PANDAS

Over a century ago, doctors made the link between sore throats caused by the common streptococcus bacteria (“strep throat”) and the development weeks later of a heart condition called rheumatic fever.  It is a glitch of the immune system: The body declares war on itself, mistaking heart cells for strep germs. A few years ago, researchers discovered a similarly disastrous and rare auto-immune response involving an area of the brain called the basal ganglia, which controls behavior.

The syndrome, called PANDAS (Pediatric Auto-Immune Neuropyschiatric Disorders Associated with Streptococcus -- type A beta hemolytic strains), strikes just one  in 1,000 cases. But it can cause the sudden onset in kids of everything from Tourrette’s-like tics and Obsessive-Compulsive Disorder (OCD), to Attention Deficit / Hyperactivity Disorder (ADHD) and, possibly, anorexia – which is essentially an obsessive-compulsive eating disorder.

High antibody levels for strep, a sign of recent infection, have been correlated to an enlargement of the basal ganglia in PANDAS patients. As the titers go down, the brain recovers and symptoms fade away.  But a new strep infection can trigger the process all over again.

In an experiment at the National Institutes of Health (NIH), researcher Susan Swedo physically filtered antibodies from the plasma of 30 PANDAS kids. More than a year later, 80% remained symptom-free.

Research in this area has exploded and it may very well turn out that many, if not most, obsessive-compulsive spectrum disorders involve an auto-immune component.

The PANDAS model is now bursting out of its own definition. Although technically a childhood condition, there are reports of adults with abrupt onset OCD symptoms. And a team from the Institute of Child Health in London suggests that a PANDAS-like auto-immune response may be behind the mystery of von Enconomo’s disease, the “sleepy sickness” or encephalitis lethargica (EL; also, the illness in Oliver Sacks’ book, Awakenings) that devastated thousands around the time of the 1918 flu pandemic.  Of 20 contemporary patients with a phenotypically similar illness, more than half had a sore throat before developing EL, and 95% tested positive for auto-antibodies reactive against basal ganglia antigens.

BORNA

Although Borna virus, named after a town in Saxony, was first seen in German horses during the 19th century – it’s named after a Saxon town – it affects a Noah’s Ark-worth of species: cats, cattle, sheep, rabbits, ostriches, chickens, monkeys and people. It causes an equally broad range of movement and behavioral symptoms and has been circumstantially linked, largely though the presence antibodies, with cases of schizophrenia, bipolar disorder and depression.

Borna-infected lab rats display symptoms resembling autism such as delayed growth, learning disabilities and repetitive behaviors. When rats are infected shortly after birth (the neurodevelopmental equivalent of a human prenatal infection), neurons critical for cognitive, emotional and motor development either die off or miss key developmental cues. If rats are infected during adolescence, when their brains are more developed, Borna alters brain chemistry and kills neurons both directly and through an overzealous immune response.

Recent research suggests that a system of  “mirror neurons” that allow humans to anticipate the actions of others and to empathize, may play a pivotal role in autism. Mirror neurons are even able to process subtle changes in facial expression at a subconscious level: the “thin-slicing” that lets us instinctively assess another’s motives. They allow us to function successfully as social beings.

Using brain scans, researchers have learned that the mirror neurons of autistic children don’t fire at nearly the rate of those of healthy controls. It will be interesting to see in the coming months and years whether borna virus attacks or arrests the development of this newly discovered neuronal system.

HERVs

According to Johns Hopkins virologist Robert Yolken, these are ancient viruses – most date back 35 million years. They are, in a sense, fossils of prehistoric viruses, remnants of pathogens whose original hosts more than likely have gone extinct.

Whatever their origins, about 100 HERVs have been identified so far, including a virus that could play a key role in the fusion of an egg and a sperm.

Like genes, HERV’s only activate in certain cells under specific circumstances.  Yolken has found one, called HERV-W, reproducing in the cerebrospinal fluid of some, though not all, schizophrenics he tested; but not in any of the healthy controls. He suspects that a second, conventional pathogen, possibly a herpesvirus or toxoplasma, may cause HERV-W to switch on, and the combination somehow then leads to psychosis. “This is a new way of looking at how different infectious agents might interact. For example, if a herpesvirus that by itself only causes cold sores, activates a retrovirus in the brain, then it might lead to CNS symptoms,” he speculates.

Yolken's lab has reported the improvement of symptoms in a small but statistically significant number of schizophrenics treated for cytomegalovirus, a common herpesvirus suspected of triggering HERV-W. 

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“Schizophrenia is probably a dozen different illnesses with the same look,” says Ron Kessler, a professor of Health Care Policy at Harvard Medical School, and the lead researcher on several projects analyzing mental health statistics both in the U.S., and internationally for the World Health Organization. The same is likely true for all psychiatric spectrum disorders, including depression, bipolar disorder and autism.

Although the “final common pathway” of neurological damage may be same no matter what the cause, understanding the origins of a particular mental illness in an individual patient may provide more and better-targeted options for treatment.

It is unnerving to think that something as casual as a sneeze or a walk in the woods could lead to a mental illness. But that also means prevention may be as straightforward as checking for ticks, washing hands, or using rapid diagnostic tests for strep in a doctor’s office instead of waiting 24 hours for lab results.

Over the last 30 years,  an endless procession of emerging and re-emerging pathogens has circled the globe, spread into new territories and species, and made headlines. It  is not unreasonable to think  that some of those pathogens are mind germs. The good news is  that advances in brain scans and molecular diagnostics, coupled with breakthrough epidemiological studies, have made it possible to connect the medical dots as never before. And with at least some of the mystery shrouding mental illness melting away comes the  hope of one day soon being able to reverse heartbreaking fate, and stopping tragedy before it happens.