DNA Analysis Shows That Schizophrenia Is Not One But Eight Genetic Disorders

It's pretty rare that mental health news lights up the ol' Facebook "trending" column—or that anything substantive does, for that matter—but the sharers of the world are way into schizophrenia this week. The reason: a new study probing the genetic roots of the disorder has found that schizophrenia traces to eight distinct gene clusters. Different combinations of activation within these clusters give rise to "harmonies" of psychopathology, and these different harmonies are the thing that we call schizophrenia.

The study, conducted by researchers at Washington University of St. Louis and published in the The American Journal of Psychiatry, looked at possible genetic influences among 4,000 schizophrenic subjects, parsing some 70,000 different genetic sites in the hunt for alterations to single units of DNA, aka "single nucleotide polymorphism." These individual changes aren't enough to predict the illness, but the study found that they can come together into clusters of interaction definitive enough to indicate anywhere from 70 to 100 percent risk for developing schizophrenia. In some, the disorder is unavoidable.

That schizophrenia is made from discrete components isn't terribly surprising. It's always been something of a "meta" or hydra illness. The shared factor in schizophrenia, the most general underlying feature, is what's often described as disordered thought, an extremely deep-rooted psychological noise. That's not a symptom though, and it's here that the illness diverges wildly.

The actual lived symptoms of schizophrenia come in clusters: some might experience delusions and paranoia, others deep withdrawal and lack of interest in the world or intense anxiety and depersonalization. One particularly brutal version of it leaves patients in a catatonic state, effectively frozen in their bodies.

Crucially, these symptom clusters can't really be attributed to varying degrees of schizophrenic severity (though that obviously factors in). It appears that some sorts of schizophrenia are just different than other sorts. There are schizophrenias, plural.

The WUStL researchers found that this traces all the way down to the genetic level. By splitting patients up by symptoms, it became clear that some gene clusters pointed at distinct symptom clusters. For example, one set of genetic features pointed toward delusions and hallucinations, while another pointed toward disorganized speech and behavior. "These disjoint genotypic networks were associated with distinct gene products and clinical syndromes, i.e., the schizophrenias, varying in symptoms and severity," the study reports.

And so there are eight of these distinct disorders—eight different pairings of altered genetic clusters and symptom clusters. This absolutely doesn't mean that schizophrenia doesn't exist, at least anymore so than the existence of different, radically distinct sorts of cancer suggest that cancer doesn't exist, or that different types of influenza suggest that the flu doesn't exist. What it does mean is that we've taken a dramatic step forward in the identification of new and more specialized schizophrenia treatments.

Imagine if there were just one or two sorts of cancer drugs. They work OK against a few types of cancer, really great against another, and all the rest you just find some middling effect. That's basically the state of schizophrenia treatment. Some clusters, such as delusions and hallucinations, can be treated quiet well. But many are basically untreatable, so far hopeless.

In the untreatable category, you'll find what are called negative symptoms. This class is roughly characterized as a profound, all-consuming disinterest in the world: flat emotions and motivation, inability to speak openly or experience pleasure. Differentiating schizophrenia and further understanding the interactions of gene clusters means better diagnostic ability and better targeted treatments.

"In the past, scientists had been looking for associations between individual genes and schizophrenia," explained Dragan Svrakic, a co-author and a professor of psychiatry at Washington University, in a WUStL statement. "When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don't act independently. They work in concert to disrupt the brain's structure and function, and that results in the illness."

The stakes are extreme. Schizophrenia is one of the most disabling health conditions out there. A full third of diagnosed patients will at least attempt suicide, according to the CDC, with a tenth likely to be successful. The unemployment rate of schizophrenics has been estimated to be as high as 80 percent. These things have everything to do with cycles of poorly-suited treatments and full relapses. Something has to have an answer, and it would seem that it's in our genes.