Source on Serotonin not being linked to depression?
Serotonin is linked to depression. The illness isn't caused by low serotonin levels, but there are lots of brain chemistry things going on in people with depression, some of which involve serotonin. It doesn't require Serotonin to be low initially for raising its level to treat depression. SSRIs do help for many depressed people, myself included.
Elevated Brain Serotonin Turnover in Patients With Depression:
We really don't know how anti-depressants or anti-anxiety work and are effective for some people. The Serotonin boost / balance is just one of the popular theories that is being studied as the cause for this. Let's not forget that for a really long time we believed the popular theory that stress caused ulcers.
I also speculate that a major reason for the popularity of this Serotonin theory is largely covert and overt pharmaceutical marketing - doctors and patients are much more likely to "trust" a medicine if they believe there is a "scientific" explanation to why a medication works.
(In case there is any doubt, I want to clarify that I that anti-depressants and anti-anxiety medications do work and relieve the symptoms of these disorders. Medical trials have been done to prove that they do work, are effective and also cause side-effects. But we really do not understand how they work with any scientific surety and hence also why they don't work for a minority of people.)
It's been known for a long time that serotonin is associated with social dominance and that drugs like the SSRI prevent and somewhat heal the brain damage that comes from being "an underdog". There is a long running question about "Why are poor people so fucked up?" that mainly answered by "being poor damages your brain".
It's an inconvenient truth because the Rx is revolution. Although justifies the use of SSRIs just well it is not a message pharma or your doc want to promote because why should we poisoning the fish in our waterways with our SSRI-contaminated urine when the problem could be dealt with more directly.
I don't find "inflammation" to be a very meaningful answer because "inflammation" is a range of very complex biological processes.
We use the same word to describe the process by which you feel pain after a muscle injury but also the effects of asthma or processes that cause damage to your heart in heart disease but there are distinctly different paths involved. Systemic corticosteroids suppress most kinds of inflammation powerfully and can save your life but they will destroy you when used chronically.
I had that CRP test the day I after I got a contusion on my upper leg that had me off my feet with inflammation but the CRP does not detect that kind of inflammation because I got a low score like I have every time I've had a CRP draw when I was or wasn't having symptoms that could be related to CRP. There is certainly some inflammation that contributes to CRP but other kinds that do not.
There are at least 14 kinds of serotonin receptor on many cells in your body, in your gut, on your platelets, on your heart valves, immune cells, etc. Most people who try a few different SSRIs can usually find one that agrees with them but many people have some uncomfortable physical symptoms with their first SSRI that may cause off-target effects: because of those receptors on platelets, SSRIs act as blood thinners
which could save you from a clotting event but kill you through a bleeding event.
If SSRIs work as advertised and raise serotonin in the junction then some will diffuse out into the fluid partition and have some effect on other cells so between that and off-target effects some immune cells must have be affected somewhat and there is some connection with "inflammation"
I am fascinated in pharmacology and biology how these systems have structure and how you can interrupt a process at multiple points, for instance there is a process by which a protein is made in the liver, cleaved by another protein in your lung (the ACE-2 receptor that COVID-19 attacks), which is regulated by a protein from your kidney that binds to a receptor. There are a few very successful drugs for high blood pressure and related conditions that block this system but there are several other hormone systems of a similar structure related to this that are not so well developed or understood. The targets of these drugs are all proteins that are coded for by genes so there is a straight line from the pharmacology to generic susceptibility to illness
are heritable. This is the complexity of what we're getting in to when we draw a line from some drug that is known to bind to certain proteins to the change in your experience and behavior comes from taking a pill. A lot gets lost when we simplify it to the kind of pithy narrative one would expect from a salesman or politician.
I saw my nurse practitioner when I expected my stress level at work to explode in the near future and she offered me an SSRI to blunt my physiological reaction to stress. That plus fanatical amounts of exercise got me through a few challenging years of developing my own business. I felt more in control when I was under stress and never get flustered or mean to people and that the SSRI was helping me be a better parent.
I eventually got back into W-2 work and after I settled in, my primary core doc asks me if I want to stop the SSRI and I say sure. It has been a long strange trip since, I did find that parts of me were suppressed by the SSRI. One day I went into a rage because the room I was in was terribly cluttered and clocked 40,000 steps on the pedometer without leaving the house, cleaning it. I have been through waves of growth and consolidation and am definitely seeing meaningful things to do with my time.
One hypothesis is that the antidepressant effect of SSRIs is due to them interacting with a different part of neurons by accident. Here’s Derek Lowe writing about a potential target that was discovered recently:
It's quite clear that SSRIs don't work... but pharma doesn't want to lose the cash cow, hence articles like this.
If treatment or cure is the goal, SSRIs don't work.
If the goal is to chemically inflate the ego of traumatized people to make them temporarily feel good about themselves while causing much worse long-term harm in exchange for profit to the drug companies, then SSRIs work great.
Here's a kicker, give someone an SSRI and a pep talk and their dopamine signalling changes as they recover from social anxiety. No SSRI and nada, no pep talk and nearly nada.
We now know that receptor density/expression/sensitivity can vary wildly among different people and is influenced by medication, especially substances that target them. Just measuring the levels of any kind of receptor binding substance and comparing it among individuals is only half of the picture.
Serotonin is linked to depression. The illness isn't caused by low serotonin levels, but there are lots of brain chemistry things going on in people with depression, some of which involve serotonin. It doesn't require Serotonin to be low initially for raising its level to treat depression. SSRIs do help for many depressed people, myself included.
Elevated Brain Serotonin Turnover in Patients With Depression:
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/...
Low receptor levels and low mood:
https://source.wustl.edu/2004/05/low-receptor-levels-and-low...
Depressed monkeys have elevated levels of serotonin in the part of the brain and decreased levels of serotonin in the hippocampus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274982/