Science Depression is probably not caused by a chemical imbalance in the brain – new study

https://theconversation.com/depression-is-probably-not-caused-by-a-chemical-imbalance-in-the-brain-new-study-186672

For three decades, people have been deluged with information suggesting that depression is caused by a “chemical imbalance” in the brain – namely an imbalance of a brain chemical called serotonin. However, our latest research review shows that the evidence does not support it.

Although first proposed in the 1960s, the serotonin theory of depression started to be widely promoted by the pharmaceutical industry in the 1990s in association with its efforts to market a new range of antidepressants, known as selective serotonin-reuptake inhibitors or SSRIs. The idea was also endorsed by official institutions such as the American Psychiatric Association, which still tells the public that “differences in certain chemicals in the brain may contribute to symptoms of depression”.

Countless doctors have repeated the message all over the world, in their private surgeries and in the media. People accepted what they were told. And many started taking antidepressants because they believed they had something wrong with their brain that required an antidepressant to put right. In the period of this marketing push, antidepressant use climbed dramatically, and they are now prescribed to one in six of the adult population in England, for example.

For a long time, certain academics, including some leading psychiatrists, have suggested that there is no satisfactory evidence to support the idea that depression is a result of abnormally low or inactive serotonin. Others continue to endorse the theory. Until now, however, there has been no comprehensive review of the research on serotonin and depression that could enable firm conclusions either way.

At first sight, the fact that SSRI-type antidepressants act on the serotonin system appears to support the serotonin theory of depression. SSRIs temporarily increase the availability of serotonin in the brain, but this does not necessarily imply that depression is caused by the opposite of this effect.

There are other explanations for antidepressants’ effects. In fact, drug trials show that antidepressants are barely distinguishable from a placebo (dummy pill) when it comes to treating depression. Also, antidepressants appear to have a generalised emotion-numbing effect which may influence people’s moods, although we do not know how this effect is produced or much about it.

Doctor writing a prescription
Around one in six people in England are prescribed antidepressants. fizkes/Shutterstock
First comprehensive review
There has been extensive research on the serotonin system since the 1990s, but it has not been collected systematically before. We conducted an “umbrella” review that involved systematically identifying and collating existing overviews of the evidence from each of the main areas of research into serotonin and depression. Although there have been systematic reviews of individual areas in the past, none have combined the evidence from all the different areas taking this approach.

One area of research we included was research comparing levels of serotonin and its breakdown products in the blood or brain fluid. Overall, this research did not show a difference between people with depression and those without depression.

Another area of research has focused on serotonin receptors, which are proteins on the ends of the nerves that serotonin links up with and which can transmit or inhibit serotonin’s effects. Research on the most commonly investigated serotonin receptor suggested either no difference between people with depression and people without depression, or that serotonin activity was actually increased in people with depression – the opposite of the serotonin theory’s prediction.

Research on the serotonin “transporter”, that is the protein which helps to terminate the effect of serotonin (this is the protein that SSRIs act on), also suggested that, if anything, there was increased serotonin activity in people with depression. However, these findings may be explained by the fact that many participants in these studies had used or were currently using antidepressants.

We also looked at research that explored whether depression can be induced in volunteers by artificially lowering levels of serotonin. Two systematic reviews from 2006 and 2007 and a sample of the ten most recent studies (at the time the current research was conducted) found that lowering serotonin did not produce depression in hundreds of healthy volunteers. One of the reviews showed very weak evidence of an effect in a small subgroup of people with a family history of depression, but this only involved 75 participants.

Very large studies involving tens of thousands of patients looked at gene variation, including the gene that has the instructions for making the serotonin transporter. They found no difference in the frequency of varieties of this gene between people with depression and healthy controls.

Although a famous early study found a relationship between the serotonin transporter gene and stressful life events, larger, more comprehensive studies suggest no such relationship exists. Stressful life events in themselves, however, exerted a strong effect on people’s subsequent risk of developing depression.

Some of the studies in our overview that included people who were taking or had previously taken antidepressants showed evidence that antidepressants may actually lower the concentration or activity of serotonin.

Not supported by the evidence
The serotonin theory of depression has been one of the most influential and extensively researched biological theories of the origins of depression. Our study shows that this view is not supported by scientific evidence. It also calls into question the basis for the use of antidepressants.

Most antidepressants now in use are presumed to act via their effects on serotonin. Some also affect the brain chemical noradrenaline. But experts agree that the evidence for the involvement of noradrenaline in depression is weaker than that for serotonin.

There is no other accepted pharmacological mechanism for how antidepressants might affect depression. If antidepressants exert their effects as placebos, or by numbing emotions, then it is not clear that they do more good than harm.

Although viewing depression as a biological disorder may seem like it would reduce stigma, in fact, research has shown the opposite, and also that people who believe their own depression is due to a chemical imbalance are more pessimistic about their chances of recovery.

It is important that people know that the idea that depression results from a “chemical imbalance” is hypothetical. And we do not understand what temporarily elevating serotonin or other biochemical changes produced by antidepressants do to the brain. We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.

If you’re taking antidepressants, it’s very important you don’t stop doing so without speaking to your doctor first. But people need all this information to make informed decisions about whether or not to take these drugs.

 

[Sicko Hunter]

So what, it's people pretending so they stay in the "Depression is cool" group?

You realize depressed people have existed decades before it became trendy, right?

 

[Foxxo]

You realize depressed people have existed decades before it became trendy, right?

It exploded once it became trendy, much like transgenderism and being a victim. But that's not my point, my point was "then what IS the cause, if it's not chemical imbalances"?

 

[Penis Drager]

what IS the cause, if it's not chemical imbalances

As others have alluded to:
It could just be that depressed people are depressed because they have depressing lives. Now of course depression will typically present itself as a set of chemical signals that are detectable based on how they differ from people who aren't depressed. What's in question here is what the cause is.
In other words: the notion on trial here isn't whether depressed people tend to have different brain chemistry. It's whether the brain chemistry is actually the thing that caused the depression.

Chicken, egg, etc.

 

[Jimjamflimflam]

It exploded once it became trendy, much like transgenderism and being a victim. But that's not my point, my point was "then what IS the cause, if it's not chemical imbalances"?

I'm just spitballin' since I'm not a doctor/ scientist. Could be that some people just have straight up different brain structure and chemistry (not chemical imbalance though) that leads to different thought processes (along with molding by culture, information and experiences in life) that makes the user arrive to different perspectives that give, unfortunately, negative conclusions and views causing a depressive state. Could explain why if you have depressed ancestors then it could be passed down since you are getting their same brain chemistry?

@Idiocy Abroad mentioned studies bring done with magic mushrooms and the positive effect it has. I remember reading studies about shrooms causing new neuron pathways in the brain. Maybe that's helping in circumventing the usual routes (along with positive emotional support) to help the person arrive to different results in their thinking then what they would normally have done.

Again not a doctor just out my ass speculation.

 

[Loony Tunes]

If not a chemical imbalance, then I would be interested in knowing what goes on during postpartum depression, especially in women who were not depressed prior to giving birth.

The woman’s hormones getting all out of wack

 

[lesser sperg]

"The passion of despondency often settles in the soul once one or all the other passions have take root and instilled disease. The sorrow and self pity that accompanies despondency and dejection often convince the soul that all its woes are the cause of external events or persons. It does not allow the despondent one to understand that its sickness lies hidden within . With this self deception in place the remaining passions can appeal to the soul. It is despondency and her friendship with pride that can drive people to suicide. This too is what drove Judas to hang himself."

Dont forget, cooming leads to dooming!

 

[NoReturn]

You realize depressed people have existed decades before it became trendy, right?

Grampy called it the Black Dog.

 

[JJLiautaud]

This fucking thing again heres a good breakdown about what psychiatrists actually believe https://slatestarcodex.com/2015/04/05/chemical-imbalance/

 

[Bagronkleton]

Once again the field of psychology parading itself around in the emperor's new clothes. Discrediting itself every step of the way while trying desperately to be taken seriously as a field of science instead of the half-cocked malarkey it always has been.

I've taken to listening to Andrew Huberman and his stance of understanding the mechanics of the body, mind, and dopamanergic interaction between the two. A lot of imbalances comes from a deficiency in Dopamine output, ergo the bank of dopamine can only lend out so much feel good coins before a debt is incurred, or depressed states inevitably follow after a surge in dopamine output. Learning to moderate and influence the mechanics behind it can make for a happier, balanced life.

So yeah, in this perspective it is indeed a chemical imbalance and an incredibly easy to avoid one with even just a little discipline. The hyper fixation on seratonin in this article is lulsy and exceptionally retarded by avoiding the larger chemical interactions of the brain-body connection.

 

[Dracula's Spirit Animal]

This is really interesting.
I think the real problem is that 'depression' is a catch-all term for so many different issues. I'm sure some people have fucked up brains and really benefit from the meds, but for many others depression has other causes, and meds shouldn't be the only or even the first treatment option.


Word. I was depressed last year, after a very stressful period. Never been depressed before, and it got extremely bad. Then one day I took some magnesium because my muscles ached terribly and I was desperately trying anything that might help, and there was an instant improvement. Took magnesium for two months and was completely back to normal. I can't imagine how many people are 'depressed' because of a high-stress life + magnesium deficiency. And that's just one possible cause.

That's the thing about it, and why we are still in the dark ages about depression and many other things. We treat it like "depression" is a thing. We don't do that with cancer. There are all sorts of kinds of cancer, and they require different treatments. Runaway cell growth is easy compared to the complexity of the brain. There are all sorts of different depressions, as well, but there has been a stranglehold by pharma and psychiatrists who look at it like chemo is the only option for cancer. It works for some, but is deleterious for other kinds.

I bet we could name ten different kinds of depression in this thread, a bunch of autists on a fringe website.

Post-partum
Grieving
Illness-related
Adolescent
Helpless-environment
Age-related
etc etc...

But what, really are 99% of depressions treated with? Medication. I wonder why? cough, Pharma cough....I suppose there are other known things, like exercise, ECT, CBT, talk therapy, yoga, sunlight.... but by and large, the system is a one-solution programme, and it's very primitive in its approach.

 

[weegrumpy]

PL: I’ve been on various ssri for 24 Years now, I’ve had a lot of bereavement when I was in my teens and twenties. After my second son was born prematurely, as was with my first lad, I had post parturition psychosis. That friends is scary shit. I was hearing a wee voice telling me to hang myself, I wasn’t needed or wanted. I had to hold onto my bed to stop complying with it.
my excellent health visitor did and assessment score , and I rated high.since then I’ve always had to be on medication or I can’t function.
yesterday I went to take my venlafaxine, I’d forgotten to reorder them, The past 30 hours were hell. Brain zaps, disorganised thinking mood lability and four hours later after getting them , I feel like myself again.
so I beg to fucking differ who wrote this article,
there’s so much more to just serotonin retention in brain. chemistry. I agree there are supplements in diets can be beneficial , I’ve used CBT, but what helped me most was a book called the happiness trap by Dr.Russ Harris.

 

[The Littlest Shitlord]

Years ago, I heard that Americans were taking too many vitamins. With phrases like Americans have the most expensive piss in the world. You have to be careful with vitamin D and only take it as directed. You can OD with vitamin D and it can kill you.

The people pushing that bullshit are Big Pharma shills. They realize that nutrition can help people their drugs can't touch, and they actually want you to be sick so they can sell you drugs for life. Remember that the core incentives for legal drug manufacturers and illegal drug manufacturers are exactly the same; they both want you hooked. Remember that lying is in most cases not just legal, but protected by the First Amendment. They have been lying for decades and no one has been stopping them. The main difference between legal drugs and street drugs is insurance coverage, and how much fentanyl has been covertly added.

I personally feel like "the microbiome" has reached a sort of scientific fad status. It's kinda like how the study of epigenetics snowballed like 15 years ago and for the next 10 years or so researchers were linking everything to the epigenome because it was what all the cool kids were researching at the time. Real progress was made and it remains an interesting field of study with a lot of potential. But the bull rush on the topic has since died down as we learned more about how limited the scope some epigenetic changes are and how others are so effectively immutable as to rival conventional genetics in what would need to be done to alter them.

The microbiome, I feel, is on the tail end of its bull rush. We know it has profound effects on a lot of things, but there is the legitimate question as far as which is the cause of the other. The link between autism and a non-diverse microbiome is more likely because autists tend to reject diverse diets than it is that fucked up microbiomes causing autism, for example. If such a correlation were found with depression (which of course there's a study demonstrating this correlation) is well established, I'd just as soon assume it's because the anhedonia associated with depression draws the afflicted individuals to bland, monotonous diets. The prospect of positive feedback playing a role is certainly not out of the question though. There's plenty of things depressed people tend to do which only heightens their depression and a shitty diet is very likely one of them.

Disagree, the microbiome is hugely important and the changes I have made in my own life have shown that beyond a shadow of a doubt as far as I am concerned. But you are right in that the dietary changes caused by autism, etc. cause microbiome changes. The issue us that the bad gut microorganisms have evolved to make us crave a diet in which they thrive. For example, candida gut yeast produces acetaldehyde which uses up our vitamin B6 to detoxify it which lowers our serotonin which causes us to crave simple carbs that feed the gut yeast. Thus, autism, schizophrenia, depression, etc. are self-reinforcing cycles.

So big pharma science is bullshit? Well that's depressing.

The science around SSRIs fails to take into account the fact that they can cause your zinc levels to tank. (There are experiments that show this, ask me by DM if you're interested.) In fact if you look at the typical SSRI side effects, most of them are shared with zinc deficiency. When your zinc levels drop, your body can't convert as much vitamin B6 to its active form (P5P) anymore, and P5P is a cofactor to make serotonin. Mainstream science thinks that it's as simple as "more SSRIs = more serotonin activity" but this is not true. Then they look at their studies through this lens and think, "Well maybe depression isn't caused by low serotonin after all" because they are missing a key piece of the puzzle. Low serotonin will absolutely cause depression and is the single most certain thing to do so. Other things can as well including low norepinephrine but low serotonin will always make you depressed.

Still hormonal. I think it may be partially unavoidable as during pregnancy the woman's body is loaded up with an ungodly amount of progesterone only for that level to crash right after giving birth (and then on top of that have some non-hormone depression that comes with suddenly having a screaming pooping baby for the next few years). Current science is thinking progesterone drop is behind PMS also only on a smaller scale and there are some expensive experimental treatments nowadays based around tricking a woman's brain into thinking higher progesterone is still around in the body.

Not just hormones, but also copper. Copper levels soar in pregnancy because the fetus needs it to grow. The problem is that excess copper causes all sorts of psychiatric problems including depression and psychosis, so once the fetus isn't there anymore to consume it, things can go to shit. Taking zinc can lower copper levels, there are also medications that can help. Chelation therapy work too, but can take out a lot of necessary minerals at the same time so be careful.

Look I'm not saying you shouldn't splurge on the pure stuff and touch grass every now and again, but you didn't mention an obvious solution:
View attachment 3514189
A USB-driven full-spectrum grow light is going to be enough you can still make enough Vitamin D to function even if you stay indoors until you're printer-paper white. Also you'll be far less likely to become as pale as a ghost. Keeping the light timed with the sun is also going to keep you in a good rhythm for your sleep schedule. You can also do red-only for those uber-1337 late night hacking sessions. The downside is it looks like you're working under a lighting rig for a troon stream.

Infrared light actually helps a ton in helping certain people feel better. Unfortunately the shift away from incandescent light means that we are getting less of it now. It's technologically trivial to produce infrared light with LEDs; in fact, infrared LEDs have been used in TV remote controls for well over half a century. The issue is just that very few people realize that we actually need it.

Funny how a lot of the modern mental issues only showed up after a strong push for outlawing the use of weed.

Biggest opponents for the legalizing and destigmatizing the use of cannabis
1. Big Pharma
2. District Attorney Unions
3. Cop Unions
4 Private prisons
5 correction officer unions.

Marijuana criminalization started over a century ago, when society was much less complex and thus less intellectually and psychologically demanding. The more complicated we have made society, the fewer people can handle it. The situations aren't directly comparable.

Y’all are probably right. I get terribly depressed during my period and the only thing that’s ever helped my depression was migraine medication. I started taking that and suddenly acted like a normal human being.

Migraines and depression are both often associated with high levels of quinolinic acid (QA). What happens is that the body is low on niacin (vitamin B3) and converts the amino acid tryptophan into it. Two problems: one is that the conversion process is absurdly inefficient, turning 60 mg of tryptophan into 1 mg of niacin, and tryptophan is also needed to make serotonin; thus niacin deficiency leads to low serotonin. The second problem is that if the body doesn't have enough riboflavin (vitamin B2), the conversion pipeline stalls out at the QA phase, and QA is excitotoxic, contributing to migraines. Megadose riboflavin (400 mg a day!!!) is known effective for migraines.

Anyway, migraine medication is dangerous and will in the long term make holes in your brain (it happened to someone I know, who had to take early medical retirement as a result). I strongly recommend you take niacin and megadose riboflavin instead. Be careful with niacin, as high doses of niacin will cause a itching, burning, skin flushing reaction which can in extreme cases result in permanent changes to skin pigmentation. Take a "no flush" form like inositol hexanicotinate. Niacinamide, although marketed as "no flush" niacin, may be less than ideal as it does not fill all of the same biochemical roles as niacin itself.

Honestly psychology has never moved out of its bloodletting and leeches phase. Nobody knows anything, it's all based on guesswork and their experiments are plagued by failure to reproduce but still treated as sound science regardless.
Hell, how are you supposed to study something you can't prove even exists outside of your own head?

Modern psychology also completely omits the spiritual component of reality, and thus has no better chance of understanding its object of study than a Pacific Island cargo cultist has of producing a working airport without understanding electronics. Even if they work on it until the end of the earth, they're completely missing a vital component, and don't even realize that it exists.

They're currently experimenting with that as a treatment along with other drugs such as psilocybin (mushrooms) and ketamine, which have shown some promising results.

Don't forget about the alcohol and tobacco industries as well.

A huge number of people just need adequate micronutrition and they'll feel tons better. Giving drugs to someone with nutritional deficits, on the other hand, will just make things worse. Ketamine makes holes in your brain for God's sake. If you saw someone starving to death, would you give them drugs instead of feeding them? Madness. If you're not even trying nutritional strategies before moving on to banned recreational drugs and/or electroshock, you're an evil and insane butcher who needs to lose their license.

 

[Penis Drager]

@The Littlest Shitlord I can't directly quote your post so:

Disagree, the microbiome is hugely important and the changes I have made in my own life have shown that beyond a shadow of a doubt as far as I am concerned. But you are right in that the dietary changes caused by autism, etc. cause microbiome changes. The issue us that the bad gut microorganisms have evolved to make us crave a diet in which they thrive. For example, candida gut yeast produces acetaldehyde which uses up our vitamin B6 to detoxify it which lowers our serotonin which causes us to crave simple carbs that feed the gut yeast. Thus, autism, schizophrenia, depression, etc. are self-reinforcing cycles.

I'll start off by saying there's a reason I likened it to epigenetics. It is a legitimate field of study and it has profound effects. What I'm trying to get across here, though, is that whenever there's a sort of "bull rush" for a field of research, you should give every claim and finding that comes from it a much heavier dose of skepticism than you normally would. Overstated or outright bullshit claims are to be expected in any field. But the sheer volume of papers being published in the hopes of being noticed makes the ratio of bad science over good science skyrocket because of the sudden popularity. Similarly, people chalking up any and all unknowns to "probably this phenomenon that we've been finding links to everything else lately" is a perfectly natural (and fallacious) reaction to have.
So long as "the microbiome" remains a common point of discussion among the general public, and even for a good time after, you should probably distance yourself from the discussion until the field becomes "boring" again and the influx of bullshit slows down and a sufficient amount of it is sifted out. This is especially true if you're relying on popular media and books for your information on the topic. Every "exciting" field is going to have its Deepak Chopra's.

As a side note, personal experience is a notoriously bad way of verifying information. "I did this and it worked for me" could be used as the same exact justification for playing the lottery as the best way to become a millionaire.

 

[Loony Tunes]

Migraines and depression are both often associated with high levels of quinolinic acid (QA). What happens is that the body is low on niacin (vitamin B3) and converts the amino acid tryptophan into it. Two problems: one is that the conversion process is absurdly inefficient, turning 60 mg of tryptophan into 1 mg of niacin, and tryptophan is also needed to make serotonin; thus niacin deficiency leads to low serotonin. The second problem is that if the body doesn't have enough riboflavin (vitamin B2), the conversion pipeline stalls out at the QA phase, and QA is excitotoxic, contributing to migraines. Megadose riboflavin (400 mg a day!!!) is known effective for migraines.

Anyway, migraine medication is dangerous and will in the long term make holes in your brain (it happened to someone I know, who had to take early medical retirement as a result). I strongly recommend you take niacin and megadose riboflavin instead. Be careful with niacin, as high doses of niacin will cause a itching, burning, skin flushing reaction which can in extreme cases result in permanent changes to skin pigmentation. Take a "no flush" form like inositol hexanicotinate. Niacinamide, although marketed as "no flush" niacin, may be less than ideal as it does not fill all of the same biochemical roles as niacin itself.

Except my vitamin levels are all normal and I take vitamins daily so I have no idea what you’re on about.
You recommend that I take something without knowing what my levels look like?
I don’t even get migraines. My Psychatrist thought this medication might help my depression because no other medication was working. I started taking it and it did. I was able to get out of bed, go to work, and function like i normal human being. I was even able to become a mother which was all I ever wanted to be.
But go ahead and pop up and tell everyone on here what to do and if they take any type of medication that they’ll get holes in their brains.

 

[The Littlest Shitlord]

Except my vitamin levels are all normal and I take vitamins daily so I have no idea what you’re on about.
You recommend that I take something without knowing what my levels look like?
I don’t even get migraines. My Psychatrist thought this medication might help my depression because no other medication was working. I started taking it and it did. I was able to get out of bed, go to work, and function like i normal human being. I was even able to become a mother which was all I ever wanted to be.
But go ahead and pop up and tell everyone on here what to do and if they take any type of medication that they’ll get holes in their brains.

I was suggesting a starting point for research. It's dangerous to just blindly do what someone else tells you even if they are a doctor. So many people I know have died, almost died, or suffered irreparable damage from blindly trusting mainstream medicine. I wouldn't want you to be one of them. Take care.

 

[ZMOT]

I was suggesting a starting point for research. It's dangerous to just blindly do what someone else tells you even if they are a doctor. So many people I know have died, almost died, or suffered irreparable damage from blindly trusting mainstream medicine. I wouldn't want you to be one of them. Take care.

to be fair, a part of medicine is also playing whack-a-mole. "I have this issue, how can it be fixed?". for most people the first treatment works, because again that's what in the statistic shows up as "highest chance to work". if it doesn't something else gets tried till something happens. not necessarily the best solution, but since it fixes the issue most people, both doctors and patients, are usually satisfied and keep it at that (unless there are enough side-effects or complications which makes them keep looking for alternatives).
not to mention a lot of patients are also more interested in the short term than the long term (if the long term effects are even known at this point, or are statistically relevant. sucks if you're one of them), depending on the severity. "this will fix your chronic pain that makes your life hell, but there's a good chance you die 10 years earlier, still wanna take it?".

 

[AGreatDipAtAFairPrice]

It was always a bunch of hooey about dopamine this and serotonin that and that there would be a "right" level of this for people to not be depressed. The last 60 years was as if 5 to 15 percent of the population spent hundreds of billions of dollars on chemical trepanation.

 

[Vince McMahon]

TL: DR for anyone reading the comments: this is a classical shitshow A&H thread, where basement dwellers of all colours come out with their fringe little ideas, just because one article in one magazine said something they agree with.