Development at Johns Hopkins University—cofounded by Daniel Weinberger, the developmental hypothesis author from NIMH—to focus on fetal health from a new angle: studying whether the risk of schizophrenia is linked to the condition of an expectant mother’s placenta. With Freedman, Weinberger has begun investigating whether choline might play a role in improving placenta health. Both researchers hope to eliminate a large number of potential schizophrenia cases in one fell swoop, before the patients are even born.
For Freedman, prevention is more than just good medicine; it’s common sense. Billions of dollars are spent each year on developing drugs to treat the symptoms of mental illness after it already manifests. What if some of that money were spent on prevention, not just in the womb but in childhood? Think of all the young people who develop mental illness out of sight of anyone who can help them. What if some of those breakdowns—even suicides—could be prevented, by shoring up the mind’s vulnerability before things get worse? “The National Institute of Mental Health spends only $4.3 million on fetal prevention research, all of it for studies in mice, from its yearly $1.4 billion budget,” Freedman noted recently. “Yet half of young school shooters have symptoms of developing schizophrenia.”
There is no way of knowing how life might have been different for the Galvin brothers if the culture of mental illness had been less rigid, less inclined to cut people off from mainstream society, more proactive about intervening when warning signs first appeared. But there is, perhaps, reason to hope that for people like the Galvins born fifty years from now, things could be different, even transformed.
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“I believe the trend is coming back to families,” Lynn DeLisi said, over coffee a short drive from her home in Massachusetts. In 2016, the same year as her SHANK2 study, she published a paper in Molecular Neuropsychiatry arguing that researching families with schizophrenia was more important now than ever. For the first time in a long time, she is not the only scientist saying this.
“I think the families have enormous importance,” said Daniel Weinberger. Once upon a time, when he worked alongside DeLisi at NIMH, Weinberger had been skeptical of studying families, all but dismissive of her approach. Now, like DeLisi, he sees the value of using families as workshops—or test kitchens—for theories that emerge from a GWAS. “Ultimately, families will be critical to translate the genetics into how individual people get sick.” Weinberger recognizes how the study of families like the Galvins can point to new pathways for treatment that no GWAS can notice. “Somebody once said to me, ‘If you genotype every person in the world, will you understand what schizophrenia is?’ My guess is you won’t understand it just from everybody’s genetic sequence. That won’t explain schizophrenia. It’ll explain a lot about what the risk state represents, but I doubt we’re going to have the full answer from that.”
DeLisi’s work went unnoticed for years. She remains an outsider today—teaching at Harvard Medical School, yes, and active in international schizophrenia research groups, but not recognized with awards or grants like her contemporaries. Even if her SHANK2 findings lead to another breakthrough, she might not get the credit. It’s the way of scientific progress—if you aren’t among the rare few who are immortalized, you are merely part of the great procession of research, a player in a larger drama. “I think in some ways it bothers me,” DeLisi said. “But I have since resolved this in my own mind. It is what I did to make all this possible that counts.”
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BY THE TIME the SHANK2 study was published, Stefan McDonough had left Amgen. Not long after that, over the phone with her old collaborator, DeLisi learned that McDonough had moved on to Pfizer, the company that had pulled the plug on her multiplex family research sixteen years earlier.
Some small part of her appreciated the irony. If you live long enough, as Mimi Galvin had known, everything comes back to haunt you.
DeLisi had never mentioned any of this to McDonough. As far as he knew, DeLisi’s data was all hers; he hadn’t known about the big split in 2000, when she got half and Pfizer got half. So, during that call, she decided to let him know that Pfizer