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

296 点作者 salmonet超过 9 年前

15 条评论

brndn超过 9 年前
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.<p>Edit: I&#x27;m glad to hear that he learned of this discovery before his death this month [0].<p>[0] - <a href="http:&#x2F;&#x2F;www.bizjournals.com&#x2F;boston&#x2F;blog&#x2F;bioflash&#x2F;2016&#x2F;01&#x2F;broad-donor-ted-stanley-learned-of-schizophrenia.html" rel="nofollow">http:&#x2F;&#x2F;www.bizjournals.com&#x2F;boston&#x2F;blog&#x2F;bioflash&#x2F;2016&#x2F;01&#x2F;broa...</a>
afro88超过 9 年前
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 &quot;dark&quot; dysfunctional subnet disconnected from the regular day to day brain&#x27;s network.<p>Then, if someone chooses to be under the influence of a drug that enables new pathways to form (pot, psychedelics etc), this &quot;dark&quot; network can potentially be reconnected. The emotional response to this connection (good or bad) strengthens this &quot;bridge&quot; 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.<p>The trick from here is to reinforce the normal network and ignore signals from the faulty network until the bridge path&#x27;s significance subsides enough to not enter day to day functioning.
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dang超过 9 年前
See also <a href="http:&#x2F;&#x2F;www.nytimes.com&#x2F;2016&#x2F;01&#x2F;28&#x2F;health&#x2F;schizophrenia-cause-synaptic-pruning-brain-psychiatry.html" rel="nofollow">http:&#x2F;&#x2F;www.nytimes.com&#x2F;2016&#x2F;01&#x2F;28&#x2F;health&#x2F;schizophrenia-cause...</a>, via <a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=10983176" rel="nofollow">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=10983176</a>.
lazyjones超过 9 年前
How do we distinguish the body&#x27;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 &quot;fix&quot; improperly wired neurons causing schizophrenia in a drastic way? The &quot;synaptic pruning&quot; genes might have evolved as a solution in lineages where schizophrenia was frequently passed on&#x2F;caused by parents&#x27; behavior. Too silly &#x2F; crazy?
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astazangasta超过 9 年前
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.
danieltillett超过 9 年前
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.
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ackfoo超过 9 年前
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.<p>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.<p>Imagine how disordered one&#x27;s thinking might become if we had no ability to interpret the spew with &quot;a grain of salt&quot;.
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nathan_f77超过 9 年前
&gt; 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.<p>I find this to be a terrifying thought. Just the idea that I have some code inside me that&#x27;s marking synapses for removal, and then they get removed. Those are my memories!<p>But I&#x27;m very excited about this. I&#x27;m not a geneticist by any means, but I hope the answer is as simple as replacing this gene with CRISPR.
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CamperBob2超过 9 年前
I&#x27;d be curious to hear how we developed successful pharmaceutical treatments for schizophrenia without knowing how the disease works. Was it just luck?
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tokenadult超过 9 年前
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<p>Gottesman, I. I., and J. Shields. &quot;Schizophrenia: geneticism and environmentalism.&quot; Human heredity 21.6 (1971): 517-522.<p>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.<p>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.<p>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, &quot;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&#x27;s analyses suggest that hundreds and more likely thousands of individual genes contribute to the liability to schizophrenia.&quot;[3]<p>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&#x27;s a start, and finding out things like this is the research to support basic science research.<p>[1] <a href="http:&#x2F;&#x2F;www.psych.umn.edu&#x2F;people&#x2F;profile.php?UID=gotte003" rel="nofollow">http:&#x2F;&#x2F;www.psych.umn.edu&#x2F;people&#x2F;profile.php?UID=gotte003</a><p><a href="https:&#x2F;&#x2F;news.virginia.edu&#x2F;content&#x2F;irving-gottesman-retired-psychology-professor-awarded-groundbreaking-research" rel="nofollow">https:&#x2F;&#x2F;news.virginia.edu&#x2F;content&#x2F;irving-gottesman-retired-p...</a><p>[2] <a href="http:&#x2F;&#x2F;www.virginia.edu&#x2F;topnews&#x2F;textonlyarchive&#x2F;March_1994&#x2F;94-03-10_Identical_Twins_Do_Not_Have_Identical_Risk_of_Mental_Illness,_New_Book_Shows.txt" rel="nofollow">http:&#x2F;&#x2F;www.virginia.edu&#x2F;topnews&#x2F;textonlyarchive&#x2F;March_1994&#x2F;9...</a><p><a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=lzDPlktZrGI" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=lzDPlktZrGI</a><p>[3] <a href="https:&#x2F;&#x2F;global.oup.com&#x2F;academic&#x2F;product&#x2F;how-genes-influence-behavior-9780199559909?cc=us&amp;lang=en&amp;" rel="nofollow">https:&#x2F;&#x2F;global.oup.com&#x2F;academic&#x2F;product&#x2F;how-genes-influence-...</a>
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amelius超过 9 年前
IANAB (not a biologist), so I wonder if the same approach can be used to study other mental disorders, such as anxiety and depression.
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bitL超过 9 年前
Funny, nature&#x27;s off-by-one&#x2F;buffer overflow error...
Estragon超过 9 年前
Oh, look, another genome-wide association study found a suggestive correlation. Didn&#x27;t we learn our lesson about this kind of bullshit in the Zeros?
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lutusp超过 9 年前
Wait, what? Does this means schizophrenia isn&#x27;t caused by refrigerator moms, as psychiatry once claimed (<a href="https:&#x2F;&#x2F;en.wikipedia.org&#x2F;wiki&#x2F;Refrigerator_mother_theory" rel="nofollow">https:&#x2F;&#x2F;en.wikipedia.org&#x2F;wiki&#x2F;Refrigerator_mother_theory</a>)? And that endless therapy won&#x27;t actually do any good, contrary to what psychiatrists and psychologists have held?<p>I expect to watch neuroscience nibble away at the territory now held by psychology, until (as Lewis Carroll wrote about the Cheshire Cat) there&#x27;s nothing left but the smile.
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mc_hammer超过 9 年前
Fake and gay.<p>Founder of psychiatry drove around in a lobotomobile for 40 years giving lobotomies to haunted people for $25 each.<p>(With an icepick) (Check the movie&#x2F;wikipedia lobotomobile)<p>the treatments since then have gotten only slightly less barbaric, like being tied down for 20 hours a day, or drugged and locked away.<p>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&#x2F;4 the population (maybe 1&#x2F;2).
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