McFarlane continues to collect data on PIER patients, but he says that of the more than 100 patients treated by PIER in Maine so far, less than 10 percent have developed a major psychosis, compared with 30 to 40 percent who may have converted without treatment. If true, those results represent many lives saved from the devastation of severe mental illness. “What we hope is that the benefits of treatment will be lifelong,” McFarlane says. “We don’t have any empirical evidence to support that yet, but what we’ve seen is that young people who still haven’t converted to psychosis after about three years of our treatment don’t seem to be at much risk. As to when or if they can go off medication, that’s hard to say. I think many of our patients don’t feel a need to stop; they certainly don’t feel oppressed by it. At a certain point it becomes a personal choice.”
The debate underscores how little is known about the biological origins and onset of schizophrenia itself, as well as how best to treat its early stages.
At the moment, the most powerful evidence for PIER may lie in the stories of its participants. Josef Bruno (not his real name) showed up at the age of 18 after struggling for years with a nonverbal learning disorder, multiple psychiatric hospitalizations for anxiety, and a growing sense that he was disconnecting from himself. Treating him has not been easy. He requires numerous medications, frequent contact with clinicians and social workers, and lots of caring attention from his parents. Yet two years into the program, he has made important strides: His mental state has improved, and he is living independently for the first time, sharing an apartment with a roommate. What’s more, he has a job at a convenience store and aspirations to go to college.
Camila and her family stuck with PIER for the four-year treatment program, which ended formally in 2005, and still keep in touch with counselors there. Though her improvement was steady, Camila’s treatment posed its own challenges. Her mother admits she was overprotective and too involved in her daughter’s illness. It was hard to back off and give Camila space to recover, she says. Her father admits to being frustrated by how Camila’s condition made parenting more complicated. “Sometimes it felt like she was manipulating us,” he says with a chuckle. “And that was difficult because we didn’t know if what we were dealing with was part of the illness, or just her being an adolescent.”
Meanwhile, Camila’s health still hinges on antipsychotic medication. In the summer of 2007 she went off the drugs for a spell and her strange feelings returned. She says the medication doesn’t bother her, though. “Sometimes I feel so good, I just forget about it and don’t think I need it,” Camila explains. “But then I start to go downhill.”
Camila’s reliance on antipsychotics does raise a couple of issues. On the one hand, it shows that the threat of psychosis hasn’t really been removed, it’s just been held in check. While McFarlane suggests that over time, some patients may be able to go off medications, he acknowledges that PIER hasn’t developed a plan for managing that process. On the other hand, PIER’s intervention may have given Camila a chance to lead a normal life. Without the medications she might have plummeted toward full-blown schizophrenia, a life-threatening outcome with tremendous costs to society. Indeed, by limiting the debate to whether PIER does or doesn’t prevent schizophrenia, it’s possible to miss a larger point, namely, that most of the patients enter the program because they are in serious need of help, without which they could succumb to psychosis, violence, or suicide. According to Anthony Lehman, chairman of psychiatry at the University of Maryland School of Medicine, “The real value here is that the program is bolstering public awareness about prodromal symptoms, and it’s providing venues for kids and their families who have these problems to get help.”
Researchers hope that a risk-free way of blocking psychosis is around the bend. Recent imaging studies—some by neuroscientist Tyrone Cannon, from the University of California at Los Angeles—are providing clues to schizophrenia’s underlying pathology. These studies suggest that prodromal symptoms emerge from a progressive loss of synapses in the brain. “It’s not that whole brain cells are lost, as is the case with Alzheimer’s disease,” Cannon explains. “It’s the elements that brain cells use to communicate with each other that are lost.” This hypothesis might help explain why prodromal symptoms occur: As connections between neurons dwindle, prodromal patients might lose, for example, the ability to filter out irrelevant sensations, which then flood the brain without any processing. That may be why Camila couldn’t deal with everyday sounds; they just came at her in a wave that would ordinarily have been picked apart and filed: a barking dog here, a car engine there.
Ideally, Heinssen says, research can lead to ways to protect the prodromal brain. The methods might include drugs to slow the loss of connections between neurons, as well as cognitive and behavioral therapies designed to strengthen imperfect circuits. “That is how we see prevention unfolding,” he says. “We want to combine neuroimaging and cognitive assays with clinical symptoms to enhance prodromal diagnosis, identify neuroprotective agents to target underlying disease mechanisms in the brain, and develop behavioral and cognitive exercises that will increase the patient’s ability to adapt.”
Remarkably, two compounds that seem to exert these neuroprotective effects—both of them a focus of intense interest in schizophrenia research—aren’t sophisticated drugs but simple compounds found in nature. Supplementing diets for three months with daily two-gram doses of fish oil, a source of omega 3 fatty acids, was shown in a forthcoming study by University of Melbourne researcher Paul Amminger to reduce conversion to psychosis among 81 high-risk patients. Another promising compound, according to Scott Woods of Yale School of Medicine, is D-serine, an amino acid. D-serine may boost the growth of synapses, he says, and has therefore attracted NIMH funding for clinical studies.
In the meantime, McFarlane treats patients with the imperfect tools science has supplied so far. Of the need, there can be no doubt. Schizophrenia afflicts roughly 1 percent of the population—some 2.4 million Americans—destroying personal relationships and setting up conditions for high rates of joblessness and drug addiction. Untreated, many patients wind up homeless, incarcerated, or dead. “I think there will be an intervention based on a biological mechanism at some point in the future,” McFarlane says. “We aim to have an identification system in place by then, and the treatments we can use in the meantime are good enough. Schizophrenia is as devastating in my mind as cancer, maybe more because it typically strikes at earlier ages and wipes out someone’s whole life. So, yes, we’re trying to forge ahead with a public health intervention, even if we don’t have the best possible treatments. I think it’s silly to wait. Wait for what?”