Promises and pitfalls of applying computational models to mental disorders
ncbi.nlm.nih.gov
ncbi.nlm.nih.gov
https://www.jcu.edu.au/news/releases/2016/june/stress-hormon...
Cortisol is produced from Cholesterol (through a couple steps [1]). Cholesterol gets turned into pregnenolone in the mitochondria. My girlfriend did a lot of damage to her mitochondria with cocaine. 5 months after meeting me, she came to appreciate that "drugs" were causing her problems, and tried to quit everything cold turkey.
Now she's getting professionally mistreated by Psychiatry. They are trying to suppress the symptom of "psychosis" without caring why it's being exhibited.
[1] https://en.wikipedia.org/wiki/File:Steroidogenesis.svg
There is a ton of "technical debt" in the study of "mental disorders". Most of the research just needs to be thrown out. It would be much more productive to assume that people with mental problems are exhausted, give them cytomel (a T3 analogue), Retinol (Vitamin A), pregnenolone, and sugar, then re-evaluate.
Cholesterol's conversion to pregnenolone requires T3-thyroid and Vitamin A (NOT 'beta carotene', which is a provitamin). By also supplementing Pregnenolone, and maybe progesterone, the patient has a better chance of being able to make Cortisol, if they need it. Also treating with sugar reduces the need for cortisol.
I have a friend in somewhat similar circumstances, though she does not appear to be manifesting overt psychosis. Nor do I have full insight into her treatment; however, the ongoing appointments are very infrequent. Hospitalization did give her 6 days with a very well regarded addiction specialist, and the ongoing medications as the result of his prescribing appear to be doing good. Among other things, she's become very consistent about getting good quantities of sleep.
She's been a bit worried about her diet and weight gain. Some of the cravings, I now see as potentially lining up with your description. Maybe she can "let this go" for a while, while her body continues to recover and rebuild -- to the extent it can.
Any opinion on exercise? She runs extensively, although some new soft tissue irritation is now potentially putting a multiple month crimp in this. That exercise is new in her life, as of a couple of years ago. I hope it is sparking her body's capacity to renew itself.
You're welcome, thanks for the feedback.
The only thing my girlfriend can do for herself while in the mental hospital is eat sugar for the stress response and caffeine-free coffee for the magnesium & Vitamin B1. The drugs they put her on are known to harm the metabolism, so she's put on a little weight, but sugar is a better source of calories than starch.
As for exercise, I think weight-bearing exercise is much more helpful than cardio (which is very stressful). Muscle burns calories; endurance runners waste away.
Can she take a vitamin supplement? Ideally, all her nutrients would be gotten through daily food.
When you're locked up in a mental hospital you're mostly helpless to do anything for yourself. The food is usually pretty bad...
I have no doubt that the food is bad. I just don't want anyone to drink coffee and think that they are getting any type of adequate intake of vitamins.
[0] https://ndb.nal.usda.gov/ndb/foods/show/4271?fgcd=&man=&lfac...
Also, running can be replaced with cycling as a less damaging cardio workout. Or swimming if possible.
However, it is not clear whether the changes in CAR are causal or symptomatic. For example, psychosis might lead to a disrupted wake-sleep cycle, which could then lead to blunted CAR. To determine whether there is a causal effect, you'd need to perform a longitudinal study, measuring CAR in patients who are at first normal but some of whom later go on to develop a psychosis, and show that the CAR differences predate the development of psychotic symptoms, instead of developing later. The paper notes that such longitudinal studies are "clearly needed."
Mental illness is complicated. While it can clearly be explained scientifically, if the answer were easy, we would have found it by now. With that said, existing treatments have been shown to improve outcomes in double-blind placebo-controlled studies, even if we can't fully explain why, and that is why they are used. There are certainly problems with these treatments: They don't work for many patients and they often have undesirable side effects. But overall, we know that they help people, which is why we use them.
There are undoubtedly better treatments out there, but either they haven't been discovered yet or they haven't been proven to help. There is no nefarious motive behind sticking to the status quo. Researchers know that, if they were to publish a paper showing spectacular results from a treatment with few side effects, it would be great for the people they're trying to help, and also for them and their career. Instead, people stick to the status quo because, historically, alternative treatments have not been as effective.
> There are undoubtedly better treatments out there, but either they haven't been discovered yet or they haven't been proven to help.
Antipsychotics have been shown again and again to be ineffective over the long term:
http://www.madinamerica.com/wp-content/uploads/2016/07/The-C...
> There is no nefarious motive behind sticking to the status quo.
Just inertia and institutional retardation.
My goal is to provide an opinion that balances yours, because there are likely many people in your situation, and I don't think they should give up on existing treatments quite so quickly. I know how it feels to see someone you know and love afflicted by mental illness, and I also know how, if treatment as usual doesn't work, it feels like there must be something out there that can help them if you can only find it. But I'm also a neuroscientist (albeit in a subfield without any connection to the study of mental illness) and I know that scientists really do the best they can, and are generally willing to pursue any route if they think it might lead to a better understanding of their subject of study, or, in the case of mental illness, a treatment that can work better than what's out there today.
> Antipsychotics have been shown again and again to be ineffective over the long term:
I am not qualified to assess this evidence, since I don't have an extensive knowledge of this field nor the time to acquire that knowledge, but here is a Cochrane review incorporating 65 RCTs that shows antipsychotics are effective for maintenance:
http://www.cochrane.org/CD008016/SCHIZ_maintenance-treatment...
It is true that the reduction in the risk of relapse appears to decrease with the duration of the study, which is definitely a disquieting finding and deserves further study, but there was still a reduction in risk in the longest study included (3 years).
W.C. Fields' advice was "... try, try again. Then quit. There's no point in being a damn fool about it." [1]
[1] http://www.quotecounterquote.com/2014/04/if-at-first-you-don...
What my girlfriend needed was sobriety, but none of her psychiatrists has been willing to give her time. They're just being 'damned fools'.
"The Case Against Antipsychotics" (linked in my earlier comment) tells of an approach called "Open Dialogue Therapy", which was developed in Finland in the 1990's (pg 33). They avoid jumping straight to medications. Most "psychotic" patients do just fine when given a supportive environment and adequate time.
I'm going back to the courts soon to ask them to protect my friend from her court-ordered medical practitioners. One of my points is that they never gave her a chance to demonstrate that the drugs were unnecessary. She escaped from her court-ordered sedation, briefly, and started to do better... She couldn't handle the stress of her new job, did NOT take a good lunch on her second day, and resumed drinking. There are some good drugs that would have been helpful for keeping her off alcohol (naltrexone, etc), but at her next appointment all she got was the SSRI she asked for. She thought this "anti-depressant" had helped years before, but really it just helped her relapse (then). This time the SSRI and the benzodiazepine caused her to 'fall apart', relapse, get arrested...
I imagine his goal was to highlight the actual claims made by the paper you linked. This is obviously and understandably personal to you, but it's not intellectually honest to say that the paper you linked supports your claims. At best it's consistent with your claims.
I'm familiar with the literature linking cocaine use to altered (often pathological) mitochondrial function. I wonder, though, how did you determine that your girlfriend had mitochondrial damage?
Again, I understand that cocaine causes such damage, but my question pertains to how you evaluated her specific case.
She invited me into her world a little at a time. As the months went buy, I observed her buy and smoke a lot of crack cocaine. The first hospital told me they wouldn't let her go because they found cocaine in her bloodwork. At the time I didn't know about cocaine's effects on the mitochondria - that HN submission was 209 days ago [1].
[1] https://news.ycombinator.com/item?id=10956058
My evaluation is based on observation and inference. Her doctors don't care to check her mitochondrial function, but I'm sure there are appropriate lab tests.
Right, I'm asking what you observed.
She'd turn into an anorexic, and become more psychotic. I'd feed her, and she'd get better. It seems to me that she needs to eat more regularly than a normal person.
I have a couple 'therapies' that help restore energy metabolism. Some of these obviously helped, but she was a difficult patient, and wouldn't use them regularly.
That's an enormous inferential leap...
I agree with you that something is a bit wrong with Psychiatry. It is in fact a very young field, and there is very little basic science or understanding behind the treatments. This is a frustrating and dire situation for patients suffering from severe mental illness.
There is a lot of interest in mental health on HN... Sometimes I watch /newest, and come across submissions that provide clues for the puzzle.
> I agree with you that something is a bit wrong with Psychiatry. It is in fact a very young field, and there is very little basic science or understanding behind the treatments. This is a frustrating and dire situation for patients suffering from severe mental illness.
The field has been entirely corrupted by the drug industry, who used an incorrect interpretation of the findings science to sell their latest patent medicines. There are some good investigative journalism pieces in the Boston Globe in 2000 about the Prozac problem...
It's especially telling that many of the 1st-generation anti-depressants were anti-serotonin drugs, while 2nd-generation "anti-depressants" are pro-serotonin drugs. There are some safe MAOI's, but these don't get used anymore because of "the cheese problem"... I think the proper use for an MAOI is for a week or two, to get someone out of bed long enough for them to start to take better care of themselves. Then the drug would be discontinued.
I think Depo Provera (the 3-month "birth control" injection) turned my girlfriend into a drug addict, 10 years earlier... Provera doesn't do that to most people, but her history made her especially vulnerable to that particular drug.
Your intuition about the best testament being vitamins and sleep gibes with mine. We don't understand how consciousness and the brain work, but there is definitely something rotten in modern psychiatry.
I think we need the notion of "mental injury" instead of mental illness. It's more like a broken leg than a tumor.
> Getting into a mess by yourself is easy, getting out is really hard.
This is well-said.
> I think we need the notion of "mental injury" instead of mental illness. It's more like a broken leg than a tumor
yes... uhm, let me think here. "mental illness" is used to imply that a person is defective... The term is basically contaminated. 'Mental injury' is moving in the right direction.
The behavioral domain is particularly problematic. Humans quite naturally use abstraction as a modeling tool, and the tendency is to construct abstract categories as a basis of sorting the "raw data" of observation. The difficulty in the behavioral realm is that phenomena are indistinct and sharply bounded "boxes" don't correspond very well to the real-world behavioral complexities.
In the article the distinction between psychotic and affective disorders is pointed out as an example of the "softness" of phenomenological boundaries. If we conceptualize the distinction as an array of cardboard boxes side by side, psychosis in one box, mood disorder in another one, the compartments of the model will not fit what is seen in a clinical setting. Rather in the real-world conditions resemble sand dunes, rounded peaks flowing into surrounding soft peaks, and no particular place where it could be said one dune stops and another starts.
Furthermore the confluence of a surprisingly huge array of factors is involved in the appearance or origin of behavior we'd consider problematic (if we could even agree on that).
I'd concur with the idea that computational models need to be consistent with and informed by the reality they are intended to represent, but experience suggests that the more fundamental issue is conceptualization of behavioral reality itself which is far more complex than our usual abstraction of it lead us to consider.
http://brain.oxfordjournals.org/content/early/2016/08/18/bra...
http://m.brain.oxfordjournals.org/content/early/2016/08/18/b...
In the "challenges" it warns against reinforcing one's own opinion by cherry-picking data that suites preferences, and also falling into chicken-and-the-egg situations, where cause and effect or symptom and disease might invert.
There aren't any actual experiments in this paper. It just says bayesian analysis is a useful tool, and cites instances of success.