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DucksNQuackers t1_iv6g79d wrote

But is it a cause or a symptom?

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dangil t1_iv75nnu wrote

The serotonin model is dead. Probably a symptom.

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dude2dudette t1_iv80mfh wrote

The Serotonin Model is probably only accurate for a subset of those with depression.

Depression itself may be a symptom, with multiple possible causes (a bit like how severe stomach pain could be caused by IBS, Crohn's, Endometriosis etc.)

There might be various neurochemical imbalances that each can cause the behavioural/cognitive outcome of 'Depression' (especially given the different subtypes of depression that exist)

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Able-Emotion4416 t1_ivb0b7k wrote

There are now tons of studies showing that it isn't necessarily an individual problem for the vast majority of people suffering from mental health. But a huge systemic and societal one. Studies after studies demonstrate that air quality is crucial to prevent depression and anxiety, that most homes and buildings have neurotoxic offgasing, that out-door air qualities in cities is even worse. And that the probability to suffer from depression and anxiety in this environment strongly increases. Same thing with artificial lighting, junk food, and lack of physical exercises...

It's time to work and intervene like animal biologists do. It's time to fix our environment and food. And make them suitable for human mental and neurological health, among others.

Time to choose building materials, food ingredients, and artificial lighting that enhance human health, not harm it. And really time to strongly improve outdoor air quality in cities... We can't continue to make individual people carry the costs and burden of grave societal mistakes...

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dude2dudette t1_ivb3d62 wrote

Behavioural/environmental mechanisms are certainly important. However, that doesn't exclude neurotransmitter mechanisms.

It could be that the environment causes neurotransmitter receptor activation changes (e.g., lived environment (work stress/poor living space/lack of exercise, etc.) modifying one's immune system could lead to opioid activation dysfunction, which could then lead to depressive symptoms - see Charles, Farias and Dunbar, 2020)

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dangil t1_iv80u4c wrote

Pro tip. It’s epilepsy

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40ozSmasher t1_iv76651 wrote

Could you elaborate?

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Grisward t1_iv7ozfc wrote

These articles are valuable components of the overall research still ongoing to understand mental health and related pharmacotherapies. They have value. They are not showing serotonin is unrelated to depression.

First “major depressive disorder” is substantially stronger diagnosis than more commonly diagnosed depression.

Second, even among this subset of patients, “SSRIs significantly reduced the Hamilton Depression Rating Scale.” Their initial overall finding was significant decrease in depression (on multiple measurement scales).

They also found increase in adverse episodes (30/1000 in treated versus 22/1000 placebo), which is a known risk with serotonin-related treatments. This risk should not be ignored, for sure. However that risk doesn’t erase the benefit of treatment in some patients, it adds a secondary factor. It is certainly valid for the authors (and other scientists and physicians) to have the opinion that the risks do not outweigh the benefits, however that isn’t the subject of the study, nor is that type of opinion factual. The risks of adverse events is higher in “major depressive disorder”, and so their opinion is based upon a very focused study that only includes the stronger depressive disorder.

The serotonin model is not dead, nor is new data showing it to be dead. The serotonin model is as yet incomplete. The benefits of treatment is not fully understood in concert with risks to each patient.

Edit: fixed typo “sowing” to “showing”. Oops.

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ampanmdagaba t1_iv7n1aw wrote

This study: n=37 with p=0.04 turning to something like 0.5 after removal of one outlier.

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IamreallynotaNPC t1_iv6jlsp wrote

If your body doesn't have a proper amount of the materials required to create serotonin will the body limit its release? If so that would be a symptom, but if the body has all it needs and still didn't release much then it would be the cause. Then I wonder how do you figure that out even...

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DucksNQuackers t1_iv6kp6j wrote

To further complicate things- does the body have the proper amount of materials, under the correct conditions, in the right location? Then, what if anything else is going on with depression in addition to the serotonin piece?

And so the rabbit hole goes. Love this stuff

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IamreallynotaNPC t1_iv6l5c7 wrote

Serotonin cannot cross the blood brain barrier either, so what is made in the body is used there, and what's made in the brain is used only there, which adds more pieces. It is good that we have some confirmation on one part though.

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mjbat7 t1_iv6ymuv wrote

Hijackingthe top comment for visibility. Copying comments from last time this was posted.

Probably could just ignore this result unless it's replicated.

"BPND was significantly reduced in the HC group (1.04±0.31 vs 0.87±0.24 , p < 0.001) but not in MDE (0.97 ± 0.25 vs 0.92 ± 0.22, ns)".

Those differences are apparently p-value significant, but the error bars overlap widely in each group.

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Grisward t1_iv7msd6 wrote

Can you describe “error bars” and why they are more important to you than the P-value? What metric would you want to see?

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mjbat7 t1_iv8rky6 wrote

I used the term 'error bars' to describe the +/- values in the listed results. Frustratingly so far I haven't been able to access the original article in full text, so I can't be sure exactly what those 'error bars' represent. Presumably they're quoting the standard error in the samples, in which case, there appears to be a lot of error in their samples, which suggests that each estimate would have wide confidence intervals, which may overlap. Obviously overlapping confidence intervals don't necessarily mean that the difference isn't real, but if they overlap widely you'd certainly be quite skeptical of the results.

More specifically, let's look at some of the data in the abstract.

In the pre-treatment groups, the baseline BPND was 1.04 +/-0.31 vs 0.97 +/- 0.25. Is this a statistically significant difference? I don't know, but my guess would be that it isn't. Post exposure, the two groups' BPND was 0.87 +/- 0.24 vs 0.92 +/- 0.22. is this a statistically significant difference? Once again, I don't know, but my guess would be that it isn't.

If depressed people weren't measurably different from healthy controls in the baseline or post-treatment measures, then the fact that there is a within-group difference in the healthy controls but not in the depressed patients is much less convincing and seems more likely to be a statistical fluke.

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Grisward t1_iv8ubsu wrote

I get what you’re saying, and to be frank I appreciate the skepticism, and the drive to reality-check the numbers. Sometimes the numbers are over- or under-stated, or not reasonable effects.

In this case the abstract actually says it’s a significant change:

> “was significantly reduced in the HC group (1.04±0.31 vs 0.87±0.24 , p < 0.001)”

They include the P-value. You’re right it’s hard to know what the +/- means, typically that’s standard deviation, and not reflective of confidence intervals. Literally the confidence interval at 95% by definition would be smaller than the difference, that is if it used the same model used by the test.

It’s a whole thing about reporting and displaying confidence intervals, versus standard deviations, etc. Sometimes it’s straightforward to report standard deviation, but is not reflective of whatever statistical model was actually used. Frustrating, but not usually an author issue, also a journal guidance issue.

Oh, and the reason standard deviation does not indicate whether effect size is significant is in part that it doesn’t account for the number of individuals, nor the actual statistical model. Standard deviation is a simple university summary.

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