Hidden Valley Road - Inside the Mind of an American Family - Robert Kolker Page 0,104

He saw that Don’s health was declining and that the sick boys were a handful. But above all, he was struck, as DeLisi had been, by Mimi’s determination to care for them all. “Medications in those days made the boys very stiff and unresponsive. So they kind of sat there like hunks and they weren’t talkative, and she was left to manage them. She was running a rooming house.”

DeLisi had tipped Freedman off to the Galvins, knowing that he had been looking for families to test his sensory gating theory. Freedman had spent the early 1980s running his double-click studies, designed to measure the brain’s ability to filter information. He continued to believe that sensory gating was a mechanism in the brain, something genetic that made certain people susceptible to schizophrenia. And he felt as if he was getting warmer. In 1984, just before meeting the Galvins, he had studied the gating abilities of schizophrenia patients and members of their immediate families, and he found that half of the immediate family members had the same gating deficits as the family members diagnosed with schizophrenia. Here was another sign that he was on the right track—evidence that sensory gating was hereditary.

Why some siblings with sensory gating issues ended up manifesting the symptoms of schizophrenia and others did not was still a mystery. Freedman’s next step was to try to locate the specific part of the brain responsible for sensory gating. Thanks to DeLisi, he now had access to a family with an unfathomably, overwhelmingly profound manifestation of schizophrenia.

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IN FEBRUARY 1986, months after her first visit with the Galvins, DeLisi used data from her families to confirm what Richard Wyatt’s NIMH team had discovered about schizophrenia’s correlation to large brain ventricle size. A year later, she used the data in a study testing a possible link between schizophrenia and human leukocyte antigens, or HLA, a gene complex involved in the regulation of the immune system. No such link was proven. Still, the multiplex family database had begun contributing to the body of knowledge about the disease. As far as DeLisi was concerned, this was only the beginning.

She sent the Galvins’ blood samples to the Coriell Institute for Medical Research, a facility in Camden, New Jersey, that preserves huge collections of cell lines from various diseases. This allowed for the possibility of others using the family’s DNA as a resource in dozens, even hundreds of future studies, conducted in labs around the world. DeLisi held fast to her belief that if she could find a marker for schizophrenia embedded in the genetic data of a family like the Galvins, schizophrenia might one day become like heart disease, an illness with particular benchmarks and risk factors that could be measured. In 1987, DeLisi was recruited away from NIMH by the State University of New York at Stony Brook, which offered her a professorship and a program of her own to run. She kept researching multiplex families there. She had forty already, including the Galvins. With a grant from NIMH, she steadily built on that list, eventually reaching one thousand families—more than anyone else had managed to assemble.

Then came several fallow years. Family studies were yielding amazing results in other diseases, including early onset breast cancer and Alzheimer’s disease, but there was no breakthrough for schizophrenia. In 1995, DeLisi published two studies drawn from her own pool of data on families. The first seemed to confirm that the same genes responsible for schizophrenia are connected to other mental illnesses like depression or schizoaffective disorder. The second failed to find a link between schizophrenia and bipolar illness, at least on one particular chromosome where bipolar illness appeared to be rooted. DeLisi remained confident that someone somewhere could find a genetic fingerprint in this pool—and show that nature, not nurture, determined this condition. “I am not a firm believer in environment having an effect at all,” DeLisi told a reporter in 1999.

DeLisi’s work still had supporters. “It is critical that we avoid premature disillusionment,” Kenneth Kendler, with the Medical College of Virginia, wrote in 1993. “The human brain is very complex and quite difficult to access.” But one of her old colleagues from Richard Wyatt’s lab at NIMH, Daniel Weinberger, started to suspect that researching families was a blind alley. “More than ninety percent of the