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azuth89 t1_j6b9qq4 wrote

Number of inputs vs lack of ethical control scenarios + difficulty due to time basically.

If, for example, you wanted to answer this question a logical experiment might be to put a bunch of kids in a controlled setting at birth, possibly their mothers if prenatal deficiency is part of the theory, and then raise them for a couple decades with a deficiency in a specific vitamin and see if they have higher rates than the population at large. Potentially do this a number of times to isolate different vitamins, levels of deficiency, timing and so on.

Sound like something you would want to do?

But we can't. So we have to wait for a statistically significant number of people to get diagnosed, hope they have decent medical records and comb through those records for a common thread which stands out from all other possible environmental and genetic influences as a stronger predictor, and then do further analysis to make sure it remains predictive. Maybe start testing a large population in a longitudinal study to see if people with that behavior, deficiency, whatever eventually get diagnosed. Of course, if it IS a vitamin deficiency that wasnt previously tested you have to wrestle with the ethics of whether to address the deficiency or let it go and see what happen when you find it.

Tldr; Anything around brain development and mental health has an astronomical number of variables and few if any ethical ways to create a controlled experiment to start isolating them. Because development takes a couple of decades at least the sheer time and effort involved is also a significant barrier. So instead these studies are often meta-analysis of scattered and inconsistent data generated from other studies.

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Beginning_Cat_4972 t1_j6can14 wrote

Just to add on here- You're probably not going to get IRB approval for raising kids on any vitamin deficit. You could do this with pregnant rats and then perform behavior tests on them during development. Or you might be able to enroll pregnant women in a study where vitamin levels/diets are tracked but not altered in anyway. Then follow up with the children at different time points.

To answer the original question- I'd probably say that the main issue is that it's hard to get a study funded without having reliable data to back up your hypothesis. I skimmed a few papers and there's not a lot of rational behind the idea that vitamin deficiencies play a role in ADHD pathogenesis. No one is presenting a good reason for thinking vitamin deficiencies are important in ADHD. On top of that it looks like there isn't any compelling data that can be cited.

Another issue you'd run into is that ADHD has such strong genetic links, and none of the genes implicated in ADHD are related to vitamin metabolism. They're all related to neurotransmitter/neuromodulatory molecule signaling and handling and neuronal proliferation. So, it doesn't make a lot of sense to argue a vitamin deficiency involvement when all the observations point elsewhere.

So, sometimes when you read that it's hard to get to the bottom of an issue, with no clear explanation of why, it might just mean it's not a great hypothesis.

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SerialStateLineXer t1_j6cnwjw wrote

>You're probably not going to get IRB approval for raising kids on any vitamin deficit.

You can't do that, but can't you select a group of children and give some of them supplements? If some of the kids in the control group don't get enough of certain nutrients...well, that was going to happen anyway.

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ilovemybrownies t1_j6d76m0 wrote

It wouldn't be as airtight of an experiment to show causality, especially since again no evidence points to vitamin deficits being a direct mechanism. You'd probably have to track prenatal health, and you'd have to measure known genetic ADHD markers to account for ADHD being highly genetic when running statistical analyses.

But good luck getting the cash to fund it if there isn't already compelling evidence that vitamin deficit is directly linked to ADHD. Investors usually don't like "taking risks for the sake of exploration" unfortunately

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squirrious t1_j6ega9e wrote

There was a recent study that found mothers' low levels of vitamin D during pregnancy to increase the risk of adhd. https://www.sciencedirect.com/science/article/abs/pii/S0890856719322324?via%3Dihub

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squirrious t1_j6etypa wrote

Here's a study that found a potential link between vitamin D deficiency and ASD, unfortunately it's in Finnish but there's a summary in English: https://www.laakarilehti.fi/tieteessa/alkuperaistutkimukset/maahanmuuttajien-lapsilla-on-suomessa-paljon-vaikeita-autismikirjon-hairioita/

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eGregiousLee t1_j6ghg1h wrote

It’s important to remember that many studies are funded by private sources (often companies) whose lines of business create a conflict of interest.

“Here is US $15M to study whether Vitamin D does (x or y).”

“Aren’t you from the supplement industry?”

“Hush! Take the money and do an objective, unbiased investigation. If you find what we want, there’s more funding where that came from…”

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LinguisticsTurtle OP t1_j6iqy4h wrote

>I skimmed a few papers and there's not a lot of rational behind the idea that vitamin deficiencies play a role in ADHD pathogenesis.

Isn't there some data showing correlation (not necessarily causation of course...people with poor self-regulation might have a poor diet for obvious commonsensical reasons) between low nutrient levels and ADHD?

Aren't nutrients implicated in all sorts of brain functions including ones related to mental-health issues, hence the burgeoning field of nutritional psychiatry?

What about the seemingly (to a layperson) straightforward experiment of just giving ADHD patients who are (e.g.) low in iron (or whatever) some iron and seeing if symptoms improve?

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reddititty69 t1_j6cgega wrote

You don’t have to design the trial that way to assess if vitamin supplements improve the treatment outcome. You would just have 2 treatment arms: standard of care (SOC) and vitamins + SOC. This is how many cancer trials are set up. You could also have a vitamin only arm since untreated ADHD isn’t a death sentence. You don’t learn if vitamin insufficiency causes ADHD, but you can at least learn if it treats it.

There’s a big problem with your proposal for discovering if vitamin deficiencies cause ADHD, though. Even if you show a causal link, it doesn’t mean that’s the only cause, or even the proximal cause, of ADHD. For instance, you might establish that a lack of cobalt in the diet is linked to ADHD symptoms, but then find that in the ADHD patient population that cobalt deficiency is not detected. What’s going on? Likely, cobalt deficiency is an upstream trigger for a common pathway to ADHD symptoms that also has multiple other endogenous and exogenous triggers. So, not only does a trial design like your example put the participants at very high risk for poor health outcomes, it also likely leads to no actionable results. This is what the IRB is going to cite when rejecting the proposal. (NB: cobalt relationship with ADHD is just a placeholder example, not a hypothesis or statement of fact).

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IlsalaciousCrum t1_j6dvt55 wrote

Another route is study review (probably not the term, brain still booting) where an unrelated, huge, long-term study comes along with a giant population, huge test datasets, good documentation practices and publicly shared datasets. It has all the information such that some scientist just working from a computer can make connections and infer an unrelated connection. So even though none of the proposed studies would ever get funding or approval, the advancement could still come along.

I am thinking of a few big ones but I can't get my neurons on the names of the studies. You wouldn't believe the number of times in the preceding paragraph I tried to remember the name for something. If you are super interested in what I am talking about poke me in comments and later I will cite the names of studies and the unrelated papers/ideas/advancements that came out of study review.

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azuth89 t1_j6dw6hv wrote

That's meta-analysis, yeah. looking at data from one or more other studies and using it as the data for a new one. Mentioned that in the last bit as what actually happens most often with stuff like this.

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hypatia_knows_best t1_j6fhib9 wrote

Actually many studies show linkages between advanced paternal ages and ADHD, autism and schizophrenia.

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azuth89 t1_j6fth5o wrote

Right, which they do by combing through existing records and looking for correlation. Covered that.

I didn't say nothing could ever be done or studied, I said controlled experiments are very difficult on multiple levels and they're often leaning on data from other sources. That leaves gaps in what can be studied, but paternal age isn't one of those in many places.

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