BREAKTHROUGH

Schizophrenia Isn’t One Disorder but Eight

In perhaps the most important study in schizophrenia’s history, researchers have identified that it is not a single inherited disorder as previously believed, but rather eight separate genetic disorders.

09.16.14 9:45 AM ET

Schizophrenia is perhaps the most misunderstood mental illness, but a research team at the Washington University School of Medicine in St. Louis has just come one step closer to understanding how it works.

After analyzing the DNA of over 4,000 patients with schizophrenia, the investigators of the study have determined that schizophrenia is not a single inherited disorder as previously believed, but rather eight separate genetic disorders that can combine into “clusters” which carry significant risks for schizophrenia.

As senior investigator Dr. C. Robert Cloninger notes, “[genes] don’t work by themselves. They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact.” Rather than focusing on the individual genes that have been associated with schizophrenia, this team looked instead at the interactions between genes in order to isolate the causes of the illness.

In an audio interview, Cloninger observes that this multi-faceted etiology of schizophrenia matches the plurality and complexity of its symptoms: “There isn’t just this one kind of schizophrenia but actually several different syndromes where some people have positive symptoms like hallucinations and delusions [and] others have negative symptoms where they’re not able to think logically and these different syndromes are associated with different groups of genes.” Instead of looking for one gene that could account for all of the possible configurations of schizophrenic symptoms, Cloninger and his colleagues looked at the way in which different configurations of genetic variations produce different symptoms in individual patients.

Washington University’s new research could be the most important breakthrough in schizophrenia research since the illness was first diagnosed. Their findings hint toward new treatment possibilities for an illness whose symptoms are almost as difficult to alleviate as they are to understand. And the clarity of their discovery could finally put the persistent cultural myths surrounding schizophrenia to rest and help the public better understand this severe mental illness.

Early treatments for schizophrenia were as ineffective as they were dangerous. As Rachel Whitehead of Rethink Mental Illness writes for the Guardian, early 20th-century physicians treated schizophrenic patients with injections of sulfur and oil. In the 1930s and ’40s, physicians struggled to find a more tenable treatment. As an article in the Canadian Journal of Psychiatry notes, Swiss psychiatrists attempted to treat schizophrenia by inducing sleep for long periods of time, often resulting in pneumonia and death. Other psychiatrists attempted to treat schizophrenia with carbon dioxide gas and artificially-induced comas. In the 1950s, the first antipsychotic drug was invented and treatment for schizophrenia has revolved around the use of pharmaceutical drugs ever since.

Currently, schizophrenic patients are treated with a combination of antipsychotic medications (e.g. Clozapine) and therapeutic treatment, most notably cognitive behavioral therapy (CBT). While schizophrenia is much more treatable now than it was a century ago, antipsychotic medications still carry significant side effects. Clozapine, for instance, can lower a patient’s white blood cell count to dangerous levels, substantially reducing the body’s ability to fight infection. And as the National Alliance on Mental Illness (NAMI) notes, Clozapine is “hard on the body and causes a risk of diabetes, weight gain, myocarditis, and other medical concerns that need to be planned for.”

Potentially serious side effects aside, recovery from schizophrenia can take years of treatment. One study in the American Journal of Psychiatry found that “the overall rate of recovery during the early years of the illness is low,” with under 14 percent of subjects maintaining “full recovery criteria for 2 years or longer.” Another study, in the British Journal of Psychiatry, examined long-term outcomes, finding that only 16 percent of people with “early unremitting cases” of schizophrenia could recover in the later years of the illness. Both studies concur that the symptoms of schizophrenia are eminently treatable with around half of schizophrenic patients finding substantive relief from their symptoms, but “full recovery” remains an elusive and arduous task. Many people with schizophrenia will die from suicide and unnatural causes before they can complete or even receive treatment. As one review article in the Archives of General Psychiatry notes, nearly 5 percent of people with schizophrenia will die by suicide alone.

After a century of ineffective treatments, risky medications, and stalled genetic research, the new findings from Washington University could be an important step forward in treating schizophrenia. For one, the treatment of schizophrenia could be further individuated to match each individual patient’s needs. By sorting the patients in their study by their symptomatology, the research team at Washington University could identify which “clusters of genetic variations” led to which symptoms. As Dr. Igor Zwir notes in the Washington University press release, “it soon may be possible to target treatments to specific pathways that cause problems.” And as research into gene therapy for schizophrenia continues, Washington University’s findings will give researchers new pathways to pursue to target symptoms of schizophrenia. In the future, the Washington University study may mark the tipping point in the successful treatment of schizophrenic patients.

In addition to potentially revolutionizing the diagnosis and treatment of schizophrenia, this discovery could finally put to rest longstanding rumors about the causes of schizophrenia. Because past researchers typically looked for a single gene that caused schizophrenia, scientists knew that the illness was inherited but struggled to understand what other imbricating factors could account for it. The National Institute of Mental Health, for instance, observes that having a relative with schizophrenia significantly increases its risk but leaves plenty of room open for the influence of “environmental factors” such as malnutrition.

The Johns Hopkins Health Library, too, notes “many factors—genetic, behavioral, and environmental—play a role in the development of this mental health condition.” While environmental factors certainly play a role in the development of any genetic disorder—schizophrenia included—the continued mystery of schizophrenia’s genetic origins has perhaps left too much room open for rampant speculation about the sort of environmental factors that cause the illness.

Some still believe the mid-20th-century rumors that schizophrenia is caused by bad parenting, alcohol abuse, or other forms of trauma, so much so that many resources on schizophrenia still find it necessary to explicitly refute these myths. NAMI notes that 6 percent of people still believe that “people diagnosed with schizophrenia did something to cause their condition.” These myths about the causation of schizophrenia stigmatize it, allowing the public to willfully misunderstand it by blaming it instead on the families who suffer the most from its symptoms. Despite the fact that millions of people and approximately 1 percent of Americans have schizophrenia, misinformation about the illness promotes the belief that schizophrenia is the result of some sort of moral failing and not genetic variation.

And the ignorance that continues to surround schizophrenia actively compounds its treatment on a cultural level. As NAMI notes in a report on the perception of schizophrenia, the “lack of knowledge” surrounding schizophrenia constitutes a “public health crisis” inasmuch as investment in treatment options requires widespread public awareness about the disorder. Only a quarter of Americans feel as if they are familiar with schizophrenia, with only Lou Gehrig’s disease and multiple sclerosis ranking lower on the scale. A substantial percentage of Americans, too, still fear people with schizophrenia at work or in their personal lives even if they are undergoing treatment. NAMI believes that this “knowledge gap” must be closed to promote a culture in which people view schizophrenia as a treatable illness. If more people could recognize schizophrenic symptoms and openly care for those who suffer with schizophrenia, more people with the illness might seek treatment during the critical early stages.

The new research from Washington University could be influential in closing this knowledge gap, as it seems to be the most definitive information about the origins of schizophrenia uncovered so far. In a country where six times as many people believe false rumors about schizophrenia as suffer from it, the conclusive discovery of the genetic clusters that contribute to schizophrenia should finally start to bury past misconceptions about the illness. In addition to possibly transforming future approaches to the treatment of schizophrenia, Washington University’s recent findings could also finally give a misinformed public the clarity it needs to promote widespread understanding of this devastating mental illness.