The Infection Connection

Examines the possible connection of microorganism with psychological problems. Cause of poor parenting; Technology that helps in revealing damage to the brain.

By Harriet Washington, published on July 01, 1999

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.