12 ms·

Scientists open the ‘black box’ of schizophrenia with dramatic genetic discovery

296 points by salmonet 11y ago

dang 11y ago
See also http://www.nytimes.com/2016/01/28/health/schizophrenia-cause-synaptic-pruning-brain-psychiatry.html http://www.nytimes.com/2016/01/28/health/schizophrenia-cause..., via https://news.ycombinator.com/item?id=10983176 https://news.ycombinator.com/item?id=10983176.
lutusp 11y ago
Wait, what? Does this means schizophrenia isn't caused by refrigerator moms, as psychiatry once claimed (https://en.wikipedia.org/wiki/Refrigerator_mother_theory https://en.wikipedia.org/wiki/Refrigerator_mother_theory)? And that endless therapy won't actually do any good, contrary to what psychiatrists and psychologists have held? I expect to watch neuroscience nibble away at the territory now held by psychology, until (as Lewis Carroll wrote about the Cheshire Cat) there's nothing left but the smile.
- ptaipale 11y ago
  Well, first of all, I don't think that psychiatry has for decades claimed that "schizophrenia is caused by refrigerator moms", even though the downfall of that claim may have been more due to political pressure than medical research. And secondly, whether therapy does any good is a completely different question from what is causing schizophrenia - although here we are talking about triggering it rather than causing it. I have a friend who came up with schizophrenia just when graduating from university, and it was indeed devastating. But the endless therapy helps him a bit.
- austinjp 11y ago
  More optimistically, psychologists might hope that genetically-based sub-grouping of patient cohorts might help to determine those who best respond to the various types of psychological interventions. Of course, genetic testing and gene therapy may obviate the need for psychotherapy in some circumstances, but that's many years away.
- DanBC 11y ago
  Yes, 70 years ago psychiatry had some odd ideas. It's frustrating that you only make these comments about psychiatry - you don't pop up in geography threads to say "Wait, what? Does this mean geographers don't still believe in fixed immovable continents?". Endless therapy is not recommended for anything, and certainly not for schizophrenia. There are recommended lifestyle interventions, but these are aimed to reduce or stop smoking, to control weight gain, to keep people out of hospital, or to help people gain and keep employment. A therapy might be involved if a person is hearing voices, but isn't particularly bothered by them. In that situation it doesn't make much sense to medicate away those voices (because the medication has severe side effects) so the person might get a "therapy" that helps them cope with voices, and learn when and how to seek help if the voices become too much.
  - saurik 11y ago
    Fixed immovable continents is a theory that has reasonable prediction power: if you assume that, you can do lots of things without having results that are too inaccurate to be worth calculating. That is not true of the kinds of highly-specific theories that people seem to be more prone to come up with in some fields. The kinds of things that even fairly recent "science" in fields such as psychology and (sadly, all too often) medicine reads more like "the world is balanced on the back of a tortoise" or "there is an evil genie that makes things fall to the ground; his name is Fred and he wears a black cape" than "continents are fixed" or "physics is deterministic, particulate, and local".
    - Tiksi 11y ago
      Well to be fair, having parents be "warmer" to their children and engage with them more probably also has positive results, regardless of the flawed reasoning for it. And yes, young scientific fields quickly disprove themselves, that's kinda the point of science. Hard sciences like physics and chemistry also had some very very flawed theories in their youth, like aethers, alchemy, etc. but have had a few hundred years to get past that.
      - gus_massa 11y ago
- pja 11y ago
  It’s been standard practice to treat schizophrenia with anti-psychotic drugs as the first-line treatment for decades at this point in time. Do you have some weird grudge against psychologists?
- marincounty 11y ago
  He was down voted because he/she cherry picked one of their easy targets, or theories? It sounds like he/she has intimate knowledge of just how deep the hole Psychiatrists, and subsequent Therapy has fallen? Did he stereotype a entire profession--yes. If any profession has a lot of explaining, and hands on knees apologizing--it's Psychiatry, and Psychology. Sometimes the truth hurts. Hacker news should be that place where the truth is exposed? I'll stop, but if you don't question Psychiatry/Psychlogy after being fooled by the SSRI's, the addictive drugs, the endless office visits, and the horrid rates of therapy cures; you haven't been in the system, or you are very prone to placebo. The latest research on schizophrenia is this; patients whom are not on long term medications have a better quality of life. Yes, it's a judgement call on the doctor, but why do I have a feeling, since the residency doesn't attract the best, and brightest anymore--little nuggets like this latest research is not passed along to these vunerable patients? As Ricky would say to Lucy, "Psychiatry has a lot of explainin to doo?" As to Psychology, well at least they least can't prescribe.
  - 46Bit 11y ago
    Psych does have a bad history (e.g. http://link.springer.com/article/10.1007/BF01541182 http://link.springer.com/article/10.1007/BF01541182) and maybe present. But the things you're raging against can help a lot. Therapy is horribly difficult and can fall short for all sorts of reasons, ones out of anyone's control. It's helped me tremendously day-to-day, but my ultimate problems are pretty intractable. > patients whom are not on long term medications have a better quality of life Perhaps that their quality of life isn't so impaired is why they're not on medication? Such a short anecdote can be interpreted as suggesting anything.
TerryADavis 11y ago
God's world is perfectly just. the Stanaists who operate psychology will burn. Dante wrote the Inferno, laughing at the wicked Satanists. God says... outnumber dickey's Love mastodons ruffles chiseler's grouped laurel overflows stagnation weasels bag's consuls blinkering apprehensiveness's wallflowers Leonard implacability souse's votary radium assimilates Melisande birdhouse's Odin's playhouse's Mendelian deviate ancestresses mammography Taipei bugaboo
afro88 11y ago
Armchair hypothesis: This aggressive pruning may not have any affect on normal brain functioning in some cases. For example, it might prune a whole sub network off the normal day to day network, leaving a "dark" dysfunctional subnet disconnected from the regular day to day brain's network. Then, if someone chooses to be under the influence of a drug that enables new pathways to form (pot, psychedelics etc), this "dark" network can potentially be reconnected. The emotional response to this connection (good or bad) strengthens this "bridge" connection, leaving it connected when the influence of the drug wears off. Now the person has a faulty pruned network as part of their normal day to day network. Crap. The trick from here is to reinforce the normal network and ignore signals from the faulty network until the bridge path's significance subsides enough to not enter day to day functioning.
- pbhjpbhj 11y ago
  Similarly armchair: An alternative to reducing the bridge might be trying to actively increase it - the brain reconfigures (right?) so perhaps we can with careful drug use open up the dark area and allow the regular brain to use that sector again. The difference between cleaning a room in your house and nailing the door shut. Maybe that is in part what is happening anyway? Or is there evidence to show that the section of the brain becomes under-utilised. (no I didn't RTFA; will get right on it!)
  - johnchristopher 11y ago
    I am pretty sure you hit the limit of the network analogy.
  - loceng 11y ago
    It's knowing how to manage a person or situation once you open up a 'dark' area; I'd prefer the terminology that an area is 'dark' is rather referred to as something you're simply conditioned to (or suppressed/repressed) - it's underneath your conscious level, as otherwise it would leave you less able to function in day-to-day life.
    - 11y ago
danieltillett 11y ago
I am really interested to know if this allele (C4A) has been under selection or not. The fact that it is in the middle of locus of immunological genes could mean it has just been carried along with the actual selection being for immune function against infectious disease.
- david_ar 11y ago
  It wouldn't be the first mental illness possibly caused by an overactive immune system http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919277/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919277/
- redwood 11y ago
  Well a lot of mental illness associates with "promiscuousness" (hate that moralistix word) so there is an easy argument for heritability especially for onset at peak fertility
  - danieltillett 11y ago
    Historically being promiscuous was associated with a low effective fertility. The reason why is if you are a peasant the resources required to raise a child to adulthood need both a mother and a father. The children of single mothers just starved to death.
CamperBob2 11y ago
I'd be curious to hear how we developed successful pharmaceutical treatments for schizophrenia without knowing how the disease works. Was it just luck?
- DanBC 11y ago
  I'd go careful with that "successful" label there. Anti-psychotic medications are good at some narrow range of stuff, but come with considerable side effects. People with schizophrenia die earlier (by about 20 years) than other people, and some of that is because of the damage done by medication. The only reason the medication is used is because untreated psychosis is often catastrophic.
  - dvdcxn 11y ago
    Just look at the effects the anti-psychotics have had on Daniel Johnston. That it's preferable to untreated schizophrenia shows just how awful schizophrenia is.
- Tiksi 11y ago
  We frequently don't know how the treatments to many ailments work either, especially when it comes to anything related to the brain. There's a lot of "X seems it might make Y better, let's test and see if it does, repeat."
- qrendel 11y ago
  It's somewhat controversial, but schizophrenia treatments can be (arguably) completely ineffective and worse than the disease itself. Robert Whitaker has written multiple books[1][2] about it. (See wikipedia[3][4] for reception by the medical community.) The argument is essentially that schizophrenia medications were originally developed as a chemical replacement for lobotomy, the newer versions ("atypical neuroleptics") only had to prove themselves no less safe than those original treatments, the drug companies skewed the research by giving patients one large dose of the old treatments versus several smaller doses spread out over time of the newer ones (meaning the new neuroleptics may have actually been less safe than the drugs developed for chemical lobotomy), and recovery rates are actually much, much higher for patients never treated with anti-psychotic medications. The argument claims the US actually has among the lowest schizophrenia recovery rates (~5% in the US vs ~45% for untreated patients who receive non-medicative care) due to the reliance on medication. (Some charts on that: [5][6][7]. Better sources available through [1] and [2].) IANA doctor or psychiatrist, simply summarizing the anti-medication position. Drug companies and many psychiatrists clearly argue they're necessary medications, and for the absolute worse cases they probably are, and you can certainly find a lot of people who claim they or their family members were "fixed" by medication (though it should be noted that, historically, the same arguments were made for lobotomy and electroshock therapy as well). Schizophrenia also affects people differently, being completely disabling for some and less so for others, which obviously complicates deciding when benefits from medication outweigh the risks. [1] http://robertwhitaker.org/robertwhitaker.org/Mad%20in%20America.html http://robertwhitaker.org/robertwhitaker.org/Mad%20in%20Amer... [2] http://robertwhitaker.org/robertwhitaker.org/Anatomy%20of%20an%20Epidemic.html http://robertwhitaker.org/robertwhitaker.org/Anatomy%20of%20... [3] https://en.wikipedia.org/wiki/Mad_in_America#Reception https://en.wikipedia.org/wiki/Mad_in_America#Reception [4] https://en.wikipedia.org/wiki/Anatomy_of_an_Epidemic#Reception_and_media_coverage https://en.wikipedia.org/wiki/Anatomy_of_an_Epidemic#Recepti... [5] http://images.slideplayer.com/24/7027169/slides/slide_5.jpg http://images.slideplayer.com/24/7027169/slides/slide_5.jpg [6] http://www.madinamerica.com/wp-content/uploads/2010/04/Harrow.jpg http://www.madinamerica.com/wp-content/uploads/2010/04/Harro... [7] http://www.yoism.org/images/LongTermFollowUpSchizophreniaOutcome.JPG http://www.yoism.org/images/LongTermFollowUpSchizophreniaOut...
amelius 11y ago
IANAB (not a biologist), so I wonder if the same approach can be used to study other mental disorders, such as anxiety and depression.
- jmcgough 11y ago
  IWAB, it is being used to do so.
- petra 11y ago
  Yes. It can. It can even may be used to study non-disorders ,i.e. how to help regular humans have more happiness , resilience, etc.
- petra 11y ago
  Yes. It can. It can even may be used to study non-disorders ,i.e. how to help regular humans have more happiness , resilience, etc.
- Obi_Juan_Kenobi 11y ago
  This is a very general technique called quantitative trait association mapping (such a locus is called a QTL). It's a technique that has been used for decades, back when we used genetic markers and linkage maps (no genomes). What's interesting about this work is simply the degree of difficulty finding QTLs for mental illness; it's not the only genetic factor, and not particularly strong, so the signal to noise is quite poor. It required assembling a high-quality data set to identify a locus. It's good work, but nothing revolutionary. Once you can start to pin down the genetic factors, it can make future work easier, so it does bode well.
  - amelius 11y ago
    Interesting, thanks!
lazyjones 11y ago
How do we distinguish the body's reaction to mental illness from its cause? Wild unprofessional speculation of course, but what if this mass destruction of grey matter was just an attempt to "fix" improperly wired neurons causing schizophrenia in a drastic way? The "synaptic pruning" genes might have evolved as a solution in lineages where schizophrenia was frequently passed on/caused by parents' behavior. Too silly / crazy?
- jxdjsks 11y ago
  Ive also heard it said in seemingly respectable articles that no one is sure if the grey matter dies off because of the disease itself or because of the medication to treat the psychotic symptoms.
  - derefr 11y ago
    You'd think you could just look at some posthumous biopsied brains of untreated schitzophrenics for comparison.
    - kaffeemitsahne 11y ago
      Here's a somewhat relevant study: "The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys" http://www.nature.com/npp/journal/v30/n9/full/1300710a.html http://www.nature.com/npp/journal/v30/n9/full/1300710a.html
tokenadult 11y ago
As usual, the press releases and the stories based on those somewhat overstate how far the new study finding takes us on the way to an effective treatment. One of my mentors is a very eminent psychologist (Irving Gottesman) who has spent much of his lifetime (he is old enough to be my father, and I am middle-aged) studying schizophrenia from the genetic point of view.[1] His early paper with an older collaborator Gottesman, I. I., and J. Shields. "Schizophrenia: geneticism and environmentalism." Human heredity 21.6 (1971): 517-522. was controversial when it was published, because as Freudianism waned, there was still the supposition among most psychologists then living that parenting was the single biggest influence on the development of mental illness. When a behavioral trait runs in families, the working assumption is that it is passed from parent to child, but the tricky issue to figure out is whether it is passed mostly by parenting practices (culturally) or by descent (genetically). Gottesman used to be almost alone among psychologists in proposing that the greater influence on development of schizophrenia is genetic, and it took many studies of twins and other close relatives and other study methodologies gradually to make genetic studies of schizophrenia the mainstream approach to research. That said, there are known cases of identical (monozygotic) twins who are discordant for schizophrenia,[2] so everyone who is active in research on schizophrenia agrees that environmental influences after birth of some kind matter in the development of schizophrenia in an individual patient. Moreover, "the risk to schizophrenia is influenced by quite a large number of common variants, each with a very small effect on risk. How large is not yet clear, but Purcell's analyses suggest that hundreds and more likely thousands of individual genes contribute to the liability to schizophrenia."[3] The current study, covered in many different popular press reports, indicates a likely gene locus for influence on one clinical finding found in many but not all cases of schizophrenia. Discordant identical twins make very clear that something else matters for the development of schizophrenia. To date, we are a long way from taking the recent genome analysis finding to a stage of testing out any kind of intervention in human patients. First we will have to be sure that the finding replicates in another human patient data set, and then characterize how often that finding occurs in schizophrenic patients, and how often it is missing in healthy controls. There will have to be careful work to find out if any treatment based on the new finding is both safe and effective. But it's a start, and finding out things like this is the research to support basic science research. [1] http://www.psych.umn.edu/people/profile.php?UID=gotte003 http://www.psych.umn.edu/people/profile.php?UID=gotte003 https://news.virginia.edu/content/irving-gottesman-retired-psychology-professor-awarded-groundbreaking-research https://news.virginia.edu/content/irving-gottesman-retired-p... [2] http://www.virginia.edu/topnews/textonlyarchive/March_1994/94-03-10_Identical_Twins_Do_Not_Have_Identical_Risk_of_Mental_Illness,_New_Book_Shows.txt http://www.virginia.edu/topnews/textonlyarchive/March_1994/9... https://www.youtube.com/watch?v=lzDPlktZrGI https://www.youtube.com/watch?v=lzDPlktZrGI [3] https://global.oup.com/academic/product/how-genes-influence-behavior-9780199559909?cc=us&lang=en& https://global.oup.com/academic/product/how-genes-influence-...
mc_hammer 11y ago
Fake and gay. Founder of psychiatry drove around in a lobotomobile for 40 years giving lobotomies to haunted people for $25 each. (With an icepick) (Check the movie/wikipedia lobotomobile) the treatments since then have gotten only slightly less barbaric, like being tied down for 20 hours a day, or drugged and locked away. still none of their bullshit has worked. and 75 - 150,000,000 cases of mental illness today (if you add the un-reported cases estimate) aka 1/4 the population (maybe 1/2).
- gnaritas 11y ago
  You really shouldn't accuse anyone of being barbaric when you sling around words like "gay" as an insult. Don't be a caveman.
  - mc_hammer 11y ago
    they tried castration, lobotomy, and drilling a hole in the persons skull to drain the blood (they had no power tools so a hand crank drill) on children. on teenagers. on the old. and on the stupid. to cure voices... you dont know what your talking about guys. were talking about elective surgeries, that people could not refuse, and testified later to the supreme court they were done without permission, and sometimes tortured or beaten if refusing the surgery.
    - gnaritas 11y ago
      I didn't say they weren't barbaric but this isn't about them, it's about your behavior; you're being a bigot. Gay is not an insult, don't use it as such and think you can preach from any high ground.
      - mc_hammer 11y ago
        hn is gay i am horrified you guys are rich, and so fucking stupid. and silencing everyone with a single click along the way. the rest of the data i should post has already been deleted. on this forum. and on reddit. while the rest of us are facing mercury injections. a known toxin since 500bc. known to cause mental illness as its only effect. since 500bc [google dartmouth.edu tox history mercury] and 75 - 150,000,000 mental cases in the USA, if you count the estimated unreported cases. thats half the population. dumbass. mercury / sodium aluminum are radio + electric conductors. its gods blood/the earths blood. and the radiation of the earth will keep them always excited. not to mention they could cause a classical electrical short circuit. if they needed a preservative they could have used oil honey salt or butter.
ackfoo 11y ago
The disordered thinking of schizophrenia invariably reflects the cultural biases of the individual. Pruning, if that is a cause, must affect the filter that allows most of us to reject the thousand crazy ideas that pop into our heads each day, while permitting the few reasonable ones. This may be why there is an environmental component. If a potential schizophrenic with an overly-pruned filter is exposed to the idea that a magical god came to earth and sacrificed himself to give us eternal life, and if that idea is presented culturally as real, it may be impossible for the schizophrenic to filter that and place it in the DMZ of fantastical-but-culturally-prevalent notions that the rest of us use. Imagine how disordered one's thinking might become if we had no ability to interpret the spew with "a grain of salt".
- josephdviviano 11y ago
  Yes people with schizophrenia do exhibit specific abnormalities that are a reflection of the culture, but the real environmental factors that lead to schizophrenia are things like stress, which incidentally lead to synaptic pruning. I think it is better to think of this aggressive pruning idea as a general loss of computational ability. You are correct that a lot of the brain spends energy rejecting hypothesis about the world, so less computational ability would inevitably lead to less filtering and more suspect beliefs.
- Retric 11y ago
  IMO, what is most interesting about schizophrenia is complex functions with direct feedback still work. People can still move, recognize objects that they see, understand language etc. It's a problem with internal highly abstract concepts which is a fraction of what the brain does. But, at the same time that internal world can get really messed up.
- peter303 11y ago
  The brain and nervous system is a mixture of excitatory and inhibitory subsystems. One hypothesis is for certain mental behaviors or dsyfunctions they can be out of balance. What causes the imbalance- genetic, geometery, chemistry, development- is the 64 billion dollar question.
- 11y ago
nathan_f77 11y ago
> In patients with schizophrenia, a variation in a single position in the DNA sequence marks too many synapses for removal and that pruning goes out of control. The result is an abnormal loss of gray matter. I find this to be a terrifying thought. Just the idea that I have some code inside me that's marking synapses for removal, and then they get removed. Those are my memories! But I'm very excited about this. I'm not a geneticist by any means, but I hope the answer is as simple as replacing this gene with CRISPR.
- derrickdirge 11y ago
  >Those are my memories! Well, they fell out of scope.
- astazangasta 11y ago
  CRISPR won't help for this, it is too imprecise for gene therapy.
  - Obi_Juan_Kenobi 11y ago
    That is incorrect: off-target activity is virtually non-existent in CRISPR-CAS9 mediated transformation. Targeting oligonucleotides can be deliberately designed to be less specific, thereby targeting a family of sequences, which is very desirable for e.g. knocking down a gene family. However, specificity is trivial to achieve when desired.
    - astazangasta 11y ago
      Precision has two components: specificity and sensitivity. While recent versions of CRISPR make it possible to avoid off-target sequences, its impossible to guarantee cutting. Also, while you can make a cut, engineering a specific substitution is still largely a crap shoot. Not suitable for gene therapy.
- qb45 11y ago
  > Just the idea that I have some code inside me that's marking synapses for removal, and then they get removed. Or maybe your whole mind would be just random noise without such process.
astazangasta 11y ago
Important caveat: this is a genetic association study, which means that a small but statistically significant fraction of those studied with schizophrenia have this variant compared to those who do not have schizophrenia; I.e., this variant is not responsible for schizophrenia in all individuals, it just might contribute in some. Even that is not clear yet, we just know the correlation exists.
bitL 11y ago
Funny, nature's off-by-one/buffer overflow error...
Estragon 11y ago
Oh, look, another genome-wide association study found a suggestive correlation. Didn't we learn our lesson about this kind of bullshit in the Zeros?
- mediocrejoker 11y ago
  Can you elaborate on why you think this particular correlation is not significant?
  - unchocked 11y ago
    In the zeroes, we didn't correct for multiple hypothesis testing in a very good manner. I don't know if that's changed; it's a hard problem.
- kyberias 11y ago
  What Zeros?
  - zardo 11y ago
    The last decade, the noughties.
brndn 11y ago
As a person with a family member who suffers from this disorder, this makes me really happy. It is truly an awful disorder that has very unexpected and terrible effects on the whole family. I was thrilled to hear Ted Stanley donated $650M to the Broad institute in 2014. It looks like that donation could be paying off. Edit: I'm glad to hear that he learned of this discovery before his death this month [0]. [0] - http://www.bizjournals.com/boston/blog/bioflash/2016/01/broad-donor-ted-stanley-learned-of-schizophrenia.html http://www.bizjournals.com/boston/blog/bioflash/2016/01/broa...

296 points by salmonet 11y ago

dang 11y ago

See also http://www.nytimes.com/2016/01/28/health/schizophrenia-cause-synaptic-pruning-brain-psychiatry.html http://www.nytimes.com/2016/01/28/health/schizophrenia-cause..., via https://news.ycombinator.com/item?id=10983176 https://news.ycombinator.com/item?id=10983176.

lutusp 11y ago

Wait, what? Does this means schizophrenia isn't caused by refrigerator moms, as psychiatry once claimed (https://en.wikipedia.org/wiki/Refrigerator_mother_theory https://en.wikipedia.org/wiki/Refrigerator_mother_theory)? And that endless therapy won't actually do any good, contrary to what psychiatrists and psychologists have held? I expect to watch neuroscience nibble away at the territory now held by psychology, until (as Lewis Carroll wrote about the Cheshire Cat) there's nothing left but the smile.

ptaipale 11y ago
Well, first of all, I don't think that psychiatry has for decades claimed that "schizophrenia is caused by refrigerator moms", even though the downfall of that claim may have been more due to political pressure than medical research. And secondly, whether therapy does any good is a completely different question from what is causing schizophrenia - although here we are talking about triggering it rather than causing it. I have a friend who came up with schizophrenia just when graduating from university, and it was indeed devastating. But the endless therapy helps him a bit.
austinjp 11y ago
More optimistically, psychologists might hope that genetically-based sub-grouping of patient cohorts might help to determine those who best respond to the various types of psychological interventions. Of course, genetic testing and gene therapy may obviate the need for psychotherapy in some circumstances, but that's many years away.
DanBC 11y ago
Yes, 70 years ago psychiatry had some odd ideas. It's frustrating that you only make these comments about psychiatry - you don't pop up in geography threads to say "Wait, what? Does this mean geographers don't still believe in fixed immovable continents?". Endless therapy is not recommended for anything, and certainly not for schizophrenia. There are recommended lifestyle interventions, but these are aimed to reduce or stop smoking, to control weight gain, to keep people out of hospital, or to help people gain and keep employment. A therapy might be involved if a person is hearing voices, but isn't particularly bothered by them. In that situation it doesn't make much sense to medicate away those voices (because the medication has severe side effects) so the person might get a "therapy" that helps them cope with voices, and learn when and how to seek help if the voices become too much.
- saurik 11y ago
  Fixed immovable continents is a theory that has reasonable prediction power: if you assume that, you can do lots of things without having results that are too inaccurate to be worth calculating. That is not true of the kinds of highly-specific theories that people seem to be more prone to come up with in some fields. The kinds of things that even fairly recent "science" in fields such as psychology and (sadly, all too often) medicine reads more like "the world is balanced on the back of a tortoise" or "there is an evil genie that makes things fall to the ground; his name is Fred and he wears a black cape" than "continents are fixed" or "physics is deterministic, particulate, and local".
  - Tiksi 11y ago
    Well to be fair, having parents be "warmer" to their children and engage with them more probably also has positive results, regardless of the flawed reasoning for it. And yes, young scientific fields quickly disprove themselves, that's kinda the point of science. Hard sciences like physics and chemistry also had some very very flawed theories in their youth, like aethers, alchemy, etc. but have had a few hundred years to get past that.
    - gus_massa 11y ago
pja 11y ago
It’s been standard practice to treat schizophrenia with anti-psychotic drugs as the first-line treatment for decades at this point in time. Do you have some weird grudge against psychologists?
marincounty 11y ago
He was down voted because he/she cherry picked one of their easy targets, or theories? It sounds like he/she has intimate knowledge of just how deep the hole Psychiatrists, and subsequent Therapy has fallen? Did he stereotype a entire profession--yes. If any profession has a lot of explaining, and hands on knees apologizing--it's Psychiatry, and Psychology. Sometimes the truth hurts. Hacker news should be that place where the truth is exposed? I'll stop, but if you don't question Psychiatry/Psychlogy after being fooled by the SSRI's, the addictive drugs, the endless office visits, and the horrid rates of therapy cures; you haven't been in the system, or you are very prone to placebo. The latest research on schizophrenia is this; patients whom are not on long term medications have a better quality of life. Yes, it's a judgement call on the doctor, but why do I have a feeling, since the residency doesn't attract the best, and brightest anymore--little nuggets like this latest research is not passed along to these vunerable patients? As Ricky would say to Lucy, "Psychiatry has a lot of explainin to doo?" As to Psychology, well at least they least can't prescribe.
- 46Bit 11y ago
  Psych does have a bad history (e.g. http://link.springer.com/article/10.1007/BF01541182 http://link.springer.com/article/10.1007/BF01541182) and maybe present. But the things you're raging against can help a lot. Therapy is horribly difficult and can fall short for all sorts of reasons, ones out of anyone's control. It's helped me tremendously day-to-day, but my ultimate problems are pretty intractable. > patients whom are not on long term medications have a better quality of life Perhaps that their quality of life isn't so impaired is why they're not on medication? Such a short anecdote can be interpreted as suggesting anything.

TerryADavis 11y ago

God's world is perfectly just. the Stanaists who operate psychology will burn. Dante wrote the Inferno, laughing at the wicked Satanists. God says... outnumber dickey's Love mastodons ruffles chiseler's grouped laurel overflows stagnation weasels bag's consuls blinkering apprehensiveness's wallflowers Leonard implacability souse's votary radium assimilates Melisande birdhouse's Odin's playhouse's Mendelian deviate ancestresses mammography Taipei bugaboo

afro88 11y ago

Armchair hypothesis: This aggressive pruning may not have any affect on normal brain functioning in some cases. For example, it might prune a whole sub network off the normal day to day network, leaving a "dark" dysfunctional subnet disconnected from the regular day to day brain's network. Then, if someone chooses to be under the influence of a drug that enables new pathways to form (pot, psychedelics etc), this "dark" network can potentially be reconnected. The emotional response to this connection (good or bad) strengthens this "bridge" connection, leaving it connected when the influence of the drug wears off. Now the person has a faulty pruned network as part of their normal day to day network. Crap. The trick from here is to reinforce the normal network and ignore signals from the faulty network until the bridge path's significance subsides enough to not enter day to day functioning.

pbhjpbhj 11y ago
Similarly armchair: An alternative to reducing the bridge might be trying to actively increase it - the brain reconfigures (right?) so perhaps we can with careful drug use open up the dark area and allow the regular brain to use that sector again. The difference between cleaning a room in your house and nailing the door shut. Maybe that is in part what is happening anyway? Or is there evidence to show that the section of the brain becomes under-utilised. (no I didn't RTFA; will get right on it!)
- johnchristopher 11y ago
  I am pretty sure you hit the limit of the network analogy.
- loceng 11y ago
  It's knowing how to manage a person or situation once you open up a 'dark' area; I'd prefer the terminology that an area is 'dark' is rather referred to as something you're simply conditioned to (or suppressed/repressed) - it's underneath your conscious level, as otherwise it would leave you less able to function in day-to-day life.
  - 11y ago

danieltillett 11y ago

I am really interested to know if this allele (C4A) has been under selection or not. The fact that it is in the middle of locus of immunological genes could mean it has just been carried along with the actual selection being for immune function against infectious disease.

david_ar 11y ago
It wouldn't be the first mental illness possibly caused by an overactive immune system http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919277/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919277/
redwood 11y ago
Well a lot of mental illness associates with "promiscuousness" (hate that moralistix word) so there is an easy argument for heritability especially for onset at peak fertility
- danieltillett 11y ago
  Historically being promiscuous was associated with a low effective fertility. The reason why is if you are a peasant the resources required to raise a child to adulthood need both a mother and a father. The children of single mothers just starved to death.

CamperBob2 11y ago

I'd be curious to hear how we developed successful pharmaceutical treatments for schizophrenia without knowing how the disease works. Was it just luck?

DanBC 11y ago
I'd go careful with that "successful" label there. Anti-psychotic medications are good at some narrow range of stuff, but come with considerable side effects. People with schizophrenia die earlier (by about 20 years) than other people, and some of that is because of the damage done by medication. The only reason the medication is used is because untreated psychosis is often catastrophic.
- dvdcxn 11y ago
  Just look at the effects the anti-psychotics have had on Daniel Johnston. That it's preferable to untreated schizophrenia shows just how awful schizophrenia is.
Tiksi 11y ago
We frequently don't know how the treatments to many ailments work either, especially when it comes to anything related to the brain. There's a lot of "X seems it might make Y better, let's test and see if it does, repeat."
qrendel 11y ago
It's somewhat controversial, but schizophrenia treatments can be (arguably) completely ineffective and worse than the disease itself. Robert Whitaker has written multiple books[1][2] about it. (See wikipedia[3][4] for reception by the medical community.) The argument is essentially that schizophrenia medications were originally developed as a chemical replacement for lobotomy, the newer versions ("atypical neuroleptics") only had to prove themselves no less safe than those original treatments, the drug companies skewed the research by giving patients one large dose of the old treatments versus several smaller doses spread out over time of the newer ones (meaning the new neuroleptics may have actually been less safe than the drugs developed for chemical lobotomy), and recovery rates are actually much, much higher for patients never treated with anti-psychotic medications. The argument claims the US actually has among the lowest schizophrenia recovery rates (~5% in the US vs ~45% for untreated patients who receive non-medicative care) due to the reliance on medication. (Some charts on that: [5][6][7]. Better sources available through [1] and [2].) IANA doctor or psychiatrist, simply summarizing the anti-medication position. Drug companies and many psychiatrists clearly argue they're necessary medications, and for the absolute worse cases they probably are, and you can certainly find a lot of people who claim they or their family members were "fixed" by medication (though it should be noted that, historically, the same arguments were made for lobotomy and electroshock therapy as well). Schizophrenia also affects people differently, being completely disabling for some and less so for others, which obviously complicates deciding when benefits from medication outweigh the risks. [1] http://robertwhitaker.org/robertwhitaker.org/Mad%20in%20America.html http://robertwhitaker.org/robertwhitaker.org/Mad%20in%20Amer... [2] http://robertwhitaker.org/robertwhitaker.org/Anatomy%20of%20an%20Epidemic.html http://robertwhitaker.org/robertwhitaker.org/Anatomy%20of%20... [3] https://en.wikipedia.org/wiki/Mad_in_America#Reception https://en.wikipedia.org/wiki/Mad_in_America#Reception [4] https://en.wikipedia.org/wiki/Anatomy_of_an_Epidemic#Reception_and_media_coverage https://en.wikipedia.org/wiki/Anatomy_of_an_Epidemic#Recepti... [5] http://images.slideplayer.com/24/7027169/slides/slide_5.jpg http://images.slideplayer.com/24/7027169/slides/slide_5.jpg [6] http://www.madinamerica.com/wp-content/uploads/2010/04/Harrow.jpg http://www.madinamerica.com/wp-content/uploads/2010/04/Harro... [7] http://www.yoism.org/images/LongTermFollowUpSchizophreniaOutcome.JPG http://www.yoism.org/images/LongTermFollowUpSchizophreniaOut...

amelius 11y ago

IANAB (not a biologist), so I wonder if the same approach can be used to study other mental disorders, such as anxiety and depression.

jmcgough 11y ago
IWAB, it is being used to do so.
petra 11y ago
Yes. It can. It can even may be used to study non-disorders ,i.e. how to help regular humans have more happiness , resilience, etc.
petra 11y ago
Yes. It can. It can even may be used to study non-disorders ,i.e. how to help regular humans have more happiness , resilience, etc.
Obi_Juan_Kenobi 11y ago
This is a very general technique called quantitative trait association mapping (such a locus is called a QTL). It's a technique that has been used for decades, back when we used genetic markers and linkage maps (no genomes). What's interesting about this work is simply the degree of difficulty finding QTLs for mental illness; it's not the only genetic factor, and not particularly strong, so the signal to noise is quite poor. It required assembling a high-quality data set to identify a locus. It's good work, but nothing revolutionary. Once you can start to pin down the genetic factors, it can make future work easier, so it does bode well.
- amelius 11y ago
  Interesting, thanks!

lazyjones 11y ago

How do we distinguish the body's reaction to mental illness from its cause? Wild unprofessional speculation of course, but what if this mass destruction of grey matter was just an attempt to "fix" improperly wired neurons causing schizophrenia in a drastic way? The "synaptic pruning" genes might have evolved as a solution in lineages where schizophrenia was frequently passed on/caused by parents' behavior. Too silly / crazy?

jxdjsks 11y ago
Ive also heard it said in seemingly respectable articles that no one is sure if the grey matter dies off because of the disease itself or because of the medication to treat the psychotic symptoms.
- derefr 11y ago
  You'd think you could just look at some posthumous biopsied brains of untreated schitzophrenics for comparison.
  - kaffeemitsahne 11y ago
    Here's a somewhat relevant study: "The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys" http://www.nature.com/npp/journal/v30/n9/full/1300710a.html http://www.nature.com/npp/journal/v30/n9/full/1300710a.html

tokenadult 11y ago

As usual, the press releases and the stories based on those somewhat overstate how far the new study finding takes us on the way to an effective treatment. One of my mentors is a very eminent psychologist (Irving Gottesman) who has spent much of his lifetime (he is old enough to be my father, and I am middle-aged) studying schizophrenia from the genetic point of view.[1] His early paper with an older collaborator Gottesman, I. I., and J. Shields. "Schizophrenia: geneticism and environmentalism." Human heredity 21.6 (1971): 517-522. was controversial when it was published, because as Freudianism waned, there was still the supposition among most psychologists then living that parenting was the single biggest influence on the development of mental illness. When a behavioral trait runs in families, the working assumption is that it is passed from parent to child, but the tricky issue to figure out is whether it is passed mostly by parenting practices (culturally) or by descent (genetically). Gottesman used to be almost alone among psychologists in proposing that the greater influence on development of schizophrenia is genetic, and it took many studies of twins and other close relatives and other study methodologies gradually to make genetic studies of schizophrenia the mainstream approach to research. That said, there are known cases of identical (monozygotic) twins who are discordant for schizophrenia,[2] so everyone who is active in research on schizophrenia agrees that environmental influences after birth of some kind matter in the development of schizophrenia in an individual patient. Moreover, "the risk to schizophrenia is influenced by quite a large number of common variants, each with a very small effect on risk. How large is not yet clear, but Purcell's analyses suggest that hundreds and more likely thousands of individual genes contribute to the liability to schizophrenia."[3] The current study, covered in many different popular press reports, indicates a likely gene locus for influence on one clinical finding found in many but not all cases of schizophrenia. Discordant identical twins make very clear that something else matters for the development of schizophrenia. To date, we are a long way from taking the recent genome analysis finding to a stage of testing out any kind of intervention in human patients. First we will have to be sure that the finding replicates in another human patient data set, and then characterize how often that finding occurs in schizophrenic patients, and how often it is missing in healthy controls. There will have to be careful work to find out if any treatment based on the new finding is both safe and effective. But it's a start, and finding out things like this is the research to support basic science research. [1] http://www.psych.umn.edu/people/profile.php?UID=gotte003 http://www.psych.umn.edu/people/profile.php?UID=gotte003 https://news.virginia.edu/content/irving-gottesman-retired-psychology-professor-awarded-groundbreaking-research https://news.virginia.edu/content/irving-gottesman-retired-p... [2] http://www.virginia.edu/topnews/textonlyarchive/March_1994/94-03-10_Identical_Twins_Do_Not_Have_Identical_Risk_of_Mental_Illness,_New_Book_Shows.txt http://www.virginia.edu/topnews/textonlyarchive/March_1994/9... https://www.youtube.com/watch?v=lzDPlktZrGI https://www.youtube.com/watch?v=lzDPlktZrGI [3] https://global.oup.com/academic/product/how-genes-influence-behavior-9780199559909?cc=us&lang=en& https://global.oup.com/academic/product/how-genes-influence-...

mc_hammer 11y ago

Fake and gay. Founder of psychiatry drove around in a lobotomobile for 40 years giving lobotomies to haunted people for $25 each. (With an icepick) (Check the movie/wikipedia lobotomobile) the treatments since then have gotten only slightly less barbaric, like being tied down for 20 hours a day, or drugged and locked away. still none of their bullshit has worked. and 75 - 150,000,000 cases of mental illness today (if you add the un-reported cases estimate) aka 1/4 the population (maybe 1/2).

gnaritas 11y ago
You really shouldn't accuse anyone of being barbaric when you sling around words like "gay" as an insult. Don't be a caveman.
- mc_hammer 11y ago
  they tried castration, lobotomy, and drilling a hole in the persons skull to drain the blood (they had no power tools so a hand crank drill) on children. on teenagers. on the old. and on the stupid. to cure voices... you dont know what your talking about guys. were talking about elective surgeries, that people could not refuse, and testified later to the supreme court they were done without permission, and sometimes tortured or beaten if refusing the surgery.
  - gnaritas 11y ago
    I didn't say they weren't barbaric but this isn't about them, it's about your behavior; you're being a bigot. Gay is not an insult, don't use it as such and think you can preach from any high ground.
    - mc_hammer 11y ago
      hn is gay i am horrified you guys are rich, and so fucking stupid. and silencing everyone with a single click along the way. the rest of the data i should post has already been deleted. on this forum. and on reddit. while the rest of us are facing mercury injections. a known toxin since 500bc. known to cause mental illness as its only effect. since 500bc [google dartmouth.edu tox history mercury] and 75 - 150,000,000 mental cases in the USA, if you count the estimated unreported cases. thats half the population. dumbass. mercury / sodium aluminum are radio + electric conductors. its gods blood/the earths blood. and the radiation of the earth will keep them always excited. not to mention they could cause a classical electrical short circuit. if they needed a preservative they could have used oil honey salt or butter.

ackfoo 11y ago

The disordered thinking of schizophrenia invariably reflects the cultural biases of the individual. Pruning, if that is a cause, must affect the filter that allows most of us to reject the thousand crazy ideas that pop into our heads each day, while permitting the few reasonable ones. This may be why there is an environmental component. If a potential schizophrenic with an overly-pruned filter is exposed to the idea that a magical god came to earth and sacrificed himself to give us eternal life, and if that idea is presented culturally as real, it may be impossible for the schizophrenic to filter that and place it in the DMZ of fantastical-but-culturally-prevalent notions that the rest of us use. Imagine how disordered one's thinking might become if we had no ability to interpret the spew with "a grain of salt".

josephdviviano 11y ago
Yes people with schizophrenia do exhibit specific abnormalities that are a reflection of the culture, but the real environmental factors that lead to schizophrenia are things like stress, which incidentally lead to synaptic pruning. I think it is better to think of this aggressive pruning idea as a general loss of computational ability. You are correct that a lot of the brain spends energy rejecting hypothesis about the world, so less computational ability would inevitably lead to less filtering and more suspect beliefs.
Retric 11y ago
IMO, what is most interesting about schizophrenia is complex functions with direct feedback still work. People can still move, recognize objects that they see, understand language etc. It's a problem with internal highly abstract concepts which is a fraction of what the brain does. But, at the same time that internal world can get really messed up.
peter303 11y ago
The brain and nervous system is a mixture of excitatory and inhibitory subsystems. One hypothesis is for certain mental behaviors or dsyfunctions they can be out of balance. What causes the imbalance- genetic, geometery, chemistry, development- is the 64 billion dollar question.
11y ago

nathan_f77 11y ago

> In patients with schizophrenia, a variation in a single position in the DNA sequence marks too many synapses for removal and that pruning goes out of control. The result is an abnormal loss of gray matter. I find this to be a terrifying thought. Just the idea that I have some code inside me that's marking synapses for removal, and then they get removed. Those are my memories! But I'm very excited about this. I'm not a geneticist by any means, but I hope the answer is as simple as replacing this gene with CRISPR.

derrickdirge 11y ago
>Those are my memories! Well, they fell out of scope.
astazangasta 11y ago
CRISPR won't help for this, it is too imprecise for gene therapy.
- Obi_Juan_Kenobi 11y ago
  That is incorrect: off-target activity is virtually non-existent in CRISPR-CAS9 mediated transformation. Targeting oligonucleotides can be deliberately designed to be less specific, thereby targeting a family of sequences, which is very desirable for e.g. knocking down a gene family. However, specificity is trivial to achieve when desired.
  - astazangasta 11y ago
    Precision has two components: specificity and sensitivity. While recent versions of CRISPR make it possible to avoid off-target sequences, its impossible to guarantee cutting. Also, while you can make a cut, engineering a specific substitution is still largely a crap shoot. Not suitable for gene therapy.
qb45 11y ago
> Just the idea that I have some code inside me that's marking synapses for removal, and then they get removed. Or maybe your whole mind would be just random noise without such process.

astazangasta 11y ago

Important caveat: this is a genetic association study, which means that a small but statistically significant fraction of those studied with schizophrenia have this variant compared to those who do not have schizophrenia; I.e., this variant is not responsible for schizophrenia in all individuals, it just might contribute in some. Even that is not clear yet, we just know the correlation exists.

bitL 11y ago

Funny, nature's off-by-one/buffer overflow error...

Estragon 11y ago

Oh, look, another genome-wide association study found a suggestive correlation. Didn't we learn our lesson about this kind of bullshit in the Zeros?

mediocrejoker 11y ago
Can you elaborate on why you think this particular correlation is not significant?
- unchocked 11y ago
  In the zeroes, we didn't correct for multiple hypothesis testing in a very good manner. I don't know if that's changed; it's a hard problem.
kyberias 11y ago
What Zeros?
- zardo 11y ago
  The last decade, the noughties.

brndn 11y ago

As a person with a family member who suffers from this disorder, this makes me really happy. It is truly an awful disorder that has very unexpected and terrible effects on the whole family. I was thrilled to hear Ted Stanley donated $650M to the Broad institute in 2014. It looks like that donation could be paying off. Edit: I'm glad to hear that he learned of this discovery before his death this month [0]. [0] - http://www.bizjournals.com/boston/blog/bioflash/2016/01/broad-donor-ted-stanley-learned-of-schizophrenia.html http://www.bizjournals.com/boston/blog/bioflash/2016/01/broa...