Prediction and Prevention

Genetic research may someday bring new treatments and understanding to psychiatric disease, but clinical researchers are already using other kinds of information about their patients to guide their treatment. Cobb professor of psychiatry Matcheri Keshavan, who is based at Beth Israel Deaconess Medical Center, says that the variability of schizophrenia is a major challenge. “No one patient is like any other in terms of how the disease behaves over time,” he says. Some people have a single psychotic episode and then recover. Some are able to manage the condition with medications, and go on to find jobs and start families. Others experience cognitive decline and are unable to function in society. What clinicians call schizophrenia, he says, is “probably a collection of multiple different syndromes, each of which might have a slightly different causation.”

One challenge to defining the illness is the lack of a “biomarker” that can be identified with a blood-draw or an MRI scan. Keshavan and other researchers are investigating strategies to use a combination of brain imaging, clinical tests, histories, and other techniques to stratify patients. Eventually, he hopes, this clinical effort will begin to connect with the emerging science of schizophrenia genetics, so that “down the road, we will able to identify a specific biological [schizophrenia] subtype which may have a specific causal factor.”

Schizophrenia runs in families, but is not solely a genetic disease. An identical twin of a person with schizophrenia, for instance, has a 50 percent risk of getting the disease, in spite of sharing all of their risk genes (a fraternal twin, in contrast, has only about a 15 percent risk). Environmental factors that have been associated with the disease include a history of abuse or neglect, cannabis use, having an older father, and growing up in a city.

Keshavan has been leading long-term studies on people with schizophrenia as well as young people at risk for the disease because of family history and other factors. The goal is to determine whether it’s possible to better predict who might develop schizophrenia, and if so, to intervene early to help with treatments, including cognitive therapy.

A family history of schizophrenia can be a heavy weight for individuals like David, a 22-year-old participant in one of Keshavan’s studies. His older sister began to have delusions about people being in contact with her, and was diagnosed with schizophrenia several years ago. Knowing his higher risk, David is careful to manage stress, eat well, and exercise. “I myself have had a lot of anxiety issues in the past, and have in turn put a huge premium on my health and wellness,” he says. His sister, meanwhile, has been able to hold a job and live a stable life thanks to medication. But the illness has been difficult for the family to speak about, he says: “The pain of the experience and the stigma surrounding mental health are so palpable.”

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