Comments on Online Discussion
Comment by: Digvijay Goel
Submitted 17 October 2007
Posted 17 October 2007
While the research issues raised by Cohen and colleagues are relevant/plausible, it is unlikely that any such study will ever be funded again. I am also unable to understand what will be gained by such research. Neither the pace, nor the direction of the social-economic-political changes taking place across the world are going to be influenced by psychiatric research, which has not been able to influence even mental health policy, as Norman Sartorius pointed out many years ago. This is an exercise in futility, and I am tempted to ask, so what?
The three reasons cited by the authors as justification for yet more, hugely costly, research in several repeatedly researched domains do not bear scrutiny. It is naive to believe that "identifying the processes that promote good prognosis," or "accurate information about the realities of the day-to-day lives of persons with schizophrenia" will ever inform national policy anywhere, least of all in low- and middle-income group countries where over a third of the population still live on less than a dollar a day and where the provision of safe drinking water and basic sanitation is still a distant dream.
As Prof Jeffrey Sachs stated in his hard-hitting keynote address at the launch of the Lancet Series on Global Mental Health, London 3 September 2007, mental health care remains unsatisfactory even in the most developed countries, despite vast volumes of research-based “evidence.” Even more breathtaking is the authors' assumption that "detailed understandings about how sociocultural and psychiatric processes interact" will help "prevent or at least limit the potential harm that may result" from the impact of globalization! In 1939, a group of several hundred psychiatrists from 30 nations had signed a noble manifesto on the prevention of war: "We psychiatrists declare that our science is sufficiently advanced for us to distinguish between real, pretended and unconscious motives, even in statesmen." (1)
I do not pretend to have even a fraction of the authors' academic and research credentials. I am also aware that anecdotal experience, such as I have, does not count for much in this evidence-based age. Having practiced psychiatry in India (where the patient was invariably brought in by the family, who also took full responsibility for treatment, and where there was huge pressure to seek/resume gainful employment owing to economic compulsions) for nearly 4 decades, and now having had the experience of working in
a “developed” OECD country (where the patient is invariably alienated from the family, with parents often obtaining legal orders prohibiting their progeny from coming within 500 meters of their house, where comorbid alcohol/substance misuse is common, and where liberal unemployment/sickness benefits act as disincentives to seek work) for the past 2 years, I have little difficulty in unpacking the “black box” of culture, or in subscribing to the impugned axiom, which has been subjected to a much more balanced
analysis by Isaac et al. in a recent communication (2).
While working as Mental Health Adviser in the Ministry of Health in India, I and my colleagues had, inter alia, used Jablensky's 1992 paper (3) to convince the policymakers that increased funding for mental health made even better economic sense in developing countries like ours. The result was a sevenfold increase in the mental health outlay during the 10th Five Year Plan (2002-2007). Now this flip-flop: “Sorry we were wrong
all along; schizophrenics fare much worse in India than in the west.” This is not to deny that questioning established dogma lies at the heart of the spirit of scientific inquiry. But the spirit of “consumerism,” which now seems to drive the research industry, feeds on a cannibalistic urge to erode the credibility of past research on the basis of ever-increasing methodological sophistry. This could eventually prove to be counterproductive and lose us whatever little clout we have at present with policymakers.
Father forgive them. They know not what they do.
1. Wedge B. Psychiatry and international affairs.
Science. 1967;157:281-285. Abstract
2. Isaac MK, Chand P, Murthy P. Schizophrenia outcome
measures in the wider international community. British
Journal of Psychiatry. 2007;191 (suppl.5o): s71-s77
3. Jablensky A, Sartorius N, Ernberg G, Anker M,
Korten A, Cooper JE, Day R, Bertelsen A.
Schizophrenia: manifestations, incidence and course in
different culture. A World Health Organisation Ten-
Country Study. Psychological Medicine 1992, Monograph
Supplement 20, Cambridge University Press, Cambridge.
View all comments by Digvijay GoelComment by: Amresh Shrivastava
Submitted 19 October 2007
Posted 24 October 2007
Outcome of schizophrenia in India
Responding to the conclusion in the present meta-analysis, which questions that schizophrenia may not have a good prognosis in developing countries, I seem to agree with the evidence.
Before any other point, the question that needs to be examined is, what is “developing country” in the context of outcome? And why should the outcome be any different, considering the etiopathology of schizophrenia and available treatment?
India is, as we believe, a developing country and may figure by some criteria largely undeveloped, while by other criteria it is quite advanced.
Western/developed countries also have seen good outcomes in schizophrenia recently, particularly in the areas of early psychosis studies and first episode psychosis.
We need to be careful about very old studies of schizophrenia conducted when the concept of diagnostic classification was evolving, whether that influenced the studies, and whether old and new studies are comparable at all.
Indian society is full of diversities and very complex. By and large, it is understood that awareness of mental illness is still poor, identification very late, treatment availability and accessibility continues to be a problem, manpower is short, psychosocial intervention is absent, and whether studies reflect ground reality is a major issue.
There is hardly any difference in recent studies of India and the West in terms of outcome after more advanced treatments are available.
To divide the world into developed and developing for studying outcome does not make much sense, because geographical location is not a determinant of disease in strict biological terms. Social changes and prevailing conditions do influence outcome, but Western countries do have their share of socially compromised populations. Homeless schizophrenics in the USA are not news.
The question certainly needs to be examined, but by parallel, good, similar design studies, and not by comparing the non-comparables.
While people in Indian society may be more tolerant, supportive, and more involved, there is a high level of organizational and governmental support and care in the Western world for schizophrenia and mental illness.
We can only compare if similar treatment facilities are put in place and the sample has a similar duration of untreated illness. And we should also study the parameters of social reintegration of the mentally ill.
View all comments by Amresh ShrivastavaComment by: Nirmala Srinivasan
Submitted 24 October 2007
Posted 1 November 2007
I am delighted to share my comments on this topic in my dual capacity: as an activist from the caregiver consumer lobby, and also as a professional in social sciences person, with rich research experience. I am in ground zero and hence contact with reality is unavoidable. I know of families who can afford $300 to $400 a day for aftercare facilities—these may be the Rockefellers of India. At the other extreme, less-than-a-dollar-a-day families have no access to medication and wander homeless. I know of patients living in positive family environments but with very poor outcomes. The reverse is the amazing case of patients from highly dysfunctional families with fair if not good progress. So the genetic factors play a decisive role; while we must give due credits to other factors, we cannot use the myopic developed-developing dichotomy in a scenario characterized by global flow of capital. As a famous Marxist economist mentioned, we have circles of development engulfing the global economy.
In that sense, I appreciate the comments of Dr. Amresh Srivastava. Family is no doubt the backbone of support as of today. But due to compulsions of global economy, migration is affecting the Indian family system. Combined with lack of policies, public care institutions and supportive legal systems, the void left by the withering away of the family is going to take a heavy toll on our mental health status. Hence while the West is good for political backup, India is sitting on a time bomb with treatment not available to 90 percent of persons with mental illness. I had to file public interest litigation in the Supreme Court and in our Provincial Court to move the government to do what is its basic commitment to ensure right to life and health enshrined in the Constitution of India. There are a few patients who are able to afford imported depot injections of risperidone; many others live on local medicines at times beyond expiry dates. Who does better depends more on the genetic rather than on external support systems. For the genetic factors to be set on track, let us follow some public mental health care models followed in the West. The debate about patient outcomes in developing vs. developed countries is not only inconclusive but also redundant.
View all comments by Nirmala SrinivasanComment by: Jonathan Burns
Submitted 2 November 2007
Posted 5 November 2007
Developing world poverty, inequality, violence, and social fragmentation are not good for outcome in schizophrenia!
The WHO studies concluded that course and outcome of schizophrenia was better in developing countries. This has become psychiatric lore. However, the reality is that significant political, social, and economic ills that characterize many countries in Africa, Latin America, and Asia constitute psychosocial stressors that mediate strongly against recovery. Economic and social underdevelopment translates into inadequate or even no access to mental health services for many patients with schizophrenia. In many regions, no services exist at all, or where they do exist, they are desperately poor. For example, throughout Africa the majority of patients have no ready access to novel antipsychotics and the prevalence of tardive dyskinesia is shockingly high. Stigma, too, abounds in the developing world—employers and communities are not tolerant and benevolent toward individuals with mental illness.
The belief that community and family life in the developing world is widely intact and that it provides a nurturing environment that facilitates recovery and promotes social and economic empowerment of the mentally ill is a myth. It is a dangerous and paternalistic myth. Continued idealization of the underdeveloped South as a haven for schizophrenia sufferers will only add to the already heavy burden experienced by these individuals, their families, and these societies in coping with this disabling disease.
If anyone is interested in putting together a collaborative multisite study of schizophrenia outcome in the developing world, e-mail me your suggestions.
View all comments by Jonathan BurnsComment by: Patricia Estani
Submitted 3 November 2007
Posted 20 November 2007
I think it is mostly impossible to compare the two samples that the article’s study compared. The definition of the variables are poorly operative, so that the comparisons are confused. The most salient example is the variable of the relationships between the occupations of the patients, the outcomes of these patients and the occupations in the developed and in the developing countries.
The study mentions the occupational demands of the recovered patients with schizophrenia in the developed and in the developing countries. The article concluded that the outcomes of the patients are better in the developing countries because the occupational market is more favorable to these patients. But, this is not possible to conclude. The social and occupational market is less demanding in the developing countries. The subject is less occupied or the subject has less work, so the prognosis could be better in this wrong sense, but this is not really a better prognosis.
In this sense, this is not only NOT a measure of a good outcome, but is a measure of a very poor outcome. This is valid not only for patients with schizophrenia but also for any patient with any mental disorder. Thus, the conclusions are very weak and it is necessary to explain which type of variables the study is based on and if these variables really mean better outcomes or artificial better outcomes. More valid data must be included in these kinds of inter-social or inter-cultural studies, and I think these data must be more precise and experimental.
View all comments by Patricia EstaniComment by: Arthur Kleinman
Submitted 17 December 2007
Posted 17 December 2007
Reprinted courtesy of Schizophrenia Bulletin
Kleinman A. Commentary on Alex Cohen et al.: "Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World" Schizophr Bull. 2007 Dec 3; [Epub ahead of print].
In the 1950s, ’60s, and ’70s, the field of cross-cultural (or transcultural) psychiatry provided what was largely Euro-American psychiatry with several useful alternatives. Based on limited research, it balanced the near hegemonic American and British research materials and conclusions with data from the non-Western world, and with new findings about established psychiatric disorders that challenged diagnoses, programs, and treatments. Cultural psychiatry still provides those contributions, but psychiatry itself has changed. We are now in an era of global psychiatry, where psychiatrists from Asia, Latin America, and Africa are contributing numerous studies on mental illness and mental health care, and these are now becoming part of psychiatric science. Not surprisingly, over the past few decades, studies of depression, suicide, psychosis, and substance abuse in a wide range of societies have greatly increased. One outcome of this increase is that we now have a much more detailed and complex view of these conditions in different socioeconomic, cultural, and political settings.
The review by Cohen et al. needs to be understood in this context of globalization. They show that the data about the course and outcome of schizophrenia are much more complicated for all societies, but especially for poor and middle income societies. They conclude that one of the conclusions of the past—namely that schizophrenia has a better outcome in those societies compared with rich nations—needs to be reconsidered. And they bring a substantial body of data to bear on that process of reassessment, along the way pointing to the deep processes of family responses, work conditions, stigma, and adult mortality, about which much more needs to be understood. I am persuaded by their comments and find their conclusion well reasoned and reasonable.
Cohen has made a career of criticizing World Health Organization (WHO) studies of schizophrenia. And many of his concerns are important. Readers need to balance the questions he and his distinguished colleagues raise with the conclusions of the WHO studies' authors. Given that we do not know the cause of schizophrenia, that many suspect it contains multiple distinctive conditions, that research on treatment has been controversial, and that the course of psychosis has been shown to be influenced by many factors, it is impressive to begin with that there is a strong cross-cultural hypothesis in the field. This hypothesis and this article's criticism have contributed, in my view, to move the field ahead conceptually and empirically. That there is still uncertainty, confusion, and controversy is a sign of how very much more we need to learn. But let us also celebrate how far we have come. What we now know about the course of schizophrenia appears to argue against any simple conclusion. The still dominant view in psychiatry that schizophrenia is a disorder of progressive, unrelenting deterioration is not supported by long-term outcome studies, even in North America. The view that schizophrenia has a more favorable outcome in poorer societies now also appears less certain. And this should lead to a more complex and sophisticated appreciation both of the biosocial course of the group of psychotic conditions that constitutes schizophrenia and of the diverse research perspectives in psychiatry that wrestle with how to make context as important as condition in the understanding of outcome.
This sense of progress in our cross-cultural understanding of mental illness can also be illustrated by other early formulations that have been proved inaccurate or inadequate. For example, when the first set of WHO studies concluded that outcome was better in low-resource societies, it was proposed that those societies were more sociocentric than psychocentric industrialized societies, and therefore outcome might reflect greater family and community support systems wrong. We have learned over the years that virtually all societies contain both strong interpersonal ties and individualistic orientations. While family connections may seem stronger in certain poor societies with powerful cultural supports for patriarchy, they have been shown to be as much a source of stress as support. The same holds for stigma. Stigma about serious mental illness seems to exist almost everywhere. Its sources and patterns may differ but its consequences for the mentally ill are terrible in rich and poor societies alike. Societies cannot be categorized as high support or low stigma. The social processes involved in the course of chronic illness are no more easily stereotyped than ethnicity is. No one can believe today that all Chinese act one way, all Americans another. Intraethnic and intrasocietal diversity is large. And this means, we need a more nuanced and complex modeling of social processes just as we require a more subtle and precise understanding of symptoms and syndromes. That recognition represents the kind of progress in cross-cultural psychiatric understanding that our improving understanding of course and outcome of schizophrenia also represents.
View all comments by Arthur KleinmanComment by: John McGrath, SRF Advisor
Submitted 21 December 2007
Posted 21 December 2007
Reprinted courtesy of Schizophrenia Bulletin
Dissecting the heterogeneity of schizophrenia outcomes
Goethe believed that data are the natural enemy of hypotheses. As new data accumulate, only a few lucky hypotheses survive the fresh empirical onslaught. Over time, most hypotheses eventually need amendment or outright rejection. Schizophrenia epidemiology has been a particularly fertile field in recent years, with new data leading to the revision of several long-standing dogmatic beliefs (McGrath, 2005; McGrath, 2006; McGrath, 2007). The target article by Cohen and colleagues (Cohen et al., 2007) questions another of the oft-repeated tenets of schizophrenia epidemiology. After close inspection of the schizophrenia outcome studies based in low- and middle-income countries, the authors reject the notion that outcomes in these sites are superior to comparable published data from high-income countries (Hopper and Wanderling, 2000). It is curious that the hypothesis related to economic status captured the attention of the research community at the expense of the more general finding to emerge from the WHO study, which was that clinical outcomes varied widely within and between sites, regardless of economic status (Jablensky et al., 1992). The review by Cohen and colleagues reminds us that crude ecological variables related to national economic status do not seem to help untangle this heterogeneity.
In recent decades there has been a substantial research effort focused on the identification of the onset of psychotic disorders (Yung and McGorry, 1996; McGlashan, 1998). However, we still struggle to understand the offset of schizophrenia (Saha et al., 2005). Categorical outcome measures (e.g., recovered versus persistent illness) are not readily operationalized for chronic disorders such as schizophrenia. Dimensional symptom outcomes (e.g., positive or negative symptoms) and more “downstream” measures of disability (e.g., employment, social functioning) tend to fluctuate over time, and show divergent trajectories. Compared to measuring incidence, prevalence, and mortality, the assessment of clinical outcomes in schizophrenia is much more of a challenge (Hafner and An der Heiden, 2003; Andreasen et al., 2005).
Apart from the multidimensional nature of outcome measures, there are methodological concerns about how best to compare results from studies with different intake criteria, and different durations of follow-up. With respect to intake criteria, outcome studies can be based on (a) incident case or (b) mixed incident and prevalent cases. Prevalent cases are enriched with those with chronic illness and depleted of those who have died. The target article draws attention to the potential for differential between-site mortality to bias assessments of clinical outcomes. A recent systematic review of mortality in schizophrenia found prominent variation between sites; however, there was no significant difference in standardized mortality ratios between sites when sorted by economic status (Saha et al., 2007). While thought-provoking, these and related ecological analyses based on economic status (Saha et al., 2006) should be treated cautiously, because of the relative lack of data from low- versus higher-income nations.
With respect to duration of follow-up, studies can measure outcome at widely different time intervals (e.g., 5 versus 25 years). Outcome measures are usually provided as “percent recovered” or proportions describing other outcome-related measures. However, is it valid to compare “proportions recovered” between studies with different durations of follow-up? Solutions such as annualized remission rates are also suboptimal (e.g., if 20 percent of a sample achieves remission criteria at 10 years follow-up, the annualized remission rate = 2 percent). This derived measure assumes that the chance of recovery is evenly distributed over time, which is an unlikely scenario for any disease.
Because we do not expect that schizophrenia outcomes will obediently map onto geopolitical boundaries, within-nation differences should also be studied alongside between-nation differences. Sites can compare the relative influence of factors known to influence the chance of remission (e.g., sex, age of onset, duration of treated and untreated psychosis), and also explore the impact of risk factors such as urban birth and/or residence, migrant status, and neighborhood-level variables related to social capital. The contours of schizophrenia epidemiology within nations may be more informative than previously appreciated (McGrath, 2007).
The take-home message from the target article is that clinical outcomes in schizophrenia are heterogeneous (as is the case for incidence [McGrath et al., 2004], prevalence [Saha et al., 2005], and mortality [Saha et al., 2007]). The heterogeneity in these estimates mirrors the marked clinical and neurobiological heterogeneity of the disorder (Tamminga and Holcomb, 2005). Cultural and socioeconomic factors would contribute to the variability in outcomes via many different pathways. Less widely canvassed, underlying genetic differences between groups may also contribute to differences in both the risk of schizophrenia and the clinical outcome. The HapMap project has demonstrated that our species shows between-group genetic variations, and while there is substantial variation within geographically-defined populations, there remains between-group differences that reflect ancient geographical origin (Tishkoff and Kidd, 2004). Some of these variations have been linked to disease susceptibility (Balaresque et al., 2007; McGrath, 2006). With respect to clinical outcomes, evidence from other chronic disorders suggests that the genetic factors that predict recovering from an illness may differ from those genetic factors that increase susceptibility to that disorder (Spitz et al., 2005; Waters and Nicoll, 2005). This may also be the case for clinical outcomes in schizophrenia.
Finally, the paper by Cohen and colleagues is timely. Understanding the interactions between incidence, prevalence, mortality, and remission underpin the calculation of the Disability-Adjusted Life Year (DALY), a metric increasingly used to prioritize health service delivery (Murray and Lopez, 1996). Detailed population-based estimates for clinical outcomes will be required for the next Global Burden of Disease study (Lopez, 2005; Murray et al., 2007). The target article by Cohen and colleagues provides a useful resource for this exercise, and should galvanize more empirical research in the field of schizophrenia outcomes.
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McGrath JJ. Variations in the incidence of schizophrenia: data versus dogma. Schizophr Bull Jan 2006;32(1):195-197. Abstract
McGrath JJ. The surprisingly rich contours of schizophrenia epidemiology. Arch Gen Psychiatry Jan 2007;64(1):14-16. Abstract
Cohen A, Patel V, Thara R, Gureje O. Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World? Schizophr Bull Sep 28 2007. Abstract
Hopper K, Wanderling J. Revisiting the developed versus developing country distinction in course and outcome in schizophrenia: results from ISoS, the WHO collaborative followup project. International Study of Schizophrenia. Schizophr Bull 2000;26(4):835-846. Abstract
Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, Day R, Bertelsen A. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. Psychol Med Monogr Suppl 1992;20:1-97. Abstract
Yung AR, McGorry PD. The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophr Bull 1996;22(2):353-370. Abstract
McGlashan TH. Early detection and intervention of schizophrenia: rationale and research. Br J Psychiatry Suppl 1998;172(33):3-6. Abstract
Saha S, Chant D, Welham J, McGrath J. A Systematic Review of the Prevalence of Schizophrenia. PLoS Med May 2005;2(5):e141. Abstract
Hafner H, An der Heiden W. Course and outcome of schizophrenia. In: Hirsch SR, Weinberger DR, eds. Schizophrenia. Cambridge: Cambridge University Press; 2003:101-141.
Andreasen NC, Carpenter WT, Jr., Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry Mar 2005;162(3):441-449. Abstract
Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry Oct 2007;64(10):1123-1131. Abstract
Saha S, Welham J, Chant D, McGrath J. Incidence of schizophrenia does not vary with economic status of the country: evidence from a systematic review. Soc Psychiatry Psychiatr Epidemiol May 2006;41(5):338-340. Abstract
McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med Apr 28 2004;2(1):13. Abstract
Tamminga CA, Holcomb HH. Phenotype of schizophrenia: a review and formulation. Mol Psychiatry Jan 2005;10(1):27-39. Abstract
Tishkoff SA, Kidd KK. Implications of biogeography of human populations for 'race' and medicine. Nat Genet Nov 2004;36(11 Suppl):S21-27. Abstract
Balaresque PL, Ballereau SJ, Jobling MA. Challenges in human genetic diversity: demographic history and adaptation. Hum Mol Genet Oct 15 2007;16 Spec No 2:R134-139. Abstract
McGrath JJ. The romance of balancing selection versus the sober alternatives: let the data rule (Commentary on Keller and Miller),. Behavioural and Brain Sciences 2006;29(4):417-418.
Spitz MR, Wu X, Mills G. Integrative epidemiology: from risk assessment to outcome prediction. J Clin Oncol Jan 10 2005;23(2):267-275. Abstract
Waters RJ, Nicoll JA. Genetic influences on outcome following acute neurological insults. Curr Opin Crit Care Apr 2005;11(2):105-110. Abstract
Murray CJ, Lopez AD. The Global Burden of Disease. Boston: Harvard School of Public Health; 1996.
Lopez AD. The evolution of the Global Burden of Disease framework for disease, injury and risk factor quantification: developing the evidence base for national, regional and global public health action. Global Health Apr 22 2005;1(1):5. Abstract
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View all comments by John McGrathComment by: John Strauss
Submitted 8 January 2008
Posted 8 January 2008
Is Prognosis in the Individual, the Environment, the Disease, or What?
This wonderful title was suggested by Will Carpenter. It
provides a perfect context for considering the problem of
prognosis in general, and more specifically, the report by
Cohen et al. on the question of cultural differences in
Often unrecognized currently, prognosis has for centuries
been one of the foundations of scientific medicine.
Hippocrates, Sydenham, and in psychiatry, Kraepelin,
utilized prognosis as the basis for identifying disease processes.
This contrasted strongly with the tendency to use
the clinical picture or ‘‘syndrome’’ at one moment in time
as the basis for defining various diseases. In fact, Kraepelin
put together three very different syndromes, considering
them one disease (dementia praecox) because of what
he believed to be their common inexorable downhill
course. Aside from its use for identifying disease processes,
prognosis also serves as a basis against which
treatment effectiveness can be measured and for identifying
healing processes. In fact, prognosis demonstrates
how the use of a longitudinal perspective can provide
one of the major ways of understanding many major
aspects of disease and disorder.
And what a neat idea that is! In the medical world
where the striking syndrome ‘‘dropsy’’ (generalized
bodily swelling) was shown over time actually to represent
several very different pathological processes involving
the kidney, heart, or other organs, the dependence on
syndromes alone to identify separate diseases was shown
to be grossly inadequate and often misleading. Perhaps, it
is because of the power of prognosis and its serving as
a base for so many of our medical concepts that there
has been so much resistance to recognizing that “schizophrenia”
(derived from Kraepelin’s original concept of
dementia praecox) in fact has a diverse range of courses
and outcomes. Since our early report on this diversity
over 30 years ago using measures of demonstrated reliability,
there have been well over 20 studies carried out
in many different centers showing the prognostic diversity
of schizophrenia no matter the choice of diagnostic
criteria, the measurement techniques for defining outcome,
or the length of follow-up. Even Kraepelin who
was an excellent observer raised a question about his theory
at one point. Nevertheless, many mental health professionals
continue to be taught and to believe that
schizophrenia is invariably chronic and very often
involves an inevitable deterioration. Incredible!
No, the desire for a simple model of prognosis in
schizophrenia, as laudable as that might be in the abstract,
has not been confirmed by scientific study. So,
where did we go wrong? And, more specifically regarding
the report of Cohen et al., what can we learn from cross-cultural
studies about the determinants of and the issues
involved in understanding the course and outcome of
To begin at the beginning, what might account for the
diversity of outcome that has been found? Biological factors
such as genetic differences of course may play a role.
But there is little data to suggest exactly how that might
operate. Environmental factors perhaps? And this is
where the international studies have been particularly important
with their suggestions regarding cultural differences.
Of course, once we let in cultural factors, the
way is open for other environmental factors, social class
as was suggested in the 1950s and 1960s, and another variable
that became politically incorrect in the 1970s, family
environmental factors. There are other potential environmental
factors as well, such as the availability and efficacy
of treatment and rehabilitation, programs
focusing on ‘‘recovery’’ and reinsertion into the community,
employment, and housing possibilities, etc.
One variable strikingly lacking from these more traditional
biological and social considerations is the possible
role of the individual in affecting the course and outcome
of disorder. This variable, too, can be ‘‘politically incorrect’’
either from the point of view of the danger of
‘‘blaming the patient,’’ for example, if he or she does
not improve or from the deviation involved in considering
the patient’s role from a narrow, sometimes considered
‘‘more rigorous,’’ version of the medical model. That
narrow version suggests that the disease, and perhaps
treatment and environment, more or less alone are the
key factors in determining prognosis. My own unrecognized
acceptance of such a narrow version of the medical
model was first severely challenged when a patient who
was a subject in a longitudinal study we were conducting
suddenly said to me, ‘‘Why don’t you ever ask me what I
do to help myself?’’ Subsequently Alan Breier and
Strauss (Breier and Strauss, 1984) began to try to answer that question, and it continues
to be a focus of my efforts (e.g., Strauss, 1996; Strauss, 2007) because it
appears to me to be such an important part of understanding
of the processes of disorder and their prognosis.
In considering the possibility of cross-cultural factors
in the report by Cohen et al., we focus on the social realm
of the triad, biologic, social, and personal. The report
demonstrates that in understanding social factors, the
problem begins with measurement and the interpretation
of that measurement. In the International Pilot Study of
Schizophrenia (IPSS), which marked one of the earliest
systematic cross-cultural investigations, anthropologists
who consulted to the study such as William Caudill
were concerned that we were not paying sufficient attention
to the assessment of cultural variations even at the
syndrome level. The primary goal of the IPSS, however,
was to discover whether we could identify ‘‘similar’’ manifestations
of a disorder schizophrenia, suggesting that
such a disorder actually existed in different cultures.
For the organizers led by the principal investigator
Tsung-yi Lin, it seemed reasonable to focus on that
goal and to recognize that one could not do everything
in one project. Thus, the exploration of diversity would
have to await other research efforts.
Even in that project, however, certain problems in
comparing clinical status across cultures signaled potential
difficulties for future research attempting to reach
specific cross-cultural conclusions about epidemiology
and the status of patient functioning. In terms of comparing
prognosis, there were issues of sampling (e.g., do the
less florid [the more ‘‘process’’] patients who also tend
to have poorer prognosis, tend not to come to the attention
of mental health professionals in developing countries?).
There were also issues of interpretation of
longitudinal functional status. For example, there was
a patient in a developing country who at follow-up
was ‘‘working full-time’’ guarding the cattle. When we
asked a person from the village what that meant in terms
of work, the response was that it was not real work because
that was usually a job reserved for young children.
In another developing country, there was the statement
that there was less stigma around mental illness than
in developed countries. When we inquired in more detail,
however, we were told that of course family members
would not let it be known that one of the sons had mental
illness because it would then be impossible for the daughters
to get married. These are only anecdotes, of course,
but they suggested that making certain cross-cultural
comparisons may need a sophisticated approach to sampling
and inquiry to assure the validity of conclusions.
These considerations, here focusing on one aspect of
the social domain, indicate the complex context within
which an understanding of the diversity of prognosis
in schizophrenia exists. But even the recognition of issues
in each of the three individual domains, the biological, environmental,
and personal, is incomplete. More than likely,
interactions between two or [among] all three of these domains will be
important influences on course and outcome, for example,
the interaction between the efforts of a person to get
better, a case worker who assists him in that process, the
availability of a helpful job and of useful medication.
Often in medical research, we try to focus on one variable
that can account for a huge amount of the variance in
a certain problem. Occasionally, we meet with relative success,
as with the pneumococcus, for example, as a major
variable in one type of pneumonia. For schizophrenia,
however, as is seen in the report by Cohen et al., even a focus
on only one of the three domains involves considerable complexity
in research design, data collection, data analysis,
and interpretation. Such complexity is nothing new, of
course, for medical research. Very often, the crucial factors
involved in aspects of illness are extremely complex. In the
study of schizophrenia, there is increasing evidence that
the diversity of prognosis is the result of a complex interaction
between the disorder, the environment including
the culture, and the characteristics of the person afflicted.
Only by considering such a model are we likely to develop
an accurate picture of the prognostic processes.
Breier A, Strauss JS. The role of social relationships in the recovery from psychotic disorder. Am J Psychiatry. 1984;141:949–955. Abstract
Strauss JS. Subjectivity. J Nerv Ment Dis. 1996;184:205–212.
Reprinted as Subjektivitet. Dialog 1999;9:37–50. Translated
into Norwegian by Rimestad S. Abstract
Strauss JS. La réalité et le concept de maladie mentale. Psychiatr Sci Hum Neurosci. 2007;125–130.
View all comments by John StraussComment by: Julian Leff
Submitted 25 January 2008
Posted 25 January 2008
Reprinted courtesy of Schizophrenia Bulletin
I agree with the authors’ criticism of the use of the dichotomy
between developed and developing countries, partly
because of the difficulty in defining these terms and partly
due to the myriad different social, cultural, and economic
factors subsumed by them. While ‘‘low income’’ and
‘‘middle income’’ can be reasonably accurately defined,
they also encompass a great diversity of factors, both
within and between countries. In addition, the authors
have aggregated 23 studies including prevalence and
incidence samples and prospective and retrospective
designs. They acknowledge that a meta-analysis is ruled
out by this diversity of sampling procedures and methods
but nevertheless proceed to treat these studies as providing
equally informative findings. An incidence study is
likely to miss a small proportion of individuals fulfilling
the selection criteria—11 percent in the AESOP study (Morgan et al., 2006), which
used case finding procedures based on those in the
International Studies of Schizophrenia (ISoS) research.
However, a prevalence study will fail to include a high
proportion of people who experience an acute first onset
of schizophrenia from which they recover completely,
thus introducing a bias toward chronicity. The International
Pilot Study of Schizophrenia was based on prevalence
samples because its aim was to determine whether it
was possible to train psychiatrists from different countries
to use assessment instruments in a reliable way,
to establish whether schizophrenia exists in all the cultures
studied, and to determine whether an international
collaborative study in psychiatry was achievable. The success
of this venture paved the way for the Determinants of
Outcome of Severe Mental Disorders (DOSMeD), the
main strength of its design being the collection of an epidemiologically
based incidence sample followed prospectively
in each center using the same instruments. Cohen
and colleagues have taken a step backwards in conflating
results from both incidence and prevalence studies.
These authors state that ‘‘Except for the China ISoS
site, sampling in all the WHO studies relied on a variety
of help-seeking agencies to identify potential subjects.’’ I
am particularly familiar with the Chandigarh site from
the DOSMeD study because I visited it several times
and went on field trips to the rural areas with the
researchers. The city of Chandigarh has a highly literate
population, 70 percent during the period of the study, and
a Postgraduate Medical Institute of considerable sophistication
in which the psychiatric facility was sited. The
proportion of incident cases derived from help-seeking
agencies would consequently be minimal. By contrast,
the rural areas around the city have populations with
a low level of literacy, 30 percent at the time, and limited access
to medical facilities. To deal with this problem, Professor
Wig, the director of the center, established a mobile team
of psychiatric professionals who made regular circuits of
the rural areas, holding outpatient clinics to identify
and treat potential subjects for the study. This procedure
increased the likelihood that all incident cases were
It is noteworthy that the data from the Nigerian center
in Ibadan were given less weight than those from other
centers in the ‘‘developing’’ countries because the case finding
procedures, compared with those in Chandigarh,
were not considered to be sufficiently comprehensive.
The role of families
More prospective first-onset studies have been conducted
in India than in any other low-income country, and
the clinical, social, and occupational outcomes are
For this reason, the family study incorporated in the
Chandigarh center’s research is of particular interest.
Two aspects of the findings need emphasis: the contrast
between the prevalence of relatives’ expressed emotion
(EE) in the city and in the rural areas and the contribution
made by the generally low levels of EE to the good
clinical outcome of the patients in this center.
The local field workers in the Chandigarh center were
trained to assess EE to an acceptable level of inter-rater
reliability. 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. At the 1-year
follow-up, levels of EE had dropped in both groups:
12.5 percent of urban relatives were rated as high EE, but
not a single rural relative (Leff et al., 1990). This latter finding has no precedent
among relatives in high-income countries. 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 (Leff and Warner, 2006).
A comparison was made between the Chandigarh
sample of first contact patients and a sample of London
patients admitted for the first time with a diagnosis of
schizophrenia, both groups being assessed with the
same instruments. The proportion of high EE relatives
was 47 percent in the London sample and 23 percent in the total
Chandigarh sample (P <0.005). The relapse rates at
1-year follow-up showed the same pattern: 29 percent and
14 percent, respectively (P<0.05). A log linear analysis of these
data revealed that the better outcome for the Chandigarh
patients was wholly predicted by the lower level of EE (Kuipers and Bebbington, 1988). I would be cautious about generalizing from these results
to the other Indian centers, let alone to all low-income
countries, but the explanatory power of relatives’ EE is
such (Butzlaff and Hooley, 1998) that it merits incorporation in further studies of
variation in outcome across countries and cultures.
Recent research indicates that socio-environmental
factors are implicated in the etiology of schizophrenia
as well as influencing its course (Morgan et al., 2007). 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.
Morgan C, Dazzan P, Morgan K, Jones P, Harrison G, Leff J, Murray R, Fearon P, . First episode psychosis and ethnicity: initial findings from the AESOP study. World Psychiatry. 2006 Feb 1;5(1):40-6. Abstract
Leff J, Wig NN, Bedi H, Menon DK, Kuipers L, Korten A, Ernberg G, Day R, Sartorius N, Jablensky A. Relatives' expressed emotion and the course of schizophrenia in Chandigarh. A two-year follow-up of a first-contact sample. Br J Psychiatry. 1990 Mar 1;156():351-6. Abstract
Leff J, Warner R. Social Inclusion of People with Mental Illness.
Cambridge: Cambridge University Press; 2006:12–13.
Kuipers L, Bebbington P. Expressed emotion research in schizophrenia: theoretical and clinical implications. Psychol Med. 1988 Nov 1;18(4):893-909. Abstract
Butzlaff RL, Hooley JM. Expressed emotion and psychiatric relapse: a meta-analysis. Arch Gen Psychiatry. 1998 Jun 1;55(6):547-52. Abstract
Morgan C, Kirkbride J, Leff J, Craig T, Hutchinson G, McKenzie K, Morgan K, Dazzan P, Doody GA, Jones P, Murray R, Fearon P. Parental separation, loss and psychosis in different ethnic groups: a case-control study. Psychol Med. 2007 Apr 1;37(4):495-503. Abstract
View all comments by Julian LeffComment by: Assen Jablensky, Norman Sartorius
Submitted 31 January 2008
Posted 31 January 2008
Comment by Assen Jablensky and Norman Sartorius
Reprinted courtesy of Schizophrenia Bulletin
What did the WHO studies really find?
The article by Cohen et al. raises important issues and
provides a useful synopsis of published studies on schizophrenia
outcomes in 11 low- and middle-income countries.
The authors use of this material to challenge what
they claim to be an ‘‘axiom’’ (i.e., a self-evident proposition
requiring no proof) of better course and outcome
in developing countries which has been ‘‘embraced’’
by international psychiatry. They impute the origin of
this belief primarily to World Health Organization
(WHO)-led international collaborative research conducted
over the past 30 years (WHO, 1973; WHO, 1979; Jablensky et al., 1992; Harrison et al., 2001) and caution that the publication
of the final report from the International Study
of Schizophrenia (ISoS) (Hopper et al., 2007) might even further bolster convictions
in the ‘‘better prognosis’’ hypothesis. Based on
evidence from research conducted outside the WHO
studies, they conduct a reexamination of the axiom.
Having been directly involved with the WHO schizophrenia
research program over decades, we wish to point
out that Cohen et al. have misunderstood key aspects of
the design and conclusions of the WHO studies. They
claim that ‘‘the sampling methods utilized in the WHO
studies may have resulted in overly optimistic perceptions
of course and outcome’’ because ‘‘case-finding methods
which focus exclusively on help-seeking agencies will miss
large proportions of seriously ill, poor prognosis individuals.’’
They state, mistakenly, that the WHO studies provide
no evidence allowing an evaluation of ‘‘the quality
of family and social interactions,’’ and impute to them by
implicating a view that ‘‘scarcity’’ of care resources is
responsible for better outcomes. Because these claims repeat
an earlier critique of the WHO 10-country study
(Determinants of Outcome of Severe Mental Disorders
[DOSMeD] [Jablensky et al., 1992]) by Edgerton and Cohen in 1994 (Edgerton and Cohen, 1994), which
was answered by us in a publication (Jablensky et al., 1994) not quoted in the
present article, we summarize briefly the relevant features,
findings, and conclusions of that study.
An unexpected finding of the follow-up stage of the
WHO International Pilot Study of Schizophrenia
(IPSS) (WHO, 1979) was a markedly better overall outcome of schizophrenia
patients in India and Nigeria at 2-year and
5-year follow-up. Because the IPSS cohort was not necessarily
representative and the finding could be an artifact
of selection, a second, epidemiologically designed study
was launched in the early 1980s. DOSMeD (Jablensky et al., 1992) was the first
large-scale study in which a unified design, stringent
methods, and standardized instruments were concurrently
applied to first-episode incident cohorts (total study
population = 1379) at 12 research sites in diverse sociocultural
settings (Colombia, Czechoslovakia, Denmark, India,
Ireland, Japan, Nigeria, Russia, United Kingdom,
and United States). The cohorts were recruited by
2-year active case finding within defined geographical
areas, aiming to intercept all new onsets at all kinds of
facilities—not just mental health services, but including
primary care, police/prisons, traditional healers, and religious
shrines (notably, 28 percent of the cases in India and
Nigeria were recruited through such ‘‘alternative’’ care
sources). For 86 percent of the cases, the duration of untreated
psychosis was less than 1 year, and only 10 percent had been
prescribed antipsychotic drugs prior to entry into the
study. Repeated ‘‘leakage’’ checks on the completeness
of case finding found that only a handful of incident cases
had been missed by this technique, thus categorically ruling
out an ascertainment bias favoring inclusion of milder
or good prognosis cases. Patients and key informants
were interviewed at baseline and at 1-year and 2-year follow-
up (78.2 percent of the cohort), and a large proportion of
the original cohort was traced and assessed again at 15
years (as part of the ISoS) (Hopper et al., 2007) in 8 of the 12 field research
centers. Throughout the study, high intra- and intercenter
reliability of assessment using the Present State Examination
(PSE) (Wing et al., 1974) was maintained by joint rating of live and
prerecorded interviews. Diagnostic stringency was ensured
by processing of the PSE data using a computerized
diagnostic algorithm (Wing et al., 1974). During the first 2 years, nested
studies were conducted on the impact of potential precipitants
of psychotic relapse: stressful life events (Day et al., 1987) (in 10 of
the centers) and expressed emotion (Leff et al., 1990) (in Chandigarh,
India). These studies did provide important information
on family and social interactions. Operationally defined
measures of course and outcome included one categorical
index (pattern of course) and six quantitative dimensions
(cumulative percentages): estimated follow-up time in
psychotic episodes, in complete or incomplete remissions,
duration of unimpaired community functioning, time in
hospital, and time on antipsychotic medication. In all
centers, disability and social functioning were evaluated
using the WHO-Disability Assessment Schedule interview.
Importantly, our analysis did not conflate measures
of clinical status and measures of social functioning.
Analysis of predictors of outcome was based on log-linear
models (log-odds) which tested 25 potential predictors
against the seven outcome variables.
The essence of the findings and conclusions of the
study are best conveyed by quoting from the DOSMeD
final report (Jablensky et al., 1992). The study demonstrated clearly a diversity
of outcomes but ‘‘did not identify any particular pattern
in the course and outcome of schizophrenic illnesses
which could be regarded as specific to a given area or culture.’’
The outcome of patients in the developing countries
was not uniformly better, as compared to the
outcome in developed countries. While high rates of complete
clinical remission were significantly more common
in developing country areas (37 percent) than in developed
countries (15.5 percent), the proportions of continuous unremitting
illness (11.1 percent and 17.4 percent) did not differ significantly
across the two types of setting. Patients in
developing countries experienced significantly longer
periods of unimpaired functioning in the community,
although only 16 percent of them were on continuous antipsychotic
medication (compared with 61 percent in the developed
countries). Across all centers, the best predictors (P <.001) of outcome were type of onset (insidious vs. acute)
and type of setting (developed vs. developing country),
followed by marital status (P <.01) gender (P <.05),
social isolation (P <.05), and drug abuse (P <.05). Neither
type of family household (extended vs. nuclear) nor
experienced avoidance by others (a putative marker of
stigma) reached statistical significance as predictor of
Having excluded a number of potential confounders,
we concluded that ‘‘it is unlikely that the variation in
course and outcome could be reduced to a single variable’’
and considered ‘‘the possibility that the clinical
conditions meeting the inclusion criteria of the study
in the 2 types of setting may be heterogeneous and
include varying proportions of etiologically and genetically
different disorders which may be indistinguishable
from one another at the level of the phenotype. This
possibility exists but it cannot be properly examined
or tested at the present time, in the absence of established
genetic markers, indicators of etiology, or
other underlying mechanisms of disease.’’ Nevertheless,
‘‘a strong case can be made for a real pervasive influence
of a powerful factor which can be referred to as ‘culture,’
as the context in which gene-environment interactions
shape the clinical picture of human disease. The
contribution of the present study is not in providing
the answer but in clearly demonstrating the existence
of the question’’ (Jablensky et al., 1992).
Cohen et al. cite and review a number of non-WHO
studies in low- and middle-income countries as providing
evidence that is contrary to the ‘‘presumed wisdom’’ allegedly
promoted by the WHO reports. Yet they note the
‘‘heterogeneity in types of samples, follow-up periods,
and outcome measures’’ used in those studies, acknowledge
that no meta-analyses were possible, and base their
reasoning on ‘‘reading of the research reports, tabulations
of the available data, and interpretations of the evidence.’’
Using the same method in our perusal of Tables 3 and 5 in
the target article, we are unable to find in this literature
evidence contradicting any of the DOSMeD and ISoS
findings and conclusions. In fact, notwithstanding the heterogeneity
of the data due to design, methods, and power,
nearly all studies report extraordinarily high proportions
of ‘‘complete recovery,’’ ‘‘no or minimal psychotic symptoms,’’
‘‘no psychotic episodes,’’ ‘‘no impairment,’’ ‘‘good
to excellent social functioning,’’ etc. We agree that mortality
is an important measure of outcome and that wherever
standardized mortality ratios (SMRs) are available, people
with schizophrenia tend to have elevated rates, compared
with the general population. In the ISoS study, five SMRs
were calculated for six schizophrenia cohorts in developing
countries and 12 cohorts in developed countries. Of the 13
SMR values significant at P <.05, four were in developing
countries and nine in developed countries. All the five highest
values (SMR >4.0) were in developed countries. Had
Cohen et al. included in their review comparable data
from course and outcome studies in high-income countries,
the contrast between the two groups of settings would
We do not argue that the prognosis of schizophrenia in
developing countries is groupwise uniformly milder or
that the existing huge gaps in mental health service provision
between high- and low-income countries are irrelevant
to the lives of millions of people affected by this
disorder. On the contrary, the erosion of social support
systems, likely to be associated with the processes of globalization (Chisholm et al., 2007), 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. Thus, the existence of outcome
differentials between populations and cultures is
not ‘‘presumed wisdom’’ but a real, complex issue which
should be addressed with standards of precision and rigor
that are customary in scientific research and discourse.
Cohen A, Patel V, Thara R, Gureje O. Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World? Schizophr Bull. 2007 Sep 28; [Epub ahead of print] Abstract
WHO. Report of the International Pilot Study of Schizophrenia,
Volume I. Geneva, Switzerland: World Health Organization;
WHO. Schizophrenia: An International Follow-up Study. Chichester, UK: John Wiley & Sons; 1979.
Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, Day R, Bertelsen A. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. Psychol Med Monogr Suppl. 1992 Jan 1;20():1-97. Abstract
Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J, Dube KC, Ganev K, Giel R, An Der Heiden W, Holmberg SK, Janca A, Lee PW, León CA, Malhotra S, Marsella AJ, Nakane Y, Sartorius N, Shen Y, Skoda C, Thara R, Tsirkin SJ, Varma VK, Walsh D, Wiersma D. Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J Psychiatry. 2001 Jun 1;178():506-17. Abstract
Hopper K, Harrison G, Janca A, Sartorius N (eds). Recovery
from Schizophrenia: An International Perspective. New York,
NY: Oxford University Press; 2007.
Edgerton RB, Cohen A. Culture and schizophrenia: the
DOSMD challenge. Br J Psychiatry. 1994;164:222–231. Abstract
Jablensky A, Sartorius N, Cooper JE, Anker M, Korten A,
Bertelsen A. Culture and schizophrenia. Criticisms of WHO
studies are answered. Br J Psychiatry. 1994;165:434–436. Abstract
Wing JK, Cooper JE, Sartorius N. Measurement and Classification of Psychiatric Symptoms. Cambridge, UK: Cambridge University Press; 1974.
Day R, Nielsen JA, Korten A, Ernberg G, Dube KC, Gebhart J, Jablensky A, Leon C, Marsella A, Olatawura M. Stressful life events preceding the acute onset of schizophrenia: a cross-national study from the World Health Organization. Cult Med Psychiatry. 1987 Jun 1;11(2):123-205. Abstract
Leff J, Wig NN, Bedi H, Menon DK, Kuipers L, Korten A, Ernberg G, Day R, Sartorius N, Jablensky A. Relatives' expressed emotion and the course of schizophrenia in Chandigarh. A two-year follow-up of a first-contact sample. Br J Psychiatry. 1990 Mar 1;156():351-6. Abstract
Chisholm D, Flisher AJ, Lund C, Patel V, Saxena S, Thornicroft G, Tomlinson M; Lancet Global Mental Health Group. Scale up services for mental disorders: a call for action. Lancet. 2007;370:1241–1252. Abstract
View all comments by Assen Jablensky
View all comments by Norman SartoriusComment by: Evelyn J. Bromet
Submitted 1 February 2008
Posted 1 February 2008
Reprinted courtesy of Schizophrenia Bulletin
Cross-national comparisons: problems in interpretation when studies are
based on prevalent cases
Cohen et al. challenge the belief, stemming largely from
the World Health Organization (WHO) schizophrenia research
program, that ‘‘schizophrenia has a better course
and outcome in countries of the developing world’’ compared
with developed countries. They thus examine
findings on illness course, mortality, and social and occupational
outcomes across an array of studies conducted
in low- or middle-income countries throughout
the world. They consider findings from all follow-up
studies of schizophrenia conducted in these countries,
without regard to case identification specification or
length of follow-up. The outcome results across the studies
identified by Cohen et al. were variable, and in some
cases, the samples fared very poorly indeed. Because none
of the studies had control groups, cross-national disparities
in the social and occupational trajectories of the
patients with schizophrenia compared with counterparts
from the same source populations are unknown.
Cohen et al. suggest that there is a need for more outcome
studies of ‘‘incident and prevalent cases.’’ Clearly,
outcome studies of incident cases, defined as first episode,
first contact with a provider, or first hospitalization, can
potentially provide insights about the course and outcome
of schizophrenia, and they are, unfortunately, fairly
rare. On the other hand, follow-up studies of consecutive
admissions to psychiatric inpatient and outpatient facilities,
or prevalent cases, appear with great regularity.
However, their findings are largely uninterpretable. As
Cohen and Cohen (1984) elegantly delineated nearly 25 years
ago, many forms of selection bias creep into prevalent
samples, particularly chronicity and comorbidity, creating
an illusion about the nature and correlates of illness
course. Studies with variable lengths of time between
illness onset and outcome determination, such as those
reviewed by Cohen et al., create ambiguity about the
course of schizophrenia rather than shed light on the
process and its mechanisms across time and place.
Thus, additional prevalent studies in low- and middle-income
countries are unlikely to improve our understanding
of cross-national differences in the course of
A prevalent sample is a mixture of recent onset and
chronically ill patients. The specific composition of the
mix will influence the findings and the inferences that
are ultimately to be drawn. In our chapter on the epidemiology
of psychosis, we showed that in a single mixed
sample, the 5-year outcome was significantly better for
the incident (first-admission) patients than for the prevalent
(rehospitalized) patients in the group (Bromet et al., 1995). Among the
incident cases, 22 percent experienced no relapse, 35 percent had one
or more relapses with minimal or no impairment, and
43 percent were impaired throughout the 5 years. Among the
prevalent cases, only 10 percent had no impairment, whereas
29 percent had multiple episodes with no/minimal impairment,
and 60 percent were impaired with no return to normality. The
more general point is that prevalent (consecutive admission)
samples are biased by chronicity, thus overrepresenting
the most severe and intractable forms of the
illness. In contrast, incident samples, even when ascertained
from clinical services, are less biased by chronicity,
although they, too, contain patients with variable durations
of untreated or undertreated illness. Population-based
incident samples identified from cohort studies,
such as birth cohorts, are the most representative and
contain the least bias.
A useful way to think about follow-up studies of
schizophrenia is to conceptualize them as clinical cohort
studies (Susser et al., 2006). The design requirements then become very clear.
A cohort is a group with a common experience that is
observed in a standardized fashion over time. Thus, a clinical
cohort is a group with a uniform starting point (the
closer to the actual onset, the better for minimizing lead time
bias), a transparent and systematic method of case
ascertainment, and a reliable method of assessment and
assignment of diagnosis. By their nature, well-designed
clinical cohort studies yield findings that are readily interpretable.
The WHO first-contact study was designed
with these basic principles in mind (Jablensky et al., 1992). As Cohen et al. point
out, the cross-cultural application was not without its
problems, but the ability to make comparisons was greatly
enhanced by the design. Two recent North American
studies were also designed with the same goals (Bromet and Fennig, 1999; Erickson et al., 1998). Thus,
in countries where ‘‘ideal’’ epidemiologic samples, such
as birth cohorts, are not available or feasible, the clinical
cohort design offers the next best alternative.
The bottom line is that Cohen et al. argue that the ‘‘better
prognosis’’ hypothesis is not correct for all poor and
middle-income countries because both good and bad outcomes
are found in socioeconomically deprived regions
of the world. In deciding about studies to include in their
review, the distinction between incident and prevalent
cases was noted but was not considered particularly germane.
It is important to emphasize that the WHO investigators
did not claim that all patients in developing
countries had good outcome trajectories. Instead, they
found that on average, the incident cohorts from developing
countries fared better than those from richer countries.
(As an aside, the World Mental Health Consortium,
a series of population-based morbidity surveys, also
found higher rates of psychiatric disorder in wealthy
countries like the United States compared with poor
countries like Nigeria [Demyttenaere et al., 2004]) From an epidemiologic perspective,
the biases in prevalent samples cannot be ignored
when evaluating and comparing prognosis across studies.
It is simply not possible to judge whether the differences
in the outcomes reported in this review, including mortality,
or the differences in the prognostic factors, represent
methodological artifacts, true differences among the populations
associated with culture or genetics, or a bit of both.
This commentary is not intended as a tutorial. Our
textbook on psychiatric epidemiology has several
chapters devoted to the design of clinical cohort studies
and considerations in specifying the criteria for selecting
cases and controls for clinical research (Susser et al., 2006). Rather, I would
like to suggest a method for undertaking new clinical cohort
studies in resource-poor environments so that we
can extend our understanding of cross-national differences
in illness course with relative expedience. Specifically,
an economical method that can be implemented in poor
settings with stable population bases is the historical cohort
design, as exemplified by the classic studies of
Ciompi (Ciompi, 1980), Huber (Huber, 1997), and Bleuler (Bleuler, 1978). This strategy requires
that the initial presentation of the illness is carefully documented
in a record, which is often the case, and also that
the likelihood of locating the patients for follow-up is not
biased by whether they remain in treatment. For example,
one of the most influential studies in the field of psychiatry
was Deviant Children Grown Up, a historical
cohort study of children evaluated for behavior problems
in 1924–1929 who were systematically assessed 30 years
later, along with classmate controls (Robins, 1966). The richness of the
original records allowed the investigator to determine the
childhood predictors of adult antisocial behavior and
mood/anxiety disorders. Historical cohort studies from
rich, middle-income, and poor countries of the world
could provide important evidence about relative differences
in the psychosocial trajectories of schizophrenia and
their risk factors, particularly if they employ similar
methodologies and measures.
I fully agree with the conclusion of Cohen et al. that
‘‘clinical, epidemiological, and ethnographic’’ strategies
are needed to identify the processes that promote good
outcome in different settings. There is no debate among
epidemiologists about how to design an informative clinical
cohort study, and such designs can be implemented
around the world. Hopefully, the next generation of
schizophrenia outcomes research will fully integrate the
three domains mentioned by Cohen et al. as well as biologic,
genetic, and treatment moderators.
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Searching for the Causes of Mental Disorders.
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View all comments by Evelyn J. BrometComment by: Karl-Ludvig Reichelt (Disclosure)
Submitted 19 February 2008
Posted 27 February 2008
One of the dominant differences between the developed world and developing world is food types. Already Prof. F Dohan pointed out that schizophrenia was rare where grains are rare (Dohan et al., 1984) Rice and maize are staple foods in large parts of the developing world. In other parts manioc, kasawa, etc., have a substantial role in the countryside. This could explain the faster recovery when patients in these countries are returned to their native villages (Lehtinen, 1987). Also, the acculturation following transition to grain-based diet makes sense (Lorenz, 1990). Thus, the increased rate when poor people move from developing countries to developed countries where grains and milk products are the cheaper foods.
It would also fit our data on the levels of exorphins in schizophrenic patients (Reichelt et al., 1996). (See also an example of data on intervention with diet [Singh and Kay, 1976]). Since one molecule of glutenin contains 15 exorphin sequences, it is clear that the strictness of dietary intervention is critical. Given the trophic changes of the brain, negative experiments on chronic and heavily drugged cases are not very useful. I doubt very much that developed societies are more egocentric than developing countries, and do not find much evidence for this at all. During the Second World War in Asia, this was definitely not my experience.
Dohan FC, Harper EH, Clark MH, Rodrigue RB, Zigas V. Is schizophrenia rare if grain is rare? Biol Psychiatry. 1984 Mar 1;19(3):385-99. Abstract
Lehtinen V. [The epidemiology of schizophrenia] Nord Med. 1987 Jan 1;102(4):112-3, 26. Abstract
Lorenz K. Cereals and schizophrenia .Adv Cereal Sci. Technol. X 1990: 435-469.
Reichelt KL, Seim AR, Reichelt WH. Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload? Prog Neuropsychopharmacol Biol Psychiatry. 1996 Oct 1;20(7):1083-114. Abstract
Singh MM, Kay SR. Wheat gluten as a pathogenic factor in schizophrenia. Science. 1976 Jan 30;191(4225):401-2. Abstract
View all comments by Karl-Ludvig ReicheltComment by: Robert Lemelson
Submitted 23 April 2012
Posted 25 April 2012
Our film series "Afflictions: Culture and Mental Illness in Indonesia" is the first film series on serious mental illness in the developing world. Three of the films in the series directly address issues of differential outcome for thought disorders/schizophrenia, issues raised by the IPSS and DOSMD studies. The series has won a number of awards, and should be useful for anyone teaching transcultural psychiatry, psychiatric anthropology, and related fields.
Information on the series is available here.
View all comments by Robert Lemelson