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OCD: Down to the Biology

 News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences

Can there be genes for too many cats?

Dr. Nestadt

“Considering that OCD is one of the world’s 10 most disabling conditions,” says Gerald Nestadt, “we know very little about its underpinnings.”

In mice, hoarding is a fact of life. A small cache of food can help the animals survive rodent-y hard times. But in humans, the behavior is an evolutionary tactic gone wrong, a pathology, whether what mounts up is canned food, newspapers or cats.

“Hoarding is a form of obsessive compulsive disorder (OCD),” says psychiatrist Gerald Nestadt, and one that is surprisingly common. Adult protective services in Los Angeles, for example, calls it their most frequent referral, he says. And though it looks like a psychiatric illness of the elderly, Nestadt suspects that hoarding behavior begins far earlier. “Hoarding’s likely both a social and biological process,” he explains. “The biological basis for it exists and may surface in one’s teens, but then, I believe, a person’s family discourages the ‘overenthusiastic collecting.’ In later years, if that person lives alone, the behavior gets full expression.”

Yet hoarding is only one band in OCD’s spectrum. In the last few decades, Nestadt and his Hopkins colleagues have encountered and described other probable but less understood subtypes of this illness that touches as much as 3 percent of the U.S. population. And lately, they’ve taken the first steps to clarify the underlying biology.

Most people recognize perpetual hand-washing as OCD, but other forms of the disorder aren’t as easily recognized. Patients can be preoccupied with taboos—a loving, caring new mother, for example, has alarming and unshakable images of stabbing her baby. Some people spend their waking hours in search of symmetry. “Almost all OCD varieties involve intrusive, unbidden thoughts,” says Nestadt, and sufferers may develop repetitive or avoiding behaviors that briefly relieve the high anxiety accompanying them.

Fortunately, about 60 percent of patients find combined behavioral and drug therapy helpful, particularly with antidepressants that raise available serotonin or serotonin and norepinephrine. But for those with no or little relief, the best hope could lie in Nestadt’s longer undertaking: identifying OCD genes.

In 2000, the group’s work showed that the disorders run in families. Recently, they’ve begun more targeted studies: a gene hunt via this country’s first extensive genome-wide scan. It coordinates efforts at six centers nationwide, including Harvard and the NIMH. “Our idea is straightforward,” Nestadt says. First, identify families with multiple members with this condition, interview them carefully—the group has been scrupulous in verifying the disease in the study’s 219 families—collect DNA and survey the genes for markers linked with OCD.

So far, the screen has revealed several possibly OCD-related chromosomal “neighborhoods.” Still, that’s not actual genes. Once the study is reproduced, Nestadt says, fine-tuning is surely necessary. That’s where the group’s careful cataloguing of subtypes comes in. By looking at the newly suspected neighborhoods but, this time, doing that in “pure” groups of, say, only patients who hoard or who crave symmetry, Nestadt hopes that genes specific to that type will stand out, as will those common to any OCD.

“Patients’ symptoms and now even brain imaging suggest different biologies,” he explains. “So having the identifying genes, of course, could open up everything to the light of day.” 

For information about this research, call 410-955-4838

Find other Hopkins Newsletter articles from past issues.