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Comment by blindriver | Hacker News Reader

"Stress alone and stress combined with traumatic brain injury (TBI) produced a few noteworthy results. Both conditions activated pathways in excitatory and inhibitory neurons associated with plasticity, which is the brain's ability to adapt to all kinds of changes—mostly to promote flexibility, but sometimes, when the changes are maladaptive, resulting in negative outcomes. "

It's weird that this study is interpreted as changes in gene activation is bad, when it's clearly mostly good. It's like saying that micro-tearing of muscles during exercise is bad, when in fact that's the process which builds more muscles. Sure, some tears of muscle are bad, but it's mostly good, and I assume that the changes in gene expression in the brain are a form of growing and reacting to new situations, not necessarily bad.

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The two processes are not entirely analogous. They are both the result of the body reacting to external stress, and to become more fit for the environment that creates the stress. In the weightlifting example this is a positive change — the body gets stronger, as long as the exercise program is good.

In the TBI and trauma cases, though, the external stresses are negative, not positive, thus the adaptations are negative as well. Teach a young brain that the world is stressful and scary and the brain will remember this, and act that way even when removed to a less scary world.

The brain "remembering" has zero link with gene expression, which is what the entire article is about. In fact nothing you mention above responds to the question of gene expression. There's no evidence whatsoever that the change in behavior of an individual after stress is linked to differences in gene expression.

That's quite the sweeping claim. Some quick googling suggests otherwise.

"Chronic stress induces significant gene expression changes in the prefrontal cortex alongside alterations in adult hippocampal neurogenesis"

>In this study, unpredictable chronic mild stress in mice resulted in a deficit in neuronal dendritic tree development and neuroblast migration in the hippocampal neurogenic niche. To investigate molecular pathways underlying neurogenesis alteration, genome-wide gene expression changes were assessed in the prefrontal cortex, hippocampus and the hypothalamus alongside neurogenesis changes. Cluster analysis showed that the transcriptomic signature of chronic stress is much more prominent in the prefrontal cortex compared to the hippocampus and the hypothalamus. Pathway analyses suggested huntingtin, leptin, myelin regulatory factor, methyl-CpG binding protein and brain-derived neurotrophic factor as the top predicted upstream regulators of transcriptomic changes in the prefrontal cortex. Involvement of the satiety regulating pathways (leptin) was corroborated by behavioural data showing increased food reward motivation in stressed mice. Behavioural and gene expression data also suggested circadian rhythm disruption and activation of circadian clock genes such as Period 2.

[1] https://academic.oup.com/braincomms/article/2/2/fcaa153/5912...

You didn't read the paper, and you didn't understand it. It didn't make a link between gene expression and behavioral changes. It just noted a change in gene expression in a handful of mice, basically the same study as the above.

>Many target genes, upstream regulators and signalling pathways involved in the PFC response in our study could be linked to dendritic remodelling and spine atrophy, a well-described effect of chronic stress on the PFC. Based on the IPA pathway and upstream regulator analysis, glutamatergic and calcium signalling, as well as Htt and Bdnf-centred networks stood out as the most significantly involved. Indeed, repeated stress is known to cause suppressed glutamate receptor expression and signalling in the PFC, which is thought to be linked to dendritic atrophy (Yuen et al., 2012). Many recent studies have explored the antidepressant potential of ketamine in chronic stress animal models of depression, strengthening the glutamatergic theory of depression (Zhu et al., 2015; Sun, 2016). In addition, disruption of glutamatergic signalling has been previously linked to hyperactivity (Procaccini et al., 2011).

The animals in the study, as expected, showed depression-associated and hyperactivity behaviors. This study wasn't looking at any specific thing in a fine-grained sense, let alone trying to establish causation. But "no link" seems like quite a stretch.

Yes, of course they showed effects from the UCMS. But not one single sentence in that report said that those effects were from gene expression. YOU are the only one adding a link there. It's easy for someone like you to just say there's a link, but not even the study pretends to say there's a link between the results of trauma are because of gene expression.

The world is often stressful and scary.

I think you’re either someone who has suffered abuse and haven’t yet unlearned the effects of it, or you haven’t suffered abuse from a child and doesn’t have firsthand experience on how much it damages you.

Is the world often stressful and scary? Yes. But the lessons that trauma teaches a child do not help the adult manage fear nor stress. For example: a child who has to care for their alcoholic parent can risk growing into an adult that doesn’t know when they’re being taken advantage because they were literally taken advantage of since childhood. A child who was severely beaten at the slightest infraction risks growing up into an adult that cannot handle even minor conflict because they associate being disagreed with to broken bones.

Oh I’m well aware.

Some have those results. Some have the opposite results and lean into learning how to handle those situations. That is also a very common reaction.

Firefighters, EMTs, Nurses, Paramedics, LEO, smoke jumpers, and many Soldiers of all stripes have the same backgrounds. 80%+ in my experience. A surprising (perhaps) numbers of skydivers and climbers too.

Including the West Point graduates, special forces (officers and enlisted), SWAT members, ICU and ED nurses, etc. that I’ve known personally.

And several CEOs of tech companies.

One that I know who I personally saw beaten (as a child) at the slightest infraction or none at all until I stepped in (as a child myself) to stop it, became a decorated officer in USSOCOM and did multiple combat tours in Afghanistan. And at least two (now) Majors and a Colonel I’ve known since they were kids.

The world is not as simple as it appears.

Most folks who end up in uncommon places did so because they experienced uncommon things and learned lessons from it that most people never will have the chance to learn.

Folks who haven’t learned those lessons tend to not survive many of those places for long.

> Some have those results. Some have the opposite results and lean into learning how to handle those situations. That is also a very common reaction.

Childhood trauma is a routine area of clinical specialization because it is so common, and I've never known anyone in that field to hold this position. Anecdotally sure yes plenty of traumatized children become successful adults but very simply and grimly most do not. Extreme survivorship bias at play here, often literally.

And separately I am not sure, in this context, considering what we now know about the behavior of american soldiers in afghanistan, that people being drawn to that environment or succeeding within it is evidence of anything positive about them.

Since psychology is expressly about dysfunction, it is a reverse survivorship bias no?

And not like anyone who has gone through these situations is going to hang a sign on them that says what they’ve gone through.

All of them I know have been quite successful however, and if you walk into any ICU or Emergency department and randomly sample a nurse or Dr, at least 80% odds you’ll find they have that background if you can get them to talk.

EMT-B or EMT-P, much higher.

The world is a dangerous and scary place many times, for everyone. Chances are, you’d be shocked if you listened to your local EMS/LEO frequencies at how much even within a few miles of where you are sitting.

Most of the time, society is able to put up a facade so there is a chance everyone doesn’t have to experience it too directly or too terribly themselves, so others have a chance to live a different life.

The sick and injured get treated, the bodies get cleaned up, the threats get dealt with quickly and effectively, etc.

The people that do that, can stare it in the eye and deal with it, and that often is because they experienced it and learned how to cope or even thrive. Usually as a child.

Respect for that is more warranted than what you’re doing. They get enough shit as it is.

They can handle it though, they deal with worse every day.

Frankly I have gone through this and I have not been successful. It has held me back in every moment and every step through life. In support groups with other survivors I hear the same things over and over again: grief and loss at the people we could have been. More than a few of your "successful" high achievement individuals in those rooms in tears with the same sentiment.

I’m sorry to hear you are still suffering. I’ve been there, and yes those high achievement individuals often have too at some point.

Part of the problem is that we often focus on what could have been, instead of the wins of what was, no? Part of what makes things hard though, is if we never process/feel the bad things, we can’t move on.

When we process the pain, we can start to let go, and the wins start to come through.

It becomes a past, not a present. We can start to see the truth of what is in front of us, instead of getting stuck in an illusion.

Some learned/were able to earlier, some later. In my experience. We can look at the future more than relive the past.

Some avoid it, and that is often where true evil takes root.

‘Toughing it out’ works in the moment, but adds up over time until we hit our limits. The longer the pain stays in, the more it calcifies. Often, if it’s ‘stuck’ it’s due to something that is very difficult to see due to how bad it is.

No one comes through life without some grief and loss and pain, literally no one. Some get more than others, some handle it more than others.

In the end, we’re all dirt anyway - what matters is what we do with the time we have. I hope you find some peace. It is possible, but it is often not natural.

If you’re still struggling, there may be alternatives that can help. They do often take time and money.

I’m happy to provide some pointers or references if you’d like. No guarantees, but I have had some significant personal relief as have others. It is possible.

This is so condescending.

I am telling you that no one is better with trauma than they would have been without it. It's a simple message please hear it. I don't need anything else from you.

I don’t know where you got from my comments where trauma is good. I said quite clearly that trauma is terrible, actually?

What I did note is trauma exists, and trauma is nearly everywhere at some point unless someone goes through a lot of work protecting others from it. But also that it’s impossible to protect everyone from it all the time forever.

And that has costs that some have learned to bear better than others, and there are tools that can help if one is willing to engage with them.

It is possible to not be in pain, eventually.

That no one can be better after experiencing it depends a lot on what you mean by ‘better’. There are easier paths, of course.

A society without the people who can handle this won’t exist for long, so these folks are important.

Society wise, I’ve known a lot of folks that society calls (justifiably, IMO) heros, and have had to trust my life to them and vice versa in situations that most people definitely, provably, can not handle. But that if not handled would cause far worse trauma to other innocent people.

And I’ve found the label appropriate. They and I have also experienced a lot of pain, and none are perfect.

I’ve held more dying men’s hands than anyone should have to. But it was important someone did it, and I was there. As to if that makes the trauma that got either of us there better, or worse, seems immaterial. It was. I feel honored to have been able to do it, and hope it provided them some peace.

I wish you and anyone else reading this the best of luck, regardless.

Absolutely not. If your brain is molded in a stressful environment, it’ll optimize for reaction to and preemption of threats, with all the anti-social behavior that entails, rather than creativity, cooperation, high-level learning, and constructive pro-social behaviors.

Do you have any references to support this? What you and the person you responded to said both seem reasonable to some extent, but without evidence It's not clear to what extent they are true.

Relatedly, does "stress" have the same meaning in what you say and others are saying? It seems reasonable (though I have no evidence or related expertise) that the optimal level of stress is non-zero (for some definition of stress, to the extent that it can be quantified). Why wouldn't the optimal level of stress promote more pro-social, creative, cooprerative, etc. behaviour than sub-optimal stress levels?

If you're old enough to be here, you've already seen all the evidence you need.

And not just humans. Pretty easy to tell if an animal has been mistreated. Kittens raised on the street, where they compete with each other for food, are nothing like those born and raised indoors.

Do you really need "hard science" for this kind of stuff?

I don't think it's unreasonable to ask for "hard science" on this. Just as you've provided an anecdote of "street kittens," I have personal anecdotes of children who grew up in abusive families who turned out to be very nice people. Of course, there may have been less visible setbacks in other parts of their development, but at the end of the day it's not a clear-and-cut A causes B to me.

You are right. It's not unreasonable to ask, however it wouldn't hurt to demonstrate some basic acknowledgement that things do seem to be strongly correlated. Even the biggest idiots understand the concept.

You are also right that not everyone (human or different animal) reacts the same. Some turn the other cheek, some will break your nose. The scars will always be there, though.

I've never seen any evidence that changes in gene expression are mostly negative. The entire point is gene expression, not that stress or trauma causes a person to behave differently afterwards. It's weird that people on this thread don't seem to understand this very important distinction.

I went down a rabbit hole about this while reading The Telomere Effect (recommended reading). The book goes into the good stress vs. bad stress paradigm and how it has a biological basis - literally at the RNA level. There’s a Goldilocks zone where, for example, the right amount of good stress actually increases your lifespan, and the lack thereof is actually bad for you. Of course bad stress is bad in any amount, with bigger consequences if you’re younger or, get this, in the womb. If a pregnant woman experiences a traumatic event or bad or chronic stress, that can result in lifelong issues for the kid. I don’t recall if the book went beyond RNA and into the neuroscience aspect or whether that was from further reading, but the neurological effects are significant too.

Update:

Harvard Medical School article: Understanding the stress response https://www.health.harvard.edu/staying-healthy/understanding...

Research on effect on neural circuits: https://jneurodevdisorders.biomedcentral.com/articles/10.118...

Harvard article on impact of early childhood adversity, including on brain: https://developingchild.harvard.edu/resources/inbrief-the-im...

All of this is talking about physiological changes, which are well known, not gene expression. Gene expression is entirely different than the repercussions of psychological trauma.

See the following study in Nature and scroll down to “Epigenetic reprogramming by ELS: the current landscape” -it gives an overview with citations and links included:https://www.nature.com/articles/s41398-022-02076-9

Telomere Effect also goes into epigenetic changes but isn’t solely focused on stress

Do I get to count as evidence? The stress they're talking about is clearly defined. It's ACE levels.

Before the age of 5 I was hospitalized for falling out of a moving truck and had an ace score of 9, after adoption at 5 I had an ace score of 6-7. I was regularly beaten over the head, yelled at, had food withheld--the whole 9 yards. Almost always related to academic performance because I already had ADHD and PTSD from before adoption.

I now am starting to realize that beyond being easily triggered due to PTSD, I can ONLY function cognitively if I am under stress. It's taken me a long time to figure out if what I'm dealing with is ADHD, PTSD, dissociation, or what--it's hard to pin down. I finally realized that I perform, socialize, play, create and cooperate better if I am angry, scared, worried I'll get fired, or various other social pressures that make people panic. I am useless otherwise. I have come to the conclusion that I am adrenaline deficient because my brain developed in a wash of adrenaline and learned to stay there.

In social situations I come across as aloof or disinterested, absent, withdrawn, and when I'm excited about something or seeking socialization I come across as confrontational, argumentative, or upset when I'm happy and joking. I mostly don't see a point in socializing when I am not perceived according to my internal experience.

The only time I've ever been normal and functional is the 6 months after my mom died, a time when most people are incapacitated due to the stress of grief.

I gotta say as an N=1, having early childhood stressors and head trauma have not exactly made me more pro-social, creative, cooperative, etc. To get that Optimal level of stress requires that I destroy my body with cortisol.

I'm sorry for the ordeals you've gone through in your life, but gene expression is entirely different than psychological trauma.

It’s not different, the two are tied. See my comments above, including my response to you related to epigenetic changes from stress.

The person you are responding to likely has notable epigenetic modifications that have lasted way past the initial negative environmental stimuli (in proportion to the trauma). It’s not a hopeless situation, there is literature on how to reverse and mitigate that, but it’s important to be aware of.

No. There's no proof that the gene activation differences that occur are negative. There's no proof that the gene activation differences are the cause of the psychological and behavioral differences seen by victims of trauma.

Little is done in psychology or the social sciences to therapeutically resocialize people who have maladaptive traits.

It's all presumed to be one's 'personal responsibility' that they were victims of their own kind.

The onus belongs on society to provide healthy and stable environments for people.

Since ‘society’ flat out isn’t going to do that, and it isn’t clear it could even afford to do so (or how), what do you propose to be the next most practical option?

I'm not sure one exists. You can't force a life form to care about others of its kind, so our potential will be limited by that nature.

Society never cares about the damage it inflicts until it's time to start talking about outcomes and results, usually after a mass killing or some other major meltdown that ends in murder.

99% of those would be avoided if mankind practiced what it preached.

Having pulled the string all the way down on a number of issues you’re identifying - your expected outcome is false.

While society can shift things around a bit, none of these underlying issues are actually ‘solvable’ without far more serious consequences.

Our current thinking and attempt at solving some of the current ‘justice’ issues for instances seems to be precipitating an even larger and more destructive evil.

The reason why you can’t force an organism to care about another of its kind, for instance, has a plausible evolutionary reason that it would be foolhardy to ignore. That others of another organisms kind have an incentive to take advantage of any sort of mechanism to capture the other organism and make it work against its interests.

Selfishness is the only viable defense against out of control selfishness.

Prior solutions create new problems and new pain, precipitating new attempts at solutions which create new problems and new pain, ad infinitum.

The wheel will continue to turn.

So there's no real reason for unity and connection, huh?

Certainly seems that way. The world is led by sociopaths who would rather see dead homeless people than miss a profit goal.

As the wheel turns, people will remember who was, and wasn't, there when things were poor, and abandon them in their greatest hour of need.

Far from it!

You’re getting your lesson reversed.

If no one is strong, there is no one to help the weak.

If one gives all their strength, then they are too weak to help anyone including themselves.

If Ukraine gave in to Russia, for example, then there would be no Ukraine, and a stronger and hungrier Russia.

Weakness breeds predators.

Strength gives options and an ability to actually help others from a place that isn’t predatory. A place that can be win-win.

Never actually helping anyone of course makes new enemies, and isn’t helping anyone either.

It’s a balance.

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