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David St Clair, MD, PhD; Mingqing Xu, PhD; Peng Wang, MD; Yaqin Yu, MD; Yourong Fang, MD; Feng Zhang, MD; Xiaoying Zheng, MD; Niufan Gu, MD; Guoyin Feng, MD; Pak Sham, MD, PhD; Lin He, PhD

JAMA. 2005;294:557-562.

Context  Schizophrenia is a common major mental disorder. Intrauterine nutritional deficiency may increase the risk of schizophrenia. The main evidence comes from studies of the 1944-1945 Dutch Hunger Winter when a sharp and time-limited decline in food intake occurred. The most exposed cohort conceived during the famine showed a 2-fold increased risk of schizophrenia.

Objective  To determine whether those who endured a massive 1959-1961 famine in China experienced similar results.

Design, Setting, and Participants  The risk of schizophrenia was examined in the Wuhu region of Anhui, one of the most affected provinces. Rates were compared among those born before, during, and after the famine years. Wuhu and its surrounding 6 counties are served by a single psychiatric hospital. All psychiatric case records for the years 1971 through 2001 were examined, and clinical and sociodemographic information on patients with schizophrenia was extracted by researchers who were blinded to the nature of exposure. Data on number of births and deaths in the famine years were available, and cumulative mortality was estimated from later demographic surveys.

Main Outcome Measures  Evidence of famine was verified, and unadjusted and mortality-adjusted relative risks of schizophrenia were calculated.

Results  The birth rates (per 1000) in Anhui decreased approximately 80% during the famine years from 28.28 in 1958 and 20.97 in 1959 to 8.61 in 1960 and 11.06 in 1961. Among births that occurred during the famine years, the adjusted risk of developing schizophrenia in later life increased significantly, from 0.84% in 1959 to 2.15% in 1960 and 1.81% in 1961. The mortality-adjusted relative risk was 2.30 (95% confidence interval, 1.99-2.65) for those born in 1960 and 1.93 (95% confidence interval, 1.68-2.23) for those born in 1961.

Conclusion  Our findings replicate the Dutch data for a separate racial group and show that prenatal exposure to famine increases risk of schizophrenia in later life.

Author Affiliations: Bio-X Center, Shanghai Jiao Tong University, Shanghai (Drs St Clair and Xu), Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences (Drs Xu and He), Fourth People’s Hospital, Wuhu, Anhui (Drs Wang and Yu), Second People’s Hospital, Huang Shan, Anhui (Dr Fang), Institute of Population Research, Peking University (Dr Zheng), Shanghai Institute of Mental Health, Shanghai (Drs Gu and Feng), Department of Psychiatry, University of Hong Kong, Hong Kong (Dr Sham), and NHGG, Shanghai Jiao Tong University, Shanghai (Dr He), People’s Republic of China; Department of Mental Health, University of Aberdeen, Scotland (Drs St Clair and Zhang); and Division of Psychological Medicine, Institute of Psychiatry, London, England (Dr Sham).

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