It’s Been a Long Time Coming
It’s Been a Long Time Coming
From the Editor
No, I’m not talking about the Crosby, Stills, and Nash song, Long Time Gone, which opened the 1970 movie, Woodstock. That song, according to David Crosby, was written after the assassination of Robert Kennedy and thus is more a lament. What I’m talking about, for a change, is some very good news coming from several fronts—all of which has taken a very long time to arrive. And it’s not a case of “all good things come to those who wait.” These happenings took long-term perseverance and hard work from many, many people.
Many of you know about the findings of the Recovery After an Initial Schizophrenia Episode (RAISE) study, conducted by a research team led by John Kane in New York.1 This study looked at the long-term outcomes, as I’ve noted before, of patients with schizophrenia. The study’s robust main findings were that people who had multimodal treatment, including not only medications but also a suite of other interventions—such as psychological support, social support (eg, job training), and other psychosocial interventions—had better outcomes than those whose primary treatments focused on medication management.
Of course, such regimens cost a lot more on the front end of a long-term treatment program. What was not clear from the RAISE study, though, was whether the additional cost of the comprehensive treatment program was worth it.
A study led by Robert Rosenheck2 at Yale and newly published in Schizophrenia Bulletin found that the additional cost was indeed worth it in terms of improved outcomes, including quality of life. As reported in the New York Times the study found:
Using standard scales applied to other health care, like medications and operations, the team found that the new approach delivered about the same value of health benefits as other widely accepted treatments, like statin drugs to prevent heart attacks, Dr. Rosenheck said, and was more cost effective than many cancer therapies.3
It’s been a long time coming, and only discrimination against psychiatric disorders will keep this approach from being reimbursed.
But that isn’t the only good news about schizophrenia.
We’ve known for many years that during late adolescence and early adulthood, there is a normally occurring process of what has been called “pruning” of synaptic connections in the brain. This normally occurring process has been postulated to be related to removal of less important connections and strengthening of others so that brain processes can function more effectively during adulthood. Because the age of onset of schizophrenia correlates with the maximal age period of this pruning process, there have been suggestions that the illness reflects in some way the pruning process gone awry. The findings that the cortex of patients with schizophrenia is thinner than that of a matched unaffected group, first seen in research that revealed larger than normal ventricular size in schizophrenia, seemed to support that hypothesis. But if, how, or why that might be true was unknown.
Now, though, a new study published in Nature from a team at the MIT Broad Institute and Harvard led by Steven McCarroll4 may have opened a window into understanding what may be going on. Using a genetic analysis from 65,000 people—clearly a very large number, which gives the findings a great deal of power—the researchers found that if an individual had inherited a specific genetic variant in a gene called complement component 4 (C4), his or her risk of schizophrenia increased significantly. C4 has been well known to play a role in immune function, but the role of the gene in the pruning process was not known before this study. Details of this landmark work can be found in our cover story.
While this is an initial report, and while much work remains to better understand the role of C4 in the pruning process, as well as how the mutation related to increased risk distorts the pruning process and potentially produces the illness, this study represents an incredible breakthrough. Eventually, the ability to prevent the pathological effect of the genetic mutation by more targeted treatments, and to better identify those at risk for the illness, could flow from this research. It’s almost like science fiction, but, it’s real.