
PANDAS revives the debate about the immune system and mental illness (2015) - dnetesn
http://nautil.us/issue/62/systems/yes-you-can-catch-insanity-rp
======
tomhoward
I have an n=1 anecdata report on this topic, that some might be interested to
know about.

I'd long experienced mild/moderate mental illness, including anxiety,
depression, obsessiveness, sluggish cognition, possibly some ASD symptoms and
possibly some personality disorder symptoms.

After my research led me to a possible link between
inflammation/immunity/chronic infections and mental illness, I started
attempting to influence this by adopting anti-inflammatory diets (paleo etc)
and other approaches to supporting the immune system and fighting off chronic
infection.

I found that at certain points, my physiological symptoms of
inflammation/infection (most notably gum/tongue inflammation, digestive
symptoms and tinnitus, all of which I'd had since early adolescence) would
rapidly resolve, and this would be accompanied by a profound change in my
mental health and sense of wellbeing: anxiety/depression would be replaced by
confidence and optimism; lethargy and mental sluggishness would be replaced by
physical energy, creativity, productivity and accomplishment; anger and
resentment towards people in my life would be replaced by kindness and
compassion; my chaotic, shambolic lifestyle would be replaced by orderliness.

However, these states of wellbeing would be accompanied by a nagging sense of
fear and dread, that this version of myself wasn't the "real me", that it was
unsafe for me to be in this state of health, and that I needed to go back to
being my anxious, depressed, sluggish old self.

Sure enough, every time, within a few days I was back to where I was before.

It was a cycle that repeated several times over several years, during which I
was torn between frustration and optimism, knowing that it was possible for me
to get into a really good state of physical and mental health, but not knowing
how to stay there long term.

The turning point came when I discovered and adopted a set of emotional
healing practices that seek to identify and resolve deeply-held traumas and
fears. I've been undertaking these practices consistently for about 6 years,
and slowly but surely, my mental and physiological symptoms are steadily
resolving, and all in a way that makes me feel very comfortable at every step
of the process.

They're not all fully resolved yet; many of the symptoms I described above are
still there to some degree, but with much less severity than when I was at my
worst, and there's been a consistent enough improvement since I started this
approach, that it feels like it's just a matter of time.

I'm well aware that it will take for me to achieve that state - for all
symptoms of inflammation AND all symptoms of mental illness to be resolved -
for my experience to be evidence of anything meaningful.

The hypothesis (which is not my own, it is from the scientist and writer whose
ideas inspired me to try this approach) is that the immune system is heavily
influenced by chronically held, unresolved emotions and unprocessed bad
experiences.

Thus, if one is chronically stuck in a state of trauma, fear, or other
negative emotion, the immune system will function in such a way that allows
chronic infections to develop, leading to inflammation, which then leads to
cascading effects on bodily systems including the nervous system, the hormonal
system (particularly the HPA axis), the mitochondrial system and many others.

It may be because the body is devoting resources to being in a fight-or-flight
state, and leaving immunity as a lower-order priority.

Or it may be that the mind/body deliberately lowers the immune system and
allows these effects to happen, as a form of self-punishment (in the case of
profound guilt) or to keep the self out of harm's way (a kind of trauma-
induced hibernation).

I'd be unsurprised to find that either mechanism could apply depending on the
preconditions, as could many others.

I raise it in the context of this article as I think it's relevant to the
question of causality with respect to infections and mental health.

Given what I've experienced, it's no surprise to me to read the story of Isak
McCune at the beginning of the article, in which the contraction of an
infection seemed to be a trigger for serious mental illness.

But one still needs to explain why only some people who contract this
infection end up with the mental illness (in Isak's case, there's no mention
that the brother who'd had four bouts of strep infections had any comparable
mental illness symptoms).

Equally, for many people who end up in a state of mental illness, it comes
after a severe trauma or a sequence of traumatic events (one can find many
studies linking PTSD with infections and inflammation). There's no need to
postulate an infection as a primary cause, as we can observe the events that
led the person into their state of mental illness

It makes sense to me, in theory and based on my own experience-to-date, that
it is a combination of genetic preconditions, experiences, emotional states,
infection exposures, immune/inflammatory responses and others, that can all
conspire to result in a state of mental illness.

~~~
laddad
My direct experience backs up your conclusions. My 8 yr old daughter went from
sweet, confident and carefree to, overnight, crippled by worries about germs,
wetting the bed and screaming about everything. From there, she rapidly
descended into what I can only describe as being possessed… hallucinations,
erratic and sometimes violent behavior, refusal to eat and so on. We did a
spect scan which showed her basal ganglia lit up, a condition uncommon for her
age, so the doctor said to suspect infection. Sure enough, her blood work
showed that she had active strep and mycoplasma infections with no traditional
symptoms (fever, etc. ).

We then embarked on a hellish journey of long term antibiotics, countless
ivigs,plasmapheresis, multiple shots of rhituximab and endless battles with
the insurance companies. Even after her blood work finally improved (and her
psychosis diminished) she still experienced crippling OCD. Her care team at
Stanford explained that her immune system had been attacking her brain and
that if the condition is not caught quickly enough it is often necessary to
re-train the brain, similar to the case of a stroke. We sent her to a
residential facility in Wisconsin, Rogers Memorial, for 4 months and they did
an incredible job bringing her back to about 90%. At this point, she is still
on long term prophylactic antibiotics - the same protocol as for cases of
rheumatic fever - and is doing well.

We met other families with kids at Rogers who did not improve even after 6
months of intensive treatment there. In one case, this was because they did
not address the active infection in their child. Our anecdotal experience
leads me to believe that it often takes a combination of intensive
immunotherapy and brain rehabilitation to get the poor souls afflicted with
this terrible disease back to baseline. There are now several research
facilities popping up around the world (USA, Sweden, China) trying to improve
upon the protocol used to treat this. Hopefully the process will continue to
improve and these cases will be caught sooner and require less treatment than
my daughter did.

~~~
drogonmead
Glad to hear your daughter is doing so much better, and it's fortunate that
you're near Stanford. We're going through this right now. A little over a year
ago, my then-6-year-old son caught a fever and quickly lost his mind. It felt
a lot like demonic possession. He progressed from OCD to psychosis, eventually
losing all of his language and academic abilities. Experiencing this as a
parent has been horrifying.

To compound things, many medical providers either don't believe in or don't
have experience in treating an autoimmune encephalopathy (brain inflammation)
when there are no known markers for it (they've only identified around 18
antibodies for this condition, but there are likely thousands). There's also
still, in the minds of many providers, an arbitrary distinction between so-
called organic (i.e., coming from the organs) and psychiatric pathogenesis.
(As an aside, the first comprehensive guidelines for treating PANS were
published only last summer ([https://home.liebertpub.com/news/revised-
treatment-guideline...](https://home.liebertpub.com/news/revised-treatment-
guidelines-released-for-pediatric-acute-onset-neuropsychiatric-syndrome-pans-
pandas/2223\)))

Anyway, my son has received steroids, antibiotics, IVIG, a tonsillectomy and,
just this past week, plasmapheresis (to say nothing of all kinds of exotic
supplements prescribed by our more fringe providers that, I think, pretty much
have no effect). We've never been able to identify a specific infection at the
root of this, although staph has been suspected at times. Post-plasmapheresis,
he's already progressed to about 50% of his baseline. The next step will be
either more plasmapheresis or rituximab.

~~~
laddad
Yes we feel fortunate to be near Stanford. During the plasmapheresis procedure
our daughter was intubated for 5 full days, which was necessary due to her
psychotic state. However, when she woke up she had to endure several days of
dealing with fentanyl withdrawal (180+ heart rate, severe hallucinations,
etc.). After getting through that, her psychosis was gone but her OCD
lingered. In our case the PEX wasn't quite enough so they did several ritux
shotx. FYI - the latest thought is that rituximab is most effective when
combined with methyltrexate, but not sure if the data on that have been
published yet.

Through it all, I've learned much more than I ever wanted to know about
horrific medical conditions, the latest research on systemic inflammation,
psych meds, navigating medical insurance claims and who my real friends are.
As an app developer, I tried to do my little part by releasing an iOS app to
help track it all, but that doesn't feel like enough. Now I have some degree
of normal back in my life, I'm looking into other ways to reach out and
support those going through what I did, so feel free to reach out if you have
any suggestions.

~~~
drogonmead
That sounds awful. I'm so glad she came through. Thanks for the note about
ritux. Honestly, the neurologist we're dealing with hasn't had a lot of cases
like this, so any more info we can get is helpful. It's been interesting to be
in a position where I've become much more familiar with the literature than
almost every doctor I speak with.

Although we're still in the thick of it, I also want to find ways to help
others and have a few ideas. An email address (anonymous on HN) is in my
profile if you'd be up for connecting.

~~~
laddad
sounds great - will drop you a line.

------
mavilia
Very interesting read. I always wonder about the criticisms of new solutions
that are working as magically as they seem to be in the article. The kids
started taking antibiotics, and soon thereafter had obvious improvement that
led to them being cured eventually. Of course you can say sample size wasn't
large enough to make any conclusions, but what is their (critics of PANDAS)
answer to the fact that the antibiotics worked? Is it pure coincidence? Or
some other mechanism in play?

If it was another mechanism in play then at the very least I would think that
autoimmune treatment should be used as a backup plan in case typical OCD,
ADHD, etc. drugs aren't working as shown through the article.

Of course I am not a medical researcher so this may have an obvious answer,
but I always wanted to know how critics go beyond the "n=1" argument to
disprove new solutions that seem to work perfectly.

~~~
TheSpiceIsLife
Someone correct me if I'm wrong, but aren't the typical ADHD medications
amphetamine and methylphenidate?

Shouldn't these two _powerful stimulants_ be medications of last resort?

~~~
testvox
They are, but ADHD is particularly unresponsive to other interventions. So
those drugs are usually what ends up being the only effective treatment
anyways.

------
sergioisidoro
This is nothing new, and I have a hunch we're going to find more subtle mental
changes associated with external infections (not just extreme dementia,
paranoia, and seizures). Things that people currently associate with innate
personality traits.

One example is the personality changes that toxoplasmosis can induce to
humans, even when being latent. And I would guess that these will go
undiagnosed for most people.

[https://www.scientificamerican.com/article/common-
parasite-l...](https://www.scientificamerican.com/article/common-parasite-
linked-to-personality-changes/)

~~~
somebodythere
There is evidence that before you develop symptoms, people with the flu are
more likely to have social interactions:
[https://www.psychologytoday.com/us/blog/darwins-
subterranean...](https://www.psychologytoday.com/us/blog/darwins-subterranean-
world/201801/does-the-flu-trick-people-being-sociable)

------
montenegrohugo
What if you grow up around insane people? What if you are daily surrounded by
people with faulty reasoning and illogical, biased conclusions? Would you not
adopt these neural mechanics too?

You are a product of your environment, and if your environment is insane, you
will be too.

~~~
WilliamEdward
It could just as easily be the opposite - seeing insane people could make you
less likely to go insane because you see how damaged they are and avoid it as
much as you can. Ultimately it still boils down to you and your own brain, not
anyone else.

~~~
montenegrohugo
I am vehemently against that notion.

If your only point of contact is people who speak spanish, you will never
learn english. If your only point of contact is people that think that the
world is flat, then most likely you will grow up believing the same. If
everyone around you is insane, then it is exceedingly like you will be too.

Again, my belief is that you are a product of 1. Your environment and 2. Your
genetic programming. And humans are social creatures, if the people that
surround you are all in a certain way, you will probably tend that way too.

~~~
naasking
Your argument depends on a huge, untenable set of assumptions. Insanity is not
comparable to languages or beliefs, they are severe dysfunctions, some or many
of them genetically linked. Non-dysfunctional children raised in such an
environment will certainly adopt odd behaviours thinking it's normal, but it's
a huge stretch to say they will actually somehow adopt insanity.

~~~
Retric
What separates Insanity from normal healthy individuals is the ability to cope
with normal society. If you believe you must wash your hands 20 times a day
that's a problem even if you have nothing biologically wrong with you.

~~~
slfnflctd
Except for people who do work that requires them to wash their hands that
often (or more), and people who live in cultures where that is part of some
daily religious ritual, and...

~~~
Retric
Actual hand-washing 20+ times for 2+ minutes each every day is extremely rare.
Sanitizing for 20 seconds is a different story. Further, doctors don't do this
on their days off which ends up being really important.

In the first case you would severely irritate the skin and end up with
noticeable medical problems. Which IMO is a reasonable line for sanity in
terms of day to day impact based on belief vs reality.

That said, sure there is something of an exception for religion.

------
wpasc
As a person who has an autoimmune illness (so I'm biased), I believe that
immune system research is woefully underfunded. I lot of literature I've been
reading recently is showing it's involvement in a whole host of "non-immune"
diseases and many autoimmune illnesses (MS, Lupus, CFS, etc.) are shrouded in
mystery.

I think that given the immune system's involvement in so many other diseases,
basic research into its workings is really underfunded when compared to many
other diseases that might derive benefit from more immune system research.

------
TheSpiceIsLife
> Today Singer says that ... Treatments and medications for OCD and ADHD
> already exist, they say, and should be enough.

Is this true? _Treatments and medications_ , yes, but do any of the mainstream
treatments or medications do _anything to actually cure these conditions?_

~~~
krageon
Children that receive methylphenidate suffer from less severe ADHD symptoms
later in life, supposedly. If you look at it through this lens it becomes
ethically problematic to deny them the medication, especially because it will
not do this in adults (obviously it still treats the symptoms in adults, it
just doesn't make them less bad over time).

------
callesgg
I believe that most psychological "issues" arise from more rationally
explainable underlying problems than our current psychological understanding
is able to explain.

We lack the models to analyze and research how different diagnoses are related
to each other.

Psychology today is a bit to obsessed with the surface structure of the mind,
and the behavior that it causes. We need something like theoretical physics
for the mind where we model more underlying functions not surface behavior.
The mind might however be so complex that it is impossible. But on some level
i think there is abstraction levels that can be modeled.

~~~
krageon
It might be impossible to model with the technology that we have right now,
but it cannot be impossible at all. Unless you believe consciousness contains
some amount of magic, in which case all bets are off.

~~~
callesgg
It might be impossible in the same way that it is impossible to beak an RSA
key. To many underlying components making it impossible to extract the
underlying components unless you already know what they are.

------
DubiousPusher
Just to be clear, PANDAS is not just "controversial". Widely, it is not
accepted as a specific condition. The sudden onset of childhood psychosis is a
recognized syndrome but including any mention of autoimmune or strep in naming
the syndrome is getting way ahead of ourselves.

[https://sciencebasedmedicine.org/a-pandas-
story/](https://sciencebasedmedicine.org/a-pandas-story/)

------
simion314
The article states as a fact that in present all mind illnesses are get blamed
on the mind and not on the environment or body but we read everywhere that the
causes for many such illnesses are in the body or environment.

The problem IMO is that it takes a long time until correlations and later
causation are found

~~~
barking
AFAIK twin studies where babies were adopted suggest that schizophrenia is
likely to be genetic in causation to a large degree.

That doesn't rule out the common environment of the womb of course.

~~~
Nasrudith
I thought the nazis proved that it /wasn't/ genetic strongly by murdering
nearly every diagnosed schizophrenic under their domain. The rates were
unchanged.

Maternal nutrition seems far more likely given the prevalence being lowest in
wealthier countries and higher in poorer countries on maps. Granted it may
technically be epigenetic.

~~~
krageon
All they proved is that murdering all people (that they could find) with
schizophrenia doesn't lower the incidence rate of schizophrenia. This paper
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800142/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800142/)
discusses a few of the reasons why that could be the case, but obviously it
doesn't make grand claims.

~~~
Nasrudith
Interesting that sufficient complexity may also work as a reason. I would have
expected some deceease in a genetic context but I suppose sickle cell anemia
is another example with simpler structuring given it is partially adaptive and
partially maladaptive given one means malaria resistant blood and two means
concave red cells bad at their job. Even if malaria vanished a thousand years
ago the trait would probably stick around today. Thanks for the link and
furthering my understanding.

I wonder how common "summed" traits are where a few to some are good to have
while too many or too few is a bad thing. I heard of one computer example
which by no means biologically proves anything apparently too high a learning
rate caused some neural networks to start making increasingly bizzare
associations and caused the convergence rate to plummet instead of improving
past a certain point as spurious correlations resulted in incoherence. The
schizophrenia thought disorder resemblance was explicitly noted.

------
Lxr
The reverse question is equally interesting - to what extent can we influence
the activity of our immune system by controlling stress levels, practicing
mindfulness, and the like? I think there is a lot still to be discovered about
this.

