What Causes Schizophrenia? New Study Indicates Markers Can Appear In Teen Years

New research has made a major breakthrough in identifying the cause of schizophrenia. The study, published in Nature on Wednesday, suggests that schizophrenia may be caused by a genetic variation that affects brain development during adolescence. Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute at MIT, found the study’s results so promising that he said, “I’m a crusty, old, curmudgeonly skeptic. But I’m almost giddy about these findings.”

Schizophrenia is a chronic mental disorder that has a severely debilitating effect on how people think, behave, and process emotion. Symptoms of schizophrenia include hallucinations, delusions, problems with memory and clear thinking, and difficulty interacting with others. According to the National Alliance On Mental Illness (NAMI), schizophrenia affects one percent of people in the U.S., and although people of any age can be diagnosed with the disorder, schizophrenia usually begins to present itself in late adolescence and early adulthood. (In men, onset typically occurs from the late teens to early 20s, while onset occurs slightly later for women, in the late 20s and early 30s).

Previous research has shown that there is a link between the risk for schizophrenia and genetic variants in a section of human DNA responsible for the immune system. What wasn’t clear was how these gene variants could cause a disorder like schizophrenia. The authors of the new study, led by Steven McCarroll and hailing primarily from the Broad Institute, Harvard Medical School, and Boston Children's Hospital, found that people with the gene variants linked to schizophrenia have unusually high levels of C4, a molecule that serves the purpose of telling the immune system which molecules to “eat.”

According to New Scientist, C4 signals to immune cells in the blood which particles should be destroyed, but it serves a secondary purpose during brain development. Teenagers go through a stage called “pruning,” in which the immune system gets rid of underused synapses (aka the connections between neurons) in the brain. C4 is responsible for telling immune cells which synapses need to be pruned away. The researchers believe that when a person’s C4 levels are out of whack, they’re signaling the immune system to destroy too many of these neural connections. Neuroscientist Beth Stevens, co-author of the study, told The Washington Post, “They are tagging too many synapses. And they're gobbled up.”

This theory would help to explain two key aspects of schizophrenia that have previously resisted explanation: Previous findings from patient autopsies showing that people with schizophrenia have fewer synapses than normal, and the fact that onset tends to happen in late adolescence or early adulthood (not too long after the brain’s “pruning” stage occurs). McCarroll told the CBC,

It's always been a mystery: why then? Why not earlier and why not later? On some level, as a model or explanation, this makes much more sense because it connects the disease to a normal developmental process that … in about one per cent of the population, somehow goes awry or out of control.

Hyman described this research as “the most significant mechanistic study about schizophrenia ever.” As important as these findings are, however, it could decades before they lead to a potential cure for the disease. McCarroll says that this new insight into why schizophrenia occurs is nevertheless a huge step forward:

At least we know where to look. If you look at the areas where there are lots of effective drugs today, like cancer … there's a biological understanding that made it possible to develop new medicines.

For illnesses like schizophrenia, we've never had that understanding.

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