
Promises and pitfalls of applying computational models to mental disorders - okket
http://www.ncbi.nlm.nih.gov/pubmed/27543973
======
tcj_phx
In June some scientists in Australia published their paper that links an
inability to produce cortisol to psychosis:

[https://www.jcu.edu.au/news/releases/2016/june/stress-
hormon...](https://www.jcu.edu.au/news/releases/2016/june/stress-hormone-link-
with-psychosis)

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](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.

~~~
simonster
The claims you are making are stronger than the claims made by that paper
([http://www.sciencedirect.com/science/article/pii/S0149763416...](http://www.sciencedirect.com/science/article/pii/S0149763416300549)).
First, the paper does not claim that cortisol _production_ is related to
psychosis. Instead, it measures the degree to which cortisol levels increase
immediately upon awakening (cortisol awakening response or CAR), and
specifically notes that CAR necessarily related to overall cortisol levels,
but suggests that it may be related to hypothalamic-pituitary-adrenal axis
function. It finds that CAR is blunted in patients with schizophrenia and
first episode psychosis.

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.

~~~
tcj_phx
What is your motivation for defending the status quo? My goal for posting was
to point out that existing mental health treatments don't work, and that there
are promising developments that point to a better model. I didn't share all my
references.

> 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...](http://www.madinamerica.com/wp-
content/uploads/2016/07/The-Case-Against-Antipsychotics.pdf)

> There is no nefarious motive behind sticking to the status quo.

Just inertia and institutional retardation.

~~~
simonster
> What is your motivation for defending the status quo? My goal for posting
> was to point out that existing mental health treatments don't work, and that
> there are promising developments that point to a better model. I didn't
> share all my references.

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...](http://www.cochrane.org/CD008016/SCHIZ_maintenance-treatment-
with-antipsychotic-drugs-for-schizophrenia)

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).

~~~
tcj_phx
I know scientists mean well, but there is something rotten at the core of
conventional psychiatric practice. Sometimes people are helped, but there's a
lot of "if at first you don't succeed, try, try again," where the
psychiatrists try pill after pill on their patients, trying to find something
that works, or helps a little.

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...](http://www.quotecounterquote.com/2014/04/if-at-first-you-dont-
succeed.html)

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...

------
jrapdx3
It's a worthy subject, that interests me from in both its computational and
behavioral aspects. As is the case in most applications of computing, the
crucial aspect is the "match" between the model and the domain being modeled.

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.

------
Houshalter
Why is this being upvoted? There is no content here.

~~~
tcj_phx
You can read the full paper if you click on the 'DOI' link at the bottom,
which takes you to this page:

[http://brain.oxfordjournals.org/content/early/2016/08/18/bra...](http://brain.oxfordjournals.org/content/early/2016/08/18/brain.aww209)

~~~
wonkaWonka
The full paper seems to be more of a study of studies, in that it mostly cites
other research projects, and groups together studies that hold water.

[http://m.brain.oxfordjournals.org/content/early/2016/08/18/b...](http://m.brain.oxfordjournals.org/content/early/2016/08/18/brain.aww209.full)

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.

