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Schizophrenia Prognosis: Debate Rages On

National comparisons may have yielded all the evidence they are going to, and epidemiologists must now "drill down" to the local and family levels to determine cultural mechanisms that impact on outcome.

Do patients with schizophrenia have a better prognosis in traditional cultures of the developing world?

Is abundance crippling? Or are the stronger social bonds believed to exist in traditional cultures a romantic fancy? Do the more advanced biomedical treatments available in the industrialized world trump those family and social bonds, in any case?

Is the epidemiological evidence about prognosis conclusive? Is it even consistent?

These questions have raised some dust in schizophrenia research circles—especially among the relatively small group of highly committed epidemiologists and anthropologists who have pursued these questions for years—following the online publication of an article in the September 2007 Schizophrenia Bulletin titled "Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World?" by Alex Cohen, Ph.D., Vikram Patel, Ph.D., R. Thara, M.D., and Oye Gureje, M.D.

Alex Cohen, Ph.D., says that to clearly delineate the effects of sociocultural factors, it is necessary to control for "exposure" to biomedical treatment. Photo courtesy of Alex Cohen, Ph.D.

Since then, the article, which was also the subject of an article in Psychiatric News (November 2, 2007), has prompted responses from a number of quarters appearing as commentary in the "advanced access" section of Schizophrenia Bulletin's Web site at <http://schizophreniabulletin.oxfordjournals.org/>. The original study by Cohen and colleagues will appear, along with the commentaries, in the print version of Schizophrenia Bulletin next month.

The debate has also been played out on Schizophrenia Research Forum at <www.schizophreniaforum.org/>. (The goal of this Web site "is to foster collaboration among researchers by providing an international online forum where ideas, research news, and data can be presented and discussed.")

If there is any resolution to the debate about prognosis in different cultures, it may be that comparisons at the national level have yielded all the evidence they are going to, and that epidemiologists must now "drill down" to the local and family levels to determine the cultural mechanisms that impact on outcome.

"I think the evidence supports the proposition that outcomes vary in different settings, but the nation is not the key to understanding the mechanism," William Carpenter, M.D., editor of Schizophrenia Bulletin, told Psychiatric News. "If the mechanisms that affect prognosis reside in the local culture—in the family or community setting—it would be good to understand what those mechanisms are so that we might know why some cultural settings are bad, good, or a little of both.

"We don't know if some local cultures are therapeutic or simply less adverse," Carpenter continued. "If the mechanisms were understood, they might translate into new clinical approaches to treatment."

WHO Studies Advanced the Field

In the September article, Cohen and colleagues reviewed literature and tabulated data from 23 longitudinal studies of schizophrenia outcomes in 11 low- and middle-income countries and examined evidence on the following domains: clinical outcomes and patterns of course; disability and social outcomes, especially focusing on marital and occupational status; and untreated samples and duration of untreated psychosis.

In general, and most strikingly, they found wide variation in outcomes from study to study and within countries. The finding challenged a long-held assumption—what Cohen termed "an axiom"—deriving from three prominent studies by the World Health Organization (WHO) that people with schizophrenia appear to have a better outcome in developing countries than in developed countries.

The three WHO studies are the International Pilot Study of Schizophrenia (IPSS), the Determinants of Outcome of Severe Mental Disorder (DOSMed), and the International Study of Schizophrenia.

Norman Sartorius, M.D., Ph.D., believes the high rates of chronic disability and dependency associated with schizophrenia in high-income countries suggest that "something essential to recovery is missing in the social fabric." Photo courtesy of Norman Sartorius, M.D., Ph.D.

Responses to Cohen's article—from Arthur Kleinman, M.D., John Strauss, M.D., Evelyn Bromet, M.D., Assen Jablensky, M.D., Norman Sartorius, M.D., John McGraft, M.D., and Julian Leff, M.D.—have agreed that prognosis across cultures is generally more complex than anyone's favorite theory. And most have congratulated Cohen for raising important research questions.

But Bromet cited methodological problems in the studies that Cohen and colleagues chose to review. And Leff, Jablensky, and Sartorius pointed to oversights by Cohen and his colleagues in the way they interpreted the WHO findings and vigorously defended those studies and the role of family and community bonds in schizophrenia outcome.

As for Cohen, he welcomes the debate and appears to be at home with scholarly controversy. But he acknowledges that he might have more explicitly recognized in his September publication the enormous role the WHO studies have played in advancing the understanding of cultural psychiatry.

"I was remiss in the review in not acknowledging the enormous importance of the WHO studies," he said. "Those studies laid the groundwork for the other research projects we reviewed on course of disease in low-income countries. That the WHO studies did this must be considered a great achievement."

But Cohen also stands by his findings, especially the failure to consider lack of access in the developing world to the kind of advanced biomedical treatments that are commonly available in the developed countries.

"Several of the commentaries raise important methodological issues about our review," he said. "But one issue that was not considered was the lack of attention to the effects of treatment in many of these studies—an issue that we raise in the review. To clearly delineate the effects of sociocultural factors, it is necessary to control for 'exposure' to biomedical treatment."

WHO Studies Oversimplified

But Assen Jablensky, M.D., and Norman Sartorius, M.D., who offered one of the most vigorous rebuttals to Cohen, said the September report erroneously described the methodology in the WHO studies and generally oversimplified their conclusions, imputing an "axiom" about better prognosis in developing countries that the WHO studies did not, in fact, uniformly find. Also, they asserted again that the role of culture in shaping disease outcome is a crucial contribution from the WHO studies.

"We do not argue that the prognosis of schizophrenia in developing countries is group-wise uniformly milder, or that the existing huge gaps in mental health service provision between high- and low-income countries are irrelevant," wrote Sartorius and Jablensky. "On the contrary, the erosion of social support systems, likely to be associated with the processes of globalization, should be a matter of grave concern.

"The sobering experience of high rates of chronic disability and dependency associated with schizophrenia in high-income countries, despite access to costly biomedical treatment, suggests that something essential to recovery is missing in the social fabric."

Sartorius led the WHO studies while director of the division of mental health at WHO, a position he held until mid-1993. Jablensky worked with the WHO studies and is now with the School of Psychiatry and Clinical Neurosciences at the University of Western Australia.

Sartorius told Psychiatric News that the study of long-term course and outcome of mental illness is a neglected area of research. "I also hope that the fact that there are differences of outcome will contribute to the willingness of readers to examine their practice and the system of care in which they work so as to identify factors that are important for the success of treatment," he said.

Need to Focus Locally

In his response, Leff, a British psychiatrist, M.D., echoed Carpenter's conviction that comparisons of outcome at the national level may be too gross a measure to yield any meaningful information about the effect of culture on outcome.

Rather, he said, investigators need to focus more closely on small family groups and stressed that research on the role of "EE"—expressed emotion, or the amount of criticism and anxious overinvolvement on the part of parents and family members of a patient—has been illuminating.

Leff worked in the London center of the IPSS and Carpenter and John Strauss, M.D., worked in the Washington center of the IPSS in the 1970s.

For instance, Leff noted that a family study in Chandigarh, India, in the DOSMeD study yielded powerful information about the role of expressed emotion, and that there were significant differences in the rates of high family EE—which is implicated in poorer prognosis—between rural and urban sites in Chandigarh, and nationally between industrialized and agrarian societies.

"The proportion of urban relatives of first-onset patients with schizophrenia who were rated as high EE was found to be 30 percent, while the comparable proportion for rural relatives was only 8 percent," Leff wrote. "A comparison across a wide variety of countries has shown that the prevalence of high EE households is greatest among the most industrialized and urbanized societies and least among rural agrarian societies.

"Recent research indicates that socioenvironmental factors are implicated in the etiology of schizophrenia as well as influencing its course," Leff wrote. "However, the role of these factors is unlikely to be elucidated at the national level. Focusing research on the local social environment for specific groups, particularly at the familial level, will prove more productive. The EE studies provide an example of the level of analysis that is likely to advance our understanding of cross-national differences in outcome."

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