Geographical variation in incidence, course and outcome of schizophrenia: a comparison of developing and developed countries
Schizophrenia was not identified as a discrete illness until the dawn of the 20th century and was once widely considered a ‘disease of civilization’. Later evidence suggested that at least some cases of schizophrenia could be identified in any community at whatever level of development, but the incidence rate of schizophrenia in developing countries is still largely a matter for bold speculation based on minimal data. In the meantime, strong evidence has emerged for a surprising result: the course of schizophrenia is more benign in the developing countries, where treatment options are minimal.
In this section, we review the evidence for differences in incidence as well as course of schizophrenia between developing and developed countries. Present day researchers often prefer the more neutral designation of ‘low-income’ versus ‘high-income’ countries, which does not imply any universal continuum of economic development. For clarity, however, we retain the term used in the literature we review.
In a recent review of schizophrenia incidence studies, the annual incidence rates ranged from 0.04 to 0.58 per 1000 (Eaton, 1999). Because the observed variation is likely to result in part from differences in the methods of individual studies (Bresnahan et al., 2000), its meaning with respect to geographic distribution is unclear. Systematic patterns of variation are obscured by these and other artifacts.
Here we have chosen to examine variation across sociocultural settings by comparing developing and developed countries. This approach is promising, in view of the high contrast between the sociocultural environments in these two settings. In addition, the division has been shown to have predictive value for studies of outcome.
Is the incidence of schizophrenia different in developing and developed countries? Our capacity to answer this question is constrained by the small number of studies conducted in developing countries. The total developing country evidence is slim and includes four published incidence studies (Jablensky et al., 1992; Hickling and Rodgers-Johnson, 1995; Bhugra et al., 1996; Mahy et al., 1999) based on first treatment contact and direct assessments in a defined population. The study locations include rural and urban Chandigarh, Trinidad, Barbados and Jamaica (Table 2.1). (One additional incidence study conducted in Madras (Rajkumar et al., 1993) ascertained cases based on a door-to-door community screening and direct assessment in a defined urban area. However, as the method was different from other studies, and the number of cases small, it has little bearing on the question at hand.)
Geographical variation: developing and developed countries
Among these four developing country studies reporting incidence, the Chandigarh study provides the most important evidence. It was part of the World Health Organization (WHO) Ten Country Study (Jablensky et al., 1992), in which both developed and developing country sites were included. In this landmark project, also referred to as the Determinants of Severe Mental Disorder Study (DOSMeD), the collection of comparable evidence in the same time period offers sound comparison of incidence rates across a variety of sociocultural settings.
Furthermore, both an urban and a rural site were studied in Chandigarh.
The Ten Country Study
The Ten Country Study is often cited, in our view mistakenly, as providing the evidence for worldwide ‘uniform’ incidence and symptom expression of schizophrenia. Twelve centres in ten countries were represented: Denmark (Aarhus), India (Chandigarh urban, Chandigarh rural, Agra), Ireland (Dublin), USA (Honolulu, Rochester), England (Nottingham), Soviet Union (Moscow), Japan (Nagasaki), Czeckslovakia (Prague), Columbia (Cali), Nigeria (Ibadan). Cases were ascertained for 2 years, identifying first-contact patients with nonaffective psychosis in welldefined populations. Equivalent methods of ascertainment, assessment and diagnosis were implemented across sites. Eight sites had suficiently complete case ascertainment to yield incidence rates. Urban and rural Chandigarh were the only developing country sites among the eight reporting incidence rates.
Two key findings were reported. The first was that the incidence of narrowly defined schizophrenia demonstrated no significant variation across sites. The observation of no significant variation for narrowly defined schizophrenia, however, was based on CATEGO S+ diagnoses, which was the definition of ‘narrow’ schizophrenia in the Ten Country Study. CATEGO S+ criteria focus exclusively on first-rank, positive symptoms during the month before interview using the Present State Examination (PSE).
Table 2.1. Selected incidence studies (ICD-9 or CATEGO)
CATEGO, computer algorithm diagnoses using Present State Exam; ICD, International Classification of Disease - ninth revision - Clinical Modification; S+, narrowly defined schizophrenia; SPO, broadly defined schizophrenia.
To facilitate comparison between developing and developed countries, only incidence study sites reporting CATEGO diagnoses or ICD-9 diagnoses are included in the table. For a more complete view of incidence studies see Eaton (1999).
a ICD-9 rates for the WHO Ten Country Study sites were calculated based on cases with 295 diagnoses reported in Jablensky et al. (1992; p. 29).
b Rates CATEGO SPO+.
c Moscow was a priori a developed country; this may be in error.
d Based on total population base and total cases over three reported ethnic groups in two health districts selected for ethnic diversity
e Based on mean rate between men and women given.
The concordance between S+ and schizophrenia under modern diagnostic systems is not high (Mason et al., 1997). Because of these uncertainties about diagnosis, it is diffcult to draw conclusions from S+ variation in the Ten Country Study. The second finding was that incidence of schizophrenia broadly defined demonstrated significant cross-country variation, with the highest rates being reported in Chandigarh, the only developing country sites.
Continuation studies of the initial WHO cohorts at both developed and developing country sites, and rediagnosis of cases using modern criteria, will contribute important information with respect to the generalizability of the S+ findings to schizophrenia currently conceived. Preliminary analyses of rediagnosed Chandigarh urban and rural site cases suggest that variation may be substantially greater than the S+ incidence findings would indicate. Cases were rediagnosed according to ICD-10 (World Health Organization, 1992) criteria, based on all information available at last follow-up. In the combined Chandigarh sites (n=209), lifetime diagnoses were assigned to 141 cases based on information available at 12 - 15 years of follow-up, to 15 based on information available at 5 - 11 years follow-up, and to 43 based on information available 0 - 4 years after intake; rediagnoses for 10 cases are currently unavailable. Based on known cases, urban and rural Chandigarh rates of lifetime ICD-10 F-20 schizophrenia in the original cohort are 1.85 (95% confidence interval (CI) 1.46 - 2.31) and 2.68 (95% CI 1.84 - 3.76) per 10000. These rates are intermediate between the rates of broadly defined schizophrenia (urban Chandigarh 3.5, rural Chandigarh 4.2 per 10000) and narrowly defined schizophrenia (urban Chandigarh 0.9, rural Chandigarh 1.1 per 10000) in the original report.
Interpretation of the Chandigarh incidence rates for ICD-10 schizophrenia is limited by the unavailability of similar incidence data from developed country sites in the Ten Country Study. However, somewhat comparable diagnoses are available for the Nottingham site. In a rediagnosis exercise, ICD-10 diagnoses were rendered based on information available at intake. The rate of ICD-10 F-20 schizophrenia was 1.41 per 10000 (95% CI 1.03 - 1.78) (Brewin et al., 1997). This rate is markedly lower than those reported above for the urban Chandigarh and rural Chandigarh sites. Therefore, comparison of the preliminary findings from Chandigarh and reports from Nottingham suggest that for ICD-10 schizophrenia there may be substantial variation across sites, as observed for broadly defined, not narrowly defined, schizophrenia in the original report.
Michaeline Bresnahan, Paulo Menezes, Vijoy Varma and Ezra Susser
Division of Epidemiology, Columbia University, New York, USA
Department of Preventative Medicine, University of Sao Paulo, Brazil
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