Could autism and schizophrenia be cousins? New research shows that people with schizophrenia have rare variations in genes that control brain development and that each person has a unique pattern of mutations. The finding is startlingly similar to new research on autism. Since April 2 is the first-ever World Autism Awareness Day, it's a good time to ponder what this odd conjunction says about building human brains—and, perhaps, how to fix them.
Tolstoy famously wrote that happy families are all alike, but that each unhappy family is unhappy in its own way. Thomas Insel, a psychiatrist who heads the National Institute of Mental Health, calls the new understanding that disorders like schizophrenia and autism have unique origins in each person a "Tolstoy moment" in mental health. Until very recently, the theory on diseases like these that run in families has been that people who get the disorders have the same genetic mutations. Scientists have spent years looking for a "schizophrenia gene" and an "autism gene," but the search has been frustrating. They have ID'd genes that make people susceptible to the disorders, but none of those genes are shared by enough people that they have proved useful for diagnosis or treatment. Given that, it's no wonder that activists in the autism and schizophrenia communities lose patience with scientists' fixation on genes and accuse them of slighting research on possible environmental causes.
In the past few years, scientists have started looking for disease genes in a totally different way. Using a new technique called whole-genome scanning to browse almost all of a person's DNA, researchers compared family members and other people with and without the disease, looking for shared patterns. They found that 15 percent of people with schizophrenia had rare deletions or duplications in their DNA, compared with 5 percent of people in the general population. The difference was even more pronounced in children with early-onset schizophrenia: 20 percent had mutations. "They're not random," says Insel. "They tend to cluster around genes that are important for brain development."
But the big surprise is that the variations differ so much from one person to the next. Each person, in other words, becomes schizophrenic in his or her own way. (There were similarities within families, however. In a group of children with early-onset schizophrenia, more than half of the children had inherited the genetic mutations from a parent.) This notion of a "personalized" disease—that there are many ways to end up with schizophrenia—is also, increasingly, how researchers are thinking about autism.
At first glance, autism and schizophrenia seem to have little in common. Autism shows up in early childhood and is characterized by problems with social interactions and communications, including understanding nonverbal cues or the inability to talk. Schizophrenia, by contrast, usually doesn't manifest itself until early adulthood. Its symptoms can include hallucinations and delusions but also what are called "negative symptoms": lack of emotion, inappropriate social skills, and impaired thinking. Both disorders can be disabling, and for each there is no known cause and no cure.
But Judith Rapoport, chief of the child psychology branch at the National Institute of Mental Health and one of the researchers, sees a similarity. She's spent the past three decades studying how children's brain development is affected by disorders like schizophrenia. The brains of children with early-onset schizophrenia are much larger than normal in the first few years of life, for instance. Children with autism also have an unusual amount of brain growth before age 3. In this new work, she and her colleagues found that two places where variations in genes tended to cluster in people with schizophrenia were also more common in people with autism. "We're very excited about the link to autism," Rapoport says. "You have to see these as risk factors, very intriguing ones."
Rapoport is convinced that there are more genetic links between schizophrenia and autism, and the researchers are now going through their data with a finer comb, looking for more correlations—and, perhaps, stronger clues as to where the brain's path goes so grievously astray. There's no insta-cure here, alas. But having a clearer view of what the genes are up to makes it more likely that genetic diagnoses and treatments could someday be created. It also could help move the debate from arguing over whether there are environmental triggers for autism to finding them and coming up with ways to protect people who are genetically susceptible.