The Infection Connection

PSYCHOLOGY HAS LONG HELD THAT MENTAL ILLNESS IS BORN OF ADVERSE
EXPERIENCES.MORE RECENTLY, RESEARCH HAS POINTED THE FINGER AT FLAWED
GENES. NOW A THIRD CULPRIT MAY BE EMERGING: INVASION BY BACTERIA AND
VIRUSES.

Eight-year-old Seth broke from the grasp of Jane, his harried
mother, for the third time in 10 minutes. Tearing across the emergency
room, he stopped short, transfixed by a piece of paper lying on the
floor. His red-rimmed eyes seemed to bulge from their sockets and his
mouth twitched violently, as if he were in pain. Indifferent to Jane's
pleas to stop, he proceeded to pick up from the floor every piece of
paper, no matter how filthy, with hands that were reddened and raw. It
was the state of his hands that had precipitated the trip to the
hospital: Seth had spent most of the night in the bathroom, washing them
over and over.

With his head jerking spasmodically and his fingers pecking at
pieces of paper and cigarette butts, the boy resembled some strange
overgrown bird. Then, suddenly terrified, he flew back to Jane and began
pulling on her arm. "Mommy, Mommy, let's leave!" he whimpered. "They're
going to kill us. They're coming!"

Jane tried her best to calm him, but she too was beginning to
panic. Two days before, Seth had been a perfectly normal little boy whose
most serious health problems were the occasional cold or sore throat. He
had become mentally ill overnight.

What caused Seth's anxiety, his tics, his obsessive-compulsive
behavior? Astonishingly, it was probably that minor sore throat, his
doctors concluded. Today, scientists are increasingly coming to recognize
that the bacteria and viruses that frequently invade our bodies and cause
sore throats and other minor ailments may also unleash a host of major
mental and emotional illnesses, including anorexia, schizophrenia and
obsessive-compulsive disorder.

It is a theory sharply at odds with earlier views of the genesis of
psychological illness. Followers of Freud long held that mental and
emotional trouble is primarily the result of poor parenting, especially
by mothers. Indeed, until about 30 years ago, psychoanalysts frequently
placed the blame for schizophrenia on "schizophrenogenic" mothers.
Obsessive-compulsive disorder, also, was put at Mom's door. "It was
thought to be the result of harsh toilet training," observes Susan Swedo,
M.D., chief of pediatrics and developmental neuropsychiatry at the
National Institutes of Mental Health. But such theories, which added
immeasurable guilt to the burdens of parents with mentally ill offspring,
have turned out to have little evidence to back them up, most experts now
agree.

Instead, in recent years, the focus has shifted to genes as the
main source of mental illness. Faulty DNA is thought to be at least
partly responsible for, among other problems, anxiety and panic
disorders, schizophrenia, manic depression and antisocial personality
disorder, which is characterized by impulsive, excessively emotional and
erratic patterns of interpersonal behavior.

Yet genetics doesn't appear to wholly account for the occurrence of
major psychiatric ailments. If heredity alone were to blame, identical
twins would develop schizophrenia with a high degree of concordance, but
in fact in only 40% of cases in which one identical twin has the disease
does the other twin have it as well. Autism, though it has been observed
to run in families, also strikes five of every 10,000 children apparently
arbitrarily. Nor can depression and other affective disorders be
completely explained by damaged DNA. Says Ian Lipkin, Ph.D., a
neuroscientist and microbiologist at the University of California at
Irvine: "Genetics doesn't hold the key to understanding how to fit these
square pegs into round holes."

Bacteria and viruses may be that key, but scientists have been slow
to grasp the idea. Consider the case of syphilis, which is caused by the
bacterium Treponema pallidum. In its final, or tertiary, stage, the
disease can precipitate psychiatric problems like dementia, mania,
depression, delusions and Tourette's like tics. Though some scientists
suspected a connection between infection with the bacterium and the
mental disturbances that may take three to five decades to emerge, the
link became widely accepted only in the 1940s after the introduction of
the antibiotic penicillin as a treatment for syphilis. In the interim,
patients with syphilis who later developed psychiatric problems were
often institutionalized as crazy. But even with the link established,
Freud's theories were in ascendance and few scientists were willing to
consider that microbes might be a common source of other mental
illness.

Now, decades later, infection has emerged as a prime suspect in
psychological illnesses. The inadequacy of genetic and experiential
explanations has prompted scientists to look elsewhere--and their gaze
has come to rest on physical ailments, such as heart disease, cancers and
ulcers, that in some cases have an infectious origin. Could the same be
true, they wonder, for mental and emotional ills?

Improved technology has made it easier to find out. Since active
only when inside other living creatures, microbes are notoriously hard to
grow, and therefore study, in the lab, but scientists' ability to do so
has increased steadily over the last few decades. Other tools have
allowed researchers to see their quarry more clearly. For about a decade,
microbiologists have used a technique called polymerase chain reaction,
or PCR, to replicate a small piece of genetic material over and over
until it forms a quantity large enough to study--and large enough to show
the lingering traces of an infection. A new variant of PCR, called
representational difference analysis, introduced in 1994, allows
scientists to go one step further and compare the differences between two
separate pieces of DNA (including healthy and diseased segments, for
instance). And the refinement of electron microscopes has permitted
researchers to follow the "footprints" left by infection in patients'
cerebrospinal fluid.

The introduction of CAT scans in the early 1970s has been another
leap forward. Before then, only an X-ray--or an autopsy--could reveal
damage to the brain, and then only in its grossest form. CAT scans show
subtle changes that can be tracked over time, giving researchers a more
accurate sense of a microbe's impact. MRI, developed in the early 1980s,
has added three-dimensionality to pictures of the brain, and PET scans,
invented soon after, have added motion. Now bacteria and viruses can be
caught red-handed.

Still, teasing out the tie between microbes and psychological
problems has proved a difficult task, in no small part because of the
cunning and guile of the pathogens themselves, which have many ways of
attacking our bodies and brains.

T. pallidum, syphilis' causative bacterium, proceeds in
straightforward fashion: it attacks and kills brain cells. After entering
the body--usually through sexual intercourse, or through the mother's
placenta into her fetus--the bacterium travels along the lymph system
until it arrives at the brain. Once it lodges there, it spares few
structures, inflaming some neurons and stripping the myelin, or
insulation, from others. (Without myelin, nerve impulses are slowed or
stopped altogether.)

Other microbes are more devious. The human immunodeficiency virus,
for example, which can cause anxiety, delirium, psychosis and suicidal
impulses, uses a Trojan horse strategy. Instead of directly attacking
brain cells, it infects macrophages, the immune-system enforcers that
roam the bloodstream, engulfing foreign cells that may pose a threat to
the body. After hitching a macrophage ride into the brain, HIV cranks out
cytokines, protein peptides that kill off neurons. The virus Chlamydia
pneumoniae may use a similar trick--slipping into the brain and
manufacturing cytokines--to cause Alzheimer's disease.

Streptococcal bacteria, like those that cause strep throat, take
yet a different tack. As they invade the body, they automatically trip
the body's defense alarm, calling up the immune system's antibody
soldiers. But once the skirmish begins, the bacteria camouflage
themselves within that very immune system. Like a wolf in sheep's
clothing, they disguise themselves through molecular mimicry, cloaking
themselves in proteins that imitate the body's own proteins, and thereby
elude attack. For reasons scientists don't yet understand, the antibodies
of some people--perhaps those with a genetic predisposition--then turn on
their bodies' own tissues, assailing neurons the basal ganglia. These
structures, located between the more primitive lower brain and the higher
cortical centers, help interpret information from the senses and are key
to healthy emotions and behavior.

The self-destruction instigated by streptococcal bacteria can be
particularly dangerous to young children. Because their immune systems
are "naive," or underdeveloped, "their bodies mount a vigorous response
to streptococci, but it is not terribly effective, and their antibodies
wind up injuring their own neurons instead of the bacteria," explains
Swedo. She believes that such self-induced damage leads some children to
develop obsessive-compulsive disorder.

In an experiment conducted earlier this year, Swedo replaced the
blood plasma of 28 children who suffered from OCD (and who had elevated
levels of streptococcus antibodies) with healthy donor plasma, reasoning
that such a switch would remove the trouble-making antibodies. Within a
month, the incidence of ties declined by half, and their other OCD
symptoms were reduced by 60%. "That was really gratifying," says Swedo.
"It means that OCD is a medical illness, and if you catch it before there
is scarring in the brain, you can cure it."

OCD isn't the only mental illness associated with streptococcus.
Though anorexia nervosa has been tied to a distorted body image, societal
pressure to be thin, discomfort with developing sexuality, and other
emotional and cultural factors, doctors have also noted that the eating
disorder sometimes appears or worsens after a case of strep throat.
Streptococcus has been implicated as well in Tourette's syndrome and in
Sydenhams chorea, which makes the arms and legs of those afflicted jerk
in a manner often likened to dancing.

Researchers think that the seeds of yet other mental illnesses may
be planted while a fetus is still in the womb, when the pregnant
mother-to-be becomes infected. Flu epidemics have been followed a
generation later by waves of schizophrenia in England, Wales, Denmark,
Finland and other countries, and a recent study published in the New
England Journal of Medicine reports higher rates of schizophrenia among
children born in crowded areas in cold weather--conditions hospitable to
respiratory ailments.

Scientists suspect that in such cases a virus, such as the one that
causes influenza or a newer candidate, the Borna virus, may insinuate
itself into the fetal brain at a crucial stage of development. The
microbe then subtly deranges the brain's neural connections in a process
that becomes apparent only as the brain reaches full maturity, in early
adulthood. In people with schizophrenia, parts of the brain--the cortex,
thalamus, limbic system and basal ganglia--shrink, while crevices and
fluid-filled spaces enlarge by as much as half, and the brain's chemical
balance shifts. Such changes might well be the terrible legacy of a
prenatal virus.

Microbes that cause mental illness can also enter the body another
way--on one's fork. In the mid-1990s, an outbreak of Creutzfeldt-Jakob
disease struck fear into meat-eaters, especially in England, where 35
people died after eating infected beef. While alive, the victims of what
was dubbed "mad cow disease" exhibited bizarre symptoms such as continual
screaming, inappropriate laughter, failure to bathe and compulsive
walking.

Scientists theorized that the "mad cows" became infected because
they were fed on sheep afflicted with the disease known as scrapie, but a
similar infection endemic to cows may be to blame. (Scrapie in sheep,
bovine spongiform encephalitis in cows and Creutzfeldt-Jakob disease in
humans are all believed to be caused by what's known as a prion, or
infectious protein, which acts in a manner similar to a virus.)
Contaminated human growth hormone, corneal transplants and surgical
instruments have also been suspected of communicating the disease to
humans. Earlier this year, the British medical journal The Lancet
reported that multiple surgeries and living on a farm are risk factors
for CJD. Though the disease is considered rare, Yale neuropathologist
Laura Manueldis, M.D., who thinks that the causative agent is actually a
small virus rather than a prion, suspects that CJD is more common than we
believe, and is often misdiagnosed as Alzheimer's.

Why doesn't every child with a strep throat develop an anxiety
disorder? Or dementia strike every adult with syphilis? Our bodies
protect us from most invasions by unfriendly microbes, but the
vulnerable-those with poor health, weakened immune systems or, perhaps,
genetic susceptibility--are less equipped to fend off the viruses and
bacteria that may eventually cause mental illness.

Continuing research is likely to bring more effective vaccines and
antibiotics, but prevention and treatment will have to be every bit as
shrewd as the infectious agents themselves, which spread and reproduce in
seemingly countless ways. More worrisome is the fact that illness-causing
organisms may be outwitting our antimicrobial strategies. With the
development of antibiotics and antivirals, researchers had hoped to
vanquish viruses and bacteria once and for all. But they underestimated
the wily ingenuity of these microbes, which soon produced strains
resistant to the new miracle medicines.

Likewise, scientists at one time believed that infectious agents
evolved to become less potent, if only to ensure their own survival: the
longer an infected host stays alive, after all, the greater the number of
people who can be exposed to the pathogen, and the more likely the
microbe is to reproduce itself. But recent research has turned up a less
reassuring reality: under some conditions, microbes can flourish with
increased virulence in crowded modern cities. These densely populated
areas can maintain dangerous pathogens that otherwise might whip through
a community and then have nowhere else to go.

To fight these pathogens successfully, doctors will have to tailor
the treatments to the specific disease. Sometimes, for example, they may
want to relieve an infected patient's fever and inflammation; at other
times, fever must be left alone to kill off heat-sensitive viruses.
Syphilis can be cured with penicillin, and doctors have had some success
in prescribing antibiotics to people with anorexia. Other illnesses
require more involved treatment, such as Swedo's plasma replacement for
children with OCD, and some ailments cannot be helped much at all. The
only way to treat HIV dementia, for example, is to try to slow the
replication of the virus itself. No current therapy does this
permanently, and many HIV-positive patients still suffer psychiatric
symptoms. (In fact, suicide is a leading cause of death among the
HIV-infected.) There's no treatment for Creutzfeldt-Jakob disease beyond
palliative care, and by the time influenza-induced schizophrenia becomes
apparent, the neurological damage is already done.

Still, science continues to offer hope that one day such infectious
agents will be controlled or even eliminated. That day can't come too
soon for Swedo, a pediatrician by training. "When I practiced medicine at
Memorial Hospital in Chicago, I saw parents suffer horribly when they
lost their children to leukemia," she says. "When I came to the NIMH, I
began to see parents lose their children to OCD and schizophrenia. These
parents' grief is so much more profound. The fact that their children's
illnesses are socially unacceptable makes their pain almost unbearable."
Now that we know many psychiatric ills begin with a microbe, rather than
a suffocating mother or remote father, "we can start treating mentally
ill people without the shame and blame. We can treat them
medically."

WHAT YOU CAN DO

Since we know so little about the viruses and bacteria that cause
some types of mental illness, it makes sense to avoid them when you can.
Here, advice on preventing infection from leading scientists (much of
which sounds uncannily like Mom's):

o Eat a healthy diet.

o Get plenty of sleep.

o Reduce stress.

o Get a flu shot each fall.

o Be aware that sex with multiple partners raises your risk of
infection.

o Wash your hands frequently. (Though you might be tempted to use
one of the many antibacterial soaps on the market, such cleansers may
promote the growth of drug-resistant "superbugs.")

o Don't eat meat that isn't well-cooked, or if you have any
questions about how it was stored or prepared.

o Find out whether you have any physical conditions that increase
your risk of infection, and discuss preventive steps with your doctor.
If, for example, you have a prolapsed mitral valve (a valve in the heart
that doesn't close properly, increasing risk of infection), your doctor
may recommend that you take antibiotics before having dental work
done.

o Pay attention to your body. Even minor symptoms--fever, chills, a
sore neck--can mean you're doing battle with an infection, and you should
discuss them with your doctor. Pay special attention to your children's
symptoms.

o If you are prescribed antibiotics, finish the entire course of
therapy.

o If you work in a medical setting--even as a technician or
clerk--be sure to seek vaccinations against hepatitis and other pathogens
you may acquire from patients.

o If you're pregnant, take special care to avoid respiratory
ailments such as influenza. Avoid contact with cat litter, which can
harbor Toxoplasma, a microbe that can cause birth defects or even
spontaneous abortion.

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