Stefansson’s Luxury Organ

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In yesterday’s New York Times article, David Goldstein makes sense: he says “We’ve looked for common variants in schizophrenia and get almost nothing. This means natural selection has done a really good job of purging them away, and we’re left with rare variants, a constant flow of them, as the principal driver of the disease.”

Which is what any reasonable person thought a long time ago: the common disease-common variant notion never made much sense for a syndrome with a large impact on fitness. That genetic heterogeneity does not make drug development easier: even if the mutations cluster in certain pathways, reactivating a broken pathway may still require mutation-specific methods, which would sure take the profit out of drug development.

But the most interesting point in the article is Stefansson’s statement – “I would have thought the brain was a luxury organ when it comes to reproductive success.” That’s a weird thing to say. For one thing we known damn well that schiz strongly impacts fitness, even in contemporary society: the affected families dwindle away, which interferes with genetic studies.

More than that, does he really believe that being insane had no effect on reproductive success back in the Malthusian past? It’s hard to find a place more Malthusian than Iceland: does he think that crazy hardscrabble farmers did just as well as sane ones? Does he think that lunatics were just as likely to become godir and hornswoggle the neighbors out of their land?

The brain burns out 20% of our calories: does he think that could continue long under natural selection if there wasn’t a big payoff?

The answer is that he _does_ think all those absurd things: he doesn’t believe in ongoing natural selection in humans, particularly above the neck. I wonder why – but once we sequence him, maybe we’ll know.

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44 Comments

  1. Oh c’mon Greg, everyone knows that in previous centuries, schizophrenics were chosen as the shamans and so actually enjoyed a fitness *boost* compared to sane folk. All those other common abnormalities — a boon when the only unsaturated niche in the labor market was circus freaks.

  2. You automatically assume that so-called schizophrenia is a “disease”. Is it a disease like diabetes or Alzheimers? Or like homosexuality is (oops, sorry, was) a disease? LOL. It’s just weird behaviour, different cultures dealt with it in various ways, our one happens to medicalise it and pretend to “treat” it.

  3. David– 
     
    While the disease label may be questionable, the interference with cognition is not. It’s not just a change in preference, like homosexuality (or any one of the more unusual, and often less accepted, sexual predilections)–it’s a tendency to vividly see, hear, and think things that are not there.  
     
    Yes, there may well be a benefit to such traits when present to a lesser extent, for example a better imagination, allowing more flexible planning and ability to “expect the unexpected” (I’m just making this example up). In some cases, it may even combine with genius, e.g. in the case of John Nash. However, in most cases, an inability to tell whether what you are hearing and seeing is real would have a strong negative effect on the ability to understand the world.

  4. This discussion of sanity is mildly ironic since I hear Kári Stefánsson himself is, if not crazy, abusive, attention-seeking and megalomaniacal. (deCODE’s HQ was featured in the Icelandic film “Mýrin” and I’m guessing it was in exchange for the mock “interview”, starring a certain Kári Stefánsson, that was also in the film. 
     
    What is it about genomics company CEOs being full of themselves? I understand Craig Venter is the same, and they both share belief in Gould’s daemon, too… Sad that those best placed to speak up for Watson instead piled on, I guess because their ambition would brook no threats.

  5. As BGC said in the other thread, “schizophrenia” is a hodgepodge diagnostic category that masks a lot of phenotypic variation — I’d love to see the results of someone running PCA on a fine-grained symptom questionnaire administered to a few thousand “schizo” patients. Bet there’d be at least four discernible subtypes. If we look at the 16 genes where common polymorphisms have shown significant correlations, there’s the kind of weird functional grab-bag you’d expect if this were the case: five neurotransmitter receptors (DRD1, DRD2, DRD4, GABRB2, GRIN2B), three enzymes that clear neurotransmitters (COMT, DAO, TPH1), two involved in neural development (PLXNA2, MTHFR), two that are plausibly involved in disease resistance (IL1B, HP), one protein that hangs around in axon terminal buttons and seems to modulate transmitter release (DTNBP1), one lipoprotein transporter that’s a generalized dementia risk (APOE), one that regulates DNA repair and apoptosis (TP53), and the serotonin transporter (SLC6A4). 
     
    The interleukin 1B and haptoglobin associations are good evidence for some sort of immune polymorphism involvement and hence for infectious causation of some subtypes (molecular mimicry?). What I’d really like to know is which of these variants is associated with mere cognitive deficits and which with florid hallucinations. Ideally some more proximal neurological markers would be nice.

  6. Matt –  
    Jay Gingrich has some work that speaks to the florid hallucinations: 
    http://www.nature.com/nature/journal/v452/n7183/abs/nature06612.html 
    Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G-protein-coupled receptor family, to form functional complexes in brain cortex. The 2AR–mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen-specific signalling and behavioural responses. In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. 
     
    Whatever happened to DISC1?  
    we report that individuals in a discordant twin sample with a DISC1 haplotype, associating with schizophrenia as well as working memory impairments and reduced gray matter density, were more likely to show deficits in sociability than those without the haplotype. Our findings demonstrate that alterations in DISC1 function during brain development contribute to schizophrenia pathogenesis. 
     
    I’m thinking that studying particular Sz symptoms is going to be more fruitful than the whole disease, but Greg’s larger point makes me despair of ever modelling schizophrenia in any satisfactory way. Treatment might be restricted to new ways to alter dopamine cycling.

  7. “WeÂ’ve looked for common variants in schizophrenia and get almost nothing,” said Dr. David Goldstein, a geneticist at Duke University and one of Dr. StefanssonÂ’s co-authors. “This means natural selection has done a really good job of purging them away, and weÂ’re left with rare variants, a constant flow of them, as the principal driver of the disease.” 
     
    David Goldstein thinks that 1% of the population has a severe mental disorder due to a constant flow of harmful mutations? (face palm) Dave, if you’re out there I urge you to pick up a copy of “The Complete Idiots Guide To Genetics.”

  8. David Goldstein thinks that 1% of the population has a severe mental disorder due to a constant flow of harmful mutations? (face palm) Dave, if you’re out there I urge you to pick up a copy of “The Complete Idiots Guide To Genetics.” 
     
    ok, you’ve got me. why is it so obvious that mutation-selection balance can’t be the primary force here? (there are, of course, some common alleles that influence schizophrenia risk, but they’re very low penetrance)

  9. Schizophrenia reminds me of autism in that if you look at the families in which it is found, you’ll often find scientists, and doctors, and writers, and mathematicians. You’ll find, basically, some very bright, high-functioning people. There’s never been an established one-to-one correlation between gene and disorder with schizophrenia; instead what you usually find is a gene that merely causes a statistical bump in disease liklihood. But what are these so-called schizophrenia genes doing in the vast majority of people who have the genes but don’t develope the disorder?  
     
    The simple answer is that these genes, in most cases, must provide a massive selective advantage of some kind in order to offset the loss. Schizophrenia is what happens when something goes wrong in how these genes are normally expressed. It is the price that is paid.  
     
    Considering that 1% of the population has schizophrenia, and considering how high that price is for those who develope the disease, the benefit to those gene carriers who don’t develope the disease must be immense.

  10. The measures of ‘schizophrenia’ in different countries actually vary widely (contrary to popular mythology) – eg. in this WHO summary the quoted incidence of ‘schizophrenia’ varies fourfold between countries, and prevalence 18 fold. 
     
    http://www.who.int/mental_health/media/en/55.pdf  
     
    Outcomes are generally much better in poor countries,  
     
    http://bjp.rcpsych.org/cgi/content/abstract/191/50/s71 
     
    probably because most people there are simply looked-after and sedated until they have spontaneous remissions – whereas in rich countries patients are sometimes killed by, but more often become damaged and dependent on, the so-called ‘antipsychotic’/ neuroleptic drugs.  
     
    http://linkinghub.elsevier.com/retrieve/pii/S0306987703002937

  11. Kaleidoscopik — Thanks, I’d seen that paper when it first came out but forgotten about it; maybe time for another gander. I was puzzled by the absence of DISC1 as well, but I haven’t got the statistical chops to argue that its association dropped out spuriously, so who am I to disagree with the meta-analysis? Low reelin expression in schizo brains plus the linkage with other genes that share pathways with reelin makes me suspect that there’s something funny going on in that protein interaction network, but I haven’t really thought it through yet. I would be surprised and annoyed if there was in fact no there there.  
     
    P-ter — Just guessing here, but I would say because it’s a little improbable. You’d need >1000 different ways to cause schizophrenia in order to get a 1% mutation-selection equilibrium frequency. It’s not impossible, but . . . maybe looking elsewhere first might be more profitable. 
     
    Kosmo — Crespi & co would agree with you.

  12. Just as a follow-up to the IL1B association, there’s this too: 
     
    http://www.jneurosci.org/cgi/content/abstract/27/40/10695

  13. Sorry, I misspoke — should have been ~500 rather than >1000, assuming a fitness hit of close to one half. Hadn’t had my tea yet.

  14. a hodgepodge diagnostic category that masks a lot of phenotypic variation 
     
    I haven’t studied this in depth, so I don’t know if this is true or not. If it is the case– that schizophrenia is just an extreme version of lots of “stacked” genetic effects, then wouldn’t the common disease-common variant approach supposedly succeed or be worth pursuing further?  
     
    And if the answer to that question is a yes, what’s the explanation for why such an approach for schizophrenia hasn’t had much success?

  15. Just guessing here, but I would say because it’s a little improbable. You’d need >1000 different ways to cause schizophrenia in order to get a 1% mutation-selection equilibrium frequency 
     
    assuming it’s recessive, that’s to get a 1% frequency of the allele, right? you’d have to have >100000 ways to cause schizophrenia to cause a 1% prevalence. or am I doing the math wrong?  
     
    math: p = sqrt(m/s). prevalence =p^2 =.01 => p = .1, assuming recessivity. if s ~50%, m/locus = 1e-8, you’d need 500K possible mutations to get an allele frequency of 10% and a prevalence of 1%.  
     
    so sure, this isn’t pure mutation-selection balance. but the disease is under pretty strong negative selection–it seems reasonable that alleles that cause it should also be under negative selection. and the stationary distribution of alleles under negative selection is skewed towards rare variants. so conditional on having a research program trying to map the genetics of the trait, it seems worthwhile to look at rare variants. is that the objection? that trying to map the genetic variance doesn’t seem fruitful?

  16. p-ter — You’re right, I was just assuming complete dominance because I wanted to be as absurdly conservative as possible. Compare this to congenital deafness, which can be caused *a lot* of different ways and might even be slightly less debilitating than schizophrenia, but is still only like 0.1% at most. The objection isn’t to looking at rare variants but to ignoring the a priori more probable possibility that infectious causation would explain the largest chunk of the variance. Congenital deafness may be a good model here too — Greg is fond of quoting the figure that rubella accounted for about about 40% of cases prior to vaccinations for it becoming commonplace.  
     
    ben g — “that schizophrenia is just an extreme version of lots of “stacked” genetic effects” 
     
    That’s not the objection. The objection is that a bunch of very different problems are being lumped under the same diagnostic category, which is likely to cause a lot of confusion when attempts to tease out aetiology are concerned.

  17. I hear that people are contemplating classifying bigotry a disease. If that ever happens I wonder if the writers of GNXP will be considered to be suffering from some sort of disease. I’m not calling the writers bigots however some would define the writers of this blog as being bigots for their views and if bigotry is ever classified as a disease doctors may share the opinion that the writers are bigots.

  18. I should say that’s Greg’s (and my) objection; since LOL is a coward I have no idea what he thinks.

  19. The objection isn’t to looking at rare variants but to ignoring the a priori more probable possibility that infectious causation would explain the largest chunk of the variance 
     
    ah, ok. but shouldn’t that be reflected in the genetics of the trait? i think I’ve argued this before, but mapping crohn’s disease has led to a number of genes involed in elimination of intracellular pathogens– a pretty important piece of evidence in any argument about its etiology. I guess not enough is known about the genes involved in schizophrenia, but the genetic approach is absolutely not incompatible with an infectious cause.

  20. Matt thanks for that link!  
     
    From the abstract: “Strong evidence of non-neutral, accelerated evolution was found for DISC1, particularly for exon 2, the only coding region within the schizophrenia-associated haplotype.” 
     
    I had no idea this study existed. It would seem prove the genes behind schizophrenia are under positive selection. Interesting stuff.

  21. Old And Busted: Common genes cause common disorders 
     
    New Hotness: Super rare mutations cause common disorders

  22. Schiz is in most cases caused by environmental damage. Another 1,000+ genetic studies aren’t going to change that. 
     
    Schizophrenia linked to immune response in womb 
     
    I could post 10 more links like this but the spam filter would block me. Toxoplasma, flu virus, TBE, extreme maternal stress can all lead to Schiz.

  23. Another good link. 
     
    Pet Cat Parasite Linked to Schizophrenia Risk  
     
    I liked this sentence, “The current study is part of a series of nested case-control studies looking at proposed associations between psychotic disorders and selected infectious agents, Dr. Niebuhr and colleagues said.” 
     
    This and other stories tells me that a lot of scientists are looking in the right direction.

  24. Matt: “You’d need >1000 different ways to cause schizophrenia in order to get a 1% mutation-selection equilibrium frequency.” 
     
    Your estimate depends on the rate of harmful mutations as well as the number of ways that failure may occur. Some types of mutation occur far more frequently than the genome average for SNP’s. 
     
    E.g., during meiosis recombination can cause duplications/deletions at DNA “hot spots” where similar DNA sequences occur multiple times along the same strand. This type of mutation occurs frequently. I’ve seen estimates that up to 5% of severe retardation cases are due to recent “hot spot” CNV’s in DNA that codes for brain proteins. The children seldom reproduce so the mutations are quickly removed from the gene pool. However the deletions occur so frequently that they account for a significant fraction of mental retardation cases. 
     
    Fragile X retardation occurs in 1 in 4000 boys and is caused when a CGG segment exceeds around 200 copies. Normally a person has between 5 and 40 copies. This type of mutation occurs frequently.

  25. Fly 
     
    The argument about 1000 different rare mutations is purely academic. Scientists know today that most cases of Schiz are the result of environmental damage. 
     
    Flu virus alone accounts for 15% to 20% of all cases. 
     
    Flu and Schizophrenia 
    Maternal Flu Linked To Schizophrenia, Autism In Child

  26. How does schizophrenia with onset in your mid-20s affect fitness? Hasn’t most of the world reproduced by then? 
     
    Where do you get the statistics for families dwindling away? Is it the same for autism?

  27. kaleidoscopik 
     
    How does schizophrenia with onset in your mid-20s affect fitness? Hasn’t most of the world reproduced by then? 
     
    Parents are more than sperm doners. They still need to raise their children and later help with their grandchildren. In the modern world most people’s genes should get them to 60 or so. I hope mine get me a lot farther than that.

  28. Punnett Square: “Scientists know today that most cases of Schiz are the result of environmental damage.” 
     
    From the DailyScience link you provided: 
     
    “Since schizophrenia and autism have a strong (though elusive) genetic component, there is no absolute certainty that infection will cause the disorders in a given case, but it is believed that as many as 21 percent of known cases of schizophrenia may have been triggered in this way. The conclusion is that susceptibility to these disorders is increased by something that occurs to mother or fetus during a bout with the flu. 
     
    Now, researchers have isolated a protein that plays a pivotal role in that dire chain of events. A paper containing their results, “Maternal immune activation alters fetal brain development through interleukin-6,” will be published in the Oct. 3 issue of the Journal of Neuroscience. 
     
    Surprisingly, the finger of blame does not point at the virus itself. Since influenza infection is generally restricted to the mother’s respiratory tract, the team speculated that what acts as the mediator is not the mother’s infection per se but something in her immune response to it.” 
     
    I.e., genes and environment together produce disease. 
     
    The brain is an exceeding complex organ. Brains can fail from a vast number of distinct causes. Factors may combine to increase the probability of failure. Schizophrenia is a type of brain failure defined by a fuzzy set of symptoms. Specific combinations of genetic factors may increase the probability of schizophrenia…twin studies show heritability over 80%. Specific environmental damage may increase the probability of schizophrenia. Genes and environment interact to produce phenotype. For complex traits such as mental function there will be many genetic and environmental causes.

  29. I.e., genes and environment together produce disease. 
     
    This is true if you have a very nuanced interpretation, but it’s misleading for the public and most smart people too. It’s like if there’s some rare variant that mediates the outcome of a gunshot wound: he died because he got shot. 
     
    Analogy: oxygen is a precondition for fire, but we never mention oxygen when a house burns down because it was “really” caused by a spark here, the flames spread there, etc.

  30. [kaleidoscopik said:] How does schizophrenia with onset in your mid-20s affect fitness? Hasn’t most of the world reproduced by then? 
     
    It’s one thing to start reproducing, but your fitness is going to be sharply subprime unless you finish reproducing (or anyway carry on reproducing until reaching at least the mean life expentancy). Until recently most children died young.  
     
    “Among the Agta, mean age at menarche is 17, mean age at first live birth is 20.14 years, mean completed parity is 6.53 and mean age at menopause is 44.” 
    http://www.ingentaconnect.com/content/tandf/tahb/1985/00000012/00000002/art00005

  31. Fly 
     
    twin studies show heritability over 80% 
     
    Do you have a link for that? I’ve never heard that Schiz or any other common mental disorder is that heritable.

  32. agnostic 
     
    It’s like if there’s some rare variant that mediates the outcome of a gunshot wound: he died because he got shot. 
     
    You nailed it.  
     
    Let me add that I’ve grown tired of the phrase “this disorder is the result of a complicated interaction betwen genes and environment.” Every trait & disorder on this planet falls into that category. That’s science double-speak for, “We don’t know.”

  33. [agnostic said:] It’s like if there’s some rare variant that mediates the outcome of a gunshot wound: he died because he got shot. 
     
    OK, true that is, if he got shot in the heart. But what if a hemophiliac gets shot through the wrist in 1936? 
     
    I agree with you, basically. The “reason” for a guy dying when he gets shot is not that he’s an organism, that he was born, or that he failed to catch the bullet in his teeth – because what we really mean is, what is the cause that he died and we didn’t. But it’s very different to dismiss his uncorrected hemophilia, or the HLA-B27 alleles as risk factors for ankylosing spondylitis, or NOD2 variants as factors in Crohn’s, or even much weaker genetic associations pertaining the various other diseases of high fitness load sensu Ewald and Cochran.  
     
    I completely agree though as far as the media and intelligensia having a false picture of diseases being “genetic.” When a new lupus gene comes out with an odds ratio or risk ratio of like 1.2, I’m excited because the protein’s function may shed light on lupus… beyond that the information is absolutely useless, but the media is very excited about it. Something with a risk ratio of like 6 is another story, and there are lots of common complex diseases with HLA associations in that range. Now, I don’t understand much about genome scanning, so I don’t know how many new loci of that significance are still out there to be discovered using improving technology, or might be sort of hidden in copy number variations, or whatever. But we already know (since decades ago) that the heritability of the common complex diseases is comparable to that of the more-heritable of the common infectious diseases.

  34. Let me add that I’ve grown tired of the phrase “this disorder is the result of a complicated interaction betwen genes and environment.” Every trait & disorder on this planet falls into that category. That’s science double-speak for, “We don’t know.” 
     
    Some people go on for like three long sentences with that mumbling, which usually (but sadly, not always) indicates that they have nothing better to say. There’s nothing worth saying beyond “genetic and environmental associations noted so far do not complete the etiology. They are: _______ [...] They show these intereactions: _______ [...]“

  35. Punnett Square: “Do you have a link for that? I’ve never heard that Schiz or any other common mental disorder is that heritable.” 
     
    Here is one representative link. I don’t view such studies as conclusive evidence of high heritability, I only conclude that schizophrenia is a complex disease that is strongly influenced by both genetic and environmental factors. 
     
    http://www.ncbi.nlm.nih.gov/pubmed/14662550‘ 
     
    “By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%). CONCLUSIONS: Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences.”

  36. Some might be interested in the book “Susceptibility to infectious disease” – see google books. 
     
    Page 78 points out the higher heritability of “several” known-infectious diseases compared to “many” autoimmune diseases. 
     
    While heritability is one thing, what really shocked me in this book was the chapter on schistosomiasis – using a segregation analysis the authors concluded that a single codominant locus was the major genetic factor for severity of schistosomiasis in the people they were studying, and apparently this was extended to other populations as well. Disclaimer, I didn’t run through their data and deductions carefully when I read this. When I read this I had never before been aware of an infection being so strongly modulated by just one locus in any mammal – other than the many recessive loss-of-function alleles like sickle cell etc etc – so I had a strong sense of like, “wow, infectious disease is more genetic than I realized.”

  37. I had a strong sense of like, “wow, infectious disease is more genetic than I realized.” 
     
    OK, not really “more genetic than I realized,” but rather, “there are more kinds of genetic involvement in infectious disease than I realized… not just recessive nonfunctional alleles or alleles with weak influence.” 
     
    You kinda wonder why that allele doesn’t fix. Maybe something about it is a little screwed up.

  38. Hey, question for all of you scientists. 
     
    I can understand depression–there is a mood-regulating system, and it gets stuck in the ‘down’ mode, sort of like an inverse hypertension. I can understand ADD–there is some attention-regulating system, and it doesn’t work well. I can understand personality disorders like histrionic and narcissistic–you have too much of a good thing. Sociopathy’s downright adaptive in the business world if you have a high enough IQ and enough self-control to avoid stealing your boss’s pens.  
     
    But schizophrenia? What brain system is there that, when it breaks down, causes you to hear voices, stop taking care of yourself, and have flat affect? It must be pretty fragile if there’s all these genes that cause it to break down? Does anyone have the neuroscience background to explain this?

  39. All those genes fall into two categories. Either they are extremely rare (extremely rare even in schizophrenics, though not quite as rare)… or else they are minor risk factors, which increase the lifetime risk of schizophrenia (which is ~1% for a randomly-chosen person) by only 1.2-fold to a few fold.  
     
    So no one really knows what their involvement is. It definitely doesn’t have to be direct involvement in brain function. It could be (random made-up possibility) that they increase the odds of some rare event in which some common virus like EBV (which almost everyone has anyway) alters your brain. 
     
    More genetic factors may yet be discovered. 
     
    Marijuana is also asserted as a minor risk factor. But correlation is not causation, so it might be that schizophrenics have certain mental charecteristics (long before getting recognizable schizophrenia) that cause them to be somewhat more likely to use marijuana. In the case of genes, correlation is causation only because it is virtually certain that getting schizophrenia can’t change someone’s genes. 
     
    Why is is so easy to produce psychosis? I don’t know; I don’t know much about the brain but I doubt there is a really satisfying answer out there, other than that the brain is really intricate, and so our nexus with reality is desperately delicate even though reality itself is deperately robust. There are loads and loads of pschotogenic factors out there: a great many different classes of drugs will do the trick, extreme sleep deprivation does nicely, as do large doses of the human immune hormone IL-2, heat stroke, some immunological diseases whose symptoms are mostly likely to have autoimmune proximal causes (systemic lupus), many chronic (syphilis) and acute infections of the brain, seizures, and other diseases. Not all such psychoses are identical, of course; far from it; but they meet the definition of psychosis because you can’t fully communicate with the person, they have false beliefs, and they can’t cooperate with other people in modestly complex activities – it’s a very broad category.

  40. One theory about what’s broken in florid paranoid schizos is the ability to keep track of what instructions your brain has issued to your own body — movements and subvocal (i.e. internal) speech being misinterpreted as being from an external source because the brain has no record of having created them. Screwy PFC wiring could do that. Imagine if a tracer signal wasn’t sent back from your eye muscles every time you moved your eyes — the whole world would feel like it was shifting around you. Similar principle.

  41. Marijuana is also asserted as a minor risk factor. But correlation is not causation, so it might be that schizophrenics have certain mental charecteristics (long before getting recognizable schizophrenia) that cause them to be somewhat more likely to use marijuana. In the case of genes, correlation is causation only because it is virtually certain that getting schizophrenia can’t change someone’s genes. 
    If you look at that literature closely it looks a lot like the marijuana/schizophrenia thing is analogous to the hemophiliac gettings shot in the wrist. Some percentage of the population that is already at risk really really needs to stay off the chronic.

  42. Fly 
     
    Thanks for the link, it’s interesting that they found Schiz so heritable. Maybe this study was at the high end or maybe certain genes really do create a lot of susceptability.  
     
    But regardless of the genes involved scientists know that maternal exposure to flu virus during the first trimester increases Schiz by about 700%! Ouch. The interesting part is that the flu virus doesn’t cause the damage. It’s the mothers immune response to the flu virus, specifically Interleukin-6 that triggers the damage. They know to look for flu virus but obviously any pathogen that triggers that protein can cause the damage that leads to Schiz. That’s going to be a LOT of things. Toxoplasma and possibly TBE appear to be instigators as well. 
     
    This link (and apparently whole site) is down right now but it talks about the 700% increase due to flu virus. 
    http://www.schizophrenia.com/sznews/archives/000458.html  
     
    (hope I got the 700% right, but the link is kaput)

  43. Yet another possible instigator. 
     
    Link found between Tick-borne encephalitis and schizophrenia 
     
    Kynurenic acid is usually present in low concentrations in the brain, but levels of the substance rise dramatically in the central nervous systems of people with TBE. The same phenomenon is seen in people with schizophrenia. 
     
    “Kynurenic acid is a substance in the brain which, put simply, can produce confusion,” said Schwieler.

  44. “the marijuana/schizophrenia thing is analogous to the hemophiliac gettings shot in the wrist. Some percentage of the population that is already at risk really really needs to stay off the chronic” 
     
    Kaleidoscopik, you have a way with words. This is EXACTLY the reason I stayed away from drugs. I’m only half sane now; I didn’t want to risk pushing myself over the edge. :)  
     
    Punnett Square: “I’ve never heard that Schiz or any other common mental disorder is that heritable.” 
     
    Pretty much ALL of them are heritable to some extent. It’s just usually not simple dominant inheritance, with a one-to-one correlation between gene and disorder– though bi-polar disorder approaches this. (In many family lines, a child of a bi-polar parent is shown to have nearly a 50% chance of themselves being bi-polar.)  
     
    ADHD also approaches simple dominant inheritance. (And correlates highly with the inheritance of the DRD4 7-repeat allele)

a