This is a fascinating article, not just about OCD, but about the pitfalls of research. I personally believe OCD is a biological disorder. I know a number of folks with OCD, one my husband, who insists his disorder (lifelong for 61 years and misdiagnosed for years) is indeed biological.
The article is long, but worth a look. This is an old arguement, but whether or not strep causes OCD in SOME children isn't the point. I believe this research will eventually lead to greater understanding of the biological cause of many mental illnesses.
D
The New York Times
May 22, 2005
Can You Catch Obsessive-Compulsive Disorder?
By LISA BELKIN
To suffer from obsessive-compulsive disorder, many patients say,
is to ''know you are crazy.'' Other forms of psychosis may envelop
the sufferers until they inhabit the delusion. Part of the torture
of O.C.D. is, as patients describe it, watching as if from the
outside as they act out their obsessions -- knowing that they are
being irrational, but not being able to stop. They describe
thoughts crowding their minds, nattering at them incessantly --
anxious thoughts, sexual thoughts, violent thoughts, sometimes all
at the same time. Is the front door locked? Are there germs on my
hands? Am I a murderer if I step on an ant? And they describe
increasingly elaborate rituals to assuage those thoughts --
checking and rechecking door locks, washing and rewashing hands,
walking carefully, slowly and in bizarre patterns to avoid stepping
on anything. They feel driven to do things they know make no sense.
There are researchers who believe that some of this disturbing
cacophony -- specifically a subset found only in children -- is
caused by something familiar and common. They call it Pediatric
Autoimmune Neuropsychiatric Disorders Associated With Streptococcal
Infection, or, because every disease needs an acronym, Pandas. And
they are certain it is brought on by strep throat -- or more
specifically, by the antibodies created to fight strep throat.
If they are right, it is a compelling breakthrough, a map of the
link between bacteria and at least one subcategory of mental
illness. And if bacteria can cause O.C.D., then an antibiotic might
mitigate or prevent it -- a Promised Land of a concept to parents
who have watched their children change overnight from exuberant,
confident and familiar to doubt-ridden, fear-laden strangers.
Child psychiatrists have long known that sometimes O.C.D. in
children can be like that, that it can come on fast, out of the
blue, like a plague, and then last anywhere from days to months. If
the typical graph of O.C.D. symptoms is a sine curve -- with
episodes that ramp up slowly, peak gradually, then abate just as
slowly -- the graph of rapid-onset O.C.D. is saw-toothed -- flat,
then a sudden spike, followed by a relatively sharp drop, then flat
again.
The patterns certainly look as if they could be two separate
disorders, with similar symptoms but different causes. Across the
country, many doctors are convinced of this and are putting young
sudden-onset O.C.D. patients on long-term doses of antibiotics.
''If I were to place bets,'' says Judith Rapoport, the child
psychiatrist who first brought O.C.D. to public attention with her
book ''The Boy Who Couldn't Stop Washing,'' that bet would be on
the side of those who believe in Pandas.
But as certain as some researchers are, there are others, just
as smart, with just as many impressive publications and titles, who
think the theory is wrong or, at best, that it is too early to
tell. And this group is warning that the Pandas hypothesis is
misguided, perhaps even dangerous. ''Equivocal, controversial,
unproven,'' Dr. Stanford Shulman, chief of infectious disease at
Children's Memorial Hospital in Chicago, says of the theory.
Pandas stands at a familiar, necessary and utterly frustrating
moment in medicine -- in the gap between what doctors think and
what they know. Practically every byte of scientific knowledge
passes through a moment like this, on its way to being accepted as
fact or dismissed as falsehood.
It has always been so, but in recent years several things about the
process have changed. Science now does its thinking in public, with
each incremental advance readily available online. And those
waiting for answers are less patient and more involved. They don't
ask their doctors; they bring their own suggestions. They don't
want to wait for the results of a two-year double-blind
placebo-controlled clinical trial before they act.
Which means that they often find themselves acting before all the
facts are in.
Can strep bacteria cause obsessive-compulsive
disorder? Do these children need penicillin or Prozac? Will we look
back on these questions years from now and think, How could we have
believed? Or, rather, How could we have doubted?
The most vocal voice in support of Pandas is Susan E. Swedo, a
pediatrician and researcher at the National Institute of Mental
Health. She was the first to identify the syndrome, and the one who
gave it a name. She has been studying the relationship between
strep and O.C.D. for her entire career.
She began her work in the 80's, a time of discovery in the world of
obsessive-compulsive disorder. Although the disease had long been
known, it was not until 20 years ago that researchers began to
understand how prevalent it was and not until a decade later that
they came to see how often it occurred in children.
In 1989, Rapoport published her best-selling book, taking the
illness into the mainstream spotlight. When the television program
''20/20'' ran a segment about her book, it prompted 250,000 calls
from worried parents who thought they recognized their children.
And a good number of them, Rapoport says, were right. She
estimates that more than one million children in the United States
suffer from O.C.D. In fact, she argues, the disorder is one that
often begins in childhood, which is why doctors should start
looking for it then. Half of all adult O.C.D. patients look back
and remember having repetitive thoughts and rituals when they were
young, which is significantly higher than the percentage of adults
with other psychiatric disorders who do.
Rapoport strongly suspected that there was a medical model for
at least some percentage of O.C.D. sufferers -- that the symptoms
were not a result of emotional trauma (Freud's belief that it is
caused by overly strict toilet training had long since fallen out
of favor) but rather were caused by a biological trigger. She and
her research fellows at the N.I.M.H. spent several years looking
into it. Swedo was one of those fellows.
Research had already shown that O.C.D. symptoms appear when
there is damage to the basal ganglia, which is a cluster of neurons
in the brain that acts as a gatekeeper for movement, thought and
emotion. ''So we set out to find every known condition that
involved abnormalities of the basal ganglia,'' Swedo remembers.
Huntington's disease was one. Parkinson's was another. Also on
the list was Sydenham's chorea -- a movement disorder known to
medicine since before the Middle Ages, when it was called Saint
Vitus' dance. About 70 percent of patients who develop Sydenham's
also develop O.C.D. Sydenham's is caused by rheumatic fever;
rheumatic fever is in turn caused by Group A beta-hemolytic
streptococcal bacteria. In other words, strep throat.[/b]
The biological cascade from strep to Sydenham's starts when the
body, thinking it is fighting the infection, begins to fight itself
in a process known as molecular mimicry. The protein sheath that
coats each invading bacterium cell is remarkably similar to the one
that coats the native cells that form a particular part of the
body. In this case, the protein code on the strep bacteria is a
close match with the code on the cells in the basal ganglia. So the
antibodies mistake the basal ganglia for strep and attack. This, of
course, will not happen to every child who has strep throat, or
even to most children, in the same way that every child who gets
strep does not get rheumatic fever. ''It's the wrong germ in the
wrong child at the wrong time,'' says Swedo, who suspects that some
children are genetically predisposed toward Pandas.
By the mid-90's, Swedo had graduated to her own research laboratory
at the National Institute of Mental Health. Back then the status of
her research looked like this: O.C.D., she knew, could be caused
by damage to the basal ganglia. Sydenham's, too, was a result of
such damage. Strep, by all accounts, was the cause of the damage in
Sydenham's patients. Sydenham's patients often developed O.C.D.
Given all that, the next logical question seemed obvious: Can strep
cause O.C.D.?
Swedo turned her attention anew to that subgroup of patients who
developed their symptoms seemingly overnight. She and her
collaborators hypothesized that this difference in onset could be
the key to something important, a separate category, a
differentiating wrinkle in a familiar pattern. It might not be
the key to decoding the cause of all O.C.D., but it might explain
some percentage of cases.
Swedo and her researchers put out a request among those who treat
and suffer from O.C.D., looking for subjects -- children whose
symptoms had come on suddenly. They received hundreds of calls and
then determined that 109 of those children could accurately be
described as having had a rapid onset of symptoms. The stories the
parents told, while different in their particulars, were remarkably
similar at their core. The symptoms came on so quickly that most
parents could tell you the exact date that their children's
personalities changed. All these children woke up one morning, in
the words of one parent, ''full-blown somebody else.''
The exact nature of the obsessions and compulsions differed from
child to child (a fact that makes all O.C.D. tricky to diagnose).
Some could not stop washing their hands or insisting they needed to
use the toilet or checking to make sure that doors were closed and
locked. Some developed overwhelming separation anxiety or worried
that they would harm someone or do something wrong.
Some had one cluster of these symptoms during their first episode
and a different set of symptoms the next time around. Nearly half
complained of joint pain, but not always of a sore throat. They
were fidgety and moody and obstinate. They had ''bad thoughts,''
some sexual, some violent, some frightening, that they could not
get out of their heads.
The children were then tested for evidence that they had recently
had strep -- either via throat culture, which would find active
infection, or by a blood test that measures antibodies remaining
after the actual infection is gone, or, when the episode was too
long ago for either test to be effective, researchers asked about a
remembered history of strep. In a striking percentage of cases, the
search for strep came up positive.
Disagreement is what propels all of science. Proof and disproof
seems almost a requirement on the road to consensus.
Copernicus's theory that the planets revolve around the sun was not
fully accepted until long after his death. Pythagoras and Aristotle
each suggested that the world was round, but the idea was not
widely accepted for many centuries. Dr. Ignaz Semmelweis was mocked
and ostracized for suggesting that by simply washing their hands,
doctors could prevent women from dying during childbirth. It would
be another quarter-century before Louis Pasteur and Joseph Lister
confirmed that destroying germs stops the spread of disease. Much
more recently, doctors were exuberant when brain surgery seemed to
halt the progression of Parkinson's disease and bone-marrow
transplants seemed to beat back breast cancer. But the excitement
dimmed as further study found the initial data to be overly
optimistic. Perhaps most significant to the discussion of Pandas,
strep has been proposed as the cause of a number of conditions over
the years, including Kawaski disease, but subsequent studies have
repudiated the theories.
''The history of medicine is full of these examples,'' says Dr.
Barron Lerner, a medical historian at Columbia University Medical
Center, describing fact later shown to be quackery, flights of
fancy that turn out to be fact and many ideas that bounce for
decades in the shades of gray between the two. ''What looks like
it's there sometimes turns out not to be there,'' Lerner says,
''and what everybody is sure of sometimes turns out not to be
certain.''
Swedo and her collaborators published several small preliminary
studies during the late 90's, and their first major paper claiming
that Pandas was a separate syndrome appeared in 1998 in The
American Journal of Psychiatry. Called ''Pediatric Autoimmune
Neuropsychiatric Disorders Associated With Streptococcal
Infections: Clinical Description of the First 50 Cases,'' it is
exactly that, a description of children who develop O.C.D. after
exposure to Type A strep.
In a way, the description is a tautology -- Pandas is classified as
O.C.D. associated with strep, and therefore the only children who
qualify for the diagnosis are those who have had recent strep.
Swedo took the 109 rapid-onset cases and narrowed those to 50 that
met her Pandas criteria, which means that 59 cases were triggered
by something other than strep throat. She considers the results
important, because at nearly 50 percent, the incidence of strep is
far higher than would be expected in the general population and
therefore statistically significant. But she agrees that her
findings do not explain the cause of all O.C.D., or even all
rapid-onset O.C.D.
Despite the details still up in the air, the existence of Pandas
was compelling to many doctors. They saw it as inherently logical,
and it gave a name to some otherwise mysterious cases that passed
through their waiting rooms. ''There is no doubt in my mind,'' says
Tamar Chansky, a child psychologist specializing in childhood
anxiety disorders and the author of ''Freeing Your Child From
Obsessive Compulsive Disorder,'' which devotes a long section to
recognizing Pandas.
Not only is it real, says Chansky, who treats several patients who
suffer from the disorder, but she has also noticed that each
episode is often worse than the one before, creating the
possibility that unless these children are treated prophylactically
for strep, their O.C.D. episodes could be longer, more intense and
more frequent.
''Yes, it is controversial, but I believe it is real,'' agrees
Dr. Azra Sehic, a pediatrician in Kingston, Pa. One of the first
times Sehic encountered Pandas was when she saw it in one of her
patients, Maury Cronauer. Just before Memorial Day in 2003, when
she was 6, Maury became ill with strep throat. She was treated with
antibiotics and one morning soon after started acting ''odd,'' says
her mother, Michelle, who is a nurse. A girl who never worried much
about germs, Maury started washing her hands constantly, the most
common symptom of O.C.D.
By the next day she was hysterical, saying horrid thoughts were in
her head. She wasn't sure she loved her parents. She thought she
was going to cheat at school or steal something. She wanted the
racing thoughts to go away, and at one point her parents found her
curled in a ball in the laundry room, her eyes crammed shut and her
hands over her ears.
Sehic mentioned to Maury's parents that the strep might be the
cause of her symptoms. She prescribed a longer course of
antibiotics, to eliminate any lingering strep bacteria, which might
signal the body to create more antibodies.
The O.C.D. went away. A year and a half later, Maury got strep
throat again, and the O.C.D. symptoms returned. She is now taking
prophylactic penicillin, an approach that is also controversial.
''It is not proven that it will help her, but it is likely that it
will, so we are trying,'' Sehic says.
As Pandas was becoming widely known, and as doctors began using
antibiotics as a first salvo against obsession, there was ever more
research under way. Swedo was a co-author of 30 journal articles
between 1998 and 2005. Across the country other lab groups took up
the subject as well, and there are dozens more publications in
which Swedo played no role.
Some of these merely confirmed the existence of the subgroup Swedo
had described. Other studies were designed to take knowledge of
Pandas to the next level -- from description to proof. What Swedo
had done was identify a group in which two things were true: O.C.D.
developed suddenly, and the children had evidence of recent strep.
But that does not prove that the strep caused the O.C.D. Nearly all
of science is a search for cause and effect -- that A made B
happen, that C made B stop.
The bane of all science is coincidence. For example, a notable
percentage of children develop their first signs of autism soon
after a vaccination, and it is tempting to blame the shot for the
symptoms. But autism as a rule tends to show itself during the
years when children are also scheduled to receive fairly regular
immunizations. So the odds are good that the two events will be
temporally linked.
Separating correlation from causation is where every research road
becomes bumpy. ''It's been more complicated to follow up on this
than we ever thought it was going to be,'' Rapoport says.
There have been studies with results that were remarkably clear-cut
-- the plasmapheresis trials, for instance. Plasmapheresis, also
known as therapeutic plasma exchange, is essentially a cleansing of
the blood, somewhat like dialysis. If strep antibodies were
responsible for O.C.D. symptoms in Pandas patients, Swedo
theorized, then clearing those antibodies from the bloodstream
should prompt improvement.
Because the procedure is so invasive, the only subjects enrolled
were those in the worst shape. Of the 29 children in the trial, 10
received plasma exchange, 9 received intravenous immunoglobulin and
10 received a placebo. According to the results published in the
journal Lancet in 1999, the children receiving plasma exchange
became markedly better, while those receiving placebo treatment did
not.
Other studies had results that were somewhat murkier. One tested
the theory that you could prevent Pandas by preventing strep.
Simply treating strep does not prevent the onset of Pandas since
the antibodies have already had a chance to form, which leaves
prophylaxis as the most promising form of treatment. That is one
way strep was first proved to cause rheumatic fever. When patients
who had had rheumatic fever were given daily antibiotics, they did
not get strep and they did not get a recurrence of rheumatic fever.
Similarly, the hypothesis went, if strep causes Pandas, then
preventing patients from getting strep would also prevent a
recurrence of an episode of Pandas.
So Swedo conducted a prophylaxis study. Half of a group of Pandas
patients was put on daily doses of prophylactic antibiotics, while
the other half was given a placebo. After several months, the
placebo and antibiotic groups were switched. If prophylaxis works,
then patients should have developed more, and more intense,
episodes of O.C.D. while they were taking the placebo than while
taking the antibiotics.
But the antibiotic chosen for this particular study was a liquid,
and unlike the case with pills, which can be counted, it was
difficult for parents to keep track of whether a dose had been
missed. Even one missed dose would leave a child vulnerable to
strep, and some children in the antibiotic group did get sick. A
percentage of those developed Pandas.
At the same time, when children in the placebo group became ill,
their parents figured out that what they had been dispensing was
sugar water and, fearing that the sore throat would lead to a
return of Pandas, went and got a prescription for penicillin. Not
nearly as many of the control group got strep or Pandas as had been
predicted.
''A lot was learned about parental behavior,'' Swedo says, ''but
not a lot about Pandas.''
Roger Kurlan, a professor of neurology at the University of
Rochester School of Medicine and Dentistry, is not a man who minces
words. ''The only thing that's a proven fact about Pandas,'' he
says, ''is that children with these symptoms have been observed.''
Everything else, most specifically the role of strep in causing the
symptoms, ''is nothing but speculation.''
Kurlan and his collaborator Edward L. Kaplan, an expert in strep at
the University of Minnesota Medical School, have become Swedo's
most vocal critics. They describe strep and O.C.D. as two things
that are ''true, true and unrelated.'' Yes, it is true that some
children develop rapid-onset O.C.D. And yes, it is true that a high
percentage of those test positive for strep. But that does not mean
that the former is caused by the latter.
''In the prior two weeks, 90 percent of these kids might also have
eaten pizza,'' Kurlan says. ''Can I make an association that pizza
is linked to O.C.D.?''
''If 100 kids fall out of a tree and break their arms and we test
them for strep, there's going to be a very high percentage of
children who have evidence of recent infection,'' echoes Stanford
Shulman of Children's Memorial Hospital in Chicago. ''That doesn't
mean strep is the reason they fell out of the tree.''
A more likely explanation for the presence of strep in children
with Pandas, these doctors say, is that any infection, in fact any
type of stress, can cause spikes in O.C.D. behavior. And they cite
as an example children with Tourette's syndrome, who frequently
have O.C.D. symptoms that ebb and flow with stress.
Children with neurological disorders ''are sensitive to any number
of things,'' Kurlan says. ''If their dog dies. If their parents are
fighting. I've seen O.C.D. get worse with a cold, with hay fever,
with pneumonia. If there is anything special about strep, I don't
think anyone has been able to find it.''
Yes, some children appear to develop symptoms more suddenly than
others, he says, but that could be because they have hidden their
earlier symptoms from their parents, which O.C.D. patients are
known to do. And, yes, he agrees, patients often improve after a
positive strep test and a regimen of antibiotics. But because
O.C.D. is cyclical, odds are that they would have improved without
the test and the medicine anyway. Add to that the fact that some
children are strep carriers. They will test positive for the
bacteria any time they happen to be cultured, further skewing the
cause-and-effect relationship that Swedo is trying to prove.
Kurlan says that he understands why the idea of a bacterial cause
for disturbing behavior is attractive to parents. A germ can be
cured. A germ is not the parents' fault. ''It's a convenient
link,'' he says, ''but it's very difficult to show a connection.''
Assigning blame where none exists can be dangerous, Kurlan says.
Part of the harm is that of commission -- giving unnecessary
medication. Patients like Maury Cronauer, he says, who take
penicillin every day to prevent strep in the first place, are
making themselves vulnerable to drug allergies and are promoting
antibiotic resistance. And he disagrees with Swedo's view that
plasmapheresis can be the answer for the most severely affected
patients. The procedure leaves children vulnerable to serious
infection, he says, which he considers too high a risk given that
the symptoms will arguably run their course over time.
A more insidious form of harm, however, is that of omission. While
turning to antibiotics to cure their child's Pandas, parents might
be ignoring other treatments that could alleviate what skeptics
believe the child actually has -- plain old O.C.D. It may come on
slowly or gradually, in the presence of strep or not; whatever the
details, a child who cannot stop washing her hands needs to be
treated with one of the many drugs and behavioral-therapy regimens
that are successful in battling O.C.D., he says.
''If families are distracted by a simple answer and are
therefore not tackling the more serious issues, that would be a
disservice,'' Kurlan says. ''Worse, that would be bad medicine.''
Individuals are not statistics, and their stories are not proof.
But as I met families and heard their tales, I came to more deeply
understand why Swedo is so certain of her theory and Kurlan is so
wary of it.
One 10-year-old girl in New Jersey, for instance, illustrates the
hazy, sometimes illusory, difference between Pandas and O.C.D. The
girl's mother (who asked that her name not be used to protect her
daughter's privacy) describes two distinct times, at age 4 and age
8, when her bubbly child became riddled with disturbing thoughts:
''My mouth is full of cavities'' or ''The waiter put poison in my
soda.''
The first time, the mother says, her daughter's doctors were
uncertain of the cause. But the mother, after doing her own
research and suspecting that it might be Pandas, called the
N.I.M.H. Someone there confirmed her suspicions. Soon after, the
girl took antibiotics, and, her mother says, the symptoms went away
in seven months. The second time it took almost a year. The girl
has had behavioral therapy but is not taking any medication for
O.C.D. because her mother does not think it is necessary. The one
precaution the family takes is keeping a supply of rapid strep test
kits in the house and using them regularly.
Learning that her daughter had Pandas saved her own sanity, the
woman says. ''It was like drowning in the middle of the ocean, and
you grab onto something that will help you float.''
And yet. The second of the girl's two episodes, the mother says,
was not brought on by strep but by a virus. By Swedo's definition,
this would mean that the child did not have Pandas; that her
parents think otherwise, Kurlan would argue, shows the danger of a
bacterial scapegoat. The mother says that whatever caused the
outbreaks -- strep infection, viral infection -- all that matters
is that, at the moment, her daughter is fine. But when I ask the
girl when she last had her bad thoughts, she tells me, ''Last
week.''
Another story of another child, however, shows the damage that
can be done if parents start with a psychological rather than a
physical assumption. (These parents also didn't want their names
used to protect their daughter's privacy.) This little girl was 6
last May, when according to her parents, she changed overnight,
becoming clingy and asking the same question over and over and over
and over again.
Her mother was pregnant at the time, and a psychiatrist her parents
knew suggested that their daughter feared the arrival of her new
sibling and was looking for attention. So first her parents
reassured her. Then they began to punish her, sending her to her
room so she could ''think about her behavior and change it,'' her
mother says.
No one in the family, not even the girl's father, himself a doctor,
linked any of this behavior to the raging strep infection she had
three weeks earlier. They kept punishing her, and she kept
insisting that she didn't want to act this way. ''Please stop
punishing me for something I can't help,'' the mother recalls her
daughter begging.
The parents took her back to the pediatrician's office (they had
already been there three times), where they were given a
prescription for an antidepressant. Instead of having it filled,
they took her to a pediatric psychiatrist, who asked, ''Has she
been sick with a sore throat?'' Blood tests showed that her level
of strep antibodies was twice as high as it should have been. Two
months later, after several weeks of antibiotics and several
sessions with Tamar Chansky for cognitive behavioral therapy, the
little girl was acting like her old self again.
From where Roger Kurlan and other doubters sit, the situation
looks simple. The theory of Pandas, they say, has not been proved.
Until the causal link to strep is made, these children simply have
O.C.D., and anyone who thinks differently is fooling himself. From
where Swedo and her supporters sit, things look equally simple.
They agree that cause and effect has not yet been definitively
proved. But they are adamant that what has been proved so far is
too significant to be ignored and that further research is more
than warranted.
In the interim, they argue, logic dictates that any child who
develops full-blown O.C.D. seemingly overnight should be given a
throat culture or a strep-antibody test before she is sent to a
psychiatrist. ''I'm all for empirical stringency,'' Chansky says,
''but in the meantime, there's something so basic that can be done.
We're talking about a throat culture and maybe a blood test. What
is the downside?''
The downside, Kurlan says, is that science is not supposed to
guess. ''We would be testing children as if the results had meaning
for their treatment,'' he says, ''and there is insufficient
evidence that it does.''
Swedo is still looking for that evidence. Her most recent
publication, in the April 2005 issue of Biological Psychiatry,
describes a new study of prophylactic antibiotics, one in which
administration of the medication was more closely controlled. The
results: Those who received the antibiotics saw ''significant
decreases'' in strep infections and in ''neuropsychiatric
exacerbations'' over the course of a year.
Kurlan, in turn, is conducting research of his own, a nationwide
study of 80 patients -- half with a history of O.C.D. that meets
the Pandas criteria and half with O.C.D. that does not. For two
years, researchers have been logging the rates of strep and the
episodes of O.C.D. in each group. If strep causes Pandas, then
O.C.D. symptoms should be intensified in the Pandas group relative
to their exposure to strep, while in the control group a variety of
system-stressing triggers should cause a spike in symptoms.
When the data are compiled and made public later this year, the
findings may prove that Swedo is wrong. Or they may instead prove
that she is right. Most likely, this latest research will simply
lead to more research, as science accumulates its evidence one bit
of data at a time.
Lisa Belkin is a contributing writer for the magazine. Her last
article was about Thomas Ellenson, a special-needs child in a
mainstream school.
Copyright 2005 The New York Times Company
The article is long, but worth a look. This is an old arguement, but whether or not strep causes OCD in SOME children isn't the point. I believe this research will eventually lead to greater understanding of the biological cause of many mental illnesses.
D
The New York Times
May 22, 2005
Can You Catch Obsessive-Compulsive Disorder?
By LISA BELKIN
To suffer from obsessive-compulsive disorder, many patients say,
is to ''know you are crazy.'' Other forms of psychosis may envelop
the sufferers until they inhabit the delusion. Part of the torture
of O.C.D. is, as patients describe it, watching as if from the
outside as they act out their obsessions -- knowing that they are
being irrational, but not being able to stop. They describe
thoughts crowding their minds, nattering at them incessantly --
anxious thoughts, sexual thoughts, violent thoughts, sometimes all
at the same time. Is the front door locked? Are there germs on my
hands? Am I a murderer if I step on an ant? And they describe
increasingly elaborate rituals to assuage those thoughts --
checking and rechecking door locks, washing and rewashing hands,
walking carefully, slowly and in bizarre patterns to avoid stepping
on anything. They feel driven to do things they know make no sense.
There are researchers who believe that some of this disturbing
cacophony -- specifically a subset found only in children -- is
caused by something familiar and common. They call it Pediatric
Autoimmune Neuropsychiatric Disorders Associated With Streptococcal
Infection, or, because every disease needs an acronym, Pandas. And
they are certain it is brought on by strep throat -- or more
specifically, by the antibodies created to fight strep throat.
If they are right, it is a compelling breakthrough, a map of the
link between bacteria and at least one subcategory of mental
illness. And if bacteria can cause O.C.D., then an antibiotic might
mitigate or prevent it -- a Promised Land of a concept to parents
who have watched their children change overnight from exuberant,
confident and familiar to doubt-ridden, fear-laden strangers.
Child psychiatrists have long known that sometimes O.C.D. in
children can be like that, that it can come on fast, out of the
blue, like a plague, and then last anywhere from days to months. If
the typical graph of O.C.D. symptoms is a sine curve -- with
episodes that ramp up slowly, peak gradually, then abate just as
slowly -- the graph of rapid-onset O.C.D. is saw-toothed -- flat,
then a sudden spike, followed by a relatively sharp drop, then flat
again.
The patterns certainly look as if they could be two separate
disorders, with similar symptoms but different causes. Across the
country, many doctors are convinced of this and are putting young
sudden-onset O.C.D. patients on long-term doses of antibiotics.
''If I were to place bets,'' says Judith Rapoport, the child
psychiatrist who first brought O.C.D. to public attention with her
book ''The Boy Who Couldn't Stop Washing,'' that bet would be on
the side of those who believe in Pandas.
But as certain as some researchers are, there are others, just
as smart, with just as many impressive publications and titles, who
think the theory is wrong or, at best, that it is too early to
tell. And this group is warning that the Pandas hypothesis is
misguided, perhaps even dangerous. ''Equivocal, controversial,
unproven,'' Dr. Stanford Shulman, chief of infectious disease at
Children's Memorial Hospital in Chicago, says of the theory.
Pandas stands at a familiar, necessary and utterly frustrating
moment in medicine -- in the gap between what doctors think and
what they know. Practically every byte of scientific knowledge
passes through a moment like this, on its way to being accepted as
fact or dismissed as falsehood.
It has always been so, but in recent years several things about the
process have changed. Science now does its thinking in public, with
each incremental advance readily available online. And those
waiting for answers are less patient and more involved. They don't
ask their doctors; they bring their own suggestions. They don't
want to wait for the results of a two-year double-blind
placebo-controlled clinical trial before they act.
Which means that they often find themselves acting before all the
facts are in.
Can strep bacteria cause obsessive-compulsive
disorder? Do these children need penicillin or Prozac? Will we look
back on these questions years from now and think, How could we have
believed? Or, rather, How could we have doubted?
The most vocal voice in support of Pandas is Susan E. Swedo, a
pediatrician and researcher at the National Institute of Mental
Health. She was the first to identify the syndrome, and the one who
gave it a name. She has been studying the relationship between
strep and O.C.D. for her entire career.
She began her work in the 80's, a time of discovery in the world of
obsessive-compulsive disorder. Although the disease had long been
known, it was not until 20 years ago that researchers began to
understand how prevalent it was and not until a decade later that
they came to see how often it occurred in children.
In 1989, Rapoport published her best-selling book, taking the
illness into the mainstream spotlight. When the television program
''20/20'' ran a segment about her book, it prompted 250,000 calls
from worried parents who thought they recognized their children.
And a good number of them, Rapoport says, were right. She
estimates that more than one million children in the United States
suffer from O.C.D. In fact, she argues, the disorder is one that
often begins in childhood, which is why doctors should start
looking for it then. Half of all adult O.C.D. patients look back
and remember having repetitive thoughts and rituals when they were
young, which is significantly higher than the percentage of adults
with other psychiatric disorders who do.
Rapoport strongly suspected that there was a medical model for
at least some percentage of O.C.D. sufferers -- that the symptoms
were not a result of emotional trauma (Freud's belief that it is
caused by overly strict toilet training had long since fallen out
of favor) but rather were caused by a biological trigger. She and
her research fellows at the N.I.M.H. spent several years looking
into it. Swedo was one of those fellows.
Research had already shown that O.C.D. symptoms appear when
there is damage to the basal ganglia, which is a cluster of neurons
in the brain that acts as a gatekeeper for movement, thought and
emotion. ''So we set out to find every known condition that
involved abnormalities of the basal ganglia,'' Swedo remembers.
Huntington's disease was one. Parkinson's was another. Also on
the list was Sydenham's chorea -- a movement disorder known to
medicine since before the Middle Ages, when it was called Saint
Vitus' dance. About 70 percent of patients who develop Sydenham's
also develop O.C.D. Sydenham's is caused by rheumatic fever;
rheumatic fever is in turn caused by Group A beta-hemolytic
streptococcal bacteria. In other words, strep throat.[/b]
The biological cascade from strep to Sydenham's starts when the
body, thinking it is fighting the infection, begins to fight itself
in a process known as molecular mimicry. The protein sheath that
coats each invading bacterium cell is remarkably similar to the one
that coats the native cells that form a particular part of the
body. In this case, the protein code on the strep bacteria is a
close match with the code on the cells in the basal ganglia. So the
antibodies mistake the basal ganglia for strep and attack. This, of
course, will not happen to every child who has strep throat, or
even to most children, in the same way that every child who gets
strep does not get rheumatic fever. ''It's the wrong germ in the
wrong child at the wrong time,'' says Swedo, who suspects that some
children are genetically predisposed toward Pandas.
By the mid-90's, Swedo had graduated to her own research laboratory
at the National Institute of Mental Health. Back then the status of
her research looked like this: O.C.D., she knew, could be caused
by damage to the basal ganglia. Sydenham's, too, was a result of
such damage. Strep, by all accounts, was the cause of the damage in
Sydenham's patients. Sydenham's patients often developed O.C.D.
Given all that, the next logical question seemed obvious: Can strep
cause O.C.D.?
Swedo turned her attention anew to that subgroup of patients who
developed their symptoms seemingly overnight. She and her
collaborators hypothesized that this difference in onset could be
the key to something important, a separate category, a
differentiating wrinkle in a familiar pattern. It might not be
the key to decoding the cause of all O.C.D., but it might explain
some percentage of cases.
Swedo and her researchers put out a request among those who treat
and suffer from O.C.D., looking for subjects -- children whose
symptoms had come on suddenly. They received hundreds of calls and
then determined that 109 of those children could accurately be
described as having had a rapid onset of symptoms. The stories the
parents told, while different in their particulars, were remarkably
similar at their core. The symptoms came on so quickly that most
parents could tell you the exact date that their children's
personalities changed. All these children woke up one morning, in
the words of one parent, ''full-blown somebody else.''
The exact nature of the obsessions and compulsions differed from
child to child (a fact that makes all O.C.D. tricky to diagnose).
Some could not stop washing their hands or insisting they needed to
use the toilet or checking to make sure that doors were closed and
locked. Some developed overwhelming separation anxiety or worried
that they would harm someone or do something wrong.
Some had one cluster of these symptoms during their first episode
and a different set of symptoms the next time around. Nearly half
complained of joint pain, but not always of a sore throat. They
were fidgety and moody and obstinate. They had ''bad thoughts,''
some sexual, some violent, some frightening, that they could not
get out of their heads.
The children were then tested for evidence that they had recently
had strep -- either via throat culture, which would find active
infection, or by a blood test that measures antibodies remaining
after the actual infection is gone, or, when the episode was too
long ago for either test to be effective, researchers asked about a
remembered history of strep. In a striking percentage of cases, the
search for strep came up positive.
Disagreement is what propels all of science. Proof and disproof
seems almost a requirement on the road to consensus.
Copernicus's theory that the planets revolve around the sun was not
fully accepted until long after his death. Pythagoras and Aristotle
each suggested that the world was round, but the idea was not
widely accepted for many centuries. Dr. Ignaz Semmelweis was mocked
and ostracized for suggesting that by simply washing their hands,
doctors could prevent women from dying during childbirth. It would
be another quarter-century before Louis Pasteur and Joseph Lister
confirmed that destroying germs stops the spread of disease. Much
more recently, doctors were exuberant when brain surgery seemed to
halt the progression of Parkinson's disease and bone-marrow
transplants seemed to beat back breast cancer. But the excitement
dimmed as further study found the initial data to be overly
optimistic. Perhaps most significant to the discussion of Pandas,
strep has been proposed as the cause of a number of conditions over
the years, including Kawaski disease, but subsequent studies have
repudiated the theories.
''The history of medicine is full of these examples,'' says Dr.
Barron Lerner, a medical historian at Columbia University Medical
Center, describing fact later shown to be quackery, flights of
fancy that turn out to be fact and many ideas that bounce for
decades in the shades of gray between the two. ''What looks like
it's there sometimes turns out not to be there,'' Lerner says,
''and what everybody is sure of sometimes turns out not to be
certain.''
Swedo and her collaborators published several small preliminary
studies during the late 90's, and their first major paper claiming
that Pandas was a separate syndrome appeared in 1998 in The
American Journal of Psychiatry. Called ''Pediatric Autoimmune
Neuropsychiatric Disorders Associated With Streptococcal
Infections: Clinical Description of the First 50 Cases,'' it is
exactly that, a description of children who develop O.C.D. after
exposure to Type A strep.
In a way, the description is a tautology -- Pandas is classified as
O.C.D. associated with strep, and therefore the only children who
qualify for the diagnosis are those who have had recent strep.
Swedo took the 109 rapid-onset cases and narrowed those to 50 that
met her Pandas criteria, which means that 59 cases were triggered
by something other than strep throat. She considers the results
important, because at nearly 50 percent, the incidence of strep is
far higher than would be expected in the general population and
therefore statistically significant. But she agrees that her
findings do not explain the cause of all O.C.D., or even all
rapid-onset O.C.D.
Despite the details still up in the air, the existence of Pandas
was compelling to many doctors. They saw it as inherently logical,
and it gave a name to some otherwise mysterious cases that passed
through their waiting rooms. ''There is no doubt in my mind,'' says
Tamar Chansky, a child psychologist specializing in childhood
anxiety disorders and the author of ''Freeing Your Child From
Obsessive Compulsive Disorder,'' which devotes a long section to
recognizing Pandas.
Not only is it real, says Chansky, who treats several patients who
suffer from the disorder, but she has also noticed that each
episode is often worse than the one before, creating the
possibility that unless these children are treated prophylactically
for strep, their O.C.D. episodes could be longer, more intense and
more frequent.
''Yes, it is controversial, but I believe it is real,'' agrees
Dr. Azra Sehic, a pediatrician in Kingston, Pa. One of the first
times Sehic encountered Pandas was when she saw it in one of her
patients, Maury Cronauer. Just before Memorial Day in 2003, when
she was 6, Maury became ill with strep throat. She was treated with
antibiotics and one morning soon after started acting ''odd,'' says
her mother, Michelle, who is a nurse. A girl who never worried much
about germs, Maury started washing her hands constantly, the most
common symptom of O.C.D.
By the next day she was hysterical, saying horrid thoughts were in
her head. She wasn't sure she loved her parents. She thought she
was going to cheat at school or steal something. She wanted the
racing thoughts to go away, and at one point her parents found her
curled in a ball in the laundry room, her eyes crammed shut and her
hands over her ears.
Sehic mentioned to Maury's parents that the strep might be the
cause of her symptoms. She prescribed a longer course of
antibiotics, to eliminate any lingering strep bacteria, which might
signal the body to create more antibodies.
The O.C.D. went away. A year and a half later, Maury got strep
throat again, and the O.C.D. symptoms returned. She is now taking
prophylactic penicillin, an approach that is also controversial.
''It is not proven that it will help her, but it is likely that it
will, so we are trying,'' Sehic says.
As Pandas was becoming widely known, and as doctors began using
antibiotics as a first salvo against obsession, there was ever more
research under way. Swedo was a co-author of 30 journal articles
between 1998 and 2005. Across the country other lab groups took up
the subject as well, and there are dozens more publications in
which Swedo played no role.
Some of these merely confirmed the existence of the subgroup Swedo
had described. Other studies were designed to take knowledge of
Pandas to the next level -- from description to proof. What Swedo
had done was identify a group in which two things were true: O.C.D.
developed suddenly, and the children had evidence of recent strep.
But that does not prove that the strep caused the O.C.D. Nearly all
of science is a search for cause and effect -- that A made B
happen, that C made B stop.
The bane of all science is coincidence. For example, a notable
percentage of children develop their first signs of autism soon
after a vaccination, and it is tempting to blame the shot for the
symptoms. But autism as a rule tends to show itself during the
years when children are also scheduled to receive fairly regular
immunizations. So the odds are good that the two events will be
temporally linked.
Separating correlation from causation is where every research road
becomes bumpy. ''It's been more complicated to follow up on this
than we ever thought it was going to be,'' Rapoport says.
There have been studies with results that were remarkably clear-cut
-- the plasmapheresis trials, for instance. Plasmapheresis, also
known as therapeutic plasma exchange, is essentially a cleansing of
the blood, somewhat like dialysis. If strep antibodies were
responsible for O.C.D. symptoms in Pandas patients, Swedo
theorized, then clearing those antibodies from the bloodstream
should prompt improvement.
Because the procedure is so invasive, the only subjects enrolled
were those in the worst shape. Of the 29 children in the trial, 10
received plasma exchange, 9 received intravenous immunoglobulin and
10 received a placebo. According to the results published in the
journal Lancet in 1999, the children receiving plasma exchange
became markedly better, while those receiving placebo treatment did
not.
Other studies had results that were somewhat murkier. One tested
the theory that you could prevent Pandas by preventing strep.
Simply treating strep does not prevent the onset of Pandas since
the antibodies have already had a chance to form, which leaves
prophylaxis as the most promising form of treatment. That is one
way strep was first proved to cause rheumatic fever. When patients
who had had rheumatic fever were given daily antibiotics, they did
not get strep and they did not get a recurrence of rheumatic fever.
Similarly, the hypothesis went, if strep causes Pandas, then
preventing patients from getting strep would also prevent a
recurrence of an episode of Pandas.
So Swedo conducted a prophylaxis study. Half of a group of Pandas
patients was put on daily doses of prophylactic antibiotics, while
the other half was given a placebo. After several months, the
placebo and antibiotic groups were switched. If prophylaxis works,
then patients should have developed more, and more intense,
episodes of O.C.D. while they were taking the placebo than while
taking the antibiotics.
But the antibiotic chosen for this particular study was a liquid,
and unlike the case with pills, which can be counted, it was
difficult for parents to keep track of whether a dose had been
missed. Even one missed dose would leave a child vulnerable to
strep, and some children in the antibiotic group did get sick. A
percentage of those developed Pandas.
At the same time, when children in the placebo group became ill,
their parents figured out that what they had been dispensing was
sugar water and, fearing that the sore throat would lead to a
return of Pandas, went and got a prescription for penicillin. Not
nearly as many of the control group got strep or Pandas as had been
predicted.
''A lot was learned about parental behavior,'' Swedo says, ''but
not a lot about Pandas.''
Roger Kurlan, a professor of neurology at the University of
Rochester School of Medicine and Dentistry, is not a man who minces
words. ''The only thing that's a proven fact about Pandas,'' he
says, ''is that children with these symptoms have been observed.''
Everything else, most specifically the role of strep in causing the
symptoms, ''is nothing but speculation.''
Kurlan and his collaborator Edward L. Kaplan, an expert in strep at
the University of Minnesota Medical School, have become Swedo's
most vocal critics. They describe strep and O.C.D. as two things
that are ''true, true and unrelated.'' Yes, it is true that some
children develop rapid-onset O.C.D. And yes, it is true that a high
percentage of those test positive for strep. But that does not mean
that the former is caused by the latter.
''In the prior two weeks, 90 percent of these kids might also have
eaten pizza,'' Kurlan says. ''Can I make an association that pizza
is linked to O.C.D.?''
''If 100 kids fall out of a tree and break their arms and we test
them for strep, there's going to be a very high percentage of
children who have evidence of recent infection,'' echoes Stanford
Shulman of Children's Memorial Hospital in Chicago. ''That doesn't
mean strep is the reason they fell out of the tree.''
A more likely explanation for the presence of strep in children
with Pandas, these doctors say, is that any infection, in fact any
type of stress, can cause spikes in O.C.D. behavior. And they cite
as an example children with Tourette's syndrome, who frequently
have O.C.D. symptoms that ebb and flow with stress.
Children with neurological disorders ''are sensitive to any number
of things,'' Kurlan says. ''If their dog dies. If their parents are
fighting. I've seen O.C.D. get worse with a cold, with hay fever,
with pneumonia. If there is anything special about strep, I don't
think anyone has been able to find it.''
Yes, some children appear to develop symptoms more suddenly than
others, he says, but that could be because they have hidden their
earlier symptoms from their parents, which O.C.D. patients are
known to do. And, yes, he agrees, patients often improve after a
positive strep test and a regimen of antibiotics. But because
O.C.D. is cyclical, odds are that they would have improved without
the test and the medicine anyway. Add to that the fact that some
children are strep carriers. They will test positive for the
bacteria any time they happen to be cultured, further skewing the
cause-and-effect relationship that Swedo is trying to prove.
Kurlan says that he understands why the idea of a bacterial cause
for disturbing behavior is attractive to parents. A germ can be
cured. A germ is not the parents' fault. ''It's a convenient
link,'' he says, ''but it's very difficult to show a connection.''
Assigning blame where none exists can be dangerous, Kurlan says.
Part of the harm is that of commission -- giving unnecessary
medication. Patients like Maury Cronauer, he says, who take
penicillin every day to prevent strep in the first place, are
making themselves vulnerable to drug allergies and are promoting
antibiotic resistance. And he disagrees with Swedo's view that
plasmapheresis can be the answer for the most severely affected
patients. The procedure leaves children vulnerable to serious
infection, he says, which he considers too high a risk given that
the symptoms will arguably run their course over time.
A more insidious form of harm, however, is that of omission. While
turning to antibiotics to cure their child's Pandas, parents might
be ignoring other treatments that could alleviate what skeptics
believe the child actually has -- plain old O.C.D. It may come on
slowly or gradually, in the presence of strep or not; whatever the
details, a child who cannot stop washing her hands needs to be
treated with one of the many drugs and behavioral-therapy regimens
that are successful in battling O.C.D., he says.
''If families are distracted by a simple answer and are
therefore not tackling the more serious issues, that would be a
disservice,'' Kurlan says. ''Worse, that would be bad medicine.''
Individuals are not statistics, and their stories are not proof.
But as I met families and heard their tales, I came to more deeply
understand why Swedo is so certain of her theory and Kurlan is so
wary of it.
One 10-year-old girl in New Jersey, for instance, illustrates the
hazy, sometimes illusory, difference between Pandas and O.C.D. The
girl's mother (who asked that her name not be used to protect her
daughter's privacy) describes two distinct times, at age 4 and age
8, when her bubbly child became riddled with disturbing thoughts:
''My mouth is full of cavities'' or ''The waiter put poison in my
soda.''
The first time, the mother says, her daughter's doctors were
uncertain of the cause. But the mother, after doing her own
research and suspecting that it might be Pandas, called the
N.I.M.H. Someone there confirmed her suspicions. Soon after, the
girl took antibiotics, and, her mother says, the symptoms went away
in seven months. The second time it took almost a year. The girl
has had behavioral therapy but is not taking any medication for
O.C.D. because her mother does not think it is necessary. The one
precaution the family takes is keeping a supply of rapid strep test
kits in the house and using them regularly.
Learning that her daughter had Pandas saved her own sanity, the
woman says. ''It was like drowning in the middle of the ocean, and
you grab onto something that will help you float.''
And yet. The second of the girl's two episodes, the mother says,
was not brought on by strep but by a virus. By Swedo's definition,
this would mean that the child did not have Pandas; that her
parents think otherwise, Kurlan would argue, shows the danger of a
bacterial scapegoat. The mother says that whatever caused the
outbreaks -- strep infection, viral infection -- all that matters
is that, at the moment, her daughter is fine. But when I ask the
girl when she last had her bad thoughts, she tells me, ''Last
week.''
Another story of another child, however, shows the damage that
can be done if parents start with a psychological rather than a
physical assumption. (These parents also didn't want their names
used to protect their daughter's privacy.) This little girl was 6
last May, when according to her parents, she changed overnight,
becoming clingy and asking the same question over and over and over
and over again.
Her mother was pregnant at the time, and a psychiatrist her parents
knew suggested that their daughter feared the arrival of her new
sibling and was looking for attention. So first her parents
reassured her. Then they began to punish her, sending her to her
room so she could ''think about her behavior and change it,'' her
mother says.
No one in the family, not even the girl's father, himself a doctor,
linked any of this behavior to the raging strep infection she had
three weeks earlier. They kept punishing her, and she kept
insisting that she didn't want to act this way. ''Please stop
punishing me for something I can't help,'' the mother recalls her
daughter begging.
The parents took her back to the pediatrician's office (they had
already been there three times), where they were given a
prescription for an antidepressant. Instead of having it filled,
they took her to a pediatric psychiatrist, who asked, ''Has she
been sick with a sore throat?'' Blood tests showed that her level
of strep antibodies was twice as high as it should have been. Two
months later, after several weeks of antibiotics and several
sessions with Tamar Chansky for cognitive behavioral therapy, the
little girl was acting like her old self again.
From where Roger Kurlan and other doubters sit, the situation
looks simple. The theory of Pandas, they say, has not been proved.
Until the causal link to strep is made, these children simply have
O.C.D., and anyone who thinks differently is fooling himself. From
where Swedo and her supporters sit, things look equally simple.
They agree that cause and effect has not yet been definitively
proved. But they are adamant that what has been proved so far is
too significant to be ignored and that further research is more
than warranted.
In the interim, they argue, logic dictates that any child who
develops full-blown O.C.D. seemingly overnight should be given a
throat culture or a strep-antibody test before she is sent to a
psychiatrist. ''I'm all for empirical stringency,'' Chansky says,
''but in the meantime, there's something so basic that can be done.
We're talking about a throat culture and maybe a blood test. What
is the downside?''
The downside, Kurlan says, is that science is not supposed to
guess. ''We would be testing children as if the results had meaning
for their treatment,'' he says, ''and there is insufficient
evidence that it does.''
Swedo is still looking for that evidence. Her most recent
publication, in the April 2005 issue of Biological Psychiatry,
describes a new study of prophylactic antibiotics, one in which
administration of the medication was more closely controlled. The
results: Those who received the antibiotics saw ''significant
decreases'' in strep infections and in ''neuropsychiatric
exacerbations'' over the course of a year.
Kurlan, in turn, is conducting research of his own, a nationwide
study of 80 patients -- half with a history of O.C.D. that meets
the Pandas criteria and half with O.C.D. that does not. For two
years, researchers have been logging the rates of strep and the
episodes of O.C.D. in each group. If strep causes Pandas, then
O.C.D. symptoms should be intensified in the Pandas group relative
to their exposure to strep, while in the control group a variety of
system-stressing triggers should cause a spike in symptoms.
When the data are compiled and made public later this year, the
findings may prove that Swedo is wrong. Or they may instead prove
that she is right. Most likely, this latest research will simply
lead to more research, as science accumulates its evidence one bit
of data at a time.
Lisa Belkin is a contributing writer for the magazine. Her last
article was about Thomas Ellenson, a special-needs child in a
mainstream school.
Copyright 2005 The New York Times Company
