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Science and technology | PANDA-monium

How common infections can spark psychiatric illnesses in children

And why many doctors do not realise it

An illustration showing the form of a person surrounded by blue and
red dots. A white scribble is where the brain would be.image: Keith
Negley
Sep 20th 2023
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It was a sunny day in September 2007 when Garrett Pohlman, then seven
years old, came home from school. Crying, he warned his mother that
radiation was coming out of the house's electrical sockets. If they
went outside, he said, birds would peck them to death. These
pronouncements were accompanied by odd facial movements. The boy
would stick his tongue out and jerk his arms and legs. The day
before, Garrett had been a normal boy. Both the paranoia and the tics
had come out of the blue, but they proved to be the start of a
horrifying mental decline.

In the end, Garrett was lucky. A hospital scan three months later
revealed a bacterial sinus infection. A course of antibiotics cured
the infection and brought about a striking improvement in his
psychiatric symptoms. Garrett had been suffering from PANDAS, which
stands for Paediatric Autoimmune-Neuropsychiatric Disorders
Associated with Streptococcus.

Many other children are not so fortunate; some have suffered
long-term damage. In plain English, Garrett's unsettling behaviour
was the result of an immune system gone haywire following an
infection with group A Streptococcus, a common bacterium. (A similar
illness, triggered by other infections, goes by the acronym PANS, for
Paediatric Acute-onset Neuropsychiatric Syndrome.)

Yet many doctors have heard of neither PANDAS nor PANS. Some have
dismissed them as fictitious diseases. Very few countries issue
guidance on their diagnosis or treatment. Diana Pohlman, Garrett's
mother, says she is "exhausted" by years spent campaigning to get
doctors to take the illnesses seriously.

That is starting to change. Scientists are beginning to characterise
the conditions in detail and determine exactly what is going wrong
with the immune systems of sufferers. On September 12th Maria
Caulfield, a British health minister, weighed in, telling legislators
that PANDAS and PANS exist and are triggered by infections.

Such efforts are starting from a low base. In a 2020 survey for PANS
PANDAS UK, a charity, 95% of parents whose children have PANDAS said
their family doctors had not offered the diagnosis, suggesting
awareness is low. Things were only a little better among specialists.
Around half of paediatricians said they had never heard of the
disease. Nearly one in five of the parents surveyed said their
paediatrician felt that the diagnosis was controversial.

That ignorance carries costs. In many countries children with PANDAS
are presented with an alphabet soup of psychiatric misdiagnoses.
These can include attention-deficit hyperactivity disorder, autism
and sensory-processing disorders. Children can be given inappropriate
drugs like antipsychotics, many of which have unpleasant side-effects
and which do nothing to treat the cause of their disease.

In some cases parents have been accused of inventing or inducing
their children's illness. The Economist has spoken to parents who say
their children have been committed to mental-health services against
their will, or removed from their care altogether. According to
testimony provided in Parliament, one doctor told a child that he
would not treat "an American illness". In 2019 several dozen children
with PANDAS and PANS were discharged from a British hospital. Their
parents were told they had a "functional neurological disorder"--a
diagnosis that has evolved from the old (and discredited) idea of
hysteria, and which some doctors joke grimly means "finding no
diagnosis".

Exactly why the diagnosis is controversial remains unclear. After
all, the idea that the aftermath of an infection can cause
psychiatric symptoms is not new. Sydenham's chorea, in which patients
suffer from jerky movements of the face and body, is likewise the
result of a streptococcal infection. The Economist contacted a number
of psychiatrists and professional bodies for comment. Some did not
reply. Others said they were unable to offer any comment. The Royal
College of Psychiatrists said it was struggling to find an available
spokesperson.

The body and the mind

But as evidence accumulates that PANS and PANDAS are real, attitudes
are beginning to shift. Scientists who study the disorder now believe
it is caused by an auto-immune reaction, in which the body's immune
system mistakenly attacks brain tissue. After infection with
Streptococcus, the theory goes, children begin producing antibodies
that cause inflammation in their own brains, which in turn causes the
psychiatric symptoms.

In 2018 Christopher Pittenger, a psychiatrist at Yale University, and
his colleagues extracted antibodies from the blood of children with 
PANDAS and introduced them into laboratory mice. They found that the
antibodies attacked cholinergic interneurons in particular, a group
of cells in parts of the brain associated with tic disorders, which
are one of the features of PANDAS. Chandra Menendez, a researcher at
the University of Oklahoma Health Sciences Centre, says she has found
a "correlation between antibodies that target dopamine receptors D1
and D2 and the PANDAS phenotype". This sort of work could help
develop diagnostic tests.

A paper by Dritan Agalliu, a neurologist at Columbia University,
currently under review by a scientific journal, suggests that
blocking a particular part of the immune system--a type of lymphocyte
called T helper 17 cells--with immune-suppressing drugs reduces damage
to the brain, at least in mice. Other work suggests that damage to
the blood-brain barrier, a filter designed to protect the brain from
potentially harmful substances in the blood, could also be part of
the story.

Such findings may have significance beyond a single obscure,
debilitating illness. For they fit an intriguing, and growing, body
of evidence that other kinds of psychiatric conditions might also
result from infections. Dr Pittenger says it is now clear that
covid-19 infections can trigger psychosis, fatigue and other
neuro-psychiatric symptoms. A misbehaving immune system is thought to
be the culprit. The idea that schizophrenia may, at least sometimes,
likewise be an auto-immune disorder is also under investigation.
(Intriguingly, people with any kind of auto-immune disorder appear to
be about 40% more likely to develop psychotic disorders such as
schizophrenia.)

How long it takes doctors to pick up on this change of thinking is
another matter. Some of the prodding now comes not from patients, but
from governments. Robin Millar, a British MP who chairs a
parliamentary group on PANDAS and PANS, says Britain's government is
committed to working out how to diagnose and assess the illnesses. It
has begun discussions with doctors, and is pondering a research
project to work out how prevalent the diseases are. A pan-European
patient group called EXPAND, founded in 2018, is also pushing to
improve understanding.

Such efforts are sorely needed. As Garrett Pohlman's case shows, if
infections are caught early, treatment can be very effective,
avoiding long-term damage. Now 23, Mr Pohlman graduated in 2022 with
high honours from the University of California, Berkeley, in chemical
engineering, and these days runs his own company. Not every patient
has been so lucky. #

Correction (September 22nd 2023): An earlier version of this article
described the use of anti-inflammatory drugs to reduce damage to the
brain. In fact, immune-suppressing drugs were used. Apologies for the
error.

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newsletter.

This article appeared in the Science & technology section of the
print edition under the headline "PANDA-monium"

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