This is absolutely fascinating. I want to stop everything I'm doing and contribute to science.
I've had this impulse my entire life, yet the economics of doing a PhD are so dystopian that the urge passes after a few minutes of rational thinking. So, what is HN's answer to the decline of institutional science? Projects like this will take decades, so crowdfunding is out.
A dozen Janelia Farms with long term funding from VCs would be great right about now.
>what is HN's answer to the decline of institutional science?
I'm not sure institutional science has declined - if anything things have gone the other way where it's hard to do science outside of an institution. Not entirely sure what the answer is. In hot areas companies will sometimes hire people to do interesting work without a PhD and even sponsor commercial work for a PhD. When I was graduating long ago, material science was hot and all the material science undergrads were offered well paid research jobs in industry providing they passed and stuff. Supply and demand I guess.
What was incredible, for me, was to realize and to accept that stress can trigger Schizophrenia. It sounds completely impossible when you first hear it. But if you look at the data, there is a very clear correlation between environmental stress factors and Schizophrenia. Until we discover a better explanation, we should accept that it's possible for stress to trigger Schizophrenia.
And that is so incredibly strange to me. How can nothing more than feeling bad for a long period of time eventually result in insanity? What have feelings got to do with physical, measurable deterioration in the brain? And yet it appears true.
To a certain degree, mind-body duality has persisted even in the absence of a belief in a "soul" -- it's just that we think of "body" and "brain" as separate entities, as if the brain is just piloting a meat-vessel around.
The key thing here is that feeling bad is completely inseparable from the physiological mechanisms that underlie it. At a very high, very superficial level, the stress mechanism is something like this:
The amygdala, which is responsible for integrating sensory perception with memory and emotional processing, determines when a situation is "stressful." The amygdala then signals the hypothalamus via the amygdalofugal pathway and stria terminalis. The hypothalamus secretes a number of hormones which basically prepare the body for fight-or-flight behavior. Of particular interest is corticotropin-releasing hormone (CRH) which, along with vasopressin, activates the hypothalamic-pituitary-adrenal, or HPA, axis -- the physiological mechanism of fight-or-flight.
CRH is responsible for stimulating the pituitary to release cortisol, which is an absolute sledgehammer of a hormone: it stimulates glucose synthesis (NEED MOAR ENERGY NAO!), regulates the sodium-potassium balance in an effort to stave off hyperkalemia (probably an adaptation to deal with tissue damage), reduces inflammation (through immunosuppression), constricts blood vessels, suppresses the parasympathetic nervous system (shutting down digestion -- not important when you're trying to avoid being eaten), and so on. These activities are the result of cortisol binding to glucocorticoid and mineralocorticoid receptors; such receptors are found in all kinds of tissues.
Cortisol also overwhelms the cortisol receptors of the hippocampus, which processes memory. The hippocampus appears to be part of the downregulatory subsystem of HPA axis homeostasis, but if its receptors are flooded, it becomes ineffective at suppressing HPA axis activities. This results in both the impairment of the memory-processing functions of the hippocampus, and a reduction in the negative-feedback mechanism of the HPA axis. In other words, you can't stop stressing, your comprehension is impaired, and your body is going into overdrive.
HPA axis stimulation is useful when stress is a rare event tied to things with sharp teeth; it's counterproductive when applied to our modern world, when stress is more likely to come from deadlines, traffic, and trying to find that last parking space at the mall on Black Friday.
It's hard to accept that a bad feeling is a result of a physical mechanism in your brain. It's obviously true. It's just hard to internalize, the same way you've internalized gravity. For example, if you accept that, then you must also accept this: It's within the capability of science to develop an anti-love potion. Want to fall out of love with someone? Drink the potion, or wear the headset. Doesn't matter how much you loved them before: you won't after.
I just want to say thank you for the absolutely stellar comment. It's the best I've read in quite awhile. Perhaps because it touches on so many mechanisms that fascinate me.
It's within the capability of science to one day develop an anti-love potion. Want to fall out of love with someone? Drink the potion, or wear the headset.
Actually, I have semi-jokingly suggested that friends in unrequited love take a certain class of antidepressant for a while, since this is one of the side effects -- it has a pretty good chance of working. So it may be easier to accept, although this is just n=1. (On the other hand, nobody has actually taken this advice..)
As someone with experience of psychiatric medicine, the way things are going at the moment in the field is, in fact, to over-emphasise the biological side of mental illness. It goes beyond the (unsubstantiated) idea that mental illnesses result from "chemical imbalances" for which no tests exist, to a total disregard for the social circumstances of the patient or their psychological profile. Sometimes the medical people will refer to a bio-psycho-social model, but it is mostly just lip service. If you want to see the Fundamental Attribution Error in action, psychiatry is the place to look. It's a variant of the FAE where the patient is held primarily responsible (through their biology) and their relationships with other people or current circumstances, or even upbringing, are ignored.
Ronnie Laing showed that for at least some sufferers from mental illness, taking them out of a pathological family environment would cause a remission. Release them back to their family, and they would get ill again. That was in the 1960s.
It can also be a result of physical mechanisms elsewhere in your body! The nervous system is large and complex. For example, feelings in your gut can trigger anxiety, and links have been studied between gut microflora and anxiety.
I'm not sure why it's hard to accept that stress can trigger schizophrenia.
Being stressed and feeling bad for prolonged periods of time can lead to a bunch of different psychological disorders.
I'm not sure if you're assuming Schizophrenia is an exclusively neurological/physiological problem, but stress also leads to physiological changes in the body, so yes, feels have an affect on us through and through :)
Stress increases your blood pressure, releases adrenaline, and forces your body to go into overdrive. Chronic stress will wear down your body faster.
Simple analogy: Drinking acidic fluids will wear down your enamel. Do it for a long time and eventually all of your enamel will be gone. That will cause lots of other problems.
Feeling "bad" i.e. stress, is probably wearing something down inside your brain. Once that "something" is gone lots of problems occur. Schizophrenia may be the result of that "something" being worn out.
There's quite a few mechanisms that can start to explain this.
We are a biological computer, and 'feeling bad' is an output of that. It's a chemical/genetic/'electric' state. We cannot perform an operation(feelings, movement, etc) without being affected by it at a very fundamental level. A well studied example would be dopamine [0].
This is a very complex, challenging, and interesting field.
We've since described retrotransposons that, while interesting, have both pathogenic and non-pathogenic purposes.
The term "junk DNA" in this article dates it; we've since found that this junk DNA is full of transposons, retrotransposons, miRNA, siRNA etc..., which is to say they are a great deal more interesting than the "junk" we once thought them to be.
The implication in Schizophrenia isn't something I've heard about, but this article is more of a description of how retrotransposons were discovered than anything to do with schizophrenia, although that's just hind-sight.
Hmmm, well, per Wikipedia (https://en.wikipedia.org/wiki/ERVWE1), it's a virus you might say we grabbed and re-purposed. In mice, there's "evidence for their absolute requirement for placenta development and embryo survival." And a couple of other genes of the original virus have been zapped. Call it a hack.
And I can't see anyone being that surprised that "Mutations in the HERV-W gene have been associated with multiple sclerosis and schizophrenia." If you mess with essential stuff, bad things can certainly happen. Although it could easily be somewhat more complicated, "correlation does not imply causation".
I guess I'm trying to say that where we got the genetic material from is more in the direction of a curiosity than something profound.
>>And I can't see anyone being that surprised that "Mutations in the HERV-W gene have been associated with multiple sclerosis and schizophrenia." If you mess with essential stuff, bad things can certainly happen.
This is a poor line of reasoning in biology where almost everything could be considered essential. As we understanding, the real question is if this can be used to find a mechanism or if elevated W type proteins can be used as an early detection scheme.
It appears GeNuero has found 47 million dollars from investment partner, Servier, and "GNbAC1 has successfully completed Phase IIa, demonstrating an optimal safety profile and encouraging signs of efficacy on a first small cohort of patients." http://www.geneuro.com/en/news.php#news
This is one of those articles that confirm a gut feeling I have had for years. I was of the opinion that wild flu viruses where responsible for some of these diseases. It is interesting to see research close in on the mechanics. What is the best source for current research in this area, or even better... is there a hacker news type forum for DNA cowboys?
The mechanism at play here is incredibly different from wild flu viruses. For one, they have to be a very rare type of virus called a retrovirus[0], like HIV, that becomes part of our genome [1].
These types of elements in our genes are very interesting. We are an organic computer. ERVs are some of the most successful viruses from a natural selection perspective.
I'm sorry to tell you that the evidence presented here does not support your gut feeling.
Don't be sorry :) . I understand that they are talking about retroviruses, but they suspect that the trigger is more common viruses included the toxo virus that has been getting so many fun write ups. Obviously there is still a whole bunch more to determine, and some of these hypothesis will be disproved, but the general idea i fascinating.
I've had this impulse my entire life, yet the economics of doing a PhD are so dystopian that the urge passes after a few minutes of rational thinking. So, what is HN's answer to the decline of institutional science? Projects like this will take decades, so crowdfunding is out.
A dozen Janelia Farms with long term funding from VCs would be great right about now.