Authors: Robert Kolker
Our culture looks at diseases as problems to solve. We imagine every ailment to be like polio: hopelessly incurable, until a miracle drug comes along that can wipe it off the face of the earth. That model, of course, only works some of the time. Too often, scientists get lost in their own silos, convinced their theory works to the exclusion of everyone else’s. Whether it’s the Freudians and the Kraepelinians or the family dynamics specialists and the geneticists, the unwillingness to collaborate leaves everyone vulnerable to confirmation bias—tunnel vision. The schizophrenia researcher Rue L. Cromwell described this dilemma in the 1970s: “
Like riding the merry-go-round, one chooses his horse. One can make believe his horse leads the rest. Then when a particular ride is finished, one must step off only to observe that the horse has really gone nowhere. Yet, it has been a thrilling experience. There may even be the yen to go again.”
But there is another model for progress—the opposite of the polio model—one in which solutions are not the same as breakthroughs. Progress comes gradually, often painfully, in fits and starts, and only after many people spend their entire careers failing and quarreling and, finally, reconciling. Sooner or later, some ideas fall away as others take hold. And, perhaps only in hindsight, we can see how far we’ve come, and decide on a path forward.
What would progress look like for schizophrenia? If the Galvin boys had been born a half century later or more—growing up today, let’s say, and not in the 1950s or 1960s—would their treatment be any different now? In some respects, little has changed. The market for new schizophrenia drugs remains sluggish. Antipsychotic drugs require expensive and risky testing, even in the early trials, where rats are no substitute for humans. And the same nature-nurture squabbles over the source of the illness have continued, if at a more granular level. Where the conversation once was about Freud, now it’s about epigenetics—latent genes, activated by environmental triggers. Researchers now argue about what might be playing the part of a trigger—something ingested, like marijuana, or infectious, like bacteria? Researchers have come up with a variety of other suspects—head injuries, autoimmune diseases, brain-inflammation disorders, parasitic microbes—all of which have their adherents and detractors. Everyone still picks their horse on the merry-go-round, and very few are willing to stop taking the ride.
There are, however, more subtle changes—as if the atmosphere around the disease has changed a little, charged with a new sense of tolerance. Anti-psychiatry, in its latest incarnation, has become a movement concerned with legitimizing and normalizing the concept of hallucinations—a
Hearing Voices Movement, not unlike the movements to legitimize deafness and blindness not as disabilities but as differences. Neurodiversity—a term used more often for other conditions, like autism—is a concept that was never considered when treating any Galvin brother decades ago. There is a robust anti-medication movement now—activists armed with studies showing that
many schizophrenia patients experience favorable long-term outcomes without prescription drugs. This movement has support from many therapists unhappy with the notion of psychiatry as a pill mill, and nostalgic for the gilded age of psychotherapy, when a doctor could spend more than just a few minutes with a patient before sending them off with prescriptions.
If there is a significant change, it’s that more people are acknowledging the elusive quality of schizophrenia diagnoses, aware that there is no one-size-fits-all definition. Each passing year brings
more evidence that psychosis exists on a spectrum, with new genetic studies showing overlap between schizophrenia and bipolar disorder, and bipolar disorder and autism. The most recent research suggests that a surprising number of us may be at least a little bit mentally ill:
One meta-analysis, published in 2013, found that 7.2 percent of the general population has experienced hallucinations or delusions;
another study in 2015 put the figure at 5.8 percent. A third of the people counted in the latter study only had one episode, while others had more persistent symptoms. Results like this suggest, at the very least, that the medical response to aberrant behavior should be more discerning about who needs traditional treatment and who might benefit from watching and waiting. The stakes in such decisions are high: Researchers have the evidence now to confirm that each successive psychotic break causes more permanent damage to a brain, a further loss of gray matter necessary for processing information.
The grave dilemma of neuroleptic drugs, sadly, remains the same: Medication, taken regularly, can stave off further breakdowns (while risking long-term side effects), but there is also ample evidence that patients who remain on drug regimens relapse as often as those who don’t. While the surviving Galvin brothers are as dependent on neuroleptics as ever, the biggest change for those who come after them could be that medication and therapy are not an either/or choice. Even the most traditionally trained schizophrenia researchers are pushing what Jeffrey Lieberman, the chief psychiatrist of Columbia University Medical Center of the New York-Presbyterian Hospital, calls an “
early detection and intervention model of care.” A relatively new wave of research supports the effectiveness of
so-called “soft interventions”: a mixture of talk therapy and family support, designed to keep the amount of medication to a minimum. For decades, countries like
Australia and Scandinavia have used this more holistic approach and reported success. (You could argue that Michael Galvin found his soft intervention inside the Rock Tumbler on the Farm, his commune in Tennessee—assuming he was ever really at risk to begin with.) The challenge is being able to tell who can be successfully treated by neuroleptic drugs, who might not be helped much at all by those drugs, and who, in the long run, might suffer from the drugs as much as the disease.
For more researchers, the watchword is prevention—the challenge of accurately diagnosing people at risk of developing schizophrenia
their first psychotic break.
Lieberman at Columbia is developing new techniques to measure the function of the hippocampus. In time, new drugs could stave off the onset of schizophrenia—just like the drugs being developed now that might fend off the symptoms of Alzheimer’s disease. And then there’s choline. In Denver, Robert Freedman is following up on his first long-term choline study with a new trial—with support from Sam and Nancy Gary, among others—tracking children from the moment their expectant mothers start taking the choline supplements, up through the time their children reach post-adolescence, the prime years for the onset of schizophrenia. As he suggested at his award ceremony in New York, Freedman will undoubtedly not be alive when the results come in. Neither will the Garys or many of the other donors. “They’re a bunch of builders, developers—oil barons like Nancy,” Freedman said. “They said, ‘Oh, yeah, let’s go all in. That’s how we run our businesses.’ ” If it doesn’t work out somewhere along the way, they told Freedman they’d all have one dinner and say it was a nice ride.
Freedman also started a collaboration with the Lieber Institute for Brain 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
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.
“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
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.”
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 still maintained possession of a set of her multiplex family samples, including many of the same families they used for their SHANK2 study.
They both knew what this might mean: Assuming they hadn’t been tossed in the trash at some point to make space in a freezer, DeLisi’s samples, including the genetic information of the Galvin family, were still sitting somewhere. DeLisi had no idea where—and even if she did, she had no say in how or when or even if it might be used again.
“Who did you deal with here?” McDonough asked. Maybe he could find that person and ask about it.
DeLisi gave him a name.
McDonough couldn’t believe it. Thousands of Pfizer employees, all around the world, and the one they were looking for happened, at that very moment, to be sitting just a few feet away from him.
McDonough could hardly resist. It was the end of the year. He had some money left in his budget. “I went ahead and had some of them sequenced,” he said. He picked out families with the largest number of relatives with schizophrenia that he could find. The Galvin family had been analyzed already, but there were others, maybe not as big, but big enough.
“Again, Lynn was ahead of her time,” McDonough said. “We intend to see if there’s anything there. Pfizer won’t be interested for its own drug discovery uses, so we have every incentive to publish them and just make the science known to the world.”
These families still have something to say. And now someone is listening.
Margaret and Lindsay barely talked or even texted in the six months after Mimi’s memorial. The one who cut off contact was Margaret. She saw Lindsay doing so much that it hurt—immersing herself in the Galvin family morass without ever coming up for air, and perhaps even damaging her relationships to her husband and children—and then turning around and admonishing others for not doing the same. Margaret did not see her ever stopping, or even slowing down. “I think there’s a lot of manipulation that takes place in our family,” Margaret said, “and I think that we’ve all been on the manipulative side and then the victim side of all of that. And so I find myself as I get older a little bit more assertive with my family, saying, you know, enough is enough.”
Only now that their mother wasn’t there as a shared focus for them did Margaret see how far apart she and her sister had grown. “Michael and Lindsay don’t like it that I don’t go in with them on the family dysfunction,” Margaret said, “but the boundary is helpful to me.”
Lindsay believed that Margaret saying that contact with the family was unhealthy for her was little more than a dodge—an attempt to preempt any criticism that she, Margaret, wasn’t helping enough. As Lindsay saw it, Margaret’s passion for self-care was really about her own unresolved fury. “She’s got a much higher level of anger towards my mother and my father for how they handled it,” Lindsay said. “She has a lot of anger towards my mentally ill brothers, particularly Donald and Jim. I still see a pretty big victim there.”
Lindsay repeated something she learned from Louise Silvern, her old therapist, and also from Nancy Gary, and, if she’s being honest with herself, from her own mother. “They taught me to embrace the cards you are dealt or it will eat you alive. If you go to the heart of your own matter, you will find only by loving and helping do you have peace from your own trauma.” This, in her view, was the major difference between her and her sister.
“We both have worked very hard to save ourselves,” Lindsay said. “But she didn’t see trying to help them as any part of that, whereas I did.”
A few years earlier, Lindsay asked Sam Gary why she wasn’t brought to their house like Margaret. “Your parents and I thought you had a stronger constitution,” Sam said. “You weren’t as fragile.” This was news to Lindsay.
But Lindsay was human. She needed help, too. For her entire adult life, when something about the family ate away at her insides, there was only one other person in the world who would understand. When she was at her lowest, her sister was there, living proof that she was not alone. Without Margaret in her life, Lindsay felt as if she’d sustained not one but two losses—a mother and a sister.
“I can’t imagine having gone through this without her,” Lindsay said.
Matt had his vehicle stolen last week after having a new truck totaled a year ago—not his fault and only liability—ugh!
Yeah, right—the poor guy cannot catch a break in life.
Like having schizophrenia is so fun…
I just ordered groceries to be delivered to his house tomorrow am. Very easy. https://www.instacart.com…
He has no way to go get them and frankly is incapable of grocery shopping.
He would like to move as he is in a really bad area—working on that with section 8 and the Villanni Family, who said they would have him on one of their buildings. It was fun to see all who knew him at Safeway. “Hey, Matt!”
I would be grateful to anyone of you who could call and offer a hello. No guilt—just asking for some genuine human kindness.
Email from Lindsay to Margaret, Michael, John, Richard, and Mark, June 2018
IT WAS UNDERSTOOD
among the surviving children of Don and Mimi Galvin that the proceeds from the sale of the house would benefit the three remaining sick brothers. Lindsay brainstormed with Michael about little things that they could do for them with the money. Matt could get a new truck. Peter could get pet therapy or music therapy; even a new tenor recorder might make him happy. Donald loved the opera; what if they hired a companion to take him to those Metropolitan Opera performances they screen at movie theaters?
When she thought about this, Lindsay realized that the person who had really known what her brothers liked, what would make a difference to them, was her mother. This was what kept Lindsay up late now: the idea that the true champion of the family, the gold medal winner in the Empathy Olympics, could have been Mimi Galvin all along. “Now suddenly without her here,” Lindsay said, “I’m understanding where she was coming from.”
Lindsay used to talk about nature and nurture with her mother. Mimi, still wary of being judged, felt that nurture couldn’t have had anything to do with what happened to her family. “Well, it was genetic,” she would say. Lindsay told her mother she was not so sure. She believed that some people have a genetic predisposition “that can go either way, depending on your life course and trauma.” Certain things can make a difference, Lindsay said, like “love and belonging.”
She stopped faulting her mother for this, though. “I really believe that my parents didn’t get us as much help as we should have had,” she said, “but they didn’t know what that looked like.”
Lindsay was determined now to channel whatever it was her mother had that helped her connect to the sick boys. So many people—including many of her well brothers—had stopped seeing Donald, Peter, and Matt as human beings a long time ago. Schizophrenia’s inaccessibility may be the most destructive thing about it—the thing that keeps so many people from connecting to the people with the illness.
But the mistake—the temptation, especially if you’re a relative—is to confuse inaccessibility with a loss of self. “
Emotions are always accompanied by some kind of cognitive process,” wrote the psychiatrist Silvano Arieti, whose volume
Interpretation of Schizophrenia
dominated the mainstream thinking about the illness in the 1950s and again, with a National Book Award–winning second edition, in the 1970s. “The cognitive process may be unconscious, or automatic, or distorted, but it is always present.”
Lindsay noticed this most in her brothers whenever they were on the receiving end of any kindness. “Matt called me this morning with just simple, plain gratitude,” she said, shortly after she’d helped him with his groceries. “I wish I could tap into that.”
Responding to some gentle prodding, some of her well brothers began reaching out to the sick ones. Richard and Renée called and asked for their phone numbers. Lindsay planned to get Colorado College hockey season tickets for Matt—something Mark might want to take him to, since they once loved playing together. “Pretty much everyone avoids them like the plague. But if I very clearly and deliberately say, ‘Hey, can you take them out for, you know, whatever, coffee and a donut?’ They’ll do it.”
IT TOOK SIX
months for the sisters to try bridging the gap. They started talking in January, after spending the holidays apart. At the end of a long face-to-face visit, Lindsay started to see things more clearly. “I found myself angry at everybody in my family for not helping me with my mom at the end,” Lindsay said. “And Margaret perceived my way of helping as not necessarily a good thing.”
Margaret, in turn, acknowledged that Lindsay was more capable of handling the family matters than she ever could have been. But a huge gulf remained between them.
They discussed Margaret’s inability to help with Mimi and how angry it made Lindsay. “I just can’t do it,” Margaret said. And Lindsay felt comfortable enough to say that her sister’s decision was not all right with her—that it made her, as she recalled later, “feel sad and frustrated and angry that I feel like I’m left with this whole bag.”
They talked a little about survivors of childhood trauma, and how they often continue to find people in their lives to victimize them, so they can continue to get help. Was Lindsay playing that role for Margaret now? Was Margaret for Lindsay?
At the end of the conversation, Lindsay posed a question to her sister: Were they willing to accept each other for who they were? Or were they going to continue down the path of thinking the other person was somehow damaged, and impossible to be close with?
After that visit, Lindsay decided that she needed to allow all of her siblings to do things their way, even as she did things her way. “It’s about everyone’s own journey,” Lindsay said, trying to find some distance of her own. “How they’re able to muddle through life and deal.”
From her family, Lindsay could see how we all have an amazing ability to shape our own reality, regardless of the facts. We can live our entire lives in a bubble and be quite comfortable. And there can be other realities that we refuse to acknowledge, but are every bit as real as our own. She was not thinking of her sick brothers now, but of everyone—all of them, including her mother, including herself.
“I could just act like I’m a multimillionaire like my brother Richard. Or I could move to Boise like John, or I could play classical guitar all day like Michael. It’s, like, we all just
. Just respecting that about each other. We all survived somehow. Everyone’s different way needs to be okay.”
Lindsay was getting closer, finally, to seeing how nature and nurture work together. Her mother had always insisted, defensively, that the illness was genetic, and in a way, Mimi was right. Biology is destiny, to a point; that can’t be denied. But Lindsay understood now how we are more than just our genes. We are, in some way, a product of the people who surround us—the people we’re forced to grow up with, and the people we choose to be with later.
Our relationships can destroy us, but they can change us, too, and restore us, and without us ever seeing it happen, they define us.
We are human because the people around us make us human.