George Francis William Ewens wasn’t the only physician trying to understand mental illness in the late nineteenth and early twentieth centuries. Doctors were just beginning to categorize the brain disorders that caused people to disconnect from reality.
For millennia, people who talked to spirits, or heard voices, or acted strangely because of thoughts they couldn’t control were called witches or demons. They faced cruel punishments and even crueler “treatments.” The first step toward modern understanding came in 1841, when a German doctor named Karl Canstatt coined the term psychosis—short for psychic neurosis, or brain disease. Canstatt was trying to connect problems in the brain with crises of the mind, to understand how misfiring neurons might lead to failures of thought.
In “Insanity in India,” Ewens offered as good a definition of mental illness as any:
Insanity is a disease of the brain causing an alteration or impediment of the mind, and by so doing altering a person’s conduct, speech, manner and habits from those of sane people or of himself prior to his illness.
But what caused the changes? Doctors couldn’t be sure:
Up to the present careful examination of the brains of most insanes after death has discovered nothing certain to which insanity can be attributed.
Still, Ewens was confident scientists would solve the puzzle:
Undoubtedly this is due to our defective powers of observation, and in all probability, it is only a question of time before such will be discovered.
More than a century later, Ewens’s optimism has proven unfounded. Understanding what is going wrong in a person suffering from psychosis is complicated enough. Fixing it is even harder. After all, consciousness itself exists within the brain; I think therefore I am. We laugh and run and fall in love thanks to the interplay of electrical impulses in our heads. They form our perception of external reality. People having psychotic hallucinations don’t lose their senses. But their brains overlay another layer of sight and sound atop the external stimuli the rest of us share. Those with delusions don’t stop thinking, but they can’t cross-check their thoughts against reality.
Rewiring the brain to undo those failures is far beyond us even now. Modern drug treatments for psychosis and schizophrenia are only moderately useful. Now called antipsychotics, they were originally known as major tranquilizers because they are more knockout drugs than anything else. They blunt hallucinations and delusions but rarely eliminate them. They do even less to help schizophrenia’s so-called negative symptoms, such as apathy and depression, or its cognitive symptoms. Besides everything else, schizophrenia damages memory and intelligence, and the losses grow with time. John Nash, the schizophrenic mathematician made famous in A Beautiful Mind, is very much the exception.
But when Ewens was practicing medicine, effective treatment wasn’t even a dream. Doctors were still working to classify mental illness. In 1893, a German psychiatrist named Emil Kraepelin coined the term dementia praecox—premature dementia—to explain why his patients suffered strange thoughts and visions in their teens and twenties.
A continent away from Kraepelin, Ewens was aware of the new term. In Insanity in India, he wrote, “There is a well-marked form of mental disease with special features termed by some Dementia Praecox.” He defined its symptoms:
A gradual change of disposition; a loss of activity and energy, the patient becoming silly, shy, irritable, obstinate and careless; unable to follow his occupation or, if it begins more rapidly, doing so usually with a period of depression, apprehension, and suspicion, with it may be a foolish attempt at suicide. The combination of this condition with some silly senseless delusion and hallucination, especially of hearing (more rarely of sight), being typical of the disease.
A modern psychiatrist would recognize a patient with those symptoms as having schizophrenia. Ewens didn’t use the term, because it hadn’t been invented yet. It first entered the medical lexicon on April 24, 1908, when a psychiatrist named Eugen Bleuler used it in a talk to the German Psychiatric Association. It meant “split mind,” and doctors rapidly adopted it for patients who had broken from reality.
Perhaps the most important characteristic of schizophrenia was the youth of its sufferers. As their peers were becoming adults, they lost their way. But even as children, before their symptoms bloomed into outright psychosis, they often seemed different. They might be socially maladjusted, intellectually impaired, or prone to violence. Sometimes they were all three.
Another defining characteristic was that treating schizophrenia was next to impossible. Early psychiatrists tried hypnosis, opiates and other drugs, and talk therapy. Nothing worked. Crueler treatments such as lobotomies or electroconvulsive therapy sometimes controlled symptoms for a while. But they rarely fixed the underlying disease.
Nonetheless, psychiatrists kept trying, because the pain psychotic disorders caused was so obvious, and because patients rarely improved on their own.
The schizophrenia diagnosis was useful, but it also proved problematic. It covered many symptoms. Some patients mainly had cognitive problems. They appeared more like people suffering from severe intellectual disability. Others had higher IQs but poor impulse control and a tendency to violence. They looked more like psychopaths. Still others fit the classic mode, with paranoia, delusions, and hallucinations.
Still, for lack of a better alternative, schizophrenia became the umbrella diagnosis psychiatrists gave people suffering from mental illness with psychotic features. Depression and manic depression—later called “bipolar disorder”—became the catchall diagnoses for people whose mental illness was centered around their mood. (Those lucky folks who were psychotic and depressed were called schizoaffective.)
Even though schizophrenia and psychosis went together, people could have psychotic episodes for many reasons, including tumors, strokes, and Parkinson’s disease. As Ewens noted, one reason that doctors were so convinced that diseases of the mind occurred because of problems in the brain was that “insanity follows sometimes on brain injury.”
Beyond physical trauma to the brain, extreme stress—such as being victimized by severe violence—could cause people to break from reality. So could manic episodes in which people went days without sleep, or even severe and long-term depression.
Drugs and chemicals, whether used recreationally or for medicinal purposes, could also make the brain go haywire. “All nations have some drug whose habitual use leads to dangerous consequences,” Ewens wrote in Insanity in India. He judged cocaine more dangerous to the brain than opium and noted that alcohol too could cause psychosis.
So, a single psychotic episode didn’t necessarily mean someone was schizophrenic. Over time, psychiatrists refined the diagnosis, recognizing its potential to stigmatize patients. Before calling a patient schizophrenic, psychiatrists had to rule out other potential causes. And the label should not be given quickly. A patient needed to have delusions or hallucinations that lasted months. Patients with less severe symptoms were called schizophreniform or schizotypal.
In other words, even experienced psychiatrists could argue over the diagnosis. One doctor might focus on psychotic symptoms and call a patient schizophrenic. Another might think the psychosis was secondary to a manic episode and say he was bipolar. Even now no blood tests or brain scans tell apart the diseases.
But by whatever name, people suffering from repeated psychotic episodes clearly needed treatment. From 1900 to 1950, that treatment came in the form of removal from the community and institutionalization. People with schizophrenia, severe depression, or bipolar disorder were permanently committed to state-run hospitals. To house them, Western nations went on a hospital-building spree. By 1955, the United States kept more than 550,000 patients in psychiatric hospitals, including 300,000 diagnosed with schizophrenia.
Some facilities were well managed and provided decent care. Others were little more than warehouses where desperately sick people moldered until they died. A few were worse, degrading patients and staff alike. But without effective medicines, doctors saw no alternative to long-term confinement.
Then, in December 1950, a French army surgeon looking for chemicals to reduce the physical stress of surgery discovered a compound called chlorpromazine. The new drug proved effective as a tranquilizer. In tests, it reduced body temperature and blood pressure, prolonged sleep, and made patients less anxious.
In this way, chlorpromazine was similar to older sedatives called barbiturates. But unlike barbiturates, it didn’t produce euphoria or dangerously slow patients’ breathing, so it was less likely to be abused or cause lethal overdoses. Physicians immediately saw its potential. It was first sold in France in 1952 under the name Largactil.
By then, two French psychiatrists had already discovered that chlorpromazine calmed their psychotic patients in ways that other drugs did not. It did not simply sedate them as barbiturates did. It actually reduced the intrusiveness of their hallucinations. In May 1952, they began to present their findings. The realization that the drug might offer a truly novel treatment for psychosis spread quickly.
Chlorpromazine’s influence in the United States was especially revolutionary. Influenced by Freud’s theories, American psychiatrists had tried for decades to cure schizophrenia with talk therapy. They had failed. Elite academic psychiatrists wanted to know if a patient was hallucinating because “of unconscious conflict over incestuous urges or stealing from his brother’s piggy bank at the age of five,” Time magazine snarkily wrote in March 1955. The correct answer: who cared? Unlike endless analysis, chlorpromazine actually helped psychotic patients.
Smith Kline & French, which sold the drug in the United States under the name Thorazine, wasn’t shy about saying so. One creepy ad featured an oversized eye and the line, “When the patient lashes out against ‘them,’ Thorazine quickly puts an end to his violent outburst.” Doctors reached for their prescription pads. Thorazine had $75 million in sales in 1955, its first full year on the market. In a 2005 history of chlorpromazine published in the Annals of Clinical Psychiatry, a Spanish psychiatrist called it “one of the greatest advances in twentieth-century medicine.”
Chlorpromazine’s success led pharmaceutical companies to introduce competing medicines with similar chemical structures and effects. The new drugs broke the grip of psychosis on patients. Keeping them hospitalized suddenly seemed unfair, unnecessary, possibly unconstitutional—and expensive. At first only a few patients were released, but year by year the momentum for deinstitutionalization grew. Books such as One Flew Over the Cuckoo’s Nest and investigative reports like Geraldo Rivera’s 1972 exposé of the filthy conditions at the Willowbrook State School, an institution for disabled children in New York, contributed to the pressure.
By 1980, the number of psychiatric inpatients had shrunk in the United States to 132,000—a 75 percent decline in just twenty-five years. Europe saw similar trends. Ultimately, Thorazine and its chemical cousins gave more than a million mentally ill people a chance to leave psychiatric hospitals.
Unfortunately, the drugs proved to be less than the perfect treatments they had seemed at first. They frequently caused ugly movement disorders. Patients involuntarily smacked their lips or jerked their arms and legs. The side effects worsened with time and could be irreversible. Patients also complained that the medicines did not so much end their psychoses as make them unable to care about their symptoms—or anything else. People taking Thorazine might no longer be delusional, but most still couldn’t work or have meaningful relationships. Some wound up more depressed than they had been when they were hospitalized.
As a result, many patients refused to take the drugs consistently. Being “off your meds” became popular shorthand for suffering mental illness. Patients would suffer a psychotic episode, be hospitalized, and be medicated until their symptoms resolved. Then they would be sent home with a pill bottle. But eventually they would stop their medicines, have another psychotic episode, and be hospitalized again.
Even worse, the drugs seemed to produce a sort of resistance in many patients.
By the mid-1960s, scientists had found that the drugs primarily bound to receptors in the brain that were activated by dopamine. Dopamine is a naturally occurring chemical that connects the brain’s nerve cells. Its release is related to desire and motivation, and it helps cause the feelings of pleasure that drugs, sex, and food produce.
Excessive dopamine release is also related to psychosis and schizophrenia, though scientists are still not entirely sure how. In the short term, Thorazine and other antipsychotics provided relief by blocking dopamine from attaching to neurotransmitter receptors. But some patients’ brains responded to the blocked receptors by producing even more of them—thus increasing their sensitivity to dopamine.
Those unlucky patients seemed to build up a tolerance to the drugs and required higher doses. But the higher doses could worsen side effects. And if patients stopped taking their medicines, they suffered what became known as rebound psychosis. In other words, cycling on and off the drugs could leave people with schizophrenia in worse shape than they had been before. Yet the side effects encouraged cycling.
In the 1990s, pharmaceutical companies introduced several new antipsychotic medicines to great fanfare. These became known as the “atypical antipsychotics” and became among the best-selling drugs in the United States. But studies showed the new drugs were generally no more effective than the older ones.
But even after doctors realized that antipsychotic medicines were not cure-alls, the move toward deinstitutionalization didn’t stop. Long-term institutionalization can cost $100,000 a year or more per patient. Few adults with schizophrenia have private insurance, so federal and state governments bear the cost. Managing patients in the community was far cheaper than leaving them institutionalized.
By 2015, the United States had fewer than 40,000 beds in psychiatric hospitals, a drop of more than 90 percent from sixty years before. Heavily supervised treatment in group homes made up some of the difference. Still, the drop represented a huge shift. Essentially, governments gambled that they didn’t have to lock people with psychosis away to keep them from becoming nuisances—or dangers. When they were wrong? Family members, neighbors, and even strangers paid the price.
• • •
Alongside the frustrating search for treatments for psychosis came an equally halting search for their causes.
From the first, scientists knew severe mental illness had a genetic component. Long before James Watson and Francis Crick discovered DNA, it was obvious that madness ran in families. Over time, researchers quantified the risk. A person with a schizophrenic parent had about a 4 percent chance of the disorder, compared to the 1 percent figure usually used for the general population. One with a brother or sister with schizophrenia had a nearly 10 percent chance. Identical twins were at much higher risk; if one was schizophrenic the other had an almost 50 percent chance of being so—even if the two twins were raised apart. That finding led scientists to say that roughly half the risk of schizophrenia was genetic.
Further research showed that calling the risk genetic wasn’t quite accurate. Identical twins didn’t just share genes. They shared the same womb, and prenatal factors also played a role in the disease. Children born to mothers who’d been undernourished or suffered a viral illness during pregnancy were more likely to be schizophrenic. Amazingly, even the season of birth seemed to matter. Large epidemiological studies showed that children born in the winter had a slightly higher chance of developing the disease. The difference was small but consistent across countries.
So, the 40 percent to 50 percent in-born risk of schizophrenia encompassed both genes and the prenatal environment. It represented the risk predetermined not from conception, but birth, an important distinction for researchers—though one that didn’t help people at risk. They couldn’t change their prenatal environments any more than they could swap out their genes.
In the 1990s, as scientists decoded the human genome—the strands of DNA that hold the information that eventually becomes us—psychiatrists hoped that they might find the genetic basis for that risk. But the genomes of people with schizophrenia or bipolar disorder didn’t contain a smoking gun. Some rare brain disorders, like Huntington’s disease, could clearly be linked to a single genetic mutation. But common mental illnesses were more like cancers, complex diseases that developed due to both genetics and environment. Like cancers, they were “associated with” dozens of genetic variations, not caused by one or two.
As for the other 50 percent to 60 percent of the risk, the cases that genes and prenatal biology could not explain? Clearly, those stemmed from factors after birth, whether in infancy, childhood, or adolescence. Every psychiatrist had a theory. People with schizophrenia were notoriously heavy cigarette smokers. But studies ultimately showed smoking resulted from rather than caused the disease. People with schizophrenia smoked because nicotine improved their alertness and lessened the side effects from antipsychotic drugs. Besides, most people with schizophrenia didn’t care much about smoking’s health risks. They had bigger problems.
Other psychiatrists noted that vitamin deficiencies seemed common in people with schizophrenia. Again, though, the relationship seemed to run the other way. Most schizophrenics ate badly—and sometimes wouldn’t eat at all if they believed their food might be poisoned.
Other theories were even more dubious. In the 1930s, ’40s, and ’50s, many psychiatrists blamed bad mothers for schizophrenia. (Yes, really.) Studies seemed to suggest that schizophrenic patients had mothers who were either “overprotective,” rejected them, or both. In 1948, the psychiatrist Frieda Fromm-Reichmann coined the term “schizophrenogenic” mothers. Mothers who rejected their children bred distrust that blossomed into paranoia, she theorized.
The theory persisted into the 1960s, despite growing evidence of the biological underpinnings of schizophrenia. Only when larger studies found no evidence that the mothers of people with schizophrenia had any particular parenting style—good or bad—did the theory mercifully wither.
“The theory of the schizophrenogenic mother (now) seems hopelessly mistaken, and more than a little embarrassing,” a 2013 article in the AMA Journal of Ethics proclaimed. But the article noted the theory still had negative effects. Its residue discouraged modern psychiatrists from discussing genuinely bad parenting decisions with the mothers and fathers of troubled children.
Researchers also looked at general environmental factors. Poverty and severe mental illness were highly connected. But epidemiologists found that poverty, like smoking, generally resulted from rather than caused mental illness. Most people with schizophrenia were unemployed and eventually slid into poverty even if they came from middle-class families.
Other studies consistently showed immigrants had higher rates of schizophrenia than native-born citizens. The immigration link remains tantalizing, but no one has fully explained it. In the United States, the fact that African Americans were more likely to be diagnosed with schizophrenia than white people led to fierce debate. Some researchers believed the gap reflected a true difference in disease rates. Others said that psychiatrists were simply more likely to label blacks, especially black men, as schizophrenic. White patients might be called bipolar with psychotic features—a diagnosis that carried less stigma. But even when psychiatrists used standardized checklists instead of relying on their own impressions to make diagnoses, the disparities remained.
A few researchers, usually psychologists or other nonphysicians, went further. They argued schizophrenia and psychosis were cultural constructs. Many patients didn’t actually want or need help, they said. In 2014, a monograph from the British Psychological Society claimed, “There is no clear dividing line between ‘psychosis’ and other thoughts, feelings and beliefs” and argued that people who didn’t want to think of themselves as being schizophrenic weren’t, not really:
Some people find it useful to think of themselves as having an illness. Others prefer to think of their problems as, for example, an aspect of their personality which sometimes gets them into trouble but which they would not want to be without . . .
In some cultures, experiences such as hearing voices are highly valued.
Those pleasant-sounding theories bore little relationship to the painful realities that many people with psychosis face. The monograph also stated—flatly and incorrectly—that “It is a myth that people who have these experiences are likely to be violent.” (Technically, they might not be likely to be violent, if likely is defined as “more than 50 percent,” but they are far more likely than healthy people.)
Of course, some people with mild schizophreniform disorder were indistinguishable from people who simply had strange ideas about alien civilizations or political conspiracies. As long as they could function, their odd ideas hardly mattered. But people who came to the attention of emergency room doctors or police officers almost by definition were not functioning.
And doctors didn’t need lectures on sensitivity to know they shouldn’t find people mentally ill for acting in ways that were culturally or religiously reasonable. A Haitian who believed in voodoo was no more psychotic than a devout Catholic who believed in the intercession of the saints. As George Ewens wrote in the introduction to his book:
Insanity in India is, of course, essentially the same as insanity anywhere else in the world, though its evidences equally, of course, are modified by the environment, habits and customs of the people.
Still, the fact that a society of British psychologists could argue in 2014 that schizophrenia might not even be real showed how little progress scientists had made since Emil Kraepelin invented the term dementia praecox. Despite a century of research, the disease’s causes remained murky and its treatments marginally effective. But the pain it caused to sufferers and their families was as severe as ever.
• • •
As they considered bad mothering, cigarettes, and vitamin deficiency, researchers also wondered if recreational drugs might cause schizophrenia. They knew stimulants like cocaine regularly provoked psychotic episodes. Opiates could cause delirium, though full-on psychosis seemed less common.
Along with the British asylum reports, letters about cannabis popped up in other scientific journals too. In 1908, for example, the Boston Medical and Surgical Journal published a report from a physician at a mining camp in Mexico. “My little camp of 700 or 800 is a perfect clinic of hysteria . . . caused by smoking a weed, growing abundantly in the hills, called ‘marihuana,’ ” he wrote. “[The] mania is extremely violent for two or three days, requiring enforced restraint: it is accompanied by hallucinations.”
In general, though, physicians assumed that drug-induced psychoses were temporary. In fact, for most of the twentieth century, no rigorous studies showed that marijuana could cause permanent psychosis.
The weakness of the science is less surprising than it might seem. Before the 1970s, cannabis use was rare in Europe and the United States. A 1969 Gallup survey showed that only 4 percent of Americans said they had ever tried marijuana. Like cocaine and heroin, the drug hardly existed outside of big cities. It was used primarily by minority groups, and a handful of whites who self-identified as members of the counterculture—most famously jazz musicians.
Further, most American marijuana at the time was quite weak, containing only 0.5 percent to 2 percent THC. Mexican sinsemilla was expensive and uncommon, and hashish even rarer. Under those circumstances, THC’s link to mental illness would had to have been incredibly strong for it to be visible on a population-wide basis.
So, the link between cannabis and mental illness remained scientifically unproven through the 1960s. Even so, lawmakers and their constituents agreed that cannabis, like cocaine and heroin, was a dangerous drug. In most states, selling even a few joints was a felony that could carry a long prison sentence—and dealing marijuana to a minor was theoretically punishable by death in some Southern states.
But that consensus was about to topple.