Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World?

doi:10.1093/schbul/sbm105

Schizophr Bull. 2008 March; 34(2): 229–244.

Published online 2007 September 28. doi: 10.1093/schbul/sbm105

PMCID: PMC2632419

Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World?

Alex Cohen,^1,² Vikram Patel,³ R. Thara,⁴ and Oye Gureje⁵

²Department of Social Medicine, Harvard Medical School, 641 Huntington Avenue, Boston, MA 02115

³Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

⁴Schizophrenia Research Foundation, Chennai, India

⁵Department of Psychiatry, University of Ibadan, Ibadan, Nigeria

¹To whom correspondence should be addressed; tel: 1-617-432-2378, fax: 1-617-432-2565, e-mail: alex_cohen/at/hms.harvard.edu.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC.

Abstract

Introduction: That schizophrenia has a better course and outcome in developing countries has become an axiom in international psychiatry. This is based primarily on a series of cross-national studies by the World Health Organization (WHO). However, increasing evidence from other research indicates a far more complex picture. Methods: Literature review and tabulation of data from 23 longitudinal studies of schizophrenia outcomes in 11 low- and middle-income countries. Results: We reviewed the evidence about the following domains: clinical outcomes and patterns of course, disability and social outcomes (marital and occupational status, in particular), and untreated samples and duration of untreated psychosis. Outcomes varied across the studies and the evidence suggests a need to reexamine the conclusions of the WHO studies. Additionally, assessments of outcomes should take excess mortality and suicide into account. Conclusions: It is time to reexamine presumed wisdom about schizophrenia outcomes in low- and middle-income countries.

Keywords: longitudinal studies, cross-cultural psychiatry, schizophrenia

Introduction

That schizophrenia has a better course and outcome in countries of the developing world has become an axiom in international psychiatry.¹^–⁵ This belief emerges from a long history of cross-national research,⁶^–⁹ with the most often cited evidence coming from 3 studies by World Health Organization (WHO): the International Pilot Study of Schizophrenia,¹⁰ the Determinants of Outcome of Severe Mental Disorder (DOSMeD),¹¹ and the International Study of Schizophrenia (ISoS).¹² These studies have been cited as “arguably the greatest achievements in psychiatric epidemiology,”¹³ and their results as constituting “the single most important” finding in cross-cultural psychiatry.¹⁴ No doubt the recent publication of the final ISoS report¹⁵ will bolster convictions in the “better prognosis” hypothesis and may lead to the conclusion that further examination of the question is not necessary. This would be unfortunate given increasing evidence, which presents a far more complex picture. In this review of research conducted independently of the WHO studies, we examine clinical outcomes and patterns of course, disability and social outcomes, and mortality and suicide in people with schizophrenia living in low- and middle-income countries. We also consider evidence about the role of families, gender effects, and the implications of evidence concerning persons with schizophrenia who have not received biomedical treatment.

METHOD

To locate research on schizophrenia outcomes in developing countries, we conducted searches of PubMed and PsycInfo using the following keywords: schizophrenia, psychosis, outcome, and developing countries. This strategy identified only a limited number of studies, and we came to rely on a combination of keyword and author searches, as well as tracking down references cited in research reports, a strategy similar to the one used by Bromet et al.¹⁶ Inclusion criteria were research site in a low- or middle-income country (as defined by the World Bank¹⁷), minimum of 1-year follow-up (either prospective or retrospective), and English language. We did not use the developing/developed country variable because it is difficult to operationalize.¹⁸^,¹⁹

Following this strategy, we found published reports from 23 research projects on schizophrenia outcomes in 11 low- and middle-income countries (Brazil, Bulgaria, China, Colombia, Ethiopia, India, Indonesia, Jamaica, Nigeria, South Africa, and Trinidad—see tables 1 and and2),2), a greater diversity of sociocultural environments than represented in ISoS. The identified studies were prospective and retrospective, had follow-up periods ranging from 1 to 20 years, included prevalent and first-episode cases, and drew samples from a variety of settings (outpatient clinics, hospital samples, and communities). Twelve of the studies followed 100 or more subjects. Rates of attrition (not due to mortality) were generally low to moderate in most of the prospective studies.

Table 1.

Prospective Studies of Schizophrenia Outcomes in Low-Income Countries

Table 2.

Retrospective Studies of Schizophrenia Outcomes in Low-Income Countries

The heterogeneity in types of samples, follow-up periods, and outcome measures made it impossible to conduct meta-analyses. Our results are based on a reading of the research reports, tabulations of the available data, and interpretations of the evidence. To provide a basis for comparison, we have included data from the following ISoS sites—Bulgaria, China, India (Agra, urban Chandigarh, and rural Chandigarh), and Colombia. To represent WHO research in Nigeria, we include data on 2-year outcomes in the DOSMeD site in Ibadan.¹¹ Even though the Madras Longitudinal Study (MLS)²⁰^,²¹ was included in ISoS, we have listed it as a separate study because it was conducted independently of the WHO research. Data for MLS are taken from reports in journals and not from the ISoS publication. Madras is the former name for Chennai. Hong Kong was excluded because it is classified by the World Bank as a high-income country.¹⁷

Three studies, the Indian Multisite Study,²² the MLS, and the one in Bali, Indonesia,²³^,²⁴ have published results from different follow-up periods. To provide as much detail as possible about these cohorts, data from each follow-up period are presented separately in the tables. It should also be noted that the MLS cohort was originally part of the Multisite Study, and that the research in Indonesia began as a 5-year retrospective study and then prospectively followed the cohort for another 6 years. Therefore, data about the same subjects are sometimes presented in more than one place in each of the tables.

Results

Clinical Outcomes and Patterns of Course

Tables 3 and and44 summarize the evidence on clinical outcomes and patterns of course. Most notable is the wide variation across studies. First, the proportion of individuals who experience chronic pattern of course ranges from 4.5% (over 5 years) in the Multisite Study in India²²^,²⁵^,²⁶ to 51.7% (over 12 years) in the ISoS China sites.¹⁵ Second, there is variation in the proportion of individuals who are assessed as suffering from severe or chronic psychotic symptoms at follow-up: from a low of 0.0% or 5.0% in the ISoS Chandigarh rural and urban sites, respectively, to 29.2% in the ISoS China sites,¹⁵ to more than 30% in 2 earlier studies in Chandigarh.²⁷^,²⁸ At 2-year follow-up, 77.9% of the cohort in rural China were assessed as experiencing either “continued marked symptoms” or “further deterioration of illness.²⁹ Third, impressions of patterns of course may change over time. This is apparent in 2 Indian studies. At 2-year follow-up, the overall patterns of course for subjects in the Multisite Study²² were Best (45.2% complete recovery or no relapses), Intermediate (44.3% ≥1 relapses with complete or incomplete remission), and Worst (10.5% chronic psychosis). By 5-year follow-up, the proportion of subjects categorized as having Best pattern of course had fallen to 28.2%, and the proportion in the Worst category had fallen to 4.5%. In contrast, the proportion of subjects categorized as having an Intermediate pattern of course had increased to 67.2%. In other words, over time, some subjects in the Best category experienced relapses and some subjects in the Worst category experienced improvement. At the end of the Multisite Study, the Madras cohort continued to be followed in the MLS.²⁰^,²¹^,³⁰ At 10-year follow-up, the cohort displayed a continued shift of more subjects into the Intermediate category: Best, 17.1%; Intermediate, 76.3; Worst, 6.6%. At 20-year follow-up, 16.4% of subjects were evenly divided into the Best and Worst categories, while the proportion in the Intermediate category had increased to 83.6%. Thus, although relatively few individuals experienced chronic symptoms, over time the majority experienced relapse.

Table 3.

Clinical Outcomes or Patterns of Course, Prospective Studies

Table 4.

Clinical Outcomes or Patterns of Course, Retrospective Studies

Disability and Social Outcomes

Tables 5 and and66 summarize the evidence on disability and social functioning. Once again, there is wide variation. In India and Indonesia disability and social outcomes tend to be good, while those in China, Brazil, and Ethiopia tend to be poor.

Table 5.

Disability and Social Outcomes, Prospective Studies

Table 6.

Disability Outcomes, Retrospective Studies

Variation Is Also Found in Two Specific Domains: Marriage and Employment

In high income countries, persons with schizophrenia have been found to have low rates of marriage. As a consequence, there is often an implicit assumption that high rates of marriage among persons with schizophrenia is an indicator of sociocultural environments that promote better course and outcome.³¹ Table 7 summarizes the data we found about marital status. If one looks at the category “ever married,” most rates are relatively high: Ethiopia (70.0%),³²^–³⁴ Nigeria (60.8%³⁵), Indonesia (63.0% at 11-year follow-up²³), and Chennai, India (60.9%³⁶and 69.7%³⁰). However, rates of marriage at times of assessment were well below those for the respective general populations (table 7). Furthermore, separation and divorce were fairly common for subjects in a number of cohorts—Brazil (15.4%),³⁷^,³⁸ Ethiopia (≈17.9),³²^,³³ and Chennai (39.6%)³⁶—and much higher than those of general populations. A retrospective study in Nigeria³⁵ found that 27.5% of the sample had experienced marital breakup while 39.2% had never been married. Regarding men, a large majority (66.1%) had never married. Gureje and Bamidele³⁵ note, “The finding that less than 40% of the male sample with a mean current age of about 36 years had ever married is indicative of severe social disability.” At the same time, 42.6% of “ever married” women had experienced divorce or separation, a rate about 16 times greater than that of the general population.

Table 7.

Marital Status

Employment status is also considered an important measure of disability in schizophrenia,³⁹ and the extent to which societies offer opportunities for gainful employment, and thus, social reintegration is thought to be associated with course and outcome.⁴⁰ Table 8 summarizes data on employment and household work. Even within India, the variation is striking: in rural Karnataka, only 13% of the sample had regular employment,⁴¹ whereas in the Multisite Study more than 80% of the sample was employed in some capacity.²²^,²⁵^,²⁶ In Brazil, more than 50% of the sample had either no occupation or were not working because they were receiving a sickness benefit.³⁸ Rates of unemployment were similar in Indonesia (41.3%)²³ and Ethiopia (45.3%).⁴²

Table 8.

Employment Status

Most research in India has found that a high proportion of persons with schizophrenia are either employed or engaged in household work, and several studies have assessed how well subjects were performing these tasks. The work by Srinivasan and Thara⁴³^,⁴⁴ is especially informative. First, occupational status was assessed annually for 10 years. Second, outcomes for men and women were considered separately because of their distinct occupational domains—employment and household work, respectively. Third, criteria were established (time in occupation and level of performance) for categorizing outcomes. At year 10, 52.5% and 47.5% of men were classified as having good or poor employment outcomes, respectively. This presents a different impression than the data on whether men had been employed during the previous year, which ranged between 63% and 73% during the follow-up period.⁴³ Two-thirds of women were rated as having good home-making functioning. However, it is difficult to determine the extent to which functional abilities were required to perform assigned household tasks (cooking, washing clothes and utensils, household maintenance, caring for children, and others in the household) because other women in the household generally helped with these tasks.

Lack of Biomedical Treatment

Several studies conducted research among persons who had not received biomedical treatment. This is of particular interest because the “better prognosis” hypothesis implies that the “natural” course of schizophrenia will be relatively benign in the developing world.²⁹

A community survey in rural China identified 510 persons who had a current diagnosis or history of schizophrenia.²⁹ Of these, 30.6% had never received treatments of any kind, while 5.9% were receiving regular antipsychotic medication, 42.7% had histories of hospitalization and/or irregular treatment, and 20.8% had received traditional Chinese treatments. At baseline, lack of treatment of any kind and duration of untreated psychosis (DUP) greater than a year were associated with poor clinical status. At 2-year follow-up, the 95 subjects who had gone without treatment were, on average, assessed as having poor clinical status.

In rural Ethiopia, a community survey identified 321 persons with schizophrenia of whom 88.8% had never received treatment with antipsychotic medication. Although data are not presented by Kebede et al.,⁴² one might reasonably conjecture that the baseline high rate of continuous course of illness (67.2%) among subjects was, at least in part, the result of lack of treatment. At 1- to 4-year follow-ups, subjects displayed a significant improvement in positive symptoms, a result attributed to the antipsychotic medication that was offered free of charge to all subjects.³³

A community survey in Chennai, India, identified a cohort of 261 persons with a diagnosis of schizophrenia, of whom 28.7% had never received treatment even though they lived within 10 km of 4 public general hospitals with psychiatric units and 1 large mental hospital.³⁶ Compared with those who had received treatment, those in the untreated group were, on average, older and more likely to be unemployed, illiterate, and living in an extended family. Clinically, the untreated group was more likely to be symptomatic and suffering from severe global disability. Free treatment was offered to those in the untreated group and 49 accepted.⁴⁵ At 1-year follow-up, 69.4% of these subjects continued in poor clinical status, an outcome that was found to be associated with DUP.⁴⁶ DUP was also found to be a predictor of outcome in South Africa.⁴⁷^,⁴⁸

In rural Karnataka, Murthy et al.⁴¹ identified 100 persons with schizophrenia who had not received antipsychotic treatment in the previous 6 months. Scores on severity of symptoms, levels of disability, and extent of family burden were all high at baseline. Following 18 months of treatment with antipsychotic medication and psychosocial care, the cohort displayed, on average, significant improvements in all domains.

In sum, these findings suggest that good outcomes cannot be assumed for untreated schizophrenia in low- and middle-income countries and that treatment does make a significant difference.

Mortality and Suicide

Throughout the world, persons with schizophrenia have rates of mortality that are significantly higher than general populations.⁴⁹ That this is the case in low- and middle-income countries is suggested by the crude mortality data in table 2. In long-term studies (≥10 years), mortality rates range from 9.0% to 30.7% in the ISoS sites (urban Chandigarh and Agra, respectively) and from 10.0% to 19.2% and 20.3% in other research sites (Chennai, Bali, Indonesia, and rural China, respectively). It is likely that the reported mortality rates are underestimates given the lack of information about subjects lost to follow-up.

Crude mortality rates do not indicate how persons with schizophrenia compare to general populations. Standardized mortality ratios (SMRs) provide that measure. Wherever SMRs are available, there is little question that persons with schizophrenia in low- and middle-income countries have elevated rates of mortality.⁴⁹^,⁵⁰ The research by Ran et al.⁵¹ is particularly revealing because of its large sample size (510), low rate of attrition (7.8%), and long-term follow-up (10 years). The SMR for the cohort was 4.0; the rate among men (4.9) was higher than it was among women (3.3). Suicide and death by accident accounted for much of the elevated SMR, but not all of it: the SMR for natural causes was 2.6. SMRs for men in the São Paulo, Brazil cohort,⁵² were (4.5), but those for women were nearly seven times as high (25.5).

Other studies offer information about the context in which high rates of mortality occur. Of 9 known deaths in a Nigerian cohort, 5 took place while subjects were “in traditional healers’ establishments” while 2 other subjects “had been beaten to death by night guards who had found them wandering.”⁵³ In Indonesia, of the 11 subjects who died of natural causes, only 2 were receiving medical treatment at the time of their deaths.⁵⁴ The average age of death in this cohort, 33.3 years, was strikingly similar to that in the MLS, 34.2 years.²⁰ In contrast, life expectancies for general populations in Indonesia and India are approximately 65 and 61 years, respectively.

Table 9 summarizes the information that is available about suicide. The studies in rural China,⁵¹ Brazil,⁵² the MLS,²⁰^,²¹ and Bulgaria¹⁵ suggest that rates of suicide are comparable to, if not higher than, the lifetime rates (4.9%–5.6%) reported by Palmer et al.⁵⁵ In contrast, there were no reported suicides in the 1-year studies in Chennai,⁴⁶ Rural Karnataka,⁴¹ and the 11-year study in Indonesia.²³^,²⁴^,⁵⁴ In general, data on suicide must be viewed with caution. For example, the reported rate of suicide in the MLS (7.8%) may have been an underestimate: “Because postmortem examinations were not done, it was not possible to determine the actual cause of death in some cases.”²⁰

Table 9.

Suicide

The Role of Families

There is a long history to the notion that the better course and outcome of schizophrenia in low- and middle-income countries is attributable to relatively high levels of family support and tolerance.⁹^,¹⁵ This view has been maintained despite a paucity of evidence.⁵⁶^,⁵⁷ The research literature reviewed here provides evidence that, at the very least, should make us question past assumptions. For example, the Indian family has been noted as being especially supportive of members with schizophrenia.⁵⁸^,⁵⁹ We do not doubt this view, but do believe it may be an overgeneralization. While it is true that over the course of 20 years, the great majority of subjects in the MLS lived with their natal or marital families,²⁰^,²¹ research also offers insights about the nature of subjects’ family relationships. At the same time that families supported mentally ill members and did not abandon or push them into homelessness, unemployed men with schizophrenia were subjected to “rejection and harsh criticism.”⁴⁴ Other evidence from Chennai suggests that living in an extended family is a risk factor for not being brought to care, even when living in close proximity to facilities that offer treatment free of charge.⁴³ Finally, ethnographic research in Chennai with a group of separated and divorced women with schizophrenia (but not part of any outcome study) found that their lives were marked by “hostility from family members.”⁶⁰

Evidence from other countries adds still more complexity. Whereas less than 2% of ISoS subjects experienced homelessness in the 2 years prior to follow-up (an admitted underestimate),¹⁵ higher rates of homelessness were found among samples in rural areas of China⁶¹ and Ethiopia⁴² (8% and 7%, respectively). In a 13-year retrospective study, Gureje and Bamidele³⁵ were surprised, “given the traditional family structure in Nigeria,” that 4% of subjects were homeless or experiencing housing instability. They speculated, “In a setting where there are no public support services for the mentally ill, it is likely that the traditionally supportive family networks break down with prolonged illness.” Evidence from rural China also belies the notion of universal family tolerance and support of members with schizophrenia in that “insufficient family care or maltreatment” was associated with poor clinical status.⁴⁸

In sum, the research literature suggests that we must not make broad assumptions about the nature of family support for persons with schizophrenia. Support certainly exists, but it may be mixed with conflict or even breakdown in the absence of supports for the families themselves.

Gender

It is generally accepted that women with schizophrenia experience better outcomes than men.⁶² Although, gender effects were not explored consistently in the research we reviewed, some observations are possible. In India, several studies found that course and outcome is better for women.¹⁵^,²¹^,²⁶^,³⁰ However, that was not the case everywhere. Men tended to have better outcomes in Colombia.¹⁵ In the ISoS China study,¹⁵ there were few gender differences, but women tended to do better in the study by Ran et al.²⁹ in rural China. In Nigeria, women seemed more likely to suffer from continuous psychosis and were particularly prone to relapse.⁶³

Outcomes in social domains also displayed gender effects. In Nigeria, women tended to fare worse than men, while women in Ethiopia tended to show greater improvement in functioning during follow-up.³³ In ISoS, men in China also tended to have higher levels of social functioning. This was in contrast to Agra where 81.8% of women were rated as having “better functioning at follow-up,” a rate more than 1.5 times that of men.¹⁵

The most striking gender effect was in Ethiopia where a community survey found a 5:1 male to female ratio in the prevalence of schizophrenia.³³ Whether this reflects an exceptional case of gender differences in frequency, excess mortality, or that women with schizophrenia are being kept extremely isolated requires further investigation.

Conclusions

During the past 30 years, international psychiatry has embraced the notion that the course and outcome of schizophrenia is better in so-called “developing” countries.²^–⁵^,¹³^,¹⁴ We believe our review of 23 studies in 11 low- and middle-income countries—a much greater range of sociocultural environments than in ISoS—provides enough evidence to justify a reexamination of this axiom.

First, there appears to be great variation in clinical outcomes and patterns of course. Whereas, some studies in India strongly support the “better prognosis” hypothesis,¹⁵^,²⁰^,²¹ outcomes do not appear to be nearly as positive in Brazil⁶⁴ and China.²⁹ Additionally, limited evidence suggests that gender effects vary cross-nationally.

Second, similar patterns are found in the domains of disability and social functioning: good in most studies in India¹⁵^,²⁰^,²¹ and Indonesia,²³ but poorer in Nigeria,³⁵^,⁵³ and much poorer in a cohort of untreated persons in Chennai, India.⁴³ Social functioning by gender also varied: in the MLS, women had high levels,²⁶^,⁴⁵ while in Nigeria women fared poorly.³⁵^,⁶³ Outcomes in occupational and marital status also varied. A more important point, however, is that status in these 2 domains must be interpreted in the context of sociocultural norms and assessed, at least to some degree, qualitatively. Viewed from this perspective, the data in table 7 suggest that rates of marriage for people with schizophrenia are relatively low and rates of divorce/separation are high.

With regard to occupational status, “the crude distinction between ‘employment’ and ‘unemployment’”³⁹ is uninformative because the role of work in shaping the course and outcome of schizophrenia has not been explored adequately.⁵⁶ For example, what are the effects on outcome of farm work in rural Ethiopia⁴² or China?²⁹ Did jobs “in the unorganized/informal sector [as] street vend[ors], shops assistants, and domestic help” impel good outcomes in the MLS?⁴⁴

Furthermore, assessment of social functioning is, in general, “fraught with problems”²⁷ given variation in sociocultural environments, norms, and attitudes.³ Unfortunately, neither the research reviewed above nor the WHO studies provide the evidence that allows us to evaluate the quality of family and social interactions, the nature of employment, and the meaning of marriage for the subjects in the various studies. Ethnographic methods are needed to gain a better understanding of the social functioning of persons with schizophrenia in a range of sociocultural environments.¹⁸^,¹⁹

Third, the WHO studies have led “to the ironic observation that abundance cripples” and that “scarcity” and “collaborative social world[s]” are responsible for better outcomes.⁵⁶ Yet, our review of the research suggests a different conclusion: wherever it is found, lack of care is associated with relatively poor outcomes and that accessing care is associated with improved outcomes. Because the individuals in many of the studies were receiving care at leading academic psychiatric facilities, one might even say that their relatively good clinical, occupational, and social outcomes reflected the effects of quality care as much as, if not more than, the effects of sociocultural environments. Thus, the favorable outcomes that have been found by some studies cannot be assumed to be representative of outcomes in low- and middle-income countries where the majority of persons with schizophrenia have little or no access to care.

Fourth, the evidence about excess mortality must not be ignored. We agree with Ran et al.⁵¹: “It may be premature to suggest that there is a better prognosis for schizophrenia in [developing] countries if withdrawals or attrition due to death…are not included in follow-up analyses.”

Fifth, further research into the role of families is necessary. Although expressed emotion studies are informative about the nature of family interactions, such research provides little understanding of the processes that for example, lead Indian families to keep members with schizophrenia out of care, or that bring about the breakdown of family support for subjects in Nigeria, or that force homelessness upon some persons with schizophrenia in China. Surveys of public attitudes in Nigeria⁶⁵^,⁶⁶ and Ethiopia,⁶⁷ as well as qualitative and survey research with families in India⁶⁰^,⁶⁸^–⁷⁰ suggest high levels of stigma about mental illness. These negative attitudes, at least in Africa, are believed to result in families abandoning mentally ill members.⁷¹ Appalling conditions in psychiatric facilities in Asia⁷²^–⁷⁴ also raise questions about whether presumed tolerance translates into better outcomes.

Sixth, variability in outcomes is evident in high-income countries, too. Reviews of long-term studies¹⁶^,⁷⁵^,⁷⁶ show variability from study to study, and ISoS¹⁵ shows variability in outcomes across high-income countries. One analysis of DOSMeD data⁷⁷ indicates that 2-year outcomes in Prague and Nottingham were similar to those in India, while outcomes in Cali were close to those in high-income countries. Given this variation, we need to find a better framework for comparing schizophrenia outcomes in different sociocultural environments.

Seventh, the evidence provided by this review suggests that the sampling methods utilized in the WHO studies may have resulted in overly optimistic perceptions of course and outcome in low- and middle-income countries. Except for the China ISoS site, sampling in all the WHO studies relied on a variety of help-seeking agencies to identify potential subjects.¹⁰^,¹¹^,¹⁵ However, community surveys in rural China,²⁹ India,³⁶^,⁴³^,⁴⁶ Indonesia,⁷⁸ and Ethiopia have shown that large proportions of persons with schizophrenia (between about 25% and almost 90%) never receive biomedical treatments. Furthermore, outcomes in these samples, whether or not subjects received treatment following inclusion in the studies, tended to be poor. Therefore, there is the possibility that case-finding methods which focus exclusively on help-seeking agencies will miss large proportions of seriously ill, poor prognosis individuals.

This review has 2 main limitations. First, our strategy to identify studies—searches of bibliographic databases and locating references cited in journal articles—may not have been comprehensive, and it is possible that we did not find all the studies that met our criteria. It is also possible that reliance on English language articles excluded a number of reports about other outcome studies. Nevertheless, because this was a narrative review and not a meta-analysis, we do not believe these potential shortcomings would have substantially influenced our conclusions. Second, a more serious limitation is the possibility that apparent variations in course and outcome were the function of methodological heterogeneity among the studies. We do not believe this was the case because the methods and instruments used in the studies were generally consistent with each other.

In conclusion, we suggest it is time to revisit the hypothesis that the course and outcome of schizophrenia is better in low- and middle-income countries. Although a host of sociocultural factors have been cited as contributing to variation in the course and outcome of schizophrenia—eg, family support and styles of interaction, industrialization, and urbanization⁴—there is little direct evidence, and what exists provides little help in unpacking the “black box” of culture.⁷⁹ Clinical, epidemiological, and ethnographic research are required to better understand how neuropsychiatric processes and social worlds interact to shape the lives of persons with schizophrenia in low- and middle-income countries.

The questions in need of investigation include:

Of the prevalent cases in each catchment area, how many are receiving psychiatric care? How many are receiving alternative forms of treatment? How many are receiving no care at all?
What are the biomedical and other treatment effects on outcome? How do variations in treatment influence variations in outcomes within and across research sites?
What are the clinical outcomes in terms of positive and negative symptomatology of incident and prevalent cases?
How might employment and nonpaid occupations influence or be influenced by clinical factors?
What is the quality of family life (natal and marital) of persons with schizophrenia and how does this influence (or is influenced by) outcome?
What are the pathways to care (biomedical and traditional) and what are the clinical and sociocultural factors associated with help-seeking decisions?
What are the circumstances that lead to suicidality and excess mortality among persons with schizophrenia?

The knowledge that will come from answering these and other questions is important for at least 3 reasons. First, identifying the processes that promote good prognosis will inform the care and treatment of persons with schizophrenia wherever they live. Second, accurate information about the realities of the day-to-day lives of persons with schizophrenia in low- and middle-income countries will inform advocacy efforts to: (a) close the enormous gap between the numbers of people in need of care and the small number who actually receive it⁸⁰; and (b) provide greater supports for families. Finally, globalization is bringing about enormous sociocultural and socioeconomic changes to the societies of low- and middle-income countries. In turn, these changes will, inevitably, transform the nature of families and the communities in which they live, the epidemiological profile of nations and regions, and the services provided by health systems. No doubt, globalization will have significant consequences for the lives of persons with schizophrenia. To prevent or at least limit the potential harm that may result, it is essential that we have detailed understandings about how sociocultural and psychiatric processes interact. For these reasons, it would make sense to put aside presumed wisdom and reexamine the question of the prognosis of schizophrenia in low- and middle-income countries.

Acknowledgments

Patel is a Wellcome Trust Senior Clinical Research Fellow in Tropical Medicine.

References

1. Patel V, Cohen A, Thara R, Gureje O. Is the outcome of schizophrenia really better in developing countries? Rev Bras Psiquiatr. 2006;28:149–152. [PubMed]

2. Bhugra D. Severe mental illness across cultures. Acta Psychiatr Scand Suppl. 2006;34(2):229–244.

3. Isaac M, Chand P, Murthy P. Schizophrenia outcome measures in the wider international community. Br J Psychiatry. 2007;191(suppl 50):s71–s77. [PubMed]

4. Kulhara P, Chakrabarti S. Culture and schizophrenia and other psychotic disorders. Psychiatr Clin North Am. 2001;24:449–464. [PubMed]

5. Mueser KT, McGurk SR. Schizophrenia. Lancet. 2004;363:2063–2072. [PubMed]

6. Kroeber AL. Psychotic factors in shamanism. Character Pers. 1940;8:204–215.

7. Devereux G. Schizophrenia: an ethnic psychosis or schizophrenia without tears. In: Devereux G, editor. Basic Problems of Ethnopsychiatry. Chicago: University of Chicago Press; 1980. pp. 214–236.

8. Murphy HB, Raman AC. The chronicity of schizophrenia in indigenous tropical peoples: results of a twelve-year follow-up survey in Mauritius. Br J Psychiatry. 1971;118:489–497. [PubMed]

9. Waxler NE. Is outcome for schizophrenia better in nonindustrial societies? The case of Sri Lanka. J Nerv Ment Dis. 1979;167:144–158. [PubMed]

10. WHO. Schizophrenia: An International Follow-up Study. Chichester, UK: John Wiley and Sons; 1979.

11. Jablensky A, Sartorius N, Ernberg G, et al. Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. Psychol Med Monogr Suppl. 1992;20:1–97. [PubMed]

12. Harrison G, Hopper K, Craig T, et al. Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J Psychiatry. 2001;178:506–517. [PubMed]

13. McIntosh A, Lawrie S. Cross-national differences in diet, the outcome of schizophrenia and the prevalence of depression: you are (associated with) what you eat. Br J Psychiatry. 2004;184:381–382. [PubMed]

14. Lin K-M, Kleinman AM. Psychopathology and clinical course of schizophrenia: a cross-cultural perspective. Schizophr Bull. 1988;14:555–567. [PubMed]

15. Hopper K, Harrison G, Janca A, Sartorius N, editors. Recovery from Schizophrenia: An International Perspective. Oxford: Oxford University Press; 2007.

16. Bromet EJ, Naz B, Fochtmann LJ, Carlson GA, Tanenberg-Karant M. Long-term diagnostic stability and outcome in recent first-episode cohort studies of schizophrenia. Schizophr Bull. 2005;31:639–649. [PubMed]

17. World Bank. Data & Statistics.

18. Cohen A. Prognosis for schizophrenia in the Third World: a reevaluation of cross-cultural research. Cult Med Psychiatry. 1992;16:53–75. 101–106. [PubMed]

19. Edgerton RB, Cohen A. Culture and schizophrenia: the DOSMD challenge. Br J Psychiatry. 1994;164:222–231. [PubMed]

20. Thara R. Twenty-year course of schizophrenia: the Madras longitudinal study. Can J Psychiatry. 2004;49:564–569. [PubMed]

21. Thara R, Henrietta M, Joseph A, Rajkumar S, Eaton WW. Ten-year course of schizophrenia—the Madras longitudinal study. Acta Psychiatr Scand. 1994;90:329–336. [PubMed]

22. ICMR. Mental Health Research in India: Technical Monograph on ICMR Mental Health Studies. New Delhi, India: Indian Council of Medical Research; 2005.

23. Kurihara T, Kato M, Reverger R, Tirta IG. Eleven-year clinical outcome of schizophrenia in Bali. Acta Psychiatr Scand. 2005;112:456–462. [PubMed]

24. Kurihara T, Kato M, Reverger R, Yagi G. Outcome of schizophrenia in a non-industrialized society: comparative study between Bali and Tokyo. Acta Psychiatr Scand. 2000;101:148–152. [PubMed]

25. Verghese A, John JK, Rajkumar S, Richard J, Sethi BB, Trivedi JK. Factors associated with the course and outcome of schizophrenia in India: results of a two-year multicentre follow-up study. Br J Psychiatry. 1989;154:499–503. [PubMed]

26. Thara R, Rajkumar S. Gender differences in schizophrenia: results of a follow-up study from India. Schizophr Res. 1992;7:65–70. [PubMed]

27. Kulhara P, Wig NN. The chronicity of schizophrenia in North West India: results of a follow-up study. Br J Psychiatry. 1978;132:186–190. [PubMed]

28. Kulhara P, Chandiramani K. Outcome of schizophrenia in India using various diagnostic systems. Schizophr Res. 1988;1:339–349. [PubMed]

29. Ran MS, Xiang M, Huang M, Shan Y, Cooper J. Natural course of schizophrenia: 2-year follow-up study in a rural Chinese community. Br J Psychiatry. 2001;178:154–158. [PubMed]

30. Thara R, Eaton WW. Outcome of schizophrenia: the Madras longitudinal study. Aust N Z J Psychiatry. 1996;30:516–522. [PubMed]

31. Thara R, Srinivasan TN. Outcome of marriage in schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 1997;32:416–420. [PubMed]

32. Kebede D, Alem A, Shibre T, Negash A, Deyassa N, Beyero T. The sociodemographic correlates of schizophrenia in Butajira, rural Ethiopia. Schizophr Res. 2004;69:133–141. [PubMed]

33. Kebede D, Alem A, Shibre T, et al. Short-term symptomatic and functional outcomes of schizophrenia in Butajira, Ethiopia. Schizophr Res. 2005;78:171–185. [PubMed]

34. Kebede D, Alem A, Shibire T, et al. Symptomatic and functional outcome of bipolar disorder in Butajira, Ethiopia. J Affect Disord. 2006;90:239–249. [PubMed]

35. Gureje O, Bamidele R. Thirteen-year social outcome among Nigerian outpatients with schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 1999;34:147–151. [PubMed]

36. Padmavathi R, Rajkumar S, Srinivasan TN. Schizophrenic patients who were never treated—a study in an Indian urban community. Psychol Med. 1998;28:1113–1117. [PubMed]

37. Menezes PR, Mann AH. Characteristics of hospital-treated schizophrenia in São Paulo, Brazil. Soc Psychiatry Psychiatr Epidemiol. 1993;28:267–274. [PubMed]

38. Menezes PR, Mann AH. The social adjustment of patients with schizophrenia: implications to the mental health policy in Brazil. Rev Saude Publica. 1993;27:340–349. [PubMed]

39. Hickling FW, McCallum M, Nooks L, Rodgers-Johnson P. Outcome of first contact schizophrenia in Jamaica. West Indian Med J. 2001;50:194–197. [PubMed]

40. Warner R. Recovery from Schizophrenia: Psychiatry and Political Economy. 3rd ed. London: Routledge; 2004.

41. Murthy RS, Kishore Kumar KV, Chisholm D, Thomas T, Sekar K, Chandrashekari CR. Community outreach for untreated schizophrenia in rural India: a follow-up study of symptoms, disability, family burden and costs. Psychol Med. 2005;35:341–351. [PubMed]

42. Kebede D, Alem A, Shibre T, et al. Onset and clinical course of schizophrenia in Butajira-Ethiopia—a community-based study. Soc Psychiatry Psychiatr Epidemiol. 2003;38:625–631. [PubMed]

43. Srinivasan TN, Thara R. How do men with schizophrenia fare at work? A follow-up study from India. Schizophr Res. 1997;25:149–154. [PubMed]

44. Srinivasan TN, Thara R. The long-term home-making functioning of women with schizophrenia. Schizophr Res. 1999;35:97–98. [PubMed]

45. Srinivasan TN, Rajkumar S, Padmavathi R. Initiating care for untreated schizophrenia patients and results of one year follow-up. Int J Soc Psychiatry. 2001;47:73–80. [PubMed]

46. Tirupati NS, Rangaswamy T, Raman P. Duration of untreated psychosis and treatment outcome in schizophrenia patients untreated for many years. Aust N Z J Psychiatry. 2004;38:339–343. [PubMed]

47. Oosthuizen P, Emsley RA, Keyter N, Niehaus DJ, Koen L. Duration of untreated psychosis and outcome in first-episode psychosis perspective from a developing country. Acta Psychiatr Scand. 2005;111:214–219. [PubMed]

48. Ran MS, Meng-Ze X, Sheng-Xian L, et al. Prevalence and outcome of schizophrenia in a Chinese rural area: an epidemiological study. Aust N Z J Psychiatry. 2003;37:452–457. [PubMed]

49. Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. In press. [PubMed]

50. Craig TJ, Tang D-I, Sartorius N, Laska EM, Cancro R. Long-term mortality experience of international cohorts of persons with schizophrenia and related psychoses. In: Hopper K, Harrison G, Janca A, Sartorius N, editors. Recovery from Schizophrenia: An International Perspective. Oxford: Oxford University Press; 2007. pp. 61–68.

51. Ran M-S, Chen EY-H, Conwell Y, et al. Mortality in people with schizophrenia in rural China: 10-year cohort study. Br J Psychiatry. 2007;190:237–242. [PubMed]

52. Menezes PR, Mann AH. Mortality among patients with non-affective functional psychoses in a metropolitan area of south-eastern Brazil. Rev Saude Publica. 1996;30:304–309. [PubMed]

53. Makanjuola ROA, Adedapo SA. The DSM-III concepts of schizophrenic disorder and schizophreniform disorder: a clinical and prognostic evaluation. Br J Psychiatry. 1987;151:611–618. [PubMed]

54. Kurihara T, Kato M, Kashima H, Takebayashi T, Reverger R, Tirta IGR. Excess mortality of schizophrenia in the developing country of Bali. Schizophr Res. 2006;83:103–105. [PubMed]

55. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62:247–253. [PubMed]

56. Hopper K. Some old questions for the new cross-cultural psychiatry. Med Anthropol Q. 1991;5:299–330.

57. Hopper K. Cervantes’ puzzle—a commentary on Alex Cohen's “Prognosis for schizophrenia in the Third World: a reevaluation of cross-cultural research” Cult Med Psychiatry. 1992;16:89–100. [PubMed]

58. Leff J, Wig NN, Bedi H, et al. Relatives’ expressed emotion and the course of schizophrenia in Chandigarh: a two-year follow-up of a first-contact sample. Br J Psychiatry. 1990;156:351–356. [PubMed]

59. Leff J, Wig NN, Ghosh A, et al. Expressed emotion and schizophrenia in north India. III. Influence of relatives’ expressed emotion on the course of schizophrenia in Chandigarh. Br J Psychiatry. 1987;151:166–173. [PubMed]

60. Thara R, Kamath S, Kumar S. Women with schizophrenia and broken marriages—doubly disadvantaged? Part I: patient perspective. Int J Soc Psychiatry. 2003;49:225–232. [PubMed]

61. Ran MS, Chan CL, Chen EY, Xiang MZ, Caine ED, Conwell Y. Homelessness among patients with schizophrenia in rural China: a 10-year cohort study. Acta Psychiatr Scand. 2006;114:118–123. [PubMed]

62. Seeman MV. Women and schizophrenia. Med women's health. 2000;5(2):2. [PubMed]

63. Ohaeri JU. Long-term outcome of treated schizophrenia in a Nigerian cohort. Retrospective analysis of 7-year follow-ups. J Nerv Ment Dis. 1993;181:514–516. [PubMed]

64. Menezes PR, Rodrigues LC, Mann AH. Predictors of clinical and social outcomes after hospitalization in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1997;247:137–145. [PubMed]

65. Gureje O, Lasebikan VO, Ephraim-Oluwanuga O, Olley BO, Kola L. Community study of knowledge of and attitude to mental illness in Nigeria. Br J Psychiatry. 2005;186:436–441. [PubMed]

66. Odejide AO, Olatawura MO. A survey of community attitudes to the concept and treatment of mental illness in Ibadan, Nigeria. Niger Med J. 1979;9:343–347. [PubMed]

67. Shibre T, Negash A, Kullgren G, et al. Perception of stigma among family members of individuals with schizophrenia and major affective disorders in rural Ethiopia. Soc Psychiatry Psychiatr Epidemiol. 2001;36:299–303. [PubMed]

68. Thara R. People with schizophrenia believe that they are stigmatised at work and in the community. Evid Based Ment Health. 2003;6:96. [PubMed]

69. Thara R, Kamath S, Kumar S. Women with schizophrenia and broken marriages—doubly disadvantaged? Part II: family perspective. Int J Soc Psychiatry. 2003;49(3):233–240. [PubMed]

70. Thara R, Srinivasan TN. How stigmatising is schizophrenia in India? Int J Soc Psychiatry. 2000;46:135–141. [PubMed]

71. Gureje O. Psychiatry in Africa: the myths, the exotic, and the realities. S Afr Psychiatry Rev. 2007;10:11–14.

72. Beech H. Hidden away. Time Asia. 2003;18 pp 34–39.

73. National Human Rights Commission. Quality Assurance in Mental Health. New Delhi, India: National Human Rights Commission of India; 1999.

74. Krishnakumar A. Deliverance in Erwadi [Electronic Version] Frontline. 2001;18 Retrieved May 14, 2007 from http://www.hinduonnet.com/fline/fl1817/18171280.htm.

75. Ram R, Bromet EJ, Eaton WW, Pato C, Schwartz JE. The natural course of schizophrenia: a review of first-admission studies. Schizophr Bull. 1992;18:185–207. [PubMed]

76. Hegarty JD, Baldessarini RJ, Tohen M, Waternaux C, Oepen G. One hundred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry. 1994;151:1409–1416. [PubMed]

77. Craig TJ, Siegel C, Hopper K, Lin S, Sartorius N. Outcome in schizophrenia and related disorders compared between developing and developed countries. A recursive partitioning re-analysis of the WHO DOSMD data. Br J Psychiatry. 1997;170:229–233. [PubMed]

78. Kurihara T, Kato M, Reverger R, Tirta IGR, Kashima H. Never-treated patients with schizophrenia in the developing country of Bali. Schizophr Res. 2005;79:307–313. [PubMed]

79. Hopper K. Interrogating the meaning of “culture” in the WHO international studies of schizophrenia. In: Jenkins JH, Barrett RJ, editors. Schizophrenia, Culture, and Subjectivity: The Edge of Experience. Cambridge, UK: Cambridge Unviersity Press; 2004. pp. 62–86.

80. WHO. Mental Health Global Action Programme. Geneva, Switzerland: World Health Organization; 2002.

81. Ran MS, Chan CL, Xiang MZ, Wu QH. Suicide attempts among patients with psychosis in a Chinese rural community. Acta Psychiatr Scand. 2003;107:430–435. [PubMed]

82. Kulhara P, Mattoo SK, Chandiramani K, Bhave S, Awasthi A. Diagnostic systems for schizophrenia. A cross-sectional study of concordance from India. Acta Psychiatr Scand. 1986;74:55–61. [PubMed]

83. Verghese A, Dube KC, John J, et al. Factors associated with the course and outcome of schizophrenia: a multicentred follow-up study. Indian J Psychiatry. 1985;27:201–206. [PMC free article] [PubMed]

84. Rajkumar S, Thara R. Factors affecting relapse in schizophrenia. Schizophr Res. 1989;2:403–409. [PubMed]

85. Eaton WW, Thara R, Federman B, Melton B, Liang KY. Structure and course of positive and negative symptoms in schizophrenia. Arch Gen Psychiatry. 1995;52:127–134. [PubMed]

86. Eaton WW, Thara R, Federman E, Tien A. Remission and relapse in schizophrenia: the Madras longitudinal study. J Nerv Ment Dis. 1998;186:357–363. [PubMed]

87. Hickling FW, Rodgers-Johnson P. The incidence of first contact schizophrenia in Jamaica. Br J Psychiatry. 1995;167:193–196. [PubMed]

88. Bhugra D, Hilwig M, Hossein B, et al. First-contact incidence rates of schizophrenia in Trinidad and one-year follow-up. Br J Psychiatry. 1996;169:587–592. [PubMed]

89. Kurihara T, Kato M, Reverger R, Yagi G. Clinical outcome of patients with schizophrenia without maintenance treatment in a nonindustrialized society. Schizophr Bull. 2002;28:515–524. [PubMed]

90. Obembe A, Famuyiwa O, Bebbington P. Outcome of functional psychoses in metropolitan Lagos, Nigeria. East Afr Med J. 1995;72:234–240. [PubMed]

91. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res. 2005;79:231–238. [PubMed]

92. U.S. Census Bureau. International Data Base.

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