Hidden Valley Road: Inside the Mind of an American Family

Mimi

As the years passed, Mimi remained a fierce advocate for her sick sons. Nevertheless, she was startled when Donald told her that he was sexually abused as a teenager by the priest who had helped Mimi convert to Catholicism. Mimi wrote this off as a delusion until Richard happened to learn that one of his own acquaintances was molested by the same priest. From that point onward, Mimi was adamant that he was to blame for the family’s misfortunes: “Didn’t it make sense, she’d say, that the priest sexually abused Donald, who in turn physically abused his brothers, at least one of whom, Jim, went on to sexually abuse their sisters? (241). These speculations had little scientific evidence to support them, but they alleviated some of Mimi’s guilt.

Meanwhile, Mimi had become increasingly critical of her husband, telling Lindsay and Margaret about Don’s history of depressive episodes and revealing that he had had several affairs. Gradually, Lindsay and Margaret’s understanding of their mother became more nuanced and sympathetic.

1998, University of Colorado Medical Center, Denver, Colorado

Freedman began his search for a common genetic variable at play in the double-click test by looking at the cells of “inhibitory neurons:” neurons that normally prevent the brain from responding to all available sensory information. By studying rats, he determined that the function of these neurons depended on a particular kind of receptor located in the hippocampus: “The α7 receptor is a master communicator, sending messages from neuron to neuron so that the circuit can work properly. But in order to do its job, this receptor needs a compound called acetylcholine, which behaves as a neurotransmitter” (245).

Using the data he’d gathered from the Galvins and other families, Freedman eventually found that those who failed the double-click test tended to have changes in a gene called CHRNA7, which was involved in the production of α7 receptors; as a result, they had fewer receptors, and lacked enough acetylcholine to make more. These changes didn’t cause schizophrenia in all cases, so Freedman was able to reassure Margaret—now married and considering starting a family—that her children wouldn’t necessarily develop the disease. However, the discovery of CHRNA7’s function did give Freedman an idea about an avenue of treatment, since nicotine was known to increase acetylcholine levels.

After confirming that nicotine did in fact inhibit the brain’s response to the double-click test, Freedman began developing a drug using a substance that mimicked the effects of nicotine. The results were promising, and different pharmaceutical companies began working on variations of the drug. However, the drugs had to be taken more than once a day, which the companies viewed as an obstacle to marketing them. As a result, they ultimately abandoned the project.

2000, State University of New York at Stony Brook

In 1995, a pharmaceutical company named Sequana Therapeutics decided to fund DeLisi’s research; with their backing and resources, she was able to expand her data on multiplex families. Unfortunately, the company was bought out by Pfizer in 2000, and the new owners canceled funding for DeLisi’s study.

Meanwhile, the Human Genome Project was working to map every human gene: “Now, all one would have to do is compare the genomes of a sampling of sick people—for any genetic disease, take your pick—with a control group, and whatever abnormality existed in the genome of the sick people would be impossible not to notice” (252). The project was finished in 2003, and by 2005, a genome-wide association study (GWAS) was underway for schizophrenia.

This study, and others like it that followed, found tens of thousands of genetic variations, sometimes in hundreds of different locations. For researchers, this posed a problem: “Each of these genetic irregularities, taken by itself, only accounted for a minuscule increased chance of an individual having schizophrenia” (254). For that reason, researchers like DeLisi continued to feel that family studies represented a more targeted way of studying the disease’s origins.

However, while DeLisi still had technical ownership of half the genetic material she had collected, she didn’t have anyone willing to fund her research; for pharmaceutical companies, there was little incentive to search for replacements for the already profitable class of antipsychotics, even if a replacement might work better.

Peter

Lindsay ultimately gave up her guardianship of Peter, and he became a ward of the state, continuing to cycle in and out of hospitals. In 2004, doctors were unable to stabilize him on any combination of drugs and decided to try electroconvulsive therapy (ECT), which had shown promise in treating bipolar disorder: “The procedure still is known to have adverse effects on patients’ memories […] [a]nd yet in some cases ECT seems to be able to adjust serotonin and dopamine levels more effectively than any medication” (258-259).

Initially, Peter received ECT once a week; it had little effect, and he fiercely resisted it. When doctors begin administering ECT three times per week, he dramatically improved and was released from the hospital. However, Peter still considered the treatments unnecessary and consequently ended up back in Pueblo the following year, at which point a court order was issued to force him to maintain regular treatments.