Hidden Valley Road

The geneticist Kevin Mitchell has noted how specific mutations can manifest differently in different people: The same mutation can trigger epilepsy in some people while in others it triggers autism, schizophrenia, or nothing at all.

In 2010, the psychiatrist Thomas Insel, then director of NIMH, called for the research community to redefine schizophrenia as “a collection of neurodevelopmental disorders,” not one single disease. The end of schizophrenia as a monolithic diagnosis could mean the beginning of the end of the stigma surrounding the condition. What if schizophrenia wasn’t a disease at all, but a symptom?
“The metaphor I use is that years ago, clinicians used to look at ‘fever’ as one disease,” said John McGrath, an epidemiologist with Australia’s Queensland Centre for Mental Health Research and one of the world’s authorities on quantifying populations of mentally ill people. “Then they split it into different types of fevers. And then they realized it’s just a nonspecific reaction to various illnesses. Psychosis is just what the brain does when it’s not working very well.”

First, he needed more proof. In 1997, Freedman devised an experiment: He gave nicotine to people with schizophrenia, usually many pieces of Nicorette chewing gum, and then measured their brain waves with his double-click test. Sure enough, people with schizophrenia who chewed three pieces of Nicorette passed the test with flying colors. They responded to the first sound and didn’t respond to the second, just like people without schizophrenia. The effects didn’t last after the nicotine wore off, but Freedman still was stunned.

The hippocampus helps remind you of where you are at any given moment, and it is less developed in the twins that, diagnosed with schizophrenia, have less of a grip on reality.

The hippocampi of the brains of people with schizophrenia were smaller than those without.

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.

If Michael was frustrated, Lindsay, back at boarding school, was surprised to find her resentment easing, her rage subsiding. Like Margaret, she had felt marginalized at her exclusive private school—but Lindsay stopped thinking that the solution ought to be to deny her family’s existence. Instead, she discovered a certain kinship with her sick brothers. They were ostracized by society. Sometimes she felt that way, too.

What if the problem with schizophrenia patients wasn’t that they lacked the ability to respond to so much stimuli, but that they lacked the ability not to? What if their brains weren’t overloaded, but lacked inhibition—forced to reckon with everything that was coming their way, every second of every day?

As an undergraduate, Freedman had been drawn to the idea that the human mind could synthesize its own, entirely separate reality. “It just seemed to me if there was ever a disease that was uniquely human and philosophical, it was having schizophrenia,” he said.

Or as one of the ventricle study coauthors, a psychiatrist at St. Elizabeths named E. Fuller Torrey, put it: “If bad parenting caused any of these diseases, we’d all be in big, big trouble.”