Early-life stress changes more genes in the brain than a head injury in rats | Hacker News Reader

Early-life stress changes more genes in the brain than a head injury in rats

medicalxpress.com

322 pointswglb146 comments

"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.

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?

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.

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.

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.

The longitudinal studies of the of the kids who were 0-10 during the pandemic are going to be fascinating.

As a tiny example: I've anecdotally heard that kids in the 5-10yo bracket need their parents in the bed to fall asleep at a higher rate than would typically be normal. Probably because parents cuddled their kids to sleep during the lockdowns as a stress reducer for both of them, rather than turning out the lights and leaving the room.

People are really blowing this covid lockdown stuff out of proportion, like seriously we had to be more indoors for a while, how is that stressful? Some children are literally living in a warzone and don't know if they will survive through the week, some live in poverty, some lose one of their parents or both.

My son is 6 so it falls neatly in that bracket and if the covid lockdown is the most stressful thing to happen in his childhood I will consider us extremely lucky.

And even so, cuddling more with parents? How will they ever recover?

> Some children are literally living in a warzone and don't know if they will survive through the week, some live in poverty, some lose one of their parents or both.

This isn't the gotcha you think it is. Yes, there are children who experience worse trauma and stress than COVID lockdowns. However, those children of war will be also be developmentally stunted, far, far, more than the children of COVID lockdowns.

This is a "yes, and" scenario. Reducing stress in all its forms during early childhood development is the goal here, and the fact that some have more than others does not mean those with less stress are worthy of casual dismissal.

Evolutionarily speaking, social isolation is more stressful than violence

Soldiers develop mental health issues more often when they return home and become socially isolated than when they are at war, surrounded by their brothers

I was no "real" soldier but due to some weird circumstances I fought in a war. The difficult part of returning home is everything is so low stakes, the freedom to ride around on a Hilux living by your wits and a rifle turns into a world where you can easily survive flipping burgers and you have a toddler screaming at you because you selected the wrong color cup and the HOA has a meltdown because they decided the wrong species of plant is growing on your yard. Boring.

Sometimes you dream of the war because life is so simple and the goal is obvious, and every decision seems impactful to your survival.

There's a section of Gustav Hasford's 'The Short Timers' that describes this well. Two soldiers have recently returned from the front lines and hitch a lift to a base, or PX, or something of that nature. The gate guard - some fat fuck who's clearly never seen the enemy face to face - won't let them in because they're Marines and Marine day is Tuesday, or something of that nature, so our man just cocks his rifle and sticks it in the guy's stomach, finger on the trigger, and looks the guy in the eye.

It's a very well written book.

I don't know really whether I should recommend war stories to a guy who's been to war but if you do enjoy reading that sort of stuff, both of his novels (The Short Timers - which turned into Full Metal Jacket - and the sequel 'The Phantom Blooper' are excellent.)

My War Gone By, I Miss It So by Anthony Loyd.

Surprisingly, perhaps less effects on the youngest cohort: https://jamanetwork.com/journals/jamanetworkopen/fullarticle...

"At 4.5 years of age, pandemic kids had higher vocabulary, visual memory, and overall cognitive performance compared with pre-pandemic kids."

The authors suggest that pandemic 2-year-olds developed better problem-solving skills, accelerating the increased cognitive performance by age 4.5

Although pandemic 2-year-olds had more socio-emotional risks early on, these seem to disappear by age 4.5

> Probably because parents cuddled their kids to sleep during the lockdowns as a stress reducer for both of them, rather than turning out the lights and leaving the room.

That's a good thing. Child has a need, Parent meets that need. That is a healthy relationship. But... the parent should have worked to ween the child from this behavior back to a normal sleeping situation.

I think "normal" is relative here. My understanding is that it's mostly Western cultures that consider co-sleeping to be a bad thing.

From my reading it isn't really good or needed. Cuddling is great but child should learn to sleep on their own.

A parent should not be meeting every want of a child.

Funny. You translated “need” to “want”. A parent should meet a child’s need. That is absolutely necessary for development. If a child is nervous and needs cuddling, do it.

Funny, how you are saying that somehow sleeping with your child is a need. It isn't.

It's not a negative either. Large parts of humanity sleep as a family and I'm not aware that it causes any problems.

Funny how you leave out that the child was stressed in this situation. Exceptions for helping a child through a stressful situation is meeting a need.

Gabor Mate has published quite a few works on the effects of stress on children, even starting in utero with effects from the mother.

Scattered minds and when the body says no connect to the effects of stress on the body and children in particular.

Dr. Gabor Mate¹ should be taken with large grains of salt when it comes to ADHD and related conditions. There is a lack of published research or dedicated expertise on the matter; Dr. Russell Barkley, a leading ADHD expert and researcher², has a good video on the subject³.

¹ https://en.wikipedia.org/wiki/Gabor_Mat%C3%A9

² https://en.wikipedia.org/wiki/Russell_Barkley

³ https://www.youtube.com/watch?v=bO19LWJ0ZnM

id probably prefer to listen to the drug opinion of the guy who doesn't have a laundry list of drug sponsors :P

Source? The article linked above makes no mention of sponsors.

oh come on thats just lazy im literally commenting on the sources haha

Sorry I don’t understand. Stress had an effect or had no effect on children’s minds?

Scattered Minds and When the Body Says No are book titles.

Children cope with their surroundings and if traumatized habituate themselves to these habits that are temporarily soothing but deleterious long term, often imitating family members who may have also carried these learned behaviors in their own life. Cycles of generations that are impoverished in comparison to their well to do neighbors are an example.

Gabor Mate expresses that stress has an effect on children. The effect is expressed in actions as children grow into adulthood.

There are these test done on hen, where stressed hen led to stressed chickens even if they never even met after laying the eggs.

Title should be "...changes gene expression levels"

So they took a cohort of baby rats, exposed one group of rats to 'stress', smacked another group of rats in the head hard enough to cause brain injury, had a control group which was 'unstressed', then sliced up their brains to measure levels of protein expression. Some rats were not chopped up and their 'natural behavior' was monitored.

This is apparently valuable research because it shows that traumatized and injured rats have different protein expression patterns in their brains from non-traumatized and injured rats and also behave differently as adults. This is applicable to humans because...???

Takeaways: (1) torturing rodents for dubious results is ethically questionable and (2) what a waste of money and resources.

> This is applicable to humans because...???

We don't know if it is applicable to humans. Some of it might, some of it might not. First you figure out how rat brains work and then you can check if human brains work the same way.

You are right that we are interested in human brains, and how to heal them. The reason we don't do these experiments on humans is mainly ethical. Simply put we value human lives more than rats. There are also logistical challenges with humans. They take too long to grow up and cost too much to raise.

> torturing rodents for dubious results

What makes the results dubious? I'm not an expert on brain research. Is it just that you have a dislike to animal analog studies? Is the gene expression changes caused by early-life stress and brain injury well understood enough that there are no open questions the experiment might answer?

No protein work. mRNA assayed.

Applicable to humans because head trauma is unfortunately very common in infants, toddlers, and children. Developing effective treatments of pediatric TBI and adverse childhood events would be a real boon to humanity.

It would literally save my life, as I would actually be able to live mine and do all the things I'm capable of instead of feeling partially locked in.

Im glad this is brought up. This research feels like dots being vaguely connected together. What am I even supposed to do with this info?

> What am I even supposed to do with this info?

Seems like a weird question. Are you a researcher in a related field? Then maybe incorporate this finding into your models for how things work or tweak your future experiments based on this data.

Are you an unaffiliated Rust developer? Then you're not really supposed to do anything with this.. it's not particularly for you. Read it if you're intellectually curious, to expand your knowledge and understanding of the world in general? Or ignore it if you don't care?

Note to readers: Take this with a grain of salt. University PR team (and HN) should wait until this work is reviewed and published as a full length paper.

This is an abstract that has not been reviewed—-a small study developing a rat two-hit model. All of the RNA work is based on three 21 day old males in the three groups. No information in abstract on the strain of rats (often outbred Sprague-Dawley).

If this work interests you then you will find hundreds of studies on stress effects on hippocampus and many also on TBI effects on cortex and hippocampus.

Other than the general shortcomings of a rat study, does this result run counter to your understanding of the effects of stress on genetic expression in the brain?

My understanding is that early childhood stress in humans has also been fairly reliably linked to things such as “psychopathic” behaviors. e.g. [0]

[0] https://www.academia.edu/download/89809148/2128.pdf

Most neuroscientists would expect TBI to be linked to regional micoglial activation. And perhaps activated GFAP-positive astrocytes. Psychosocial stress will have different effects mediated in part by the hypothalamus-pituitary-adrenal system.

There may be some postmortem RNAseq studies of humans, even small pediatric cohort, but I did not find them in PubMed. I did find this treatment approach for TBI (yes, in mice)

https://pubmed.ncbi.nlm.nih.gov/33540074/

Isn’t it more that it is just extremely difficult if not impossible to do the necessary longitudinal study in humans? You’d need verified quantified early trauma, lack of possible TBI, and early death, and RNAseq processing postmortem which is a recent development.

I think about it evolutionarily: if an animal was subject to significant early trauma (i.e. divergence from expected early environment), the most likely cause is early loss of a parent and no surrogate caretaker.

This suggests a markedly different environment generally, and especially socially, and would warrant a significant behavior shift if it were evolutionarily possible to accomplish.

It doesn’t seem so implausible to me.

You are correct.

As someone who both experienced childhood trauma (refuged to another continent at the age of 4) and has received a fair share of blows to the head (many years in martial arts) - this does kind of resonate. Mood disorders and ADHD like symptoms are things I've dealt with but which I'm learning to control with age. It did take several decades and much introspection to introduce some sort of self-control and awareness about when I'm acting irrational though.

Off: Did you stop martial arts? If no, How did you cope/manage?

Just curious.

The article doesn't say explicitly, but I assuming this is talking about epigenetics rather than mendelian mutations?

I'm convinced that stress is the single biggest factor in aging and overall health. Look at the careers of people who live to 100+ -- they almost always worked in something where they weren't dealing with a lot of trauma and high stakes. You read this blue zones stuff and at the center of all of it is low-stress. Not necessarily "leisure," but activities that are intended to be calming and thoughtful - exercise baked into the day, shared meals prepared at home, community interaction.

In rats, not humans. Interesting nonetheless

CTRL+F did not disappoint. Thank you.

Thanks - I've inratsed the title above.

I swear I'm stating to experience increasing levels of the Mandela effect (might not be the proper explanation) over the last few years, because this is the first time I've ever heard of genes being a thing which could change. Granted, I'm not a biologist, but we have sayings like "good genes" or "it's in the genes", and I've heard countless medical explanations that things are passed down "in the genes". Aren't genes directly linked to one's dna, and not a thing that any physical trauma or stress can physically modify? Why does this seem like it directly clashes with my life long understanding of "genes"? I'm possibly going insane, because odd things like this keep popping up and are a bit troubling in some odd dejavu kind of way

As you may have noticed, say from technologyland, some words are hopelessly overloaded.

"Gene" is such a word in biology.

In its purest essence, a gene is "An inheritable trait."

This is from when they were an idea, not a particular thing (yet).

I won't go through biology's "central dogma" but encourage all to do so [1].

This will start to shed light on some of the basic different molecules that are at various times refered to as genes.

But this easily understandable frmework is only the start as there will be exceptions to everything, and nuances everywhere.

If you need a set of decoder rings to read a message are the rings part of the message? Is the message really a message without the rings. and so on off into opinionland. (like I just did)

[1] https://duckduckgo.com/?t=lm&q=biology%27s+%22central+dogma%...

If you had read the article you'd understand that it's talking about changes in gene expression, not changing of genes entirely.

My question still remains. Even if the gene isn't altered, but the expression is, which I assume is the important part in determining outward influence the gene has, I wasn't aware anything short of radiation could alter that. If stress can change you at the gene level, or metal state in general, wouldn't we all be able to "fix ourselves" or otherwise change our gene expressions by submitting ourselves to various metal states to invoke the wanted gene response?

TL;DR, I wasn't aware anything regarding genes could change, that's all, and I'm more curious why I keep discovering so many large gaps in things I personally considered life long, common knowledge. My question was almost rhetorical for myself.

Disconcerting, like returning to someone's comment, and it's subtly different from how you remembered (before you knew of the recent editing feature).

Most (all?) scientific ideas are simplifications. e.g. that species are separate. That the relationships between species can be represented by a tree.

Yes, it used to be taught that genes don't change. But there's methylation and telomeres and "gene therapy" is a thing. I agree that changing gene expression sounds like sophistry, since the point of genes is their effect. Sounds like Lamarckism to me.

Everything you've been taught is wrong - in that however thoroughly something is known, there's always more to it.

Yes, your body does something called methylation to alter gene expression, and yes, medicine is trying to use this fact for diagnostics at the moment.

If you experience stress, your body will upregulate expression of cortisol and other hormones. If you remove the stressor, it will downregulate. Chronic stress can break these processes and require medical intervention. This is all (in theory) detectable with methylation analysis of the genome, but it will take a decade to fully flesh the technology out.

It is relatively new discovery. We now understand that DNA strands are usually tightly wrapped around histones. This resembles strings wrapped around beads.

Gene expression is talking about the myriad number of things that causes the DNA strands to relax and unwound from the histone. By exposing that piece of DNA strand the gene can be expressed and the resulting protein is formed. I don’t believe we have a complete understanding yet of what causes genes to be expressed or not expressed. There seem to be multiple factors at play.

My understanding of telomeres is that is primarily a mechanism to prevent cancer. After a cell replicates itself a number of times the telomeres grow shorter and shorter and at a certain point it stops replicating because the assumption is the DNA has now been damaged by environmental factors. Some cells don’t have this mechanism and can replicate infinitely eg skin cells.

Epigenetics is the catch-all term. “Evolution in Four Dimensions” is an interesting if slightly dated book going into many of the ways that the expression of your genetic material can chance who you are.

I think this might be a fun opportunity to accept that things are complicated and to be excited to learn new things. But I always personally knew that gene expressions can change with circumstance: that’s why arctic foxes have winter and summer coats, and why point coated cats have dark fur on the extremities of the body.

Appropriate username

The headline is wrong, as the article clearly shows, and instead of reading the article to check, your first instinct is the Mandela effect and doubting your sense of reality?...

I don't say this often but you should probably go to a therapist

Obviously I didn't say that because of this article alone, which is why I said "increasing levels of". I, like many people here, am an engineer, and like to consider myself a pragmatic and logical person, and have not jumped to such an explanation immediately. It was also half said in jest, because I'm logical enough to know the real answer is my lack of knowledge on the subject, and a bit of superstition surrounding coincidences in my personal life that literally just this weekend a friend randomly started talking about being able to "will past trauma and fix your genes", to which I said they were nuts, then this article hits the front page.

Thanks for your recommendation, if it was said in good faith and not as a put down, but I'm well grounded in our shared interpretation of this thing we call reality.

Also, I'm all for therapy and have been many times, but CBT won't fix a schizophrenic who has detached from reality, which is what you're trying to convey with the selective bits of my original message used, so your "go see a therapist" suggestion isn't helpful, even if your intent was, and based on the tone of your message I'm assuming that your intent was not to be helpful anyway.

Which therapy do you think will help you?

Idk, which ice cream flavor do you think will stop all murder around the world?

Genes are the blueprint but they can be damaged and replicate wrong. That is how stress or poverty "changes" them.. (feel free to correct me). Cancer is also wrong copying dna etc.

Is this epigenetics? Don't want to assume anything, but maybe this wasn't well known when you were in school. I vaguely remember reading about this a decade ago.

Be careful with this article, it’s based on a poster at a scientific meeting, not a peer reviewed publication.

A poster at a conference stand a good chance to get more and better peer feedback than what is afforded to the peer review of the average journal paper.

Hmm, not the case in my experience going to Society for Neuroscience for 25 years. If you are luck you get useful (non-critical) feedback from 5 people. Why would one “review” a poster seriously? They are often years away from submission even to bioRxiv.

3 cases id single-cell RNA-seq per group, all males. I hope you all appreciate the amazing noise level of single-cell RNAseq. This study should have used bulk RNAseq to keep noise lower.

Perhaps, but that feedback won’t be reflected in the poster itself, maybe the publication, if there is one.

Ever since I heard someone describe ADD as your "fight or flight response going haywire", I've realized that a lot of people in my life with true ADD have experienced trauma in their childhood.

But I'm no doctor, just making observations and trying to understand the world.

I am fairly certain that for many people, adhd is their brain being on constant alert / hyper-vigilance due to instability and trauma growing up, and needing to become very sensitive to people's behaviours to anticipate bad responses.

Yes, I am speaking from experience.

Isn't this what the PTSD label is for? Or is the implication that this another "spectrum" where we've historically had some discrete labels?

Not necessarily; i was thinking more about hyper-vigilance. It doesn’t necessarily have all the issues of PTSD.

I guess the implication is that ADD is what PTSD in children could evolve into.

With ADHD, there are issues that bring up similar symptoms, but is not ADHD. A person can be 'distracted' if they are sleep deprived, anxious, have PTSD or are depressed, and part of diagnosing it is ruling out those other conditions. Giving a 'normal' anxious person stimulants can be a bad combo for example, where it will amp their anxiety up a shit ton instead.

Also there are different forms of ADHD. An inattentive ADHD type person could be said to have the opposite problem of their 'fight or flight response going haywire' for example. They can often be quite relaxed, maybe a bit too relaxed.

I agree with your statement - I know it's anecdotal, etc. etc. but it seems to have some credibility to it given my upbringing and my experiences.

You don't learn executive functioning skills when the opposite is modeled by your parents. You also don't learn them from other people in your community when you're focused on trying to survive day to day and constantly dread going home to an environment where you're not respected.

Every day is a struggle but I feel I'm starting to come around and realize that I can change myself for the better.

I hope everyone else experiencing the same can come to this realization too.

Also not a doctor, but from the arm chair research I've done (I have ADHD), in the case of having trauma in childhood it's more likely that those people have PTSD (not ADHD). Certain types of PTSD have overlapping symptoms with ADHD and are commonly misdiagnosed.

Also, people imagine PTSD comes specifically from war, starvation, physical injury, etc. but it actually comes from emotional trauma. Emotional trauma to children can be just as bad from a high conflict or high stress household, even if the family is financially secure.

Having rich parents that fight constantly and emotionally neglect their children is probably emotionally worse than being a homeless war refugee with kind and loving parents... I suspect PTSD is widespread among kids in the middle and upper class, but people categorically deny the possibility of it, and these kids may instead be diagnosed with something else.

The book "Simplicity Parenting" by Kim John Payne was really interesting, because he was actually a psychologist that worked with children in war refugee camps, and later worked with middle class American children from stressful households, and found many of them to be experiencing similar issues, with similar symptoms.

Anybody got references for this?

Original article:

https://news.osu.edu/early-life-stress-changes-more-genes-in...

Sapolsky has been at this for many years. Here's a great talk on one of his older books.

https://www.youtube.com/watch?v=D9H9qTdserM

Especially with regards to his commentary on Selye's theories/lab work with rats.

Makes sense if you've read a good number of books on stress (i.e. Stress of Life, Sapolsky's work, etc)

Kids have a lot of stress today. It often starts in the kindergarten. I wonder what covid induced Stress for kids will have in the future.

I can't imagine my childhood with the pressure to maintain an idyllic image on social networks which seems to be the number one priority of kids today.

I don’t know that I would particularly expect a head injury to primarily change genes, but rather just to damage the structure of the brain itself. I don’t have any reason to doubt the study itself, but the article here is not very useful. Which genes are changed? Is it necessarily bad that genes are changed? Articles such as this are one of the reasons why people badly misunderstand (and overestimate) the effects of epigenetics.

> I don’t know that I would particularly expect a head injury to primarily change genes (...)

It doesn't change genes, it changes gene expression. The headline is wrong.

> "We found many, many, many more genes were differentially expressed as a result of our early life stress manipulation than our traumatic brain injury manipulation,"

Judging from the rest of the comments no one else read the link either.

I have never heard this either, and I spent a few years dealing with a TBI (traumatic brain injury) in a loved one.

The finding that really surprised me is that whole brain atrophy is seen ~11 months after mild and moderate TBI:

https://www.ajnr.org/content/23/9/1509

Only the headline is wrong, the article itself says something different.

> stress changed the activation level of many more genes in the brain than were changed by a bump to the head.

> "We found many, many, many more genes were differentially expressed as a result of our early life stress manipulation

> First author Michaela Breach, a graduate student in Lenz's lab, examined the gene expression changes

All of the people who I know who are actual geniuses had early childhood trauma.

>Researchers temporarily separated newborn rats...

Not worth my click.

Key question: are the genetic changes passed on, or are the changes limited to expression rather than encoding?

Gabor Mate has taken a close look at the epigenetics of trauma. He suggests it takes a few generations to clear up, but it's unclear if that's an epigenetic thing or just a re-traumatizing thing.

It makes sense. Children takes cues about what's normal, what's rewarded, etc, from the behavioral patterns of their parents. If your parents are victims of bone fide trauma, the patterns will be different from what they would have been otherwise. So a trauma victim might display signs of hypervigilance, and children will observe this hypervigilance (in behavior, in the words used, in the attitudes adopted and result from it). So the child will be conditioned, but also, the child will likely infer the mental state of their parents to some degree. If you look hypervigilant, the child will infer "there must be danger". If maintained consistently enough, the inference is "the world is a highly dangerous place", blown out of proportion with the situation.

Neither can change the genes, the headline is wrong, probably intentionally to generate clicks.

Genes are made of DNA which degrades and does change. The mRNA vaccine and viruses also change your DNA. It won't change your gender or race but it will affect you mentally and your phenotype. Cancer is another way genes can change.

Why would a physical injury change much in terms of genes to begin with?

...in rats.

we typically use rats for stress tests.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915631/

Does amount of genes even say something?

Uh, yes. The difference between the human and chimp genomes is only like 1% but that minute variance clearly makes a massive difference. Different expressions of individual genes can vastly change appearance such as eye color, hair color, etc. These are physical traits but obviously, a similar concept applies to other traits.

In rats.

This refrain is beginning to sound like the "checkmate atheists" of people who don't understand biology

Can you elaborate?

Pointing out that biologists use animal models that don't map perfectly to our biology is a lazy criticism. It's not a good-faith way of engaging with research, and demonstrates ignorance to the purpose of modelling in any field.

12 October 2023 - Reproducibility trial: 246 biologists get different results from same data sets https://www.nature.com/articles/d41586-023-03177-1

I think it's perfectly far to be very very critical of these paper especially because of the impact they can have on society, medicine, and legislation.

We should be very harsh and disciplined.

GP isn't saying we shouldn't be critical, hard and disciplined. They are saying we shouldn't just lazily dismiss any results as "in rats."

I fully agree with your comment out of context, and I think it actually backs up GP's point about not lazily dismissing stuff as "in rats"

It's not a lazy criticism, if the data is so variable when it comes to various conclusions of the same data set, imagine the difference when it goes from rats to humans!

I would agree, it definitely isn't always a lazy criticism. But to be unlazy it should include something that expounds on why it might matter. When the entirety of the response to the study is "in rats" that doesn't seem helpful to me

It is not a lazy criticism.

These animal studies are way too preliminary to waste time discussing by non-biologists. I think that the press popularizing these very preliminary studies as science actually serves to undermine the perception of science in the general population.

This info is conventionally added to HN titles since articles have the bad habit of omitting it so HN users often point it out. You can read it as equivalent to comments pointing out publication year so it can be added to a title.

Certain experiments are not ethical nor possible to do in human subjects, so scientists rely on model systems to interrogate biological questions. It has become somewhat common for people to immediately dismiss scientific findings on the basis that this research was done in a mouse, and therefore not applicable to human biology.

I agree that this should be a part of the title. It could then mention how applicable this is to humans, but that is another story.

Related, you can read about nadine burke harris and adverse childhood experiences (ACE).

Tl;dr: childhood mental trauma manifests in physical issues.

For a solid intro, check out her ted talk: https://www.ted.com/talks/nadine_burke_harris_how_childhood_...

Edit: ah, referenced in the article: https://www.cdc.gov/vitalsigns/aces/index.html

Thanks for the CDC link. What I got out of it is traumatized children when they become adults have an increased risk of depression and risky behavior.

Is there any advantage for being depressed in a traumatic environment? I read one argument is that by shutting down higher order mental and physical processes, we can use the saved energy to heal? Does that hold any water?

If a child’s caretaker or environment are hostile, a reduction in the normal childhood activity that is likely to attract subsequent negative attention can be beneficial for survival to the extent it allows for possible reproduction. “The nail that sticks up gets hammered”.

To be clear, this is typical evolutionary speculation. Sounds reasonable, but I’ve not seen anything that would be able to prove this and there are likely many other considerations that complicate such a nice and easy conclusion.

This was actually the case with me. Constantly told children should be seen and not heard, don't speak unless spoken to, all manner of things like that. My wings were clipped good.

It is more profound than "increased risky behavior."

https://onlinegrad.baylor.edu/resources/adverse-childhood-ex...

Increases in autoimmune diseases, cancers, and even COPD controlled against smoking habits are observed. The body doesn't handle increased stress hormones well during childhood development.

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