be. There was a nice paper back from 2005 by Thomas on Parasitic manipulation, which could be found here:

http://tiny.cc/5h45a

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and if you reread the artic... (Below threshold)

June 26, 2010 11:33 PM | Posted, in reply to RC's comment, by Anonymous: | Reply

and if you reread the article SLOWLY then you might have remembered that the levels of toxoplasmosis infection seemed to be decreasing in the human population.

In short, it's probably not the cause of ADHD. The rise in ADHD is better explained by current diagnostic practice.

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A lot of you are being waaa... (Below threshold)

June 27, 2010 1:47 AM | Posted by Anonymous: | Reply

A lot of you are being waaay to literal.

If an organism can somehow affect the nervous system of rats resulting in what can only be called illogical and disorganized behavior of cat-seeking, it is not at all unreasonable to think this organism could destroy/alter the nervous system in a similar way in humans creating schizophrenic symptoms.


YOu are falsely reading into this that T. Gondii creates "fearlessness" or that it creates "fear seeking" in rats. There is absolutely zero evidence that T. Gondii is making rats fearless or fear seeking. The only evidence is that T. Gondii makes the rats behave in an illogical reckless, i.e. disorganized way.

Schizophrenics also behave in an illogical, reckless, disorganized way.

Humans are not rats. We do not have a rat nervous system. If we were, maybe these types of "schizophrenics" would simply seek out cats, as opposed to having complex crazy ideas about the government planting chips in their head.

Humans have a complex mind, with the ability to think extremely abstract intricate thoughts, emotions... the outcome of any nervous system disturbing agent (e.g. T. Gondii) is going to have a VERY different effect on a human nervous system than a rat nervous system.

The logical, orderly human mind says "I'm going to get up today, get dressed for the season appropriate way, go outside, go to work, beat rush hour traffic". The crazy brain says "there are people outside listening to my thoughts. I cannot leave the house, satan will get me. I need to plan for the end of the world. The government is inserting thoughts in my brain".

All in all, it's not that much different than a rat running toward cats. It's just a lot bigger, in a much more complex brain. Chaos and irrationality.

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First, I'm so flattered tha... (Below threshold)

June 27, 2010 3:38 AM | Posted, in reply to Anonymous's comment, by Anonymous: | Reply

First, I'm so flattered that you find my comment worthy of your time and scrutiny.

Second, I thought I had conveyed with the word "perhaps" that I don't know what causes ADHD. I hadn't expected somebody to take this suggestion so seriously. You do make a good point though.

Third, none of what you mention should overshadow my final point: "Or, more likely, perhaps rats are not the best subjects to model human behavior."

(Note the use of "perhaps" again, with all the uncertainty the word entails.)

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First, I'm so flattered tha... (Below threshold)

June 27, 2010 3:38 AM | Posted, in reply to Anonymous's comment, by RC: | Reply

First, I'm so flattered that you find my comment worthy of your time and scrutiny.

Second, I thought I had conveyed with the word "perhaps" that I don't know what causes ADHD. I hadn't expected somebody to take this suggestion so seriously. You do make a good point though.

Third, none of what you mention should overshadow my final point: "Or, more likely, perhaps rats are not the best subjects to model human behavior."

(Note the use of "perhaps" again, with all the uncertainty the word entails.)

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This reminds me of Richard ... (Below threshold)

June 28, 2010 1:16 AM | Posted by Basil: | Reply

This reminds me of Richard Feynman's talk on "Cargo Cult Science", so called because it has the outward appearance of good science while tending to generate mixed to bad results.

In this case "we think a certain type of disordered thinking is caused by mechanism X and so is treatable by something that we think uses mechanism Y" becomes "schizophrenia is caused by dopamine in the mesolimbic pathway and so we'll treat it with an antipsychotic"-- like wildly searching for a destination and, when you miraculously find the way, saying you knew the route the whole time.

Feynman's talk: http://www.lhup.edu/~DSIMANEK/cargocul.htm

BTW, it's extremely lazy (and also somewhat ironic) to just pepper your statements with "perhaps" and similar caveats when commenting (I say "commenting" as opposed to "debating" because you're not making a point, or at least, not one that wasn't implicit). If you think TLP's wrong, or off-base, or whatever, then find or conduct a study/experiment to prove it.

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Lazy? Are you serious? An... (Below threshold)

June 28, 2010 3:00 AM | Posted, in reply to Basil's comment, by RC: | Reply

Lazy? Are you serious? And "somewhat ironic"? Would you care to explain that one?

When somebody, as I did, says "perhaps," "correct me if I'm wrong," and "I'm not an expert," he is not being lazy or even remotely ironic, he is recognizing his own limitations. I'm not a psychiatrist! Although, I'd like to think that even if I were an expert I would still approach a discussion topic with humility.

Also, citing studies is one way of supporting an argument (or if you want to waste time splitting hairs, a "comment lacking a point that was not implicit"). Another is sharing personal experience. Having lived with ADHD my whole life, I do think I know quite a bit about the nature of this disease, not necessarily from a scientific standpoint but FROM ACTUAL EXPERIENCE.

[In the same way, cancer patients often know more about their disease than their oncologists do. Doctors make a huge blunder when they don't realize this.]

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thanks for a great post! i ... (Below threshold)

June 28, 2010 10:30 AM | Posted by medsvstherapy: | Reply

thanks for a great post! i believe the main flaw is the confidence man approach: when teh head-shrinkers act and feel confident. the sad thing is that the head-shrinkers act quite knowledgeably, but how often do they satisfactorily resolve a problem? especially in someone with schizophrenia symptoms?

maybe a meteorologist is a good analogy: with all of those charts and such, but fail to predict rain tomorrow. should a head-shrinker give a forecast with a margin of error?

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i am right now in a researc... (Below threshold)

June 28, 2010 10:57 AM | Posted by medsvstherapy: | Reply

i am right now in a research conference paper session, and in a parallel universe: increase of prescribing of psych meds for kids of families in distress, pre/post acute stressor administrative data study design, must mean the kids have a biologically based brain disorder. we all calmly accept the data presentation unblinkingly. after all, the powerpoint slides are so well developed, and the analyses included a handful of covariates. god help us.

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"Lazy? Are you serious? And... (Below threshold)

June 28, 2010 1:25 PM | Posted by Basil: | Reply

"Lazy? Are you serious? And "somewhat ironic"? Would you care to explain that one?"

Sure. Saying "perhaps" or "I'm not an expert" and then continuing on regardless contributes noise absent signal to the conversation. If you're not willing to actually become an expert or at least informed enough so you don't have to hedge with "perhaps", then you're not helping someone reach understanding, you are just playing linguistic games. "Of that which we cannot speak..." and all that.

It's lazy because it allows you to talk without having anything worth saying, and it's ironic because this very propagation of ignorance is what allows a supposedly rational, scientific field like medicine to devolve into word manipulation and pseudo-science.

http://en.wikipedia.org/wiki/Weasel_word

I hope that clarifies.

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I still don’t understand ho... (Below threshold)

June 28, 2010 2:29 PM | Posted, in reply to Basil's comment, by Anonymous: | Reply

I still don’t understand how I was being “somewhat ironic” – your explanation is not logical – but it’s VERY IRONIC when somebody prefaces criticism with the weasel word “somewhat,” then subsequently denounces the use of weasel words for how it “contributes noise absent signal to the conversation [sic].”

Overall, you are assuming WAY too much about my intentions. When somebody is “playing linguistic games,” he/she is INTENTIONALLY trying to deceive and manipulate others. How the hell do you know what I’m doing? You don’t and you can’t.

As your wikipedia article states, “for a statement to be a weasel expression, it needs other indications of disingenuousness.” As I said before, I AM NOT A PSYCHIATRIST!! I am not trying to pass myself off as an expert, and I am not trying to deceive anybody.

I follow and participate in this blog, not because I’m interested in “helping someone reach understanding,” not because I am a member of a “supposedly rational, scientific field like medicine,” but for one reason only: BECAUSE IT IS FUN!! Don’t assume everybody who follows this blog does so with the same reasons as you.

Instead of calmly and rationally explaining why my points (excuse me, COMMENTS) were wrong, you’ve resorted to mudslinging and insults. Now, instead of talking about psychiatry, I’m here trying to defend my integrity, to show I’m not an ignorant/lazy/ironic weasel, or something like that. Alone calls this “the cognitive kill switch,” but less educated, low-brow folks like me describe it more bluntly with four letter words.

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zombie snails, what?... (Below threshold)

June 28, 2010 4:54 PM | Posted by Anonymous: | Reply

zombie snails, what?
http://www.i-am-bored.com/bored_link.cfm?link_id=21122

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Going from cat to rat is... (Below threshold)

June 29, 2010 9:35 AM | Posted by Jack Coupal: | Reply

Going from cat to rat is easy. But how is it supposed to get back to cat?

Because cats eat rats they catch??

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Good post, however there ac... (Below threshold)

June 29, 2010 2:23 PM | Posted, in reply to Basil's comment, by Anonymous: | Reply

Good post, however there actually is quite a lot of evidence for the relationship between dopamine, catecholamines, and hallucinations.

It is shown that using dopaminergic drugs such as bromocriptine and carbidopa will induce hallucinations in people. Note, this doesn't turn into frank psychosis and schizophrenia, but it DOES create "positive symptoms" particularly visual hallucinations... particularly in people with noted brain problems (e.g. elderly with parkinsons are more vulnerable to hallucinating on dopaminergics than healthy young with in tact non-messed up brains).

Speaking personally, I experienced carbidopa-like hallucinations from an OTC tyrosine supplement. While taking lots of tyrosine, I began to have simple visual hallucinations such as bugs and small animals and occasionally crazy thoughts in my head (which I knew weren't true but none the less was prone to having crazy thoughts). Tyrosine converts to carbidopa and dopamine fyi.
I am young, although I have a strong family history of insanity and psychosis and I myself am a bit mental so perhaps I am more vulnerable than the average person to the crazy making effects of slightly elevated catecholamines/precursors.

Either way, it really is a fact that positive sypmtoms are a function of dopamine and junk.

This doesn't mean the illness of psychosis and schizophrenia is CAUSED by dopamine, but it does mean that medications which block the stuff will reduce crazy thoughts - no matter what class they are (i.e. antiemetics like reglan / metocloprimide are also effective antipsychotics).

Psychiatry is mostly palliative care for the mind.

The problem is psychiatry is they pretend to be in the business of understanding disease and curing it. That's more neurology's bag.

Psychiatry is equipped, fundamentally, to only really offer medications that reduce symptoms of distress and functional impairment. As a BEST case scenario. It is palliative care for the mind.

If psychiatry stopped pretending and posing like their palliative treatments were cures, we would all be much less upset, I think.

If morphine sulfate as part of hospice care reduces the subjective and objective behavior of chronic pain, no one says "morphine sulfate is curing the disease of pain". Unfortunately, psychiatrists make this statement when they say haldol treats schizophrenia.

Dopamine blockers do not have any ability to treat disease with mental symptoms. All they can due is reduce the most significant symptoms of it, and so allow people to function a bit better, until one day science (neurologists, immunology, whoever) discovers what actually CAUSES these problems and how to fix it, if it is possible to fix it.

Dopamine blockers for psycohsis isn't any different than morphine sulfate for stage 4 cancer w. mets, the only difference is that the doctors who prescribe the dopamine blockers lie to patients and tell them the medication treats the disease.

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Dopamine Anonymous: to add ... (Below threshold)

June 29, 2010 6:27 PM | Posted by medsvstherapy: | Reply

Dopamine Anonymous: to add to the discussion abt causes, labels, and symptoms around the concept "schizophrenia:" I have worked with and gotten to know, across time, maybe a hundred people who reasonably were dx with schizophrenia. we did not regard visual hallucinations as indicating likely schizophrenia. the ppl with vis hallucination almost always had a readily identifiable organic cause - head injury, someone who played around with LSD, someone with head injury, and so on.

we weren't the first to figure this out. schneider gets the credit.

at leas