When Worry Hijacks The Brain

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Saxena, who has conducted extensive scanning research, has even come to recognize the neural fingerprint that distinguishes one less common type of OCD behavior--hoarding--from better-known ones. Hoarders who live alone have been known to crowd themselves into small areas of their home, with clear paths left from sofa to kitchen to bathroom, and the rest piled high with debris. When Saxena scanned the brains of these highly particular people, he found that they had equally particular abnormalities. Instead of hyperactivity in any area, they had reduced activity in the anterior cingulate gyrus, the part of the brain that helps you focus your attention and make decisions. "Those are things that compulsive hoarders have a lot of trouble with," he says.

GENES AND GERMS

ALTHOUGH SCANS CAN TELL YOU THE landscape of the obsessive-compulsive brain, they can't tell you how it got to be that way. As with many other psychological disorders, research is revealing that ocd has a powerful genetic component. Having any blood relative with ocd puts your risk of the disorder at 12%, and while that seems low, it's still more than four times as high as that of the U.S. population as a whole.

If the disorder comes to you through the genes, the next job is to determine which ones. A team of investigators at Johns Hopkins University last summer discovered half a dozen areas in the human genome that appear to be linked to the development of OCD. Analyzing 1,008 blood samples from 219 families in which at least two siblings had the disorder, they discovered gene markers at six sites on five chromosomes that appear more frequently in those kids than in family members and other people without OCD. That study did not tease out how those genes do their damage, but another group has identified a seventh gene whose mechanism is clearer.

Located on the ninth chromosome, that gene--discovered in two studies by researchers at several universities including the University of Michigan and the University of Toronto--appears to regulate a brain chemical known as glutamate. One of a number of substances that stimulate signaling among neurons, glutamate works fine unless you've got too much on hand. Then the signals just keep coming. In the case of the alarm centers in the brain, that means the warning bell just keeps on ringing. "Glutamate has to be taken up quickly because otherwise it becomes toxic to the brain cells," says Vladimir Coric, director of OCD research at Yale University and a leader in studies of the chemical.

What makes the glutamate-related gene especially suspect is the particular people it affects the most. OCD strikes males and females about evenly, but early-onset forms tend to target boys more than girls. This is particularly true in cases in which the boys also exhibit the involuntary tics or vocalizations often associated with Tourette's syndrome. Interacting with the glutamate gene are three genes related to androgens, or masculinizing hormones. Interacting with those is another gene that has been implicated in Tourette's. Gather all these together in the same chromosomal neighborhood, and they can make trouble. "Kids who start early tend to be boys, tend to have tic disorders and, in genetic analyses, tend to have parents with tic disorders too," says John March, chief of child psychiatry at Duke University.

Other compelling, if controversial, research has long pursued an entirely different cause of OCD: streptococcal infection. As long ago as the 17th century, British physician Thomas Sydenham first noticed a link between childhood strep and the later onset of a tic condition that became known as Sydenham's chorea. Modern researchers who saw a link between tics and OCD began wondering if, in some cases, strep might be involved with both.

Last year investigators from the University of Chicago and the University of Washington studied a group of 144 children-- 71% of whom were boys--who had tics or OCD. All the kids, it turned out, were more than twice as likely as others to have had a strep infection in the previous three months. For those with Tourette's symptoms, the strep incidence was a whopping 13 times as great.

The tics and OCD are probably the result of an autoimmune response, in which the body begins attacking its own healthy tissue. Blood tests of kids with strep-related tics and OCD have turned up antibodies hostile to neural tissue, particularly in the brain's caudate nucleus and putamen, regions associated with reinforcement learning. "There certainly seems to be an epidemiological relationship there," says Dr. Cathy Budman, associate professor of psychiatry and neurology at New York University, "but what it means needs to be further investigated."

HOW TO FIX IT

NO MATTER HOW OR WHEN THE DISORDER hits, the first step in striking back is usually comparatively short-term behavioral therapy, using a technique known as exposure and response prevention (ERP), in which OCD sufferers don't try to avoid their particular source of anxiety but actually seek it out. Eventually, emotional nerve endings grow desensitized to the stimulus. The point is to tough it out until that happens.

At the Obsessive Compulsive Foundation convention in Atlanta last summer, Grayson, the Pennsylvania-based clinical psychologist, gave those in attendance who had OCD a quick taste of ERP. Inviting the ones in the audience with dirt and germ anxieties to come forward, he instructed them to sit beside him on the ballroom carpet. Then he told them to touch the carpet and bring their fingers to their lips. Left to themselves, most would have refused or, if they went along, would have then found the nearest bathroom and spent long minutes--perhaps long hours--scrubbing. Instead, they sat with Grayson and the anxiety, learning a very early lesson that the pain does subside. Extended ERP treatment involves a graduated series of such exposures, each a bit more challenging than the one before it.

Such tactical jujitsu works for all manner of OCD, though it's not always easy to find a doctor skilled at administering it. Patients obsessed about their sexual orientation, who become intolerably anxious if they so much as notice an attractive member of the same sex, are assigned to do just that: flip through magazines for scantily clad same-sex models. People plagued by what's known as relationship substantiation, who become consumed by inconsequential defects in a partner, are encouraged to seek out those flaws and even exaggerate them in their mind.