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Not only we don’t understand the mechanism causing depression, we don’t really understand (as far as I am aware) why medications work or don’t work. I deal with mild depression sometimes, but this scares me off of considering medication for it. I’ve encountered so many horror stories of withdrawal symptoms... you really need to be at a point of desperation to consider drugs for it, imo.
Sadly this is true. "depression", like so many diseases, is named after its symptoms rather than etiology. So if we even have an effective drug, it will only be effective on a subset of the sufferers.

Plus we understand so little macro neurochemistry we don't even understand which apparently correlated biomarkers are causal and which are consequential. The same problem exists with other neurological diseases such as Alzheimers. With depression, as it seems to affect higher function, we even have difficulty (and treatment affordances) with non-chemical stimuli.

Still, it's very much worth working on -- people are suffering such serious debilitation.

I’ve benefited greatly from various medications combined with non-chemical strategies. When I first considered medication I talked with my Doctor, talked with some friends that are Doctors, and did my own research and every resource came up with the same basic info, we don’t actually know that much... Add onto that finding a combination of things that ‘worked’ was a trial and error process that took over a year, all while I was dealing with my mental health issues.

Sadly so many people in a similar situation don’t have the flexibility, access and/or support to go down the path that I did. Often they will opt out because of the stigma associated with having mental health issues.

The fact that we know so little leaves tons of room for improvement in addressing mental health, but I worry that we have a very long road to giant leaps in addressing mental health unless we can destigmatize mental disabilities (and other neurological conditions)

I think a larger problem is that it’s such a crapshoot about which treatments will work for a given individual, pharmaceutical or not. It took me about 10 therapists with varying backgrounds before I finally found one that would help. It also took me trying several different medications to find a combination that’s actually effective. It’s a lot of work and effort, and most people suffering through depression, anxiety, or another debilitating mental health disorder don’t have the energy to keep trying over and over again after failing. For me it was actually a matter of life or death and needing to keep going for my family that drove me to keep trying.
I had a very similar experience to what you’re describing and most other folks I know that have ‘figured out’ a treatment share a similar experience as well (more info in a comment below).
what worked in your case?
I have bipolar disorder and take a stimulant, a mood stabilizer, and sometimes an antidepressant. I’ve done my best to make my personal and professional work schedule comfortable, do mindful breathing exercises, take almost all my meeting outside and walking, and try to exercize 3 times a week. It’s a lot to manage while having a family but it’s very worth it IMO
I suffer from PTSD due to childhood trauma which is ultimately the cause of my anxiety, depression, mood swings, etc,. Right now I’m seeing a therapist who specializes in trauma and going through EMDR (eye movement desensitization and reprocessing) treatment. I’ve also taken Wellbutrin (anti-depressant) and Lamictal (mood stabilizer) for the last 18 months or so.

I also just have to constantly keep busy. I fill my time with work and activities with my family. I rarely take downtime because if I do the dread and flashbacks rear their ugly heads.

Have you ever tried Psilocybin? In combation with your therapy I could see success.
I'm also on Wellbutrin and Lamictal and think it is a very underrated combination.

I highly recommend you read The Body Keeps The Score. Immensely insightful and well researched book that will change the way you think about overcoming trauma

That book is great! I picked it up when I started with EMDR. There are so many things I didn’t even consider until I started seeing a therapist specializing in PTSD and trauma and after reading that book. For the most part I didn’t even recognize my experience as traumatic until it was presented that way to me.
My first experience with an antidepressant left me feeling quite ill. Ironically, its one of the ones that gets prescribed often because it has little side-effects. Turned out that this wasn't true, and I was one of the small percentage who experienced Discontinuation Syndrome (https://www.karger.com/Article/FullText/370338).

Having such a bad reaction to it lead me down a wild goose chase toward finding out the way my body processes serotonin ala a gene test, helped me figure out what was causing the depression to begin with.

Another reply here talks about how it seems to be a crapshoot for finding effective drugs and a lot of trial and error. I think that there may be promise in doing drug targeting genetic tests and possibly microbiome sampling as a way to help people avoid the run-around. In my case, knowing this ahead of time would have helped me avoid a lot of suffering and 3 years of obsessively searching for answers.

Genetic tests seem pointless. It's cheaper and faster to take the drug and find out if one is a responder.
I think what s/he's referring to are tests for mutations in certain liver enzymes that are known to interfere with a drugs function. These are cheap and quick tests (these aren't sequencing based tests) and quite good at predicting non-responders

On the other hand it can take 4-6 weeks to see if someone responds to a drug, and the drug can cause adverse events in addition to not treating the disease

So in this case it is cheaper, faster and safer to take the test before prescribing

The side effects of many of the medications can be quite harsh and severely affect your mental state when they don't agree with you.

The most obvious example of such would be the significant number of people who experience suicidal ideation or commit it/make attempts as a result of going on certain medications.

But at the less extreme end, you're likely looking at least a month or two, more likely 3 or 4 for each medication attempt. That's going on, taking it for long enough to have an effect, going back off, repeat.

With how severe the side effects can be for many, that's enough time to lose a job, fail out of college, etc. And you're asking them to potentially spend years in that cycle to maybe fine something that works.

Depression is just as serious as cancer. There is a lot at stake. In some cases ketamine may be a good alternative.

But harsh side effects seem like they would be acceptable if depression is as problematic as you claim.

If you don't mind, could you share some more details on what tests you did, what was causing the depression, and how the tests led you to find out?
Most medications DON'T work for most people. For example here[1] is a meta-analysis from 2004 of the top 6 antidepressants which finds that 80% of the effect is achieved by placebo, and the remaining effect is statistically, but not clinically, significant (that is, the effect size is tiny). Here[2] is another follow-up that shows that there may be effects only in the most severely-depressed patients. In addition the theoretical foundation of many drugs is lacking - the seratonin theory underlying SSRIs, for example, is now widely rejected (although SSRIs continue to be prescribed for some reason probably relating to drug company profits).

Given the well-known addictive nature of most anti-depressants, I have always advised my friends to steer away from them, or wean themselves off, and favor talking therapies instead. Everyone else should do the same.

[1] https://www.researchgate.net/publication/228550299_The_Emper...

[2] https://journals.plos.org/plosmedicine/article?id=10.1371/jo...

Do none of your friends have severe depression? CBT doesn't work for severe depression without medication in my experience.
(comment deleted)
That seems a strange reply to a comment that acknowledged medication only really has a real effect in severe cases.

Even for a friend who is severely depressed, which medication will work? How long does each one need to be tried for? What is meant by ‘work’ exactly? Meanwhile, the serious side effects aren’t even fully understood, and you’ll be buying them from companies that actively denied and hid such information from legislators and the public.

You're taking my comment completely out of context. Please reread.
Do you know you're listing a paper widely described as one of the most controversial psychology papers?

Here's a response, using the same data, but getting different results: https://annals-general-psychiatry.biomedcentral.com/articles...

> The results reported here conclude the debate on the efficacy of antidepressants and suggest that antidepressants are clearly superior to placebo. They also suggest that baseline severity cannot be utilized to dictate whether the treatment should include medication or not. Suggestions like this, proposed by guidelines or institutions (e.g. the NICE), should be considered mistaken.

I'd expect any paper that shits on an entire field and especially on a massively profitable industry to be controversial. Here is Kirsch's reply to Fountolakis's paper, by the way: https://academic.oup.com/ijnp/article/15/8/1193/659638
Note that in this case it's psychologists calling the paper controversial. Psychologists in BPS, the organisation that put out shit like Understanding Psychosis[0] or Power Threat Meaning Framework[1] - for an anti-psychiatry organisation to call an anti-psychiatry document "controversial" shows the document is pretty poor.

[0]Here are links to critiques of both version of Understanding Psychosis: https://www.nationalelfservice.net/mental-health/psychosis/u...

https://www.nationalelfservice.net/mental-health/schizophren...

[1] Here's a link to critiques of PTMFramework https://www.nationalelfservice.net/mental-health/power-threa...

Having gone off antidepressants cold turkey 4+ times withdrawal stuff is wildly overblown, which is corroborated by almost all the literature

It probably has more to do with a relapse back into depressive symptoms than anything in most cases

I have found for myself that taking Ibuprofen eases both anxiety and depression. It's not a cure but it surprises me how much of a mental effect a mild analgesic has.
Would anyone have an idea why this could potentially be?
I'd caution anyone making a link between depression and NSAIDs from that paper. Most of those people probably climbed out of depression because they specifically administered pain medication to subjects with osteoarthritis. Suddenly being rid of chronic pain can be liberating.
Rethinking this relationship is a major point of the original thread/article.
We don't know about severity of the depression when we say depression.

My friend has racing thoughts, feeling tired all time, unable to move, unable to think.

Negatives thoughts amplifying to point where nothing no longer makes sense.

Can such depression be treated?

When she was born, she had a serological conflict.

1. She first recognized it at age 8.

2. Now she's 18

3. Tried sucide at 16

It's not like she doesn't want to get better. She has everything good going for her but her body/brain isn't helping her.

Now, this article makes me wonder if she had this depression since birth and only understood it by 8.

And wether she is still affected by antibodies eating out her cells?

Tho i don't have any real sister but she is like my own sister.

I am willing to spend all my money to see her cured from this depression. But nothing has worked so far.

i think its warranted to go see a doctor.
Pardon me for saying something she has already tried. But here are some ideas.

- put her on a strict meat & veggies only diet (without nightshades) - Look into low dose naltrexon therapy, there is a LDN facebook group where you can ask questions.

Oh and of course, visit many doctors and ask them about treatment.

I wonder if changing the gut bacteria might provide her a route to health. A serological impact would deprive her of bacteria that could reduce imflamation
Take a look at neurofeedback, I had a friend with deep depression who was able to recover with that.
You could have her try a zero-carb (carnivore) diet. Nothing but beef, salt and water for a month. Probably won't work but considering all the anecdotal evidence and the fact that it's cheap and easy, I'd say it's worth a shot.
This is very important. It’s not yet fully understood, but something is missing yet in our understanding of inflammation.

It’s not everything, just like antibiotics weren’t everything, but progress here will mean curing an incredible amount of human suffering.

The book linked below, a late 2015 text on Molecular Neuropharmacology, is fascinating. Every chapter has a mention of inflammation and usually ibuprofen. It’s that important.

Particularly fascinating is the connection with ADHD, Parkinson’s, and Schizophrenia. All of the diseases have something to do with dysregulation of Dopamine. In particular, it seems like Ibuprofen helps with reducing the effects of Dopamine overload, which is essentially what Schizophrenia is. It’s an inflammation of the mind that is somewhat similar to how we now think sugar causes harm/inflammation. Anyway this overload eventually can lead to underload, or Parkinson’s. ADHD individuals are often overloaded as well due to the treatment with stimulant medication (which is good but can be abused).

I’m not kidding when I say there are Nobel prizes being left on the table here right now.

https://www.amazon.com/Molecular-Neuropharmacology-Foundatio...

Interesting definitely adding this to my reading list for self serving reasons. I independently came to similar ideas about inflammation, mostly because I have to take a lot of Ibuprofen for chronic pain and what works best is taking some preemptively on non painful days. That is, I always tried to think up more reasons for why this isn't a terrible idea.
Ibuprofen may cause ulcers, bleeding, or holes in the stomach or intestine.
Always possible, but I've taken taking 200 mg ibuprofen 2X per day for 30 years w/o a problem. I also take an 81 mg aspirin every night. I take turmeric and cinnamon with my coffee in the morning. If I get a bad headache I take two 325-mg aspirin also.

I have no stomach problems unless I drink too much Starbucks coffee over a 3-day period.

Why so much ibuprofen?
This is very little actually, this is what I take on non-painful days. When it hurts it's 800mg every 4-6 hours (up to 3200mg daily) combined with either 500mg or 1g acetaminophen depending on severity. Usually 1 or two rounds are enough, but definitely hit the limit a few times. These are pretty common dosages for anybody with serious pain.

Around 3 years on that regimen so far.

That's enough for me. The directions on the bottle recommend 1 x 200 mg pill every 4-6 hours. But it is possible to take a lot more: the max is 3200 mg/day. I've never had any stomach problems with ibuprofen or other NSAIDs.

I once cracked a rib and my doctor put me on 800 mg ibuprofen twice a day. _All_ pain went away as my swim times dropped steadily - so much so that it was upsetting the swim team's male hierarchy. Each new day I was recovered and invigorated, much to the irritation of my teammates. This went on for a month until the prescription expired. My swim times rose over the next 3 days as swimming became harder and the usual day-to-day pains returned.

Some people say that NSAIDs will prevent you from improving your ability in athletic events but that was not true for me and ibuprofen.

tumeric might be more powerful.
Curcumin/theracurmin yes, turmetic no.
Was having a similar discussion about this subject with my brother today, I completely agree on the importance. The shift from it being all in the head to recognizing that in many cases there is a physical and treatable illness going on will be a revolution. And not an easy one either.
It’s incredible. This last year this very link has become glaringly obvious to me. When depression kicks into overdrive inflammation seems to be right there with it. I’ve had some somewhat chronic issues and I’m really not sure if I should approach it in a physical sense (pt, excercise, etc) or if I should be doing more mental work.

Can’t wait for the science to mature a bit here for better direction. Pain killers (ibuprofen and others) scare the hell out of me now more than ever because they seem like an easy way out (read: temporary solution). And that’s a dark, dark path to tread on.

Ibuprofen therapy is a common treatment for the inflammation in my condition. Dietary changes helped me eventually get off daily ibuprofen. I was on it about six years.
It’s not yet fully understood, but something is missing yet in our understanding of inflammation.

Inflammation can have chemical roots. It can also be a side effect of infection.

It seems to me that this is why it's so complicated. Correlation does not prove causation. In order to treat conditions associated with inflammation, wecmay need to identify and resolve the things causing the inflammation.

I suffered from suicidal depression, anxiety, mania, psychosis, paranoia, panic attacks and more.

I flirted with diagnosis of schizoaffective disorder to bipolar.

My life was pretty out of control.

I didn’t like the outcomes I saw of people who were on meds their entire life and I didn’t buy the story from mainstream psychiatry.

I found MDMA therapy via an underground practice and it transformed my life over the course of a few session.

I was able to get to the root of all symptoms and heal what was beneath.

Combined with Holotropic Breathwork and NARM / somatic therapy for integration, this approach blew anything the psychiatrists were offering out of the water.

I’ve been experimenting with CBD and it seems to offer and even deeper level of clarity and non-anxiety.

No psychiatric meds, no symptoms and my creative and romantic life now has something to grown from - before this everything was in a constant cycle of boom and bust.

I am very glad this worked for you, but isn't MDMA a psychiatric med?
It started as one but after it found broad use as a recreational drug it was made illegal. It's Schedule I in the US and illegal in most countries (source: wikipedia).

Which is a shame because holy crap the one time I had MDMA sure broke me out of a major depression I'd been in for a couple decades.

It’s currently in Phase 3 for PTSD after spending a couple decades in prohibition.

It’s not a sanctioned medicine yet, and historically has been outside the bounds of western psychiatry.

And when I mean no psychiatric meds I mean nothing ongoing.

Bit late to the thread, but here's a link to where I assume the poster is referring to:

https://maps.org (Multidisciplinary Association for Psychedelic Studies)

Can you point to anything scholarly about Holotropic Breathwork? I'm curious, but my searches turn up very... "crystal woo-woo" stuff. :(
Stan Grof developed it as an alternative to LSD psychotherapy after prohibition.

Basically the framework I formed looked like this:

Depression and other mental illness are very often caused by an adaptive response to trauma.

Trauma heals in the space of non-ordinary states of conciousness in the right set and setting.

There are numerous paths into non-ordinary states, including psychedelics, EDMR and Breathwork.

Breathwork uses loud rythmic music and hyper ventilation in a supported group context to induce a useful non-ordinary state.

I should say, I thought this was woo woo bs. But holy shit, it will take you on a journey- I was blown away. And also it was super useful to integrate the MDMA sessions.

Have you used classical psychedelics therapeutically?

If so how would you compare their efficacy for your issues

A frame that was useful for me has been this: MDMA is useful for integrating existing information and experience (trauma, childhood stuff, etc).

Classic Psychedelics (LSD, DMT, Psilocybin) are useful for generating new information which then needs to be integrated.

MDMA was a much more predictable space to work. Psilocybin tended to take me to deeper as more frightening material - often on the cultural level.

I don’t think I would take psi to work with mania / hypomania; with MDMA it has worked beautiful to create more space to integrate and express the part of myself that was frightening.

That said, I have much more experience w MDMA in a therapeutic setting as an adult, and I could see how Psi could be just as effective.

If there is trauma to be dealt with, I’d personally start with mdma — but again, I’m bias from my personal experience.

so serendipitous - the other day ago I was putting down some wood flooring in my house and hurt my back a little - something that happens from time to time in exactly the same place - so I knew that I should get on top of it and take a couple of ibuprofen.

So I take a the ibuprofen, and take a break for an a couple hours - and as I noticed the back pain go away - I also noticed a distinct improvement in my mood! I had the exact reaction described in the article "of course, your back doesn't hurt ..duh".

The article makes me wonder if there is another explanation for the mood improvement ..

The risk is your back is hurt because it’s damaged. It needs time to heal. Taking ibuprofen hides the pain but doesn’t fix the problem in MOST cases.
One of the best things I've ever done for my mood is to switch to a plant based diet full of natural anti inflammatory foods. I noticed a big lift in my mood after the first week and it's stuck with me almost two years later.

Check this video for more details: https://youtu.be/4xbNNxQZEgA

Did you also eat less sugar/carbs? Because I think sugar is the main culprit.
Sugar and refined carbs can also cause inflammation but I cut those out of my diet years ago. I didn't see the real benefits until I switched to a plant based diet.
I don't want to be that guy again (I've been heavily downvoted in every nutrition threads I contributed in HN), please understand that I'm trying to learn and improve myself. But I'm curious how did you come up with a plant-based diet that's not high in sugar. As far as I know pretty much all (except very few) plant based food are very high in sugar. Especially most fruits have exorbitant amounts of fructose. I usually eat high fiber veggies (like broccoli, brussel sprouts, soybeans etc...) but it doesn't give much variety. Remember that most animal based food (eggs, most cheese, chicken, turkey, red meat, fish etc) are 0 sugar. Also, nuts are low carb, high fat but they're very high in Omega 6 (except walnut and some seeds like flaxseed) and there is some research indicating synergy between sugar and Omega 6 for inflammation (I can find the link if you want, but I'm too tired right now). I'm all for veganism but I can never find a suitable vegan cookbook. People say veganism is easy, as far as I'm concerned this is simply not true. If you go full vegan you have absolutely no choice other than soybeans to get adequate amount of protein. Any other protein source such as beans are very high in carbs (e.g. 600 cal of black beans have only 40g of protein (which is only 1/3 of my daily need as a bodybuilder) but have 116g of carbs only 30g of which fiber, in my book a very unhealthy food). And since you cannot supplement your diet with seafood, you have very few choices of Omega 3 sources (various seeds, acai berry, walnut come to mind).

To make myself clear: I think vegan diet is efficient, sustainable and ethical. But there is simply no easy way to go full vegan and get enough macro nutrients (in particular protein, and fats) without getting a lot of sugar. I have a lot of problem with inflammation and even 5g of sugar is too much for me, so it seems like the only plant based food I can eat are soybeans and broccoli. Maybe I'm missing something. Care to help?

A nutritionist/dietitian would be your best bet. But my 2c about the sugar in fruits, they're not as bad as refined sugar because of the fiber. You have to look at food as a whole, not as macronutrients combined together.
Nutritionists are mostly useless ; you are better off doing self-experimentation.
There is a huge difference between complex carbohydrates bound up in natural fiber and refined starches and sugars. The former are the foundation of the healthiest diets around the planet. The latter are unhealthy. The current anti carb hysteria fails to make a distinction between the two.

I think you'll find you can eat plenty of carbs if you stick to whole grain, unprocessed carbs and also avoid oil. I've been on this diet for two years now and I've lost weight and feel amazing.

You can get enough Omega 3 from non animal sources but if you're worried about it you can supplement with algae-derived Omega 3. Fish get it from algae anyway so you're just cutting out the middle man.

I recommend Michael Greger's book "How Not to Die" for a lot more detail on a healthy plant based diet. I think you'll find it a lot easier to eat this way than you might think.

Refined sugar is not inherently unhealthy.
Could you be more specific? Why do you think it’s not inherently unhealthy. I’ll argue the contrary here. Humans are primates; we evolved to eat an unrefined plant-based diet.

Consuming refined sugar is inherently unhealthy because it’s consumption causes insulin spikes and eventually insulin desensitization which leads to diabetes which is a strong predictor of inflammation. The same logic applies to any refined foods with concentrated amounts of fat or salt.

No whole plant-based food has the concentrated amount of macronutrients that are in processed food. You could argue that honey might be one, but honey’s been refined from pollen by bees.

When I consume refined sugar, I digest it and use it for energy - like any other food. Perhaps some people have intolerance to refined sugar, resulting in the negative outcomes you described.
You should take a look at Dr Fuhrman’s Eat to Live and Dr Michael Greger’s How Not to Die.

You should take into account that some whole plant high sugar or high starch foods like fruits and beans come packaged with fiber and other nutrients as well that serve to balance the nutritional profile and glycemic impact of the food.

That being said, if you do have a problem with sugar, stay away from sweet or high starch foods that lack fiber like ripened bananas and cooked white potatoes. Beans are healthy because they contain resistant starches that act like fiber.

You should be eating a variety of whole plant foods with high fiber and high nurtrient density.

Dr Fuhrmans list of foods you should consume everyday for a healthy immune system. G-BOMBS Greens Beans Onions Mushrooms Berries Seeds

Have you tried the carnivore diet?
Devil's Advocate (also personal experience): http://meatheals.com
Carnivore diets can help people with damaged guts. But you’re much better off fixing your gut than adopting a diet that is longer term going to cause a lot of other serious problems.
Fixing the gut is impossible in certain cases. And carnivore diet has be shown to cause no long-term problems in subjects before.
A strict carnivore diet contains no vitamin C, so you’ll get scurvy if you follow it religiously. And a diet so high in saturated fat and cholesterol will massively increase your risk of heart disease. This is documented in literally hundreds of studies. Annecdotally I have several friends that have dramatically improved their cholesterol levels by cutting out all animal products from their diet.

I think it’s also worth mentioning that the carnivore diet is the absolute worst diet imaginable in terms of the environment and animal welfare. It’s a selfish diet for rich people.

The only populations we know of that eat this way have serious athlerosclerois issues and short life spans or, in the case of the Masai, a rare mutation that makes it easier for them to live on this kind of diet.

I'd like to hear of even one of those hundreds of studies that shows that a strict carnivore diet (not a hybrid diet) leads to those problems.

I bet you can't because they don't exist.

If so the words you write here are but reflective of your beliefs. Which is not gonna help anyone (I'm certainly glad that I did not come across these words while looking to resolve a chronic medical condition).

There are plenty of studies of populations that historically have eaten essentially carnivore diets. The Masai and the Inuit are the two most common. They have all the problems I've enumerated.

If you think about it for even five minutes a diet with zero fiber and zero vitamin C makes no sense.

I prefer to be well-informed[1] than think about it for five minutes.

And no wonder you can't cite any specific study I requested for. :P

[1] https://youtu.be/isIw2AN_-XU

I am a huge fan of "Dr. Berg" on Youtube he helped me a lot with doing Keto/OMAD correct and reducing inflammation. He also has an interesting Video on depression.

The 6 Causes of Depression: https://www.youtube.com/watch?v=OV5OlaPZ6C4

Also fascinating is a lot of interesting medical knowledge he gathers by reading patent applications.

The 6 main causes he says are btw: Omega3, B12, Vit.D or B1 deficiency, too much Cortisol or Insulin Resistance.
This psychiatrist spouting off the "serotonin imbalance" marketing speak from big pharma like it's science is frightening. This has actually never been proven to exist, which is why every ad for SSRIs states "the way this drug is believed to work is...".

And then there's all the terrible side effects they never tell you about before you start taking them, and the fact you likely won't be able to stop using them without horrible withdrawal symptoms...

So much about psychiatry is still more akin to shamanism than actual science and medicine it's frightening.

SSRIs are known to have a substantial anti-inflammatory effect though, as well as other drugs like Wellbutrin.

I don't know if you have actually used SSRIs but the stuff about withdrawal is wildly overblown. Believing scare mongering about terrible side-effects and dependence issues kept me severely depressed and is one of the biggest regrets of my life.

kind of a long yakkety article and not much on tangibles. Yes there's a correlation between depression and inflammation, but there's a much bigger bucket of potential factors going on in this area: depression, sedentary lifestyle, sugar intake, obesity, inflammation, gut bacteria, visceral fat, and a whole lot more. As a clinical depression sufferer, if I change any one of those things, all the others change too. So yes keep looking into it but my own anecdotes and reading suggest there's a more complex ecosystem than just "inflamation == depression" going on.
There have been experiments directly relating the administration of inflammatory endotoxins to immediate depressive symptoms.

All of the stuff you mentioned pertains to inflammation. If gut bacteria is disharmonious or not getting enough fiber it consumes intestinal mucous which creates inflammation

I was diagnosed with inflammation through having a mold intolerance. Taking cholestyramine and synapsin changed everything. The CFS dissipated and everything seemed to come alive. The main thing that changed though was my mind. Brain fog had gone and a much better mood.