Postnatal events such as a head trauma in early childhood increase the risk of developing schizophrenia. Lifetime stress plays a role, too; the risk is particularly high among immigrants who go from underdeveloped settings to cities—people confronting exponential unfamiliarity. The most consistent postuterine environmental factor associated with a worsening of psychotic symptoms is the abuse of recreational drugs, including alcohol, methamphetamines, hallucinogens, cocaine, and marijuana, particularly in adolescence. When the Japanese gave methamphetamines to workers to increase productivity during the postwar recovery, they provoked epidemic levels of psychosis; although many people recovered after they stopped using the drugs, others had transient recurrence, and some had prolonged and even permanent impairment. A seminal study done in the 1980s with some fifty thousand Swedish conscripts showed that those who had used marijuana more than fifty times were six times more likely to develop schizophrenia. “The relationship between drug abuse and psychosis is perhaps like that between smoking and lung cancer,” said Cyril D’Souza, a psychiatrist at Yale. “It’s a contributing, not a necessary, cause. But some studies suggest that if you were able to eliminate cannabis, you could reduce world rates of schizophrenia by at least ten percent.”
In schizophrenia, some gene-environment combination causes the neurotransmitters dopamine, glutamate, norepinephrine, serotonin, and GABA to become dysregulated, leading to excess activity in one dopamine pathway. This induces psychosis and other positive symptoms. Artificially releasing too much dopamine can provoke the symptoms of schizophrenia even in healthy subjects; suppressing it can mitigate those symptoms. Underactivity in another dopamine pathway creates impaired cognition and other negative symptoms. Antipsychotic medications block the ability of the brain to process high levels of neurotransmitters in some areas; they mimic controlled levels of those neurotransmitters in others. All successful antipsychotics lower dopamine levels, but lowering dopamine is not by itself enough consistently to remit all of the symptoms of schizophrenia, and new research focuses on drugs that will affect particular receptors for glutamate and other transmitters. Anissa Abi-Dargham at Columbia University is delineating which dopamine receptors are overstimulated and which are understimulated, to map ever more specific goals for medications.
Nonchemical interventions can play a meaningful secondary role. Talk therapies can help in the management of symptoms that do not respond to medication. Though cognitive behavioral therapy (CBT), which teaches people to redirect their present thoughts and behaviors, has the strongest track record, many other talk therapies have powerful exponents, and the law professor Elyn Saks has written movingly of her redeeming experiences with psychoanalysis in her battle with schizophrenia. What you do with your brain changes it, and if you can get someone with schizophrenia into a rational mode for some time, the positive effects are substantive. The theory is that much as someone who loses speech in a stroke can relearn talking through speech therapy, someone with psychosis may be able to train his way partially out of it.
Since the disease is associated with a progressive loss of grey matter in the brain, it makes sense that if you identify people quickly, treat them, and keep them well, you can limit the morbidity of the illness and prevent people from becoming irreversibly impaired. “The therapeutic nihilism that pervaded the field for the better part of the twentieth century is really no longer warranted,” said Jeffrey Lieberman, chairman of the Department of Psychiatry at Columbia and director of the New York State Psychiatric Institute. “There is no better time in the history of mankind to have a mental illness than now, as long as you know where and how to obtain good treatment fast.” As with autism, early detection and intervention may be key, an idea that has now engendered an International Early Psychosis Association. Early behavioral intervention in autism can diminish the expression of symptoms; the training seems to affect the brain’s actual development. Early intervention may be equally promising in schizophrenia, even if early means age eighteen years rather than age eighteen months. Thomas McGlashan, a professor of psychiatry at Yale, has proposed that earlier diagnosis and medication during someone’s first dip into psychosis may actually truncate the brain degeneration that otherwise characterizes advancing schizophrenia.
Given the inadequacy of cures, the increasing focus is on getting in even earlier—on prevention at the prodromal (pre-psychotic) stage. Patients are in what Lieberman calls a “Humpty Dumpty situation,” in which “with our current tools it’s easier to prevent the morbidity of schizophrenia from occurring than to restore people after it’s happened.” As Jack Barchas, chairman of the Department of Psychiatry at Cornell, points out, the longer you can keep someone functioning, the more solid psychic history he has to fall back on—so even delaying the onset of schizophrenia would have value. Experts have devised a menu of symptoms that indicate the prodromal stage: suspiciousness; unusual, magical, or bizarre thinking; extreme changes in behavior patterns; decreased functioning; inability to go to school or function at a job. Confusingly, many of these are also symptoms of ordinary adolescence. In studies that have followed subjects identified as prodromal, only a third have actually developed schizophrenia, though many others will develop serious disturbances. Starting in 2003, McGlashan tried giving the antipsychotic olanzapine (Zyprexa) to apparently prodromal people and showed that the rate of developing schizophrenia was somewhat reduced; it also made many people who might not have gone on to develop the syndrome obese, sluggish, and glassy-eyed. “The positive result was only marginally significant, and the negative result was clear,” he said. It’s difficult to figure out what to do with these mathematics, because while powerful medications may block the onset of psychosis, those medications have too many undesirable effects to be used on people who may just be presently grumpy, and we cannot now tell the difference.
Studies in England and Australia show that cognitive-behavioral and other nonbiological therapies can diminish or delay the onset of symptoms. Antioxidants and other neuroprotectants such as omega-3 fatty acids may delay the onset of psychosis without side effects. “It doesn’t seem to matter what the intervention is,” McGlashan said. “The psychocognitive behavioral intervention was just as good as medication. If you can keep them engaged, and relating, and challenging their symptomatic experiences, you can delay this crescendo into an acute psychotic episode. It could be that you are helping to prevent loss of learned connections in the brain.” The families of people at high risk of developing schizophrenia should learn what to watch for, and doctors should meet frequently with patients, since they can escalate to psychosis in a few days. While antipsychotics are not recommended until psychosis sets in, aggressive response to anxiety and depression is in order.
A strong movement to categorize the prodromal phase as its own illness in the DSM-5—the diagnostic and statistical manual that is psychiatry’s bible—as “psychosis risk syndrome” or “attenuated psychosis syndrome” was abandoned in the spring of 2012. The diagnosis would have given doctors protections and compensation for treating patients aggressively—but because the degree of psychosis risk in any individual is so difficult to quantify, the framers of the new DSM eventually determined that there was too much potential for unnecessary, stigmatizing, and harmful treatment. It makes sense that someone at risk for developing schizophrenia be treated with benign interventions and close monitoring, but the issue of stigma cannot be ignored, as it pertains to both self-image and medical insurance. McGlashan wrote, “The bottom line for me is that the psychosis-risk syndrome should be treated as a bona fide psychiatric disorder; it is real, and it can be very dangerous if ignored.” John Krystal, however, pointed out, “The earlier you are in any mental disease process, the less you know what you’re dealing with. Earlier intervention is almost always preferable and harder—sometimes so hard that it’s not preferable. What they do in the DSM is a fashion question, like skirt lengths. But we have a dichotomous medical system. Good clinicians will lie about their patients’
symptoms to get them insurance coverage and treatment if they seem to be sick, while poor ones will punish patients on this checklist basis.”
Even with early identification, it can be a challenge to sustain treatment over the life span. Lieberman tells of a patient he treated early in his career: “He was twenty-one years old, Ivy League school, top of his class, popular, athlete, seemed to be destined for greatness. He developed psychotic symptoms, and I diagnosed schizophrenia and gave him medication. He had almost complete remission. Then he wanted to go back to school, and he didn’t like the medication, so he stopped taking it. He became sick again, came back, we treated him, he improved, went back to school, and relapsed again. We treated him, and he made progress. Repeated again. The next time, he didn’t get better. He never recovered.”
• • •
George Clark is a physicist at MIT who works on theoretical astrophysics; he is both kind and almost entirely occupied by intellect. His wife, Charlotte, is capable of toughness after a tough existence, at once judgmental and sympathetic, as though it were her habit to find weakness everywhere around her and then forgive it. She has bright blue eyes behind wire-rimmed spectacles, snow-white hair neatly kept, and capable hands that she uses for punctuation when she speaks. They were both in their eighties when we met, and I saw with what gratitude George handed difficulty over to Charlotte.
When George and Charlotte married in 1980, each had a problematic daughter. George had Jackie, then nineteen, diagnosed with schizophrenia four years earlier. Charlotte’s daughter Electa, the same age as Jackie, was disjointed and bewildering, but would not receive a diagnosis for another eighteen years. Charlotte told me that George had had a harder time than she because Jackie had once been so promising, whereas Electa had been odd all along. “I knew the day I gave birth that she was different,” Charlotte said. “She was limp, like a bag of sugar.” Charlotte tried to be the same mother to this child that she had been to her other children, but the connection was effortful. “She was oblivious. Other children were afraid of her; they saw that something was strange there.” The family was living in Pakistan because Electa’s father was working for USAID. The older children thrived at the international schools, but at five, Electa couldn’t follow what was going on. A year later, her father was transferred to Jordan. She went to the American school in Amman, had a remedial tutor, and was coached by Charlotte. “By eight, she could read,” Charlotte said. “But she wasn’t interested; in fact, she wasn’t interested in anything.”
When Electa was nine, her father died suddenly of a heart attack, and Charlotte moved the family to Washington, DC. Electa was bullied in the local fourth grade; Charlotte put her in a special school, which helped briefly. By fourteen, she was out of control. “She was fucking, if you’ll excuse the expression, anybody who would, and she was flunking out,” her mother recalled. “So I sent her to boarding school. She was very unhappy there. I said, ‘I was unhappy when you were here. You have to graduate from high school.’ So she earned her GED. Then she said she would be a hairdresser. I thought, ‘Hairdresser?’ But she loved it and did well at it. Those were her best days. But slowly, slowly, she was going crazy.”
One bright October morning, Charlotte called Electa, then thirty-seven, and Electa said, “I can’t talk on the phone.” Charlotte said, “Come over and have a cup of coffee.” When Electa arrived, she said, “I can’t talk in the house.” So Charlotte said, “Let’s go for a walk.” Electa explained that she couldn’t talk on the pavement, either; she could talk only if they walked in the middle of the road. So they dodged cars while Electa explained that the Mafia at MIT was after George, and that he might be part of it. A few months later, Charlotte received a call: one of Electa’s friends had found her at the gym curled up in the fetal position, crying. The friend took her to the emergency room, where the doctors tried to do an EKG. Electa began screaming and thrashing and ended up in the psychiatric ward, where she finally received a schizophrenia diagnosis; she was also an alcoholic.
Over the following years, Electa’s psychosis was contained by medication, but she suffered endless side effects. Her weight ballooned to over three hundred pounds. “She can hardly walk,” Charlotte said. “She used to be the beauty of the family.” Her enunciation was slowed, and she slept long hours. She met another schizophrenic, Tammy, who became her romantic partner. Then after ten years on clozapine, Electa’s condition began to deteriorate in early 2006. “I remember saying to her, ‘You’re not taking your meds, are you?’” Charlotte recalled. “She said, ‘I don’t need my meds,’ in a very aggressive tone.” By October, she wouldn’t answer the door, and her phone was disconnected. Neither Tammy nor Charlotte could find out what was going on. “She had a credit card on my account,” Charlotte said, “and I yearned for the bill so that I could see where she had been and know that she was still alive, but when the bill hit ten thousand dollars, I had to cancel it.”
Charlotte finally convinced a judge to authorize the police to break in. “The sink was stopped up, and there was food all over the place and it was crawling with maggots. I had to go back to court twice to have her committed, and when she went to the hospital, they couldn’t even get her into a shower. Two nurses had to hold her down when they were washing her. But gradually the medication took hold. She began washing herself, and then she began being happy to see us.” Electa, now fifty, hasn’t worked since the breakdown. “She still can cut hair, but not as well as she used to,” Charlotte said. “I encourage her to cut my hair once in a while, and she cuts Tammy’s. It keeps some part of her alive.”
Charlotte and George were childhood friends long out of touch; when Charlotte was widowed and George was divorced, they were reintroduced. They deliberately bought a house that didn’t have enough space for Jackie and Electa to live with them. “Jackie had been beautiful, highly energetic, and popular,” Charlotte said. “She showed early signs of her father’s intellect. She was a brilliant flautist, and a champion chess player.” When Jackie was fifteen, the math that had come so easily to her a year earlier was suddenly incomprehensible, and George found that he could not explain to her the simple equations that she could once have explained to him. George went to see the chief therapist at MIT, who said that Jackie was schizophrenic. Jackie’s mother walked out on them both, leaving a marriage that was already in disarray.
When Charlotte and George got together, Jackie was nineteen and had just been evicted from a group home. “This was when I was deciding whether I wanted to live with George myself,” Charlotte said. “I decided I was up for it. Jackie was supposedly taking Thorazine. She was actually flushing it down the toilet. Over dinner the first night after I moved in, Jackie took a plate and threw it across the room. Nobody’s ever done that before or since at my table.” Charlotte began to lay down ground rules. Shortly after Jackie turned twenty, Charlotte told her to make her bed, and she blew up. George heard her shouting and came downstairs. “He’s very strong,” Charlotte said. “So is she. He took her by both wrists; she was spitting in his face. He kept holding her. Finally she said, ‘Dad, I don’t know what’s wrong.’”
A few months later, Jackie hitchhiked from Massachusetts to New York to surprise her estranged mother. When her mother asked her how the trip was, she said she was “only raped five times.” Charlotte said, “Of course, you never know what to believe. You don’t know what happened and neither does she.” In the years that followed, Jackie was in and out of mental hospitals, group homes, and other protective arrangements that varied with the fluctuations of her psychosis. Eventually, clozapine came along. “She’s very sweet, now that she’s medicated,” Charlotte said.
By the time I met Jackie, she was forty-nine and had been on clozapine for fifteen years, and she was living in a group home with seven other women. She spent her days at a day program that she referred to as “the club.” If her caseworker deemed it necessary, she was hospitalized for a few days or weeks. Unlike most schizophrenics, Jackie did not become ob
ese on antipsychotic medications. She plays tennis, swims a mile every day, and does yoga. She is antithetical to Electa’s melancholy sluggishness.
Every Saturday, Charlotte and George have Jackie and Electa over. Electa often brings Tammy; Jackie sometimes brings one of the other women from “the club” or the group home. “Thankfully, Jackie and Electa like each other as much as schizophrenics ever like anybody,” Charlotte said. “I don’t want to say I don’t want to be their mother anymore. But there comes a point when you’re eighty-one and should not have to be taking care of your children as if they were five-year-old tiddlywinkies. I’m not even convinced it’s making them happy. Electa remembers how it was to be well, which gets in the way of her being happy. Jackie is too out of it to be happy.”
I went to one of Charlotte’s lunches. Jackie was instantly engaged, intense and full of questions, while Electa was a manatee, vast, slow-moving, benign. Jackie substituted words for no particular reason, calling her car “my visa,” for example. She began lunch by reciting Rilke at a breakneck pace and without expression, but when Charlotte asked her to repeat the poems more clearly, she said, “I can’t; it’s too painful.” She told me proudly how she memorized poetry in the bathtub: “I recite to myself in cold water.” She talked persuasively about the importance of physical exercise in the treatment of mental illness, then added, “When I play tennis with my sister, I can tell when she’s cheating. She has this way of planning for the future. That’s cheating.”
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