The pattern for most diseases is clear: the richer and more developed the country, the better the patient outcome. Schizophrenia appears to be different. This paradox first came to light 40 years ago. Studies from Mauritius and Sri Lanka appeared to show better outcomes than developed countries: patients experienced fewer delusions and hallucinations, less disorganized speech, and improved social functioning. But these studies lacked standardized diagnostic criteria and assessment methods, and had varying attrition rates. In the late 1960s, in an effort to standardize research methods, the World Health Organization (WHO) launched the first of the following three landmark international studies: the International Pilot Study of Schizophrenia (IPSS); the Determinants of Outcomes of Severe Mental Disorders (DOSMeD); and the International Study of Schizophrenia (ISoS). The IPSS enrolled a total of 1,202 patients in nine countries: three developing countries (Colombia, India and Nigeria) and six developed ones (Denmark, Taiwan, the United Kingdom, the United States, the Soviet Union and Czechoslovakia). The patients’ outcomes were assessed by using three indicators — the percentage of time with psychosis symptoms, the type of remission after each episode, and the degree of social impairment — and were classified on a scale of one (best) to seven (worst). At the five-year follow-up, India had the most success, with 42% of cases reporting ‘best’ outcomes, followed by Nigeria with 33% of cases. By contrast, the developed countries had poor showings: ‘best’ outcomes were seen in only 17% of cases in the United States, and in fewer than 10% in the other developed nations. Beginning in the early 1980s, the DOSMeD study examined schizophrenia incidence, prevalence and outcomes in 12 centres across 10 countries (the IPSS countries plus Ireland). Its 1,379 patients were assigned to 1 of 9 categories, ranging from a single episode of psychotic illness followed by complete remission, to continuing illness. The study found that developing countries had higher rates of complete recovery: an average of 37% compared with 15.5% in developed countries. The rates of chronic illness, however, were similar: 11.1% in developing and 17.4% in developed countries. Patients in developing countries experienced longer periods of unimpaired social functioning, even though far fewer of them were on continuous antipsychotic medication. The researchers concluded that “a strong case can be made for a real pervasive influence of a powerful factor which can be referred to as ‘culture’ in the context of gene–environment interactions that influence a disease. The contribution of the present study is not in providing the answer but in clearly demonstrating the existence of the question.” The ISoS study returned to the IPSS and DOSMeD patients after 15 and 25 years, and included two other groups, to test whether the better outcomes observed in the previous studies continued in the long term. It traced about 75% of the patients, finding that about half had favourable outcomes, but there was wide variation across different centres. The study concluded that socio-cultural conditions can modify the long-term disease course, and that early intervention programmes with social and pharmacological treatments could have longer-term benefits.